bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of atrial natriuretic peptide in systemic responses to acute isotonic volume expansion
Authors: Watenpaugh D. E. , Yancy C. W. , Buckey J. C. , Lane L. D. , Hargens A. R. , Blomqvist C. G.
Published: December 2017

Atrial natriuretic peptide (ANP) may activate multiple mechanisms that protect against circulatory volume overload. We hypothesized that a temporal relationship exists between increases in cardiac filling pressure and plasma ANP concentration and also between ANP elevation and vasodilation, fluid movement from plasma to interstitium, and increased urine volume (UV). We infused 30 ml/kg isotonic saline at 100 ml/min in seven supine male subjects and monitored responses for 3 h postinfusion. Right atrial pressure (RAP) was measured via a central catheter. ANP (pmol/l) was measured by radioimmunoassay. Transcapillary fluid transport (TFT) equaled infused volume minus UV, insensible fluid loss, and change in plasma volume (PV, measured with Evan's blue). Systemic vascular resistance (SVR) was calculated as (mean arterial pressure-RAP)/cardiac output (determined by acetylene rebreathing). Plasma oncotic pressure (OP) was measured directly. During infusion, mean TFT (+/- SE) increased from net reabsorption during control of 111 +/- 27 ml/h to net filtration of 1,219 +/- 143 ml/h (P < 0.01). At end infusion, mean RAP, heart rate, and PV exhibited peak increases of 146, 23, and 27%, respectively. Concurrently, SVR and OP achieved nadirs 29 and 31% below control, respectively. Mean plasma ANP and UV peaked (45 and 390%, respectively) at 30 min postinfusion. Systemic vasodilation and capillary filtration resulted from and compensated for infusion-induced circulatory pressure increases and hemodilution. By 1 h postinfusion, most cardiovascular variables had returned toward control levels, and net reabsorption of extravascular fluid ensued.(ABSTRACT TRUNCATED AT 250 WORDS)
Skeletal muscle and liver glutathione homeostasis in response to training, exercise, and immobilization
Authors: Sen C. K. , Marin E. , Kretzschmar M. , Hanninen O.
Published: December 2017

Female beagle dogs were treadmill trained 40 km/day at 5.5–6.8 km/h, 15% upgrade, 5 days/wk for 55 wk. With training, hepatic and red gastrocnemius (RG) total glutathione increased, glutathione peroxidase (GPX) and glutathione reductase (GRD) increased in all the leg muscles studied, and hepatic glutathione S-transferase (GST) activity increased. Joint immobilization (11 wk) did not affect GPX, GRD, and GST of RG, but total glutathione decreased. Male Han Wistar rats were treadmill trained 2 h/day at 2.1 km/h, 5 days/wk for 8 wk. With training, hepatic total glutathione and leg muscle GPX increased but GRD of RG decreased, perhaps because of an increased muscle flavo-protein breakdown during exhaustive training. gamma-Glutamyl transpeptidase was higher in the trained leg muscles. Exhaustive exercise decreased muscle gamma-glutamyl transpeptidase of only control leg muscle, depleted muscle (lesser extent in trained rats) and liver total glutathione of both groups, decreased GRD only in untrained RG, and increased hepatic GST. Endurance training elevated the antioxidant and detoxicant status of muscle and liver, respectively.
Oxidation of exogenous medium-chain free fatty acids during prolonged exercise: comparison with glucose
Authors: Massicotte D. , Peronnet F. , Brisson G. R. , Hillaire-Marcel C.
Published: December 2017

The purpose of this study was to compare the oxidation rate of exogenous 13C-labeled medium-chain triacylglycerols (MCT) with that of an isocaloric amount of exogenous [13C]glucose and to evaluate their respective effects on endocrine and metabolic responses to moderate prolonged exercise. To take into account changes in isotopic composition of 13CO2 arising from oxidation of endogenous substrates because of exercise and/or substrate ingestion that overestimates the oxidation rate of exogenous substrates, two levels of 13C enrichment were used for each substrate. Six young healthy males (20–26 yr of age) completed five 2-h periods of exercise at 65 +/- 3% maximal O2 uptake (VO2max) on a cycle ergometer at 7-day intervals: one control exercise with water ingestion, two trials with ingestion of 25 g of [13C]MCT (trioctanoate) 1 h before exercise, and two trials with 57 g of [13C]glucose (dissolved in 1,000 ml of water) ingested during exercise. Exogenous MCT and glucose began to be oxidized within the first 30 min of exercise, and the oxidation rate increased progressively until the end of exercise for both substrates. Over the 2-h period of exercise, 13.6 +/- 3.5 g of ingested MCT and 36.4 +/- 8.2 g of exogenous glucose were oxidized, which represent 54 and 64%, respectively, of the total amount ingested. The contribution of MCT (119 +/- 31 kcal) and glucose (140 +/- 36 kcal) was not significantly different and represented 7 and 8.5%, respectively, of the total energy expenditure.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of graded dehydration on hyperthermia and cardiovascular drift during exercise
Authors: Montain S. J. , Coyle E. F.
Published: December 2017

