Characteristics of fast voluntary and electrically evoked isometric knee extensions during 56 days of bed rest with and without exercise countermeasure The contractile characteristics of fast voluntary and electrically evoked unilateral isometric knee extensions were followed in 16 healthy men during 56 days of horizontal bed rest and assessed at bed rest days 4 , 7 , 10 , 17 , 24 , 38 and 56 . Subjects were randomized to either an inactive control group -LRB- Ctrl , n = 8 -RRB- or a resistive vibration exercise countermeasure group -LRB- RVE , n = 8 -RRB- . No changes were observed in neural activation , indicated by the amplitude of the surface electromyogram , or the initial rate of voluntary torque development in either group during bed rest . In contrast , for Ctrl , the force oscillation amplitude at 10 Hz stimulation increased by 48 % -LRB- P < 0.01 -RRB- , the time to reach peak torque at 300 Hz stimulation decreased by 7 % -LRB- P < 0.01 -RRB- , and the half relaxation time at 150 Hz stimulation tended to be slightly reduced by 3 % -LRB- P = 0.056 -RRB- after 56 days of bed rest . No changes were observed for RVE . Torque production at 10 Hz stimulation relative to maximal -LRB- 150 Hz -RRB- stimulation was increased after bed rest for both Ctrl -LRB- 15 % ; P < 0.05 -RRB- and RVE -LRB- 41 % ; P < 0.05 -RRB- . In conclusion , bed rest without exercise countermeasure resulted in intrinsic speed properties of a faster knee extensor group , which may have partly contributed to the preserved ability to perform fast voluntary contractions . The changes in intrinsic contractile properties were prevented by resistive vibration exercise , and voluntary motor performance remained unaltered for RVE subjects as well . Introduction Previous research has shown that exposure to actual or simulated spaceflight leads to pronounced muscle atrophy in humans . The associated muscle weakness significantly impairs the performance of various motor tasks -LRB- for reviews see Adams et al. 2003 ; Desplanches 1997 ; Edgerton and Roy 2000 ; Fitts et al. 2000 -RRB- . Muscle function -LRB- e.g. , maximal isometric force -RRB- is often further impaired by adaptations in the central motor control system , as indicated by reductions in the amplitude of the surface electromyogram -LRB- EMG -RRB- during maximal voluntary contractions -LRB- Berg et al. 1997 ; Deschenes et al. 2002 ; di Prampero and Narici 2003 ; Gondin et al. 2004 ; Schulze et al. 2002 -RRB- . Compared to steady-state contractions , much higher levels of neural activation are needed for contractions where torque develops as rapidly as possible . This is seen for both voluntary -LRB- de Ruiter et al. 2004 -RRB- as well as for electrically evoked contractions -LRB- de Haan 1998 ; de Ruiter et al. 1999 -RRB- . In daily life , elderly individuals who lack sufficient motor speed or possess poor lower extremity strength have an increased risk of fall-related bone fractures -LRB- Shigematsu et al. 2006 -RRB- . The same may hold for astronauts suffering from muscle atrophy , neural deconditioning and increased bone fragility following space missions -LRB- Smith and Heer 2002 -RRB- . The adaptive physiological responses in the human body as a consequence of real or simulated space flight may be offset by means of efficient countermeasures . With respect to the neuromuscular system , it appears that resistance exercise -LRB- strength training -RRB- is effective to maintain , or at least to minimize changes in muscle mass and strength during bed rest -LRB- Akima et al. 2001 ; Ferrando et al. 1997 ; Kawakami et al. 2001 -RRB- . Previously , we have shown by means of the twitch interpolation technique , as well as by means of EMG recordings that neural deconditioning was absent during 56 days of bed rest for maximal steady-state contractions , regardless of whether subjects participated in an exercise countermeasure program -LRB- Mulder et al. 2006 , 2007 -RRB- . Nonetheless , based on the above , it can be hypothesised that the neural activation of explosive isometric contractions is more deteriorated by bed rest than the activation of steady-state contractions -LRB- Mulder et al. 2007 -RRB- . The first aim of the study was to test the hypothesis that , in the absence of an exercise countermeasure , the maximal rate of voluntary isometric torque development would show a greater decrease during 56 days of bed rest than the maximal steady-state torque , due to reduced neural drive during the fast voluntary contractions . Such an effect was expected to be prevented by combining daily resistive exercise training with vibration training , which was hypothesized to provide a better protection against musculoskeletal deconditioning during bed rest than heavy-resistance training only -LRB- Rittweger et al. 2006 -RRB- . Although the individual merits of resistance training versus vibration training can not be quantified with such a study design , the efficacy of this combined countermeasure to preserve neural activation and maximal steady-state torque is reported elsewhere -LRB- Mulder et al. 2007 -RRB- . Apart from neural activation , the rate at which muscle force develops under voluntary command is also determined by peripheral factors , such as the intrinsic contractile muscle fibre speed -LRB- Andersen and Aagaard 2006 -RRB- and the stiffness of the series elastic component -LRB- Bojsen-Moller et al. 2005 -RRB- . Both factors are known to be altered by exposure to actual or simulated space flight , but their effect is opposite . Whereas faster intrinsic contractile speed characteristics -LRB- Talmadge 2000 -RRB- can partly or fully compensate for the effect of atrophy on power output of single muscle fibres -LRB- Widrick et al. 1998 -RRB- , the power output of whole muscles -LRB- with intact tendons -RRB- would be diminished by decrements in tendon stiffness -LRB- Kubo et al. 2000 ; Reeves et al. 2005 -RRB- . The second aim of the study was to assess whether changes in peripheral factors influenced the voluntary rate of torque development during bed rest . The functional change in peripheral factors , i.e. , the combined effect of intrinsic muscle and tendon characteristics , were investigated by applying percutaneous muscle stimulation . This is a frequently used methodology to assess muscle properties irrespective of central neural influences -LRB- Binder-Macleod et al. 1995 ; de Haan et al. 2000 ; Gerrits et al. 2001 ; Harridge et al. 1996 -RRB- . We hypothesized that the muscle -- tendon complex of the knee extensors would acquire the intrinsic contractile properties of a faster muscle , which would be prevented by the current countermeasure design , conceivably due to the large number of contraction -- relaxation cycles during resistive vibration exercise -LRB- Blottner et al. 2006 -RRB- . Methods Subjects A total of 16 subjects participated in the present study . All subjects were in good health and were involved in normal physical activity before participation in the large-scale Berlin Bed Rest study -LRB- Rittweger et al. 2006 -RRB- . At the start of the study the subjects were randomly assigned to an experimental group or an inactive control group . The experimental group -LRB- RVE , n = 8 ; mean age , height and body mass ± SD : 33.0 ± 1.9 years , 1.84 ± 0.03 cm and 79.5 ± 3.8 kg -RRB- participated in a progressive resistive vibration exercise -LRB- RVE -RRB- training program during the bed rest . The subjects of the inactive control group -LRB- Ctrl , n = 8 ; mean age , height and body mass ± SD : 34.3 ± 2.5 years , 1.82 ± 0.02 cm and 76.8 ± 1.8 kg , respectively -RRB- were restricted to bed rest without exercise countermeasure . All subjects were familiarized with the concepts of the experiments , procedures , and the equipment during a familiarization session that was scheduled 3 days prior to the start of bed rest . The local Ethics committee of the Charité , Campus Benjamin Franklin Berlin approved the study and all participants gave their written informed consent . General design All subjects underwent 56 days of strict horizontal bed rest at the Charité Benjamin Franklin Hospital , Berlin , Germany . During the bed rest , the subjects were not allowed to stand up , to lift their trunk in bed more than to 30 ° of trunk flexion , to move their legs briskly , or to elicit large forces with their legs muscles other than during testing sessions or during training sessions . Adherence to this protocol was controlled for by continuous video surveillance and by force transducers in the frames of the bed . The diet was balanced using the Harris -- Benedict equation and ingestion of alcohol or nicotine , excessive doses of caffeine , as well as the regular intake of any drug or medication was prohibited -LRB- details in Rittweger et al. 2006 -RRB- . Exercise countermeasure RVE subjects performed resistive exercises on a vibration system that was specifically developed for application under microgravity and bed rest conditions -LRB- Galileo Space ; Novotec , Pforzheim , Germany -RRB- . The applied equipment and protocol for countermeasure exercise are described in detail elsewhere -LRB- Rittweger et al. 2006 -RRB- . In short , the training device consists of a vibration platform , which is vertically suspended on a trolley . Elastic springs were attached to the trolley for the subjects to attach themselves through belts with their shoulders , hips , and hands . During bed rest , RVE subjects trained in the supine position , two times daily for 6 days/week . In each training session , four resistive exercises were performed in the following order : squats , heel raises , toe raises and explosive squats . All exercises were performed while the platform was vibrated at a frequency of 19 Hz . Vibration frequency was progressively increased during the 56-day bed rest period to ∼ 26 Hz at the end of bed rest -LRB- Rittweger et al. 2006 -RRB- . Experimental set-up Isometric force recordings were made from voluntary and electrically evoked contractions of the knee extensor group of the right leg . Subjects were tested in the supine position using the same equipment as previously described -LRB- Mulder et al. 2006 -RRB- . Force signals were digitized using a sampling rate of 1 kHz and stored on disc for immediate and off-line analysis . Torque -LRB- N m -RRB- was off-line calculated as the product of force and external moment arm . Experimental procedures During bed rest , all subjects participated in seven experimental sessions , which were scheduled at days : 4 , 7 , 10 , 17 , 24 , 38 and 56 , the latter being the last day of the bed rest period . The baseline experiment was conducted on the fourth day of bed rest -LRB- BR4 -RRB- for logistical reasons . Although this prevents us to address rapid initial changes in strength and contractile characteristics of the quadriceps -LRB- Berg and Tesch 1996 -RRB- , which might result in an underestimation of the effect of bed rest on the measured parameters , it does not compromise the comparison between groups during bed rest , because the RVE subjects started their exercise training program on the fourth day of bed rest , which was scheduled after the completion of the functional testing conducted on that day . In addition , in this way all experiments were conducted under methodologically similar conditions . That is , at the baseline experiment subjects were already minimally 72 h bedridden , each subject was tested at the same time of day , and subjects of the RVE group were always tested before their morning training session . To minimize potential damage to muscle and tendon structures due to maximal and explosive contractions after a long period of strict muscle inactivity , subjects started each experimental session by performing a standardised warm-up set that consisted of eight to ten unloaded dynamic contractions -LRB- right leg not yet strapped to the force transducer -RRB- , followed by eight sub-maximal isometric contractions at 70 ° of knee flexion . Further force recordings were obtained at the individually determined pre-bed rest optimal knee flexion -LRB- either 60 ° or 70 ° , whereby a knee flexion angle of 0 ° corresponds to full knee extension ; see Mulder et al. 2006 for details -RRB- . Subjects were asked to perform two to three maximal voluntary contractions -LRB- MVC -RRB- of 2 -- 4 s in duration . Attempts were interposed with 2 min of rest . After this procedure , the quadriceps muscle was stimulated through two self-adhesive surface electrodes -LRB- model 283100 , Schwa-Medico , Nieuw Leusden , The Netherlands -RRB- of 80 mm × 130 mm . The stimulation intensity was progressively increased until 40 % of the MVC torque was obtained during a 700 ms tetanic contraction at 150 Hz -LRB- Mulder et al. 2006 -RRB- . The quadriceps muscle was then electrically stimulated with trains of the same single pulse intensity at low -LRB- 7 pulses at 10 Hz -RRB- and high -LRB- 24 pulses at 300 Hz -RRB- stimulation frequency . The trains were applied in this order and interposed with 1 min of rest . Following the electrically evoked contractions , the stimulation electrodes were removed and the skin over the lateral vastus muscle was re-prepared for the positioning of a high-density surface EMG system -LRB- HD-sEMG , Active One , BioSemi Inc. , Amsterdam , The Netherlands -RRB- . The system consisted of 130 densely spaced skin-surface electrodes , arranged in a rectangular 10 × 13 matrix with 5 mm inter-electrode distance -LRB- Blok et al. 2002 -RRB- . Before mounting the grid to the skin , the skin was scrubbed with alcoholic pads and slightly rubbed with electrode paste . Prior to each test , the skin-electrode impedance was checked and , if necessary , the skin was re-prepared . The grid was positioned over the distal -LRB- third -RRB- , anterio-lateral part of the right vastus lateralis muscle , such that the columns of 13 electrodes were aligned parallel to the muscle fibre orientation of the muscle and with the motor endplate zone around the centre of the columns of the grid -LRB- Mulder et al. 2007 -RRB- . The pre-amplified 130 monopolar signals -LRB- referenced to the patella -RRB- were bandpass filtered -LRB- 16 -- 400 Hz -RRB- and simultaneously AD-converted -LRB- 16 bits with a resolution of 1 μV/bit at a rate of 2 kHz/channel -RRB- . Data were stored on hard disk for subsequent off-line processing . With the sEMG system properly positioned , each subject performed another MVC of 2 -- 4 s . If the torque deviated more than 5 % from the highest torque attained during the previous MVC-task -LRB- i.e. , the highest value of the attempts before the application of electrical stimulation -RRB- , another attempt was made . Lastly , each subject performed three fast -LRB- explosive -RRB- isometric contractions to assess the neural control of these contractions , as well as the initial rate of torque development during these attempts . Subjects were instructed to contract `` as fast and forcefully as possible '' on a given signal from the test leader -LRB- 3-2-1 `` Go '' -RRB- . Subjects were required to reach a minimum of 80 % of the current MVT and to maintain torque at the highest attained level for approximately 1 s , i.e. , ` kicks ' were always disqualified . Attempts with an initial countermovement -LRB- identified by a drop in the torque signal exceeding 1 N just before the onset of torque development -RRB- were also disqualified -LRB- Aagaard et al. 2002 ; de Ruiter et al. 2004 -RRB- . Attempts were interposed with 2 min of rest . Data analysis Fast voluntary isometric knee extensions The neural activation of muscle fibres at the start of a contraction greatly determines the performance of specific voluntary motor functions , such as the rate at which muscle force develops during fast and forceful voluntary isomeric contractions -LRB- de Ruiter et al. 2004 -RRB- . Even so , the maximal rate of isometric torque development did not differentiate subjects according to their ability to generate high neural activation levels at the very start of the contraction . Instead , the time torque integral , calculated as the area under the time torque curve over the first 40 ms after the onset of torque development , showed to be more sensitive to the initial level of neural activation -LRB- de Ruiter et al. 2004 -RRB- . Based on these findings , we calculated the voluntary time torque integral -LRB- vTTI40 -RRB- as an estimate of maximal isometric tension development under voluntary command -LRB- Fig. 1 -RRB- . The onset of torque development was thereby defined as the point at which the torque curve exceeded baseline torque by more than three standard deviations . Fig. 1Voluntary torque -LRB- thick line -RRB- and rectified surface EMG of the vastus lateralis muscle -LRB- thin line -RRB- time traces , obtained from a representative subject during an isometric voluntary knee extension performed as fast and forcefully as possible . The arrow and diamond at time 0 ms indicate the start of voluntary torque development . The shaded area under the voluntary torque trace reflects the vTTI40 , calculated the first 40 ms after onset of torque development . The horizontal bar indicates the 40 ms immediately preceding the onset of torque development -LRB- i.e. , from − 40 to 0 ms -RRB- for which the root mean square -LRB- RMS -RRB- of the surface EMG was calculated . Subsequently , both vTTI40 and RMS − 40 -- 0 were normalized to the steady state maximal isometric knee extension condition at the day of testing Voluntary neural activation during the fast isometric knee extensions was assessed by averaging the amplitude -LRB- based on root mean square , RMS -RRB- of the monopolarly recorded sEMG signals -LRB- Fig. 1 -RRB- over 40 ms before the onset of torque development -LRB- RMS − 40 -- 0 -RRB- . Unlike a single bipolar recording , the HD-sEMG system allowed for the assessment of monopolar recordings , and allowed for the spatial selection of the grid column with the highest amplitude . The latter was based on the mean of all electrodes within one column . To investigate how neural activation related to the relative maximal rate of torque development for each individual , vTTI40 values were corresponded to RMS − 40 -- 0 data , whereby each accepted contraction of each session was included . For the evaluation of both RMS − 40 -- 0 and vTTI40 as a function of bed rest duration , only the data of one single fast contraction per session were incorporated into the analyses . The contraction with highest level of EMG activity was selected for this purpose . Since we were interested to compare the neural activation during fast voluntary contractions with the neural activation during voluntary contractions where torque is developed more slowly , the contractile and electromyographic data were normalized to the steady-state maximal isometric knee extension condition at the day of testing . These data are also part of another study and are reported elsewhere -LRB- Mulder et al. 2007 -RRB- . Electrically evoked contractions For each experimental session , the peak torque -LRB- T -RRB- attained during the 10 Hz -LRB- T10 -RRB- train was expressed relative to the maximal tetanic torque reached during the 150 Hz tetanus -LRB- T150 -RRB- , i.e. , expressed as a T10/T150 ratio . The force profiles of the 10 Hz tetanus showed clear oscillations -LRB- Fig. 2 -RRB- . The force oscillation amplitude -LRB- FOA -RRB- relative to the mean force was also calculated and used as a measure of the degree of force-fusion -LRB- Gerrits et al. 1999 ; Vøllestad et al. 1997 -RRB- . Fig. 2Methods used for evaluation of contractile properties of the quadriceps femoris muscle evoked by electrically evoked muscle stimulation at 10 Hz . The torque elicited at 10 Hz stimulation was first expressed as a percentage of the maximal torque evoked at 150 Hz -LRB- T150 -RRB- . T10 was the peak value of the 10 Hz torque trace . The force oscillation amplitude -LRB- FOA -RRB- was determined by expressing the mean amplitude of the torque oscillation -LRB- Os -RRB- between the fourth and seventh stimulus as a fraction of the mean torque -LRB- Tm -RRB- during this time The contractile characteristics at high pulse frequency stimulation -LRB- i.e. , 300 Hz -RRB- were quantified by assessing the time to peak tension from the start of the evoked contraction -LRB- TPT300 -RRB- . The start of contraction was defined as the instant the first pulse of the 80 ms train was delivered . Half-relaxation time was determined for each session as the time needed for the elicited torque to decay to half the maximal value following the last pulse of the 150 Hz tetanus -LRB- HRT150 -RRB- . Force data were filtered using a fourth-order , 50 Hz low-pass filter . This filter was found not to affect the course of torque development ; it only removed high-frequency noise from the signal . Statistical analysis Values are expressed as mean ± SE -LRB- standard error of the mean -RRB- . Independent-samples t tests were used to determine whether the absolute values of variables related to muscle strength , neural activation and contractile properties of the quadriceps femoris muscle differed at baseline -LRB- BR4 -RRB- . Changes in muscle strength and contractile properties after 56 days of bed rest were assessed by means of linear regression , and expressed as a percentage change with respect to the value at BR4 . One-sample t tests were used to determine whether the normalized slope -LRB- slope/intercept on y-axis -RRB- of the linear regression was significantly different from zero . Independent-sample t tests were used to determine whether the groups differed in their response to bed rest . Pearson 's correlation coefficients were calculated to establish significance of correlation . The level of significance was set at P < 0.05 . Results Fast voluntary isometric knee extensions Data of neural activation and steady state isometric strength are presented elsewhere -LRB- Mulder et al. 2006 -RRB- . Briefly , whereas neural activation remained unaltered for Ctrl , maximal voluntary isometric steady-state strength significantly declined after 56 days of bed rest by about 17 % . For the RVE group neural activation increased by approximately 30 % , whereas voluntary steady-state torque was maintained . The ability to perform fast voluntary contractions showed a substantial variability during bed rest . There was considerable variation in vTTI40 as well as in RMS − 40 -- 0 during these contractions , both within one session as well as across sessions . Nonetheless , significant positive linear relationships -LRB- P < 0.01 -RRB- between RMS − 40 -- 0 and the vTTI40 were obtained for 12 of the 16 subjects in the present study -LRB- 4 RVE subjects and 8 Ctrl subjects -RRB- . Significant Pearson 's correlation coefficients -LRB- r -RRB- ranged from 0.52 to 0.90 ; with a median value of 0.74 . When individual data were pooled per group , each group had a significant relationship between normalized EMG amplitude and normalized vTTI40 -LRB- RVE , r = 0.572 ; P < 0.01 ; Ctrl , r = 0.758 ; P < 0.01 -RRB- . However , as can be seen in Fig. 3 , for neither group did RMS − 40 -- 0 , or vTTI40 change during the course of the bed rest . Fig. 3Mean values -LRB- ± SE -RRB- of the voluntary time torque integral over the first 40 ms -LRB- TTI40 -RRB- after torque development -LRB- vTTI40 ; a -RRB- and the sEMG amplitude 40 ms before the onset of torque development -LRB- RMS − 40 -- 0 ; b -RRB- obtained during 56 days of bed rest -LRB- BR -RRB- . For each session , both vTTI40 and RMS − 40 -- 0 are expressed as a percentage of the corresponding values at the steady-state maximal voluntary torque -LRB- MVT -RRB- of that session Intrinsic contractile properties The contractile properties obtained from electrically evoked contractions during bed rest are shown in Fig. 4 . The course of FOA during bed rest was significantly different for Ctrl and RVE subjects -LRB- P < 0.05 -RRB- . For Ctrl , the FOA increased substantially -LRB- by 47.5 ± 10.0 % , P < 0.01 -RRB- during the bed rest study -LRB- Fig. 4a -RRB- . In contrast , no change in the FOA was observed for RVE . The groups also differed in their response to bed rest with respect to contraction time as indicated by TPT300 -LRB- P < 0.01 -RRB- . TPT300 declined significantly by 6.8 ± 0.9 % -LRB- P < 0.001 -RRB- for Ctrl , whereas no changes were observed for RVE -LRB- Fig. 4b -RRB- . Furthermore , in the Ctrl group the HRT150 tended to be somewhat shortened by 2.5 ± 1.1 % -LRB- P = 0.056 -RRB- after 56 days of bed rest , whereas for RVE it again remained unaltered -LRB- Fig. 4c -RRB- . Group differences in HRT150 did , however , not reach significance . Interestingly , the T10/T150 ratio increased for both Ctrl -LRB- by 15.0 ± 5.5 % ; P < 0.05 -RRB- and RVE -LRB- by 40.6 ± 17.1 % ; P < 0.05 -RRB- and these changes were not significantly different between groups -LRB- Fig. 4d -RRB- . Fig. 4Mean values -LRB- ± SE -RRB- of the force oscillation amplitude -LRB- FOA ; a -RRB- time to peak tension at 300 Hz stimulation -LRB- TPT300 ; b -RRB- , half relaxation time at 150 Hz stimulation -LRB- HRT150 -RRB- , and peak torque at 10 Hz stimulation expressed as a fraction of the maximal torque obtained during tetanic stimulation at 150 Hz -LRB- T10/T150 -RRB- obtained during 56 days of bed rest -LRB- BR -RRB- Discussion Contractile characteristics of electrically evoked knee extensions The rate at which muscle force develops during a fast voluntary contraction is influenced by both peripheral factors and neural activation properties . In order to separate these influences , the contractile response of the knee extensor group was also assessed by means of percutaneous sub-maximal muscle stimulation . This is a reliable method , which has been used to assess intrinsic muscle characteristics in various human populations -LRB- Binder-Macleod et al. 1995 ; de Haan et al. 2000 ; Gerrits et al. 2001 ; Harridge et al. 1996 -RRB- . Although it is not possible to assess the specific characteristics of the portion of the muscle fibre population that is recruited during the sub-maximal stimulation procedure of the present study , the activation of about 40 % of the muscle fibres suffices to represent the global contractile characteristics of the quadriceps muscle . Previous studies have shown that the torque frequency relationship , as well as the contractile properties of the twitch are not intrinsically influenced by the absolute force level , provided that a force between 20 and 50 % MVC is reached during maximal tetanic stimulation -LRB- Binder-Macleod et al. 1995 -RRB- . In the absence of the exercise countermeasure , the knee extensors exhibited characteristics of a faster muscle following 56 days of bed rest . The degree of fusion at 10 Hz stimulation was decreased , the time to reach peak torque at 300 Hz stimulation was reduced and relaxation after tetanic stimulation at 150 Hz tended to be faster . The possibility of an error seems unlikely , since we found complementary changes towards enhanced contractile speed at all frequencies studied . In addition , these changes were observed only for the inactive control group . The stiffness of the series elastic component is amongst the factors known to affect the rate of torque development -LRB- Bojsen-Moller et al. 2005 -RRB- . Although not measured in the present study , from previous other studies it appears that with muscle unloading tendon stiffness often decreases -LRB- Kubo et al. 2000 ; Reeves et al. 2005 -RRB- . This would tend to result in a reduced rate of torque development of the whole muscle -- tendon complex , opposite to what we observed . The increased rate of torque development , as well as the tendency towards a faster rate of relaxation in the present study could , however , be explained by an elevated rate of cross-bridge cycling -LRB- Unsworth et al. 1982 -RRB- . Although at odds with some previous findings -LRB- e.g. , Davies et al. 1987 ; Gondin et al. 2004 ; Narici et al. 2003 -RRB- such interpretation would be consistent with documented elevations in maximal unloaded shortening velocity -LRB- Caiozzo et al. 1994 ; Widrick et al. 2001 ; Yamashita-Goto et al. 2001 -RRB- potentially linked to shifts in muscle fibre phenotype from slow to fast as a direct consequence of muscle unloading -LRB- Fitts et al. 2000 ; Gerrits et al. 2003 ; Ohira et al. 1999 ; Talmadge 2000 ; Trappe et al. 2004 -RRB- . Because the assessed muscle torque in the present study is the resultant of the entire muscle -- tendon complex , and given a likely increase in tendon compliance by bed rest , the observed enhanced contractile speed characteristics , might even underestimate the underlying intrinsic changes in the present study . Despite faster contractile properties , torque production at 10 Hz stimulation relative to maximal tetanic stimulation was increased after bed rest . Although consistent with previous research -LRB- Seki et al. 2001 -RRB- , the higher relative torque responses at low frequency stimulation did not result from a significant enhancement of twitch summation , as previously opted -LRB- Gondin et al. 2004 -RRB- . In contrast , the level of force fusion substantially decreased during bed rest period in the present study . At present , the exact processes responsible for these anomalous findings remain unclear , but a similar phenomenon was reported in the paralyzed muscles of individuals with spinal cord injury -LRB- Gerrits et al. 1999 -RRB- , which may be considered as an extreme model for muscle unloading . In part , our data supports the hypothesis postulated by Rittweger et al. -LRB- 2006 -RRB- that the large number of contraction -- relaxation cycles during resistive vibration exercise -LRB- Blottner et al. 2006 -RRB- may be effective in preserving muscle fibre contractile properties . Indeed , no changes in time to reach peak torque at 300 Hz stimulation , the rate of relaxation after tetanic stimulation at 150 Hz , or the level of force fusion at low stimulation frequency -LRB- i.e. , the FOA -RRB- were observed in the exercise trained subjects . The significant difference between some baseline values , e.g. , FOA and T10/T150 ratio -LRB- Fig. 4a , d -RRB- , and the tendencies for TPT300 -LRB- P = 0.098 -RRB- and HRT150 -LRB- P = 0.057 -RRB- to be lower in RVE compared to Ctrl at baseline deserves attention , since it may point towards a difference between groups with respect to muscle fibre type at the start of the study , with RVE exhibiting a faster muscle . Nonetheless , at least for the FOA it has been demonstrated that it is still much higher -LRB- i.e. , 0.65 in Gerrits et al. 1999 -RRB- in paralyzed muscles of people with spinal cord injury . This makes it unlikely that the preservation of FOA in the present study resulted from a ceiling effect for RVE . Despite the observation that speed characteristics were unaltered for the exercise-trained group , the relative peak torque at low stimulation frequency also increased for this group . As the level of force fusion remained unaltered during bed rest for RVE , other factors are likely involved . Once possibility is that the peak torque during 10 Hz stimulation increased as a consequence of an enlarged twitch response . Although not directly measured in the present study , the torque developed during the first response of the 10 Hz tetanus increased during the course of the bed rest by about 26 % , which was comparable to the elevation in 10 Hz peak torque -LRB- ∼ 40 % -RRB- for RVE . Interestingly , the relative torque production of the first response of the 10 Hz contraction also increased -LRB- by about 30 % -RRB- for the inactive control group . However , the reduced fusion of successive individual twitches diminished the increase in peak torque at 10 Hz stimulation to about 15 % . Despite the differences in contractile speed characteristics , the percent change in 10 Hz peak torque after 56 days of bed rest was not different between groups . At present , the selectivity of the exercise countermeasure paradigm to prevent changes in contractile speed properties , but not in the torque response at low frequencies of stimulation , remains difficult to explain . Indeed , more research is needed to determine the effectiveness of resistive vibration exercise as a countermeasure , since the individual merits of resistance training versus vibration training could not be quantified in the present study . Fast voluntary isometric knee extensions at maximal effort Adequate preservation of the rate at which muscle torque develops during a forceful volitional contraction is imperative for astronauts , as neuromuscular deconditioning , coupled to a weakened load-bearing skeleton , increases the risk of fall-related bone fractures after prolonged space missions . To add to the concern , compared to steady-state contractions , much higher levels of neural activation are needed for contractions where torque develops as rapidly as possible -LRB- de Haan 1998 ; de Ruiter et al. 1999 -RRB- . As such , we hypothesised that the ability to perform fast and forceful voluntary contractions would be more deteriorated by bed rest confinement than the ability to perform maximal steady-state contractions . Surprisingly , and at odds with the finding of others -LRB- di Prampero and Narici 2003 ; Koryak 1998 -RRB- , we found no evidence for such bed rest induced functional impairment in either group -LRB- Fig. 3 -RRB- . For the same inactive control subjects as used in the present study , we previously reported an absence of neural deconditioning for maximal voluntary steady-state contractions , whether examined by the twitch interpolation technique , or by the assessment of electromyographic activity of the quadriceps femoris muscle -LRB- Mulder et al. 2006 , 2007 -RRB- . We concluded that the preservation of neural activation of this specific motor task was likely associated with the repeated functional retesting sequence employed during bed rest . The observation that the percent reduction in maximal isometric knee extension strength of the left leg , which was not repeatedly retested during bed rest , exceeded the level of atrophy by a factor of two after 8 weeks of bed rest , strengthened this notion -LRB- Mulder et al. 2006 -RRB- . Based on the findings of the present study , we are inclined to suggest that the repeated retesting regime also served as a contributory factor in maintaining neural activation during fast isometric knee extensions . Although such an effect was not intended at the time , this supposition is important since it suggests that neural activation of different isometric motor tasks can be maintained during bed rest without rigorous exercise training regimes . In part , the absence of loss of muscle functionality following bed rest might have resulted from changes in the contractile properties of unloaded muscles . Widrick et al. -LRB- 1998 -RRB- reported significant atrophy of single human soleus muscle fibres after 17 days of spaceflight . Absolute peak power of these fibres was , however , partly or fully preserved by an elevated contraction velocity . In the present study , the examined muscle group in the inactive control group also acquired mechanical characteristics of a faster muscle during the course of the bed rest . As selective neural deconditioning could not be demonstrated for the fast voluntary contractions , the expectation might arise of an increased rate of voluntary torque development for the inactive control group . Such a systematic change was not observed . Although it seems difficult to explain this absence based on the changes in intrinsic contractile characteristics , it is clear that neural activation and the subsequent mechanical response during voluntary contractions are much more variable than the activation and response when contractions are electrically evoked . To overcome this variability , larger alterations than those observed in intrinsic contractile characteristics would have been required to allow for detectable changes for the fast voluntary isometric actions . Interestingly , an increase in the rate of torque development could have also been expected for the exercise trained RVE group . For this group we previously found that the amplitude of the surface EMG during the maximal steady-state contractions was substantially increased at the end of bed rest -LRB- by ∼ 30 % ; Mulder et al. 2007 -RRB- . The latter was suggested to result from an increase in the mean motor unit firing rate , due to a change in the excitability of the alpha motoneurons -LRB- Mulder et al. 2007 -RRB- . Such modulation has been associated with increased rate of force development after resistance training -LRB- Holtermann et al. 2007 -RRB- . However , in the present study the neural activation during the fast voluntary contractions and the subsequent initial rate of torque development remained unaltered for the exercise trained group . The current exercise-training regime consisted mainly of relatively slow dynamic loaded contractions while vibration was simultaneously applied to the feet . Such a motor task is quite different from the isometric contractions performed during the testing of the subjects . Based on the selectivity of training , and the fact that the number of exercise training sessions by far outweighed the number of testing sessions -LRB- 89 vs. 7 -RRB- , it is likely that neural activation strategies employed by the subjects were more guided towards optimal performance during the training sessions , than optimal performance during the fast voluntary isometric actions during testing . In conclusion , in the subjects who were confined to 8 weeks of bed rest without preventive measures the knee extensor muscle group acquired intrinsic contractile properties of a faster muscle . Resistive vibration exercise proved effective to counteract these changes at the muscle level . An unexpected finding of the present study was that neither group showed deterioration in the capacity to maximally activate the knee extensors at the very start of a voluntary contraction performed as fast and forcefully as possible . For the RVE group this might indicate an effective countermeasure design . However , considering that neural activation and voluntary muscle function were also maintained in the Ctrl group , it is also conceivable that the multiple retesting of the subjects resulted in or at least contributed to these preservations .

O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

unloading
force oscillation amplitude
emg


Lack of Relationship Between Chronic Upper Abdominal Symptoms and Gastric Function in Functional Dyspepsia To determine the relationship between gastric function and upper abdominal sensations we studied sixty FD patients -LRB- 43 female -RRB- . All patients underwent three gastric function tests : 13C octanoic gastric emptying test , three-dimensional ultrasonography -LRB- proximal and distal gastric volume -RRB- , and the nutrient drink test . Upper abdominal sensations experienced in daily life were scored using questionnaires . Impaired proximal gastric relaxation -LRB- 23 % -RRB- and a delayed gastric emptying -LRB- 33 % -RRB- are highly prevalent in FD patients ; however , only a small overlap exists between the two pathophysiologic disorders -LRB- 5 % -RRB- . No relationship was found between chronic upper abdominal symptoms and gastric function -LRB- proximal gastric relaxation , gastric emptying rate , or drinking capacity -RRB- -LRB- all P > 0.01 -RRB- . Proximal gastric relaxation or gastric emptying rate had no effect on maximum drinking capacity -LRB- P > 0.01 -RRB- . The lack of relationship between chronic upper abdominal sensations and gastric function questions the role of these pathophysiologic mechanisms in the generation of symptoms . Introduction Functional dyspepsia -LRB- FD -RRB- is a common disorder seen in daily clinical practice , characterized by the presence of pain or discomfort in the upper abdomen in the absence of organic , systemic , or metabolic disease -LSB- 1 -RSB- . Functional dyspeptic patients complain about a variety of symptoms , which are frequently intermittent , and mostly related to food intake -LSB- 2 -RSB- . For that reason , a subdivision of patients has been proposed , in order to clarify the heterogeneity of this disorder and to direct treatment options -LSB- 3 -RSB- . Attempts have been made to subdivide patients according to their symptoms ; however , a large overlap of symptoms exists and many patients do not fit into one of the subgroups -LSB- 1 -RSB- . Currently , many efforts are being made to subdivide patients according to gastric -LRB- dys -RRB- function , and to find new ways of treating these proposed pathophysiologic disorders -LSB- 4 -RSB- . Three pathophysiologic mechanisms have been described as possible etiologic factors : -LRB- 1 -RRB- a delayed gastric emptying , -LRB- 2 -RRB- impaired proximal gastric accommodation , and -LRB- 3 -RRB- visceral hypersensitivity . Delayed gastric emptying is present in approximately 30 % of FD patients , and may be one of the underlying mechanisms for symptoms -LRB- vomiting and postprandial fullness -RRB- -LSB- 5 -RSB- . Impaired proximal gastric relaxation may be an important etiologic factor in the pathophysiology of functional dyspepsia , considering the high prevalence of approximately 40 % in FD patients , and a possible association with early satiety , weight loss , and fullness -LSB- 6 , 7 -RSB- . Finally , an increased visceral sensitivity is highly frequent in FD patients , and even though difficult to measure , an important etiologic factor in the pathophysiology of FD -LSB- 8 -RSB- . However , when targeting specific pathophysiologic mechanisms by the use of pharmacologic agents , the effect on symptoms is questionable -LSB- 6 , 9 , 10 -RSB- . In other words , the relationship between specific upper abdominal sensations and the above-mentioned mechanisms remains to be matter of debate . We conducted a study to assess the relationship between gastric function and upper abdominal sensations . Gastric emptying rate , proximal gastric relaxation , and maximum drinking capacity were assessed in FD patients . The symptoms experienced in daily life -LRB- chronic upper abdominal symptoms -RRB- were assessed and related to the primary outcome parameters of the gastric function tests . We hypothesised that chronic upper abdominal symptoms and specific pathophysiologic mechanisms have no correlation in functional dyspepsia . Materials and methods Patients All patients visiting the outpatient clinics at our hospital , fulfilling the Rome II criteria for functional dyspepsia -LSB- 1 -RSB- , were subjected to three non-invasive functional tests of the stomach . A total of 60 functional dyspeptic patients were prospectively evaluated ; 43 female -LRB- median age 40 years ; range 18 -- 65 -RRB- and 17 male -LRB- median age 37 years ; range 21 -- 64 -RRB- . The inclusion criteria were -LRB- a -RRB- the presence of dyspeptic symptoms , assessed using the questionnaire described below ; -LRB- b -RRB- no evidence of macroscopic inflammation of the esophageal mucosa or focal lesions of the esophagogastroduodenal mucosa at upper gastrointestinal endoscopy -LRB- performed within 1-year prior to inclusion -RRB- ; -LRB- c -RRB- no abnormalities seen during upper abdominal ultrasonography -LRB- performed within 1 year prior to inclusion -RRB- ; -LRB- d -RRB- absence of serious concomitant illness ; and -LRB- e -RRB- the absence of major gastrointestinal surgery -LRB- excluding appendectomy -RRB- . The protocol was approved by the ethics committee of the University Medical Center Utrecht . All patients gave written informed consent for inclusion in the trial . Chronic dyspeptic symptoms questionnaire Each patient completed a reproducible dyspepsia questionnaire -LSB- 5 , 6 , 11 -RSB- . Patients were asked to score six different symptoms -LRB- pain or discomfort centered in the upper abdomen , early satiety , bloating in the upper abdomen , fullness , nausea , and vomiting -RRB- from 0 to 5 -LRB- 0 = none , 1 = very mild ; awareness of symptoms but easily tolerated , 2 = mild ; tolerated without interference with usual activity , 3 = moderate ; enough to cause some interference with usual activity , 4 = severe ; enough to cause significant interference with usual activity , 5 = very severe ; incapacitating with inability to work or do usual activity -RRB- . For inclusion , two of these symptoms had to be scored as moderate , severe or very severe and these symptoms needed to be present for at least 12 weeks , not necessary consecutive , in the preceding 12 months . Study protocol All patients underwent three functional tests of the stomach on three separate days ; the ¹³ C-octanoic breath test , three-dimensional ultrasonography of the stomach , and a nutrient drink test . The order of the three study days was arbitrary . Each of the study days started at 08:00 h after an overnight fast of at least 10 h . The time interval between the tests was three days to 2 weeks . Patients were asked to discontinue any medication known to influence gastrointestinal motility or sensitivity for at least 7 days prior to the study , including PPI therapy . The use of narcotics , anticholinergic medication , serotonergic medication -LRB- including selective serotonin reuptake inhibitors -RRB- , and antidepressants was considered an exclusion criterion . None of the patients were on NSAID therapy . 13C-octanoic breath test The rate of gastric emptying was assessed using the 13C-octanoic breath test . The test meal consisted of two fried eggs , one slice of bread , 5 g margarine and 150 ml water -LRB- total caloric value of 294 kcal and a nutrient composition of 16 g protein , 16 g carbohydrate , 18 g fat -RRB- -LSB- 12 -RSB- . The egg yolk of one egg was labelled with 100 mg 13C-sodium-octanoic acid -LRB- 598 μmol ; Campro Scientific , Veenendaal , The Netherlands -RRB- , dissolved in 1 ml distilled water . Breath samples were taken at baseline , before the meal and from start of ingestion of the meal every 2 min the first 30 min , every 5 min for the next 30 min and every 15 min thereafter up to 4 h. Three-dimensional ultrasonography Total - , proximal - , and distal gastric volumes were assessed before and after ingestion of a nutrient drink using 3D-US -LSB- 13 -- 16 -RSB- . Ultrasonographic data were acquired in a sitting position , while fasting and at 5 , 15 , 30 , 45 , and 60 min after ingestion of a nutrient drink . The nutrient drink -LRB- 500 ml -RRB- consisted of 200 ml lactose - and fiber-free milk drink , containing 12.0 g proteins , 11.6 g fat and 36.8 g carbohydrate -LRB- 300 kcal -RRB- -LRB- Nutridrink , Nutricia , Zoetermeer , The Netherlands -RRB- mixed with 300 ml of water , and was ingested within 3 min . The 3D imaging system consisted of an ultrasound scanner with a 3.5 MHz curved probe and a tracking system -LRB- Esaote-Pie Medical , Maastricht , The Netherlands -RRB- . The tracking system consisted of a transmitter generating a spatially varying magnetic field and a small receiver , firmly attached to the ultrasound probe , containing three orthogonal coils to sense the magnetic field strength -LSB- 17 -RSB- . A standardized ultrasound-scanning pattern was used , starting at the left lateral subcostal margin and then moving distally towards the pylorus having the probe in a vertical position -LSB- 14 -RSB- . The 2D sagittal planes were used to draw the region of interest , corresponding to the inner layer of the stomach wall -LRB- the interface between the outer profile of the gastric wall mucosa and the liquid nutrition -RRB- . A 3D reconstructed image of the stomach and the gastric volume was obtained using software with rendering and volume estimation capability -LRB- In Vivo ScanNT , Medcom GmbH , Darmstadt , Germany -RRB- . The proximal gastric volume was defined as the gastric volume between the diaphragm and a dividing plane 10 cm below the point where the fundic top reaches the diaphragm . Similarly , a distal part was separated , defined as the gastric region between the antral area -LRB- the sagittal ultrasound plane in which the antrum , the left liver lobe , the superior mesenteric vein and the abdominal aorta are seen simultaneously -RRB- and the gastroduodenal junction -LSB- 18 -RSB- . At every time point , we subtracted fasting total or partial gastric volume leaving the change in total or partial gastric volume . Proximal and distal gastric volume ratios were calculated by dividing proximal or distal gastric volume by total gastric volume . Recently , we defined impaired proximal relaxation as the average of the proximal gastric volume ratios of 5 and 15 min smaller than the lower limit of the 95 % confidence interval -LRB- 0.32 -- 0.57 -RRB- of healthy controls ; 35 healthy controls -LRB- 16 male ; mean age 31 -LRB- 18 -- 53 -RRB- years -RRB- -LSB- 7 -RSB- . All measurements were made by a single investigator -LRB- N.v.L. -RRB- who was blinded for the results of the gastric emptying test and the drink test . Nutrient drink test The nutrient drink test was used to measure the drinking capacity and the symptoms evoked by a nutrient drink -LSB- 19 , 20 -RSB- . Patients were asked to ingest a nutrient drink -LRB- Nutridrink ; 1.5 kcal/ml -RRB- at a constant rate of 15 ml/min . At 5-min intervals , they scored satiety using a graphic rating scale that combines verbal descriptors on a scale graded 0 -- 5 -LRB- 0 = no satiety , 5 = maximum satiety -RRB- . The test ends when the subject reaches maximum satiety . In healthy controls , maximum satiety occurs after ingestion of 1005 ml -LRB- 1508 kcal -RRB- . The lower limit of normal was 653 ml -LRB- 979 kcal -RRB- -LSB- 19 -RSB- . In the same study , FD patients ingested 361 ml -LRB- 542 kcal -RRB- before reaching maximum satiety . Statistical analysis The main focus of our analysis was -LRB- a -RRB- to analyse a possible relationship between the rate of gastric emptying , total or partial gastric volumes after meal ingestion , and drinking capacity , and -LRB- b -RRB- to compare the outcome of the 13C-octanoic breath test , the 3D-US test , and the drink test with the symptoms of patients experienced during daily life -LRB- chronic symptoms -RRB- . The primary end points of the gastric function tests are dichotomous and continuous . The relationship between the outcomes of the three gastric function tests was studied using a Pearson 's correlation between continuous variables -LRB- half-emptying time , retentions after 120 min , fasting gastric volume , proximal gastric volume ratio , distal gastric volume ratio , and maximum drinking capacity -RRB- . Secondly , patients were subdivided in two groups , according to postprandial proximal gastric relaxation -LRB- normal or impaired -RRB- , and according to the rate of gastric emptying -LRB- normal or delayed -RRB- , in order to compare multiple variables between the sub-groups using the Students ' t-test . Chronic upper abdominal symptoms -LRB- ordinal variables -RRB- were compared between FD patients with normal - or delayed gastric emptying or a normal or impaired proximal gastric relaxation -LRB- dichotomous variable -RRB- , using the χ2 test . Secondly , the relationship between chronic upper abdominal symptoms and half-emptying time , retention after 120 min , fasting gastric volume , proximal gastric volume ratio , distal gastric volume ratio , and maximum tolerated volume -LRB- continuous variable -RRB- was analysed using one-way analysis of variance -LRB- ANOVA -RRB- . We have analysed the effect of age , height , weight , BMI , and sex on the outcome of the gastric function tests and the chronic symptoms using a regression analysis . All variables were tested in single models and using multivariable analysis . Due to the high number of comparisons made , we considered a P value of < 0.01 as statistically significant . All statistical analysis was performed using commercially available software -LRB- SPSS 11.0 for Microsoft windows -RRB- . For the χ2 test and the Students ' t-test , on the basis of a Cohen 's effect size of 0.8 , a power of 0.80 was obtained with 60 subjects -LRB- considering α = 0.01 -RRB- -LSB- 21 -RSB- . With the same number of subjects , there was good power -LRB- 0.80 -RRB- to detect an R value of 0.40 with an α = 0.01 . Results Combined assessment of the 13C-octanoic breath test , 3D-US , and the nutrient drink test was performed in 60 FD patients . The frequency of upper abdominal sensations scored as moderate or higher was upper abdominal pain -LRB- 80 % -RRB- , early satiety -LRB- 59 % -RRB- , bloating -LRB- 77 % -RRB- , fullness -LRB- 71 % -RRB- , and nausea -LRB- 51 % -RRB- . Vomiting was present in 13 % of patients -LRB- Table 1 -RRB- . Table 1Frequency of severity grading for each of six dyspeptic symptoms in 60 dyspeptic patients -LRB- chronic symptoms -RRB- 0 -LRB- None -RRB- 1 -- 2 -LRB- Very mild -- mild -RRB- 3 -LRB- Moderate -RRB- 4 -- 5 -LRB- Severe -- very severe -RRB- Upper abdominal pain1 -LRB- 2 -RRB- 11 -LRB- 18 -RRB- 18 -LRB- 30 -RRB- 30 -LRB- 50 -RRB- Early satiety7 -LRB- 12 -RRB- 18 -LRB- 30 -RRB- 19 -LRB- 32 -RRB- 16 -LRB- 27 -RRB- Bloating4 -LRB- 7 -RRB- 10 -LRB- 17 -RRB- 27 -LRB- 45 -RRB- 19 -LRB- 32 -RRB- Fullness2 -LRB- 3 -RRB- 15 -LRB- 25 -RRB- 26 -LRB- 43 -RRB- 17 -LRB- 28 -RRB- Nausea10 -LRB- 17 -RRB- 19 -LRB- 32 -RRB- 14 -LRB- 23 -RRB- 17 -LRB- 28 -RRB- Vomiting46 -LRB- 77 -RRB- 6 -LRB- 10 -RRB- 2 -LRB- 3 -RRB- 6 -LRB- 10 -RRB- Numbers in parentheses represent row percentages Gastric emptying and proximal gastric relaxation Figure 1 shows the frequency of a delayed gastric emptying rate , defined as a half emptying time ≥ 120 min and/or a retention after 120 min ≥ 40 % , and impaired proximal gastric relaxation , defined as an average proximal gastric volume ratio of 5 and 15 min postprandially ≤ 0.32 -LRB- 95 % CI healthy controls -RRB- in the patient group -LSB- 7 -RSB- . A delayed gastric emptying with a normal proximal gastric relaxation was found in 33 % of patients . Impaired proximal gastric relaxation with a normal gastric emptying rate was observed in 23 % of patients . In 38 % of all patients , none of both pathophysiologic disorders were found . Finally , only a small overlap exists between the two pathophysiologic disorders -LRB- 5 % of patients -RRB- . These numbers are in concordance with literature -LSB- 5 , 6 -RSB- . Fig. 1Gastric emptying and proximal gastric relaxation in 60 FD patients : 33 % of patients have a delayed gastric emptying and normal proximal gastric relaxation -LRB- black -RRB- , 23 % of patients have impaired proximal gastric relaxation and a normal gastric emptying rate -LRB- striped -RRB- , 38 % of patients have none of the pathophysiologic disorders -LRB- white -RRB- , and 5 % of patients have both disorders -LRB- grey -RRB- Nutrient drink test The average amount of nutridrink ingested before reaching maximum satiety was 399.8 -LRB- 344 -- 447 -RRB- ml -LRB- 600 kcal -RRB- . Table 2 summarizes the results of the nutrient drink test . No effect of age or BMI on MTV and upper abdominal sensations was observed -LRB- all P > 0.01 -RRB- . Male patients had a maximum tolerated volume -LRB- MTV -RRB- of 500 -LRB- 381 -- 618 -RRB- , and female patients of 359 -LRB- 301 -- 417 -RRB- -LRB- P = 0.017 -RRB- . Table 2The effect of age , BMI , and sex on maximum tolerated volume -LRB- MTV -RRB- and the change in upper abdominal sensations after the nutrient drink testAgeBMISexβ0β1β0β1FemaleMaleMTV329 -LRB- 160 -- 499 -RRB- 1.7 -LRB- − 2.2 -- 5.6 -RRB- 363 -LRB- 3 -- 725 -RRB- 1.6 -LRB- − 14 -- 18 -RRB- 359 -LRB- 301 -- 417 -RRB- 500 -LRB- 381 -- 618 -RRB- Delta symptoms Pain11 -LRB- 0 -- 35 -RRB- 0.02 -LRB- − 0.5 -- 0.6 -RRB- 24 -LRB- 0 -- 74 -RRB- -0.5 -LRB- − 3 -- 2 -RRB- 10 -LRB- 0 -- 20 -RRB- 14 -LRB- 0 -- 28 -RRB- Fullness49 -LRB- 23 -- 76 -RRB- -0.1 -LRB- − 0.7 -- 0.5 -RRB- 49 -LRB- 0 -- 100 -RRB- -0.1 -LRB- − 2 -- 2 -RRB- 48 -LRB- 37 -- 59 -RRB- 42 -LRB- 29 -- 55 -RRB- Nausea46 -LRB- 20 -- 72 -RRB- -0.5 -LRB- − 1 -- 0.1 -RRB- 28 -LRB- 0 -- 85 -RRB- -0.2 -LRB- − 3 -- 2 -RRB- 21 -LRB- 11 -- 31 -RRB- 31 -LRB- 12 -- 50 -RRB- Hunger − 28 -LRB- − 50 -- 0 -RRB- 0.09 -LRB- − 0.4 -- 0.6 -RRB- − 7 -LRB- − 52 -- 40 -RRB- − 0.8 -LRB- − 3 -- 1.2 -RRB- − 24 -LRB- − 33 to − 15 -RRB- − 25 -LRB- − 37 to − 14 -RRB- β0 : intercept of the model . β1 : slope of the corresponding variable . Numbers in parenthesis represent the 95 % confidence interval of βI . MTV and delta symptoms in female and male patients are presented as mean -LRB- 95 % confidence interval for mean -RRB- . No effect of age , BMI , or sex on MTV or the change in upper abdominal sensations after the nutrient drink test was observed -LRB- all P > 0.01 -RRB- Relationship between gastric emptying , total and partial gastric volume , and drinking capacity Table 3 displays some of the patient characteristics in FD patients with normal or impaired proximal gastric relaxation and with normal or delayed gastric emptying . Age or BMI did not influence proximal gastric relaxation or the rate of gastric emptying . Patients with a normal gastric emptying rate had an MTV of 439 ml -LRB- 359 -- 519 -RRB- whereas patients with a delayed gastric emptying had a MTV of 334 ml -LRB- 279 -- 389 -RRB- -LRB- P = 0.032 -RRB- . MTV in patients with normal or impaired proximal relaxation was very similar -LRB- 404 and 384 ml respectively -RRB- . In patients with normal proximal gastric relaxation , an average fasting gastric volume of 50 ml -LRB- 41 -- 59 -RRB- was determined , opposed to 34 ml -LRB- 24 -- 44 -RRB- in patients with impaired proximal relaxation -LRB- P = 0.029 -RRB- . The fasting gastric volume in patients with normal or delayed gastric emptying was 44 and 47 ml , respectively . Table 3Characteristics of FD patients , subdivided according to the extent of proximal gastric relaxation or the rate of gastric emptying -LRB- n = 60 -RRB- Proximal gastric relaxationGastric emptyingNormal -LRB- n = 43 -RRB- Impaired -LRB- n = 17 -RRB- Normal -LRB- n = 37 -RRB- Delayed -LRB- n = 23 -RRB- Age41 -LRB- 36 -- 45 -RRB- 42 -LRB- 35 -- 49 -RRB- 40.9 -LRB- 36 -- 45 -RRB- 41 -LRB- 35 -- 48 -RRB- BMI22 -LRB- 21 -- 23 -RRB- 23 -LRB- 21 -- 25 -RRB- 22 -LRB- 21 -- 23 -RRB- 22 -LRB- 21 -- 23 -RRB- MTV -LRB- ml -RRB- 404 -LRB- 346 -- 461 -RRB- 384 -LRB- 237 -- 530 -RRB- 439 -LRB- 359 -- 519 -RRB- 334 -LRB- 279 -- 389 -RRB- Fasting gastric volume -LRB- ml -RRB- 50 -LRB- 41 -- 59 -RRB- 34 -LRB- 24 -- 44 -RRB- 44 -LRB- 33 -- 55 -RRB- 47 -LRB- 37 -- 56 -RRB- Data are presented as mean -LRB- 95 % confidence interval for mean -RRB- . No effect of age and BMI on proximal gastric relaxation or gastric emptying was observed Twenty out of 43 female patients had a delayed gastric emptying -LRB- 47 % -RRB- and 18 % of all male patients had a delayed gastric emptying -LRB- P = 0.038 -RRB- . The prevalence of impaired proximal gastric relaxation in male and female patients was 21 % and 35 % respectively -LRB- not shown in the table -RRB- . A positive correlation was observed between the proximal gastric volume ratio -LRB- 3D-US -RRB- and half emptying time -LRB- r = 0.32 , P = 0.015 -RRB- and the retention after 120 min -LRB- r = 0.30 , P = 0.024 -RRB- -LRB- 13C breath test -RRB- . No correlation was found between the distal gastric volume ratio and the main outcome parameters of the gastric emptying test . Relationship between chronic symptoms and gastric function No effect of age , sex , or BMI on any of the chronic upper abdominal sensations was observed , except that patients with a higher BMI or a higher weight scored lower on symptoms of early satiety -LRB- both P = 0.007 -RRB- . Figure 2 shows the chronic upper abdominal symptoms in FD patients with normal or delayed gastric emptying and normal or impaired proximal gastric relaxation . No differences were observed in the percentage of patients who scored any of the upper abdominal symptoms as moderate or higher between these groups -LRB- all P > 0.01 -RRB- . We did not find any correlation between half emptying time , retention after 120 min , proximal gastric volume ratio , distal gastric volume ratio , fasting gastric volume , and any of the chronic upper abdominal symptoms -LRB- all P > 0.01 -RRB- . Fig. 2Chronic upper abdominal symptoms scored from 0 -LRB- nonexistent -RRB- to 5 -LRB- very severe ; incapacitating with inability to work or do usual activity -RRB- . The figure shows the number of the patients who scored three -LRB- moderate -RRB- or higher on the questionnaire -LRB- expressed as a percentage of the total -RRB- in subgroups with ; -LRB- Fig. 1A -RRB- normal - -LRB- □ -RRB- or delayed -LRB- ■ -RRB- gastric emptying , and -LRB- Fig. 1B -RRB- normal - -LRB- □ -RRB- or impaired -LRB- ■ -RRB- proximal relaxation Figure 2 depicts all FD patients categorized according to their chronic complaints ; mild -LRB- 1 -- 2 -RRB- , moderate -LRB- 3 -RRB- , and severe -LRB- 4 -- 5 -RRB- . No difference in maximum drinking capacity was observed between the three groups -LRB- all P > 0.01 -RRB- -LRB- Fig. 3 -RRB- . Interestingly , patients who reported early satiety as moderate or higher have a comparable drinking capacity with patients who do not experience this symptom in daily life . Fig. 3Nutrient drink test : maximum tolerated volume in FD patients , categorized according to the chronic symptoms . No difference in drinking capacity was observed between patients experiencing mild -LRB- 1 -- 2 -RRB- , moderate -LRB- 3 -RRB- , or severe -LRB- 4 -- 5 -RRB- pain , early satiety , fullness , or nausea in daily life -LRB- all P > 0.01 -RRB- Discussion The following were the most important findings of this study : -LRB- 1 -RRB- no relationship was found between chronic upper abdominal symptoms and gastric function -LRB- proximal gastric relaxation , gastric emptying rate , or drinking capacity -RRB- , -LRB- 2 -RRB- a third of all FD patients had a normal gastric emptying rate and a normal proximal gastric relaxation , and only a small overlap existed between the two pathophysiologic disorders -LRB- 7 % -RRB- , and -LRB- 3 -RRB- there was an absence of any relationship between maximum drinking capacity and proximal gastric relaxation or gastric emptying rate . The observation that approximately 40 % of FD patients had a delayed gastric emptying , and approximately 30 % of FD patients had impaired proximal gastric relaxation , is confirmatory of previous studies -LSB- 5 , 6 -RSB- . The relative small overlap between the two pathophysiologic mechanisms may suggest that one abnormality excludes the other . However , no significant positive correlation between the proximal gastric volume ratio and half emptying time or retention after 120 min was found . The rate of gastric emptying is most likely dependent on many factors , including fundal , antral , pyloric , and duodenal motility -LSB- 22 -RSB- . For that reason , gastric emptying and postprandial gastric relaxation should be considered as two separate mechanisms -LSB- 23 -RSB- . For assessment of partial gastric volumes we used 3D-US as a noninvasive alternative for the barostat technique . Recently , a head-to-head comparison between the barostat and 3D-US was performed , in which it was shown that 3D-US was able to identify almost all patients with impaired accommodation assessed by barostat . It was , however , emphasized that the two techniques are not interchangeable , which is likely to be due to the difference in invasiveness of both techniques . Since there is no absolute concordance between the two techniques , we must preserve some reservations in generalizing the results of the current study . The nutrient drink test has been suggested as a tool to measure meal-induced satiety , and as a non-invasive alternative for the detection of normal - or impaired accommodation of the stomach -LSB- 6 , 19 -RSB- . Furthermore , a positive relationship between the rate of gastric emptying and the amount of Kcal ingested during the nutrient drink test has been described , thereby suggesting that the maximum tolerated volume is not only influenced by gastric accommodation -LSB- 24 -RSB- . However , many studies have shown conflicting results , displaying no relationship between drinking capacity and barostat or SPECT findings , -LSB- 25 , 26 -RSB- and a negative relationship between gastric emptying rate and maximum tolerated volume -LSB- 27 -RSB- . Since the results from different studies do not correspond , it remains a mystery what it is we are testing with the nutrient drink test . The suggestion that the nutrient drink test can be used to discriminate between FD patients with normal or impaired visceral sensitivity is disputable -LSB- 9 -RSB- . In the current study , we did not observe any relationship between MTV and chronic upper abdominal symptoms or between MTV and proximal gastric relaxation or gastric emptying rate . Most studies do agree that the drink test differentiates between FD patients and healthy controls , as we have found in the present study . Notably , the average amount of nutridrink ingested until maximum satiety , was very similar to what others have found -LRB- approximately 360 ml -RRB- -LSB- 19 -RSB- , which is below the 95 % confidence interval of healthy controls . No effect of age or BMI on MTV was observed in the current study , however we did observe a modest effect of gender , although this did not reach statistical significance -LRB- P = 0.017 -RRB- -LSB- 20 -RSB- . The nutrient drink test is also being used in pharmacological trials , and a resemblance between symptoms evoked by the meal challenge and symptoms experienced in daily life has been observed -LSB- 27 -RSB- . Recently , we have performed a double blind , placebo-controlled , crossover trial , in which the activity of a new drug was tested , using the outcome of the nutrient drink test as one of the end points in the study -LSB- 28 -RSB- . FD patients who participated in the pharmacological trial drank significantly more compared to the FD patients in the current study ; 569 ± 90 ml and 360 ± 30 ml respectively -LRB- P < 0.001 -RRB- . A strong placebo effect and cognitive influences like motivation should therefore be considered as confounding factors . No differences in age , sex , BMI , chronic symptoms , or upper abdominal sensations experienced during the drink test were observed between the patients who participated in the pharmacological trial and those who did not . In summary , the maximum drinking capacity of FD patients , seen at a tertiary referral practice , is not influenced by gastric emptying rate or proximal gastric relaxation . The question is raised what usefulness this test has , in terms of diagnosis or treatment options , in FD patients and as a tool to analyze gastric function or upper abdominal sensations . Since we did not find any relationship between upper abdominal symptoms and MTV , the nutrient drink test can not be regarded as an alternative for measuring visceral perception , as can be done by gastric barostat . In our opinion , many subjective factors , like motivation , probably play an important disturbing factor in the outcome of the test . In conclusion , in spite of a high prevalence of impaired proximal accommodation and delayed gastric emptying in FD patients , the lack of correlation between chronic upper abdominal sensations and gastric function questions the role of these pathophysiologic mechanisms in the generation of symptoms . Consequently , gastric function does not serve as a clear marker for the symptoms experienced by FD patients in daily life , and limited effect on symptoms may be expected when targeting these specific mechanisms . Finally , despite many efforts , no -LRB- measurable -RRB- motoric disorder can be appointed as a possible pathophysiologic mechanism underlying the presence of upper abdominal symptoms . Most likely , other factors like visceral perception play a vital role in functional dyspepsia .

O O O O O B I I O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O B I O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O B I I O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O B I O O O O O B I O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O B I O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O B I O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B I O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O B I O

functional dyspepsia
stomach
gastric emptying
nutrient drink test
upper abdominal symptoms