This investigation determined the effect of different rates of dehydration, induced by ingesting different volumes of fluid during prolonged exercise, on hyperthermia, heart rate (HR), and stroke volume (SV). On four different occasions, eight endurance-trained cyclists [age 23 +/- 3 (SD) yr, body wt 71.9 +/- 11.6 kg, maximal O2 consumption 4.72 +/- 0.33 l/min] cycled at a power output equal to 62-67% maximal O2 consumption for 2 h in a warm environment (33 degrees C dry bulb, 50% relative humidity, wind speed 2.5 m/s). During exercise, they randomly received no fluid (NF) or ingested a small (SF), moderate (MF), or large (LF) volume of fluid that replaced 20 +/- 1, 48 +/- 1, and 81 +/- 2%, respectively, of the fluid lost in sweat during exercise. The protocol resulted in graded magnitudes of dehydration as body weight declined 4.2 +/- 0.1, 3.4 +/- 0.1, 2.3 +/- 0.1, and 1.1 +/- 0.1%, respectively, during NF, SF, MF, and LF. After 2 h of exercise, esophageal temperature (Tes), HR, and SV were significantly different among the four trials (P < 0.05), with the exception of NF and SF. The magnitude of dehydration accrued after 2 h of exercise in the four trials was linearly related with the increase in Tes (r = 0.98, P < 0.02), the increase in HR (r = 0.99, P < 0.01), and the decline in SV (r = 0.99, P < 0.01). LF attenuated hyperthermia, apparently because of higher skin blood flow, inasmuch as forearm blood flow was 20–22% higher than during SF and NF at 105 min (P < 0.05). There were no differences in sweat rate among the four trials. In each subject, the increase in Tes from 20 to 120 min of exercise was highly correlated to the increase in serum osmolality (r = 0.81-0.98, P < 0.02-0.19) and the increase in serum sodium concentration (r = 0.87-0.99, P < 0.01-0.13) from 5 to 120 min of exercise. In summary, the magnitude of increase in core temperature and HR and the decline in SV are graded in proportion to the amount of dehydration accrued during exercise.
Theoretical analysis of occlusion techniques for measuring pulmonary capillary pressure
Authors: Baconnier P. F. , Eberhard A. , Grimbert F. A.
Published: December 2017

We have developed a model including three serial compliant compartments (arterial, capillary, and venous) separated by two resistances (arterial and venous) for interpreting in vivo single pulmonary arterial or venous occlusion pressure profiles and double occlusion. We formalized and solved the corresponding system of equations. We showed that in this model 1) pulmonary capillary pressure (Pc) profile after arterial or venous occlusion has an S shape, 2) the estimation of Pc by zero time extrapolation of the slow component of the arterial occlusion profile (Pcao) always overestimates Pc, 3) symmetrically such an estimation on the venous occlusion profile (Pcvo) always underestimates Pc, 4) double occlusion pressure (Pcdo) differs from Pc. We evaluated the impact of varying parameter values in the model with parameter sets drawn either from the literature or from arbitrary arterial and venous pressures, being respectively 20 and 5 mmHg. Resulting Pcao-Pc differences ranged from 0.4 to 5.4 mmHg and resulting Pcvo-Pc differences ranged from -0.3 to -5.0 mmHg. Pcdo-Pc was positive or negative, its absolute value in general being negligible (< 1.1 mmHg).
Effect of zymosan-activated plasma on the deformability of rabbit polymorphonuclear leukocytes
Authors: Inano H. , English D. , Doerschuk C. M.
Published: December 2017

Intravascular infusion of inflammatory mediators causes a sudden neutropenia due to the sequestration of polymorphonuclear leukocytes (PMN) within the microvasculature of the lung and other organs. This sequestration could be due to a decrease in the ability of PMN to deform and pass through the narrow capillary bed. The purpose of this study was to determine if the complement fragments present in zymosan-activated plasma (ZAP) caused a rapid stiffening of PMN. The PMN deformability was determined by measuring the pressure required to pass PMN through a polycarbonate filter containing 5-micron pores at a constant flow rate as well as the extraction of PMN compared with red blood cells and 125I-labeled albumin by the filter. The role of the cytoskeleton in PMN deformation was examined in studies where F-actin formation was inhibited using cytochalasin B or microtubule assembly was inhibited using colchicine. The results showed that treatment with ZAP induced a rapid decrease in PMN deformability. Inhibiting the formation of F-actin made the unstimulated PMN more deformable and reduced the stiffening induced by ZAP. In contrast, inhibition of microtubule reassembly did not alter either normal deformability or the ZAP-induced decrease in deformability. In vivo, colchicine increased normal PMN margination but did not inhibit the rapid sequestration of PMN induced by infusion of ZAP. These studies indicate that ZAP induces a rapid decrease in PMN deformability that is mediated through the cytoskeleton. They suggest that this decrease is due to the polymerization of F-actin.
Effect of bilateral vagotomy on oxygenation, arousal, and breathing movements in fetal sheep
Authors: Hasan S. U. , Rigaux A.
Published: December 2017

To investigate the effects of bilateral cervical vagotomy on arousal and breathing responses, we studied eight sham-operated and eight chronically instrumented unanesthetized vagotomized sheep fetuses between 136 and 144 days of gestation (term approximately 147 days). Each fetus was instrumented to record sleep states, diaphragmatic electromyogram, blood pressure, pH, and blood gas tensions. In a randomized order, fetal lungs were distended with four different O2 concentrations: 0 (100% N2), 21, 50, and 100% at a continuous positive airway pressure of 30 cmH2O via an in situ Y-endotracheal tube. Under control conditions, inspiratory time and the duration of the single longest breathing episode decreased from 598 +/- 99 (SD) ms and 24 +/- 10 min in sham group to 393 +/- 162 ms and 11.0 +/- 3.0 min in vagotomized group (P = 0.04 and 0.033), respectively. In response to lung distension with 100% N2, breathing time decreased from 44 +/- 17 to 20 +/- 18% (P = 0.045) in sham-operated fetuses, whereas it remained unchanged in the vagotomized group. In response to 100% O2, fetal arterial PO2 increased in five of eight fetuses sham-operated from 18.2 +/- 5.1 to 227 +/- 45 Torr (P = 0.0001) and in six of eight vagotomized fetuses from 18.5 +/- 4.4 to 172 +/- 39 Torr (P < 0.001). Although arousal was observed in all oxygenated fetuses at the onset of breathing, the duration of arousal was markedly attenuated in vagotomized fetuses (14 +/- 10 vs. 46 +/- 29 min in sham group; P = 0.024). Frequency and amplitude of breathing and respiratory output (frequency x amplitude) increased only in sham group (P = 0.02, 0.004, and 0.0002, respectively). We conclude that in response to lung distension and oxygenation, arousal and stimulation of breathing during active and quite sleep are critically dependent on intact vagal nerves.
A new animal model for modulating myosin isoform expression by altered mechanical activity
Authors: Caiozzo V. J. , Ma E. , McCue S. A. , Smith E. , Herrick R. E. , Baldwin K. M.
Published: December 2017

The purpose of this study was to develop a new rodent model that is capable of delineating the importance of mechanical loading on myosin heavy chain (MHC) isoform expression of the plantar and dorsi flexor muscles of the ankle. The essential components of this system include 1) stimulating electrodes that are chronically implanted into a muscle, allowing for the control of the activation pattern of the target muscle(s); 2) a training apparatus that translates the moment of the ankle into a linear force; and 3) a computer-controlled Cambridge 310 ergometer. The isovelocity profile of the ergometer ensured that the medial gastrocnemius (MG) produced forces that were > 90% of maximal isometric force (Po), and the eccentric contractions of the tibialis anterior (TA) were typically 120% of Po. Both the concentric and eccentric training programs produced statistically significant increases in the muscle mass of the MG (approximately 15%) and TA (approximately 7%) as well as a decrease in myofibrillar adenosinetriphosphatase activity. Both the white and red regions of the MG and TA exhibited significant increases in the relative content of the type IIa MHC and concomitant decreases in type IIb MHC expression. Although the red regions of the MG and red TA contained approximately 10% type I MHC, the training programs did not affect this isoform. It appears that when a fast-twitch muscle is stimulated at a high frequency (100 Hz) and required to contract either concentrically or eccentrically under high loading conditions, the expression of the type IIa MHC isoform will be upregulated, whereas that of the type IIb MHC will be concomitantly downregulated.
Reliability of extravascular lung thermal volume measurements by thermal conductivity technique in sheep
Authors: Kambara K. , Jerome E. H. , Serikov V. B. , Arakawa M. , Staub N. C.
Published: December 2017

We tested the accuracy, sensitivity, and reproducibility of a new lung water computer, based on the thermal conductivity technique, in 22 anesthetized closed-chest ventilated sheep with different treatments: 1) controls (n = 8), 2) 0.05 ml/kg of oleic acid + 100 ml/kg of lactated Ringer solution (n = 6), and 3) airway instillation of saline [3.1 +/- 1.3 (SD) g/kg, n = 8]. After 4 h, we determined the extravascular lung water gravimetrically. We found a significant overall correlation between the final extravascular lung thermal volume and the gravimetric extravascular lung mass (P < 0.001). Although the average ratio of extravascular lung thermal volume to extravascular lung mass was 0.97 +/- 0.25 ml/g for all groups, the computer overestimated extravascular lung mass in controls by 10% (17 g) and underestimated it in sheep with oleic acid by 15% (95 g) and in sheep with airway instillation by 8% (37 g). The computer also underestimated the small quantities of saline placed via the airway in the alveolar space by 75% (61 g). Reproducibility of three consecutive measurements was 4.3% (SE). We conclude that the thermal conductivity technique has an ability to detect the baseline extravascular lung mass but has a poor ability to detect an accurate increment of the extravascular lung water under poor tissue perfusion in anesthetized ventilated sheep.
Acute heat stress protects rats against endotoxin shock
Authors: Ryan A. J. , Flanagan S. W. , Moseley P. L. , Gisolfi C. V.
Published: December 2017

The purpose of this study was to determine 1) whether prior (24-h) heat stress could render rats cross-resistant to the lethal activity of bacterial lipopolysaccharide (LPS) and 2) whether this acquired state of resistance is associated with endotoxemia during the heat stress event. Four groups (n = 7/group) of rats were examined: 1) saline treated, 2) LPS treated, 3) heat stressed and saline treated, and 4) heat stressed and LPS treated. Saline or LPS (Escherichia coli, serotype 0111:B4, 20 mg/kg body wt) was given intravenously 24 h after exposure to heat (ambient temperature 47–50 degrees C, relative humidity 30%) for heat-stressed rats and at the same time of day for nonheated rats; survival was monitored for 48 h. Thermal responses were similar (P > 0.05); values for maximum core temperature (Tc) and time above Tc of 40 degrees C were 42.7 +/- 0.1 and 42.6 +/- 0.1 degrees C (SE) and 44.0 +/- 2.1 and 47.9 +/- 3.7 (SE) min for the heat-stressed saline-treated and heat-stressed LPS-treated rats, respectively. Administration of LPS to nonheated rats resulted in 71.4% (5 of 7 rats) lethality. In contrast, all (7 of 7) rats subjected to a single nonlethal heat stress event 24 h before LPS treatment survived (P < 0.05). Endotoxin was not detected in arterial plasma immediately after heat stress in rats (n = 6) exposed to a Tc of 42.9 +/- 0.1 degrees C. These findings demonstrate that acute heat stress can protect rats from the lethal activity of LPS.
Cardiac cycle length variability in ponies at rest and during exercise
Authors: Rugh K. S. , Jiang B. , Hatfield D. , Garner H. E. , Hahn A. W.
Published: December 2017

We evaluated cardiac cycle length variability in ponies at rest and during strenuous exercise with and without premedication with atropine. In the absence of premedication, cardiac cycle length at rest was 1,112 +/- 53 ms, the individual cardiac cycle length standard deviation (SDCL) was 75 +/- 23 ms, and the individual cycle length coefficient of variation (CVCL) was 6.32 +/- 1.62. Exercise significantly decreased (P < 0.05) all three indexes (290 +/- 9 ms, 5 +/- 1 ms, and 1.65 +/- 0.20, respectively). Atropine premedication significantly reduced resting cardiac cycle length (685 +/- 46 ms), SDCL (10 +/- 2 ms), and CVCL (1.45 +/- 0.19) compared with nonpremedicated values. Cardiac cycle length was significantly decreased by exercise after atropine premedication, but no statistically significant changes occurred in SDCL or CVCL. Thus, although considerable cardiac cycle length variability exists in nonpremedicated ponies at rest, it is nearly completely abolished by strenuous exercise. The absence of significant differences between the indexes of variability during exercise without premedication, at rest after atropine, and during exercise after atropine indicates that cardiac cycle length variability in the pony is mediated primarily through activity of the parasympathetic system.
Dehydrogenase conversion to oxidase and lipid peroxidation in brain after carbon monoxide poisoning
Authors: Thom S. R.
Published: December 2017

The conversion of xanthine dehydrogenase to xanthine oxidase and lipid peroxidation were measured in brain from carbon monoxide- (CO) poisoned rats. Sulfhydryl-irreversible xanthine oxidase increased from a control level of 15% to a peak of 36% over the 90 min after CO poisoning, while the conjugated diene level doubled. Reversible xanthine oxidase was 3–6% of the total enzyme activity over this span of time but increased to 31% between 90 and 120 min after poisoning. Overall, reversible and irreversible xanthine oxidase represented 66% of total enzyme activity at 120 min after poisoning. Rats depleted of this enzyme by a tungsten diet and those treated with allopurinol before CO poisoning to inhibit enzyme activity exhibited no lipid peroxidation. Treatment immediately after poisoning with superoxide dismutase or deferoxamine inhibited lipid peroxidation but had no effect on irreversible oxidase formation. Biochemical changes only occurred after removal from CO, and changes could be delayed for hours by continuous exposure to 1,000 ppm CO. These results are consistent with the view that CO-mediated brain injury is a type of postischemic reperfusion phenomenon and indicate that xanthine oxidase-derived reactive oxygen species are responsible for lipid peroxidation.
Phosphocreatine hydrolysis by 31P-NMR at the onset of constant-load exercise in humans
Authors: Binzoni T. , Ferretti G. , Schenker K. , Cerretelli P.
Published: December 2017

The kinetics of phosphocreatine (PC) breakdown in human plantar flexors at the onset of constant-load aerobic exercise was determined by high-resolution 31P-nuclear magnetic resonance spectroscopy (NMRS). The half time of the process (t1/2PC) was obtained by fitting curves (n = 13) from five subjects at various aerobic work loads for which muscle pH was not different from that at rest. Steady-state PC concentration ([PC]) was not < 70% of the resting value and was linearly related to the work load (w) ([PC] = -3.01 +/- 0.08 w + 1 (r = 0.48, 2P < 0.1)). The average t1/2PC was 16.2 s and was independent of work load. Because the half time of the muscle PC kinetics reflects the half time of the O2 uptake (MO2) kinetics (t1/2MO2), the latter is equal to that found earlier in the isolated perfused dog gastrocnemius. Whereas in the dog the above t1/2MO2 compares well with the homologous half time of the O2 uptake at the alveolar level, in humans such equivalence is found only at extremely low work loads, when the transient contribution by anaerobic glycolysis is negligible.
O2 cost of breathing: ventilatory vs. pressure loads
Authors: Cala S. J. , Edyvean J. , Rynn M. , Engel L. A.
Published: December 2017

We compared the O2 cost of breathing (VO2resp) at high levels of ventilation (HV) with that against high inspiratory pressure loads (HP) using an external elastance when end-expiratory volume, work rate (W), and pressure-time product (P) were matched at two levels of ventilation and elastic loading. Each of five normal subjects performed three pairs of loaded runs (one HV and one HP) bracketed by two resting runs. Mean O2 consumption from the pairs of resting runs was subtracted from that of each of the loaded runs to give VO2resp during loaded breathing. Matching for W and P was within 15% in all 15 pairs of runs. During HV runs, ventilation was 398 +/- 24% of corresponding values during HP runs (P < 0.01). Although there was no difference in W (P > 0.05), the VO2resp during HV runs was 237 +/- 33% of that during HP (P < 0.01) and efficiency of HV was 51 +/- 5% of that during HP (P < 0.01). When W was normalized for the decrease in maximum inspiratory pressure with increased mean lung volume, efficiency during HV and HP runs did not differ (P > 0.05). In the second series of experiments, when both HV and HP runs were matched for W but P was allowed to vary, efficiency increased by 1.42 +/- 0.42% (P < 0.05) for each percent decrease in P during HV runs but was unchanged (P > 0.05) during HP runs despite a 193 +/- 10% increase in P.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of PEEP on respiratory mechanics in anesthetized paralyzed humans
Authors: D′Angelo E. , Calderini E. , Tavola M. , Bono D. , Milic-Emili J.
Published: December 2017

With the use of the technique of rapid airway occlusion during constant flow inflation, respiratory mechanics were studied in eight anesthetized paralyzed supine normal humans during zero (ZEEP) and positive end-expiratory pressure (PEEP) ventilation. PEEP increased the end-expiratory lung volume by 0.49 liter. The changes in transpulmonary and esophageal pressure after flow interruption were analyzed in terms of a seven-parameter “viscoelastic” model. This allowed assessment of static lung and chest wall elastance (Est,L and Est,W), partitioning of overall resistance into airway interrupter (Rint,L) and tissue resistances (delta RL and delta RW), and computation of lung and chest wall “viscoelastic constants.” With increasing flow, Rint,L increased, whereas delta RL and delta RW decreased, as predicted by the model. Est,L, Est,W, and Rint,L decreased significantly with PEEP because of increased lung volume, whereas delta R and viscoelastic constants of lung and chest wall were independent of PEEP. The results indicate that PEEP caused a significant decrease in Rint,L, Est,L, and Est,W, whereas the dynamic tissue behavior, as reflected by delta RL and delta RW, did not change.
Eccentric exercise training as a countermeasure to non-weight-bearing soleus muscle atrophy
Authors: Kirby C. R. , Ryan M. J. , Booth F. W.
Published: December 2017

Although various exercise paradigms have been tested, none has completely prevented muscle atrophy during non-weight bearing. Because loaded eccentric contractions occur during normal daily activity but are absent during non-weight bearing, this investigation tested whether eccentric resistance training could prevent soleus muscle atrophy during non-weight bearing. Adult female rats were randomly assigned to either weight bearing +/- intramuscular electrodes or non-weight bearing +/- intramuscular electrodes groups. Electrically stimulated maximal eccentric contractions (4 sets of 6 repetitions at approximately 0.2 fiber lengths/s, 128 degrees range of motion) were performed on anesthetized animals at 48-h intervals during the 10-day experiment. Non-weight bearing significantly reduced soleus muscle wet weight (28–31%) and noncollagenous protein content (30–31%) compared with controls. Eccentric exercise training during non-weight bearing attenuated but did not prevent the loss of soleus muscle wet weight and noncollagenous protein by 77 and 44%, respectively. The potential of eccentric exercise training as an effective and highly efficient counter-measure to non-weight-bearing atrophy is demonstrated in the 44% attenuation of soleus muscle noncollagenous protein loss by eccentric exercise during only 0.035% of the total non-weight-bearing time period.
Effect of lung volume on plateau response of airways and tissue to methacholine in dogs
Authors: Robatto F. M. , Simard S. , Orana H. , Macklem P. T. , Ludwig M. S.
Published: December 2017

We have recently shown in dogs that much of the increase in lung resistance (RL) after induced constriction can be attributed to increases in tissue resistance, the pressure drop in phase with flow across the lung tissues (Rti). Rti is dependent on lung volume (VL) even after induced constriction. As maximal responses in RL to constrictor agonists can also be affected by changes in VL, we questioned whether changes in the plateau response with VL could be attributed in part to changes in the resistive properties of lung tissues. We studied the effect of changes in VL on RL, Rti, airway resistance (Raw), and lung elastance (EL) during maximal methacholine (MCh)-induced constriction in 8 anesthetized, paralyzed, open-chest mongrel dogs. We measured tracheal flow and pressure (Ptr) and alveolar pressure (PA), the latter using alveolar capsules, during tidal ventilation [positive end-expiratory pressure (PEEP) = 5.0 cmH2O, tidal volume = 15 ml/kg, frequency = 0.3 Hz]. Measurements were recorded at baseline and after the aerosolization of increasing concentrations of MCh until a clear plateau response had been achieved. VL was then altered by changing PEEP to 2.5, 7.5, and 10 cmH2O. RL changed only when PEEP was altered from 5 to 10 cmH2O (P < 0.01). EL changed when PEEP was changed from 5 to 7.5 and 5 to 10 cmH2O (P < 0.05). Rti and Raw varied significantly with all three maneuvers (P < 0.05). Our data demonstrate that the effects of VL on the plateau response reflect a complex combination of changes in tissue resistance, airway caliber, and lung recoil.
Cardiovascular responses to voluntary and nonvoluntary static exercise in humans
Authors: Friedman D. B. , Peel C. , Mitchell J. H.
Published: December 2017

We have measured the cardiovascular responses during voluntary and nonvoluntary (electrically induced) one-leg static exercise in humans. Eight normal subjects were studied at rest and during 5 min of static leg extension at 20% of maximal voluntary contraction performed voluntarily and nonvoluntarily in random order. Heart rate (HR), mean arterial pressure (MAP), and cardiac output (CO) were determined, and peripheral vascular resistance (PVR) and stroke volume (SV) were calculated. HR increased from approximately 65 +/- 3 beats/min at rest to 80 +/- 4 and 78 +/- 6 beats/min (P < 0.05), and MAP increased from 83 +/- 6 to 103 +/- 6 and 105 +/- 6 mmHg (P < 0.05) during voluntary and nonvoluntary contractions, respectively. CO increased from 5.1 +/- 0.7 to 6.0 +/- 0.8 and 6.2 +/- 0.8 l/min (P < 0.05) during voluntary and nonvoluntary contractions, respectively. PVR and SV did not change significantly during voluntary or nonvoluntary contractions. Thus the cardiovascular responses were not different between voluntary and electrically induced contractions. These results suggest that the increases in CO, HR, SV, MAP, and PVR during 5 min of static contractions can be elicited without any contribution from a central neural mechanism (central command). However, central command could still have an important role during voluntary static exercise.
Interrelationships between left ventricular volume and output during exercise in healthy subjects
Authors: Adams K. F. , McAllister S. M. , el-Ashmawy H. , Atkinson S. , Koch G. , Sheps D. S.
Published: December 2017

To better characterize the relationship between left ventricular volume response and improved ventricular ejection and output during supine exercise in normal subjects, 36 healthy asymptomatic volunteers (age 39 +/- 17 yr) were studied with radionuclide ventriculography during recumbent bicycle ergometry. Relative changes in left ventricular end-diastolic and end-systolic volume were measured at rest and during exercise by a modification of the radionuclide counts-based method that accounted for variability in stress blood pool counts. A biphasic response was noted in left ventricular end-diastolic volume with an initial increase in early exercise (8.5 +/- 11% at 200 kpm/min and 11 +/- 12% at 300 kpm/min) followed by a progressive and significant decline at peak exercise (-3.3 +/- 18% at 547 +/- 140 kpm/min; P < 0.05). There was substantial variation in end-diastolic volume response at peak exercise in the group as a whole, which could be more closely related to changes in end-systolic volume (r = 0.84, P < 0.0001) than in heart rate (r = -0.57, P < 0.01) or age (r = 0.36, P < 0.05) of the study subjects. Despite the decline in ventricular filling, systolic function appeared to improve dramatically at peak exercise (change in left ventricular ejection fraction 15.5 +/- 6.4, P < 0.0001). Although not directly related to increasing systolic ejection, end-diastolic volume was directly related to the percent change in stroke volume at peak exercise among the study subjects (r = 0.88, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Force-velocity shifts with repetitive isometric and isotonic contractions of canine gastrocnemius in situ
Authors: Ameredes B. T. , Brechue W. F. , Andrew G. M. , Stainsby W. N.
Published: December 2017

The force-velocity (F-V) relationships of canine gastrocnemius-plantaris muscles at optimal muscle length in situ were studied before and after 10 min of repetitive isometric or isotonic tetanic contractions induced by electrical stimulation of the sciatic nerve (200-ms trains, 50 impulses/s, 1 contraction/s). F-V relationships and maximal velocity of shortening (Vmax) were determined by curve fitting with the Hill equation. Mean Vmax before fatigue was 3.8 +/- 0.2 (SE) average fiber lengths/s; mean maximal isometric tension (Po) was 508 +/- 15 g/g. With a significant decrease of force development during isometric contractions (-27 +/- 4%, P < 0.01, n = 5), Vmax was unchanged. However, with repetitive isotonic contractions at a low load (P/Po = 0.25, n = 5), a significant decrease in Vmax was observed (-21 +/- 2%, P < 0.01), whereas Po was unchanged. Isotonic contractions at an intermediate load (P/Po = 0.5, n = 4) resulted in significant decreases in both Vmax (-26 +/- 6%, P < 0.05) and Po (-12 +/- 2%, P < 0.01). These results show that repeated contractions of canine skeletal muscle produce specific changes in the F-V relationship that are dependent on the type of contractions being performed and indicate that decreases in other contractile properties, such as velocity development and shortening, can occur independently of changes in isometric tension.
Modifying pulmonary ischemia-reperfusion injury by altering ventilatory strategies during ischemia
Authors: Hamvas A. , Park C. K. , Palazzo R. , Liptay M. , Cooper J. , Schuster D. P.
Published: December 2017

We used an intact in vivo canine model of pulmonary ischemia-reperfusion (IR) injury to evaluate the differential effects of alveolar hypoxia and ventilation during 2 h of unilateral warm lung ischemia. Serial measurements of regional pulmonary blood flow, extravascular density (EVD), and transcapillary protein flux were made after reperfusion with the quantitative imaging technique of positron emission tomography. Twenty-seven animals were divided into five experimental groups: VENT O2 (n = 5) in which the left lung was ventilated with 40% O2 during ischemia, STATIC O2 (n = 4) in which the left lung was statically inflated with 40% O2 during ischemia, VENT N2 (n = 5) in which the left lung was ventilated with 100% N2 during ischemia, VENT N2/CO2 (n = 5) in which the left lung was ventilated with 95% N2–5% CO2 during ischemia, and STATIC N2 (n = 8) in which the left lung was statically inflated with 100% N2 during ischemia. These groups were compared with a control group (CONT, = 3) that was studied previously. Protein flux was significantly increased in the previous ischemic lung only for the STATIC N2 group [median 175 x 10(-4) min-1 (range 53–1,217) for the STATIC N2 group vs. 50 x 10(-4) min-1 (range 40–56) for the CONT group] 0.25 h after reperfusion and did not change over 3 h. EVD also increased but not significantly. Protein flux and EVD in the other groups were not different from CONT.(ABSTRACT TRUNCATED AT 250 WORDS)
EDRF inhibition attenuates the increase in pulmonary blood flow due to oxygen ventilation in fetal lambs
Authors: Moore P. , Velvis H. , Fineman J. R. , Soifer S. J. , Heymann M. A.
Published: December 2017

At birth, pulmonary vasodilation occurs during rhythmic distension of the lungs and oxygenation. Inhibition of prostaglandin synthesis prevents pulmonary vasodilation during rhythmic distension of the lungs but not during oxygenation. Because endothelium-derived relaxing factor (EDRF) modulates pulmonary vascular tone at birth, at rest, and during hypoxia in older animals, we hypothesized that EDRF may modulate pulmonary vascular tone during oxygenation in fetal lambs. We studied the responses to N omega-nitro-L-arginine, a competitive inhibitor of EDRF synthesis, in nine near-term fetal lambs and to drug vehicle in six of these lambs and the subsequent responses to in utero ventilation with 95% O2 in these fetal lambs. In all fetal lambs, prostaglandin synthesis was prevented by meclofenamate. N omega-nitro-L-arginine increased pulmonary and systemic arterial pressures by 28% (P < 0.05) and 31% (P < 0.05), respectively, and decreased pulmonary blood flow by 83% (P < 0.05). In the controls, ventilation with 95% O2 increased pulmonary blood flow by 1,050% (P = 0.05) without changing pressures, thereby decreasing pulmonary vascular resistance by 88% (P = 0.05). During N omega-nitro-L-arginine infusion, ventilation with 95% O2 increased pulmonary blood flow by 162% (P = 0.05) and decreased pulmonary vascular resistance by 74% (P = 0.05). This suggests that EDRF may play an important role in modulating resting pulmonary vascular tone in fetal lambs and in the vasodilatory response to ventilation with O2 in utero.
Pulmonary vasodilation by inhaled nitric oxide after endothelial injury
Authors: Rimar S. , Gillis C. N.
Published: December 2017

Inhaled nitric oxide gas (NO) has recently been shown to reverse experimentally induced pulmonary vasoconstriction. To examine the effect of free radical injury and methylene blue exposure on inhaled NO-induced pulmonary vasodilation we studied ventilated rabbit lungs perfused with Krebs solution containing 3% dextran and indomethacin. When NO gas (120 ppm) was added to the inhaled mixture for 3 min, the elevated pulmonary arterial perfusion pressure (Ppa) induced by the thromboxane analogue U-46619 was significantly reduced [8 +/- 2 (SE) mmHg]. Acetylcholine similarly reduced Ppa (9 +/- 1 mmHg). After free radical injury and methylene blue exposure, inhaled NO again produced significant vasodilation (5 +/- 1 and 9 +/- 2 mmHg, respectively), but acetylcholine resulted in an increase in Ppa (-9 +/- 3 and -4 +/- 1 mmHg, respectively). These data demonstrate that pulmonary vasodilation produced by inhaled NO is unaffected by free radical injury or methylene blue in the intact lung despite concomitant reversal of acetylcholine-induced vasodilation.
Human temperature regulation during narcosis induced by inhalation of 30% nitrous oxide
Authors: Mekjavic I. B. , Sundberg C. J.
Published: December 2017

The study investigated the effect of inhalation of 30% nitrous oxide (N2O) on temperature regulation in humans. Seven male subjects were immersed to the neck in 28 degrees C water on two separate occasions. They exercised at a rate equivalent to 50% of their maximum work rate on an underwater cycle ergometer for 20 min and remained immersed for an additional 100 min after the exercise. In one trial (AIR) the subjects inspired compressed air, and in the other trial (N2O) they inspired a gas mixture containing N2O (20.93% O2–30% N2O-49.07% N2). Sweating, measured at the forehead, and shivering thermogenesis, as reflected by O2 uptake, were monitored throughout the 100-min recovery period. The threshold core temperatures at which sweating was extinguished and shivering was initiated were established relative to resting preexercise levels. Neither the magnitude of the sweating response nor the core threshold at which it was extinguished was significantly affected by the inhalation of N2O. In contrast, shivering thermogenesis was both significantly reduced during the N2O condition and initiated at significantly lower core temperatures [change in esophageal temperature (delta T(es)) = -0.98 +/- 0.33 degrees C and change in rectal temperature (delta T(re)) = -1.26 degrees C] during the N2O than during the AIR condition (delta T(es) = -0.36 +/- 0.31 degrees C and delta T(re) = -0.44 +/- 0.22 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)
Respiratory instability during sleep onset
Authors: Trinder J. , Whitworth F. , Kay A. , Wilkin P.
Published: December 2017

It has been hypothesized that regulatory control in the respiratory system is state dependent. According to this view respiratory instability during sleep onset is a consequence of repeated fluctuations in arousal state. However, these speculations are based primarily on measurements during stable sleep, not during sleep onset itself. The aim of the present study was to assess changes in ventilation and gas tensions during sleep onset as a function of arousal state. Twenty-one subjects (12 males and 9 females, mean age 20 yr) were assessed over an average of 11.3 sleep onsets. The subject's state was classified as alpha, theta, body movement, or stage 2 sleep, and expiratory tidal volume, minute ventilation, respiratory rate, and end-tidal CO2 and O2 were measured by means of a face mask, valve, and pneumotachograph on a breath-by-breath basis. Respiratory instability during sleep onset was found to be a result of two factors. The first factor was a between-state effect in which transitions from alpha to theta were associated with falls, and from theta to alpha with increases, in ventilation. The magnitude of the change was a positive function of metabolic drive at the time of the state change (as indicated by alveolar PCO2 and PO2 levels). The second was a within-state effect in which ventilation fell during consecutive alpha breaths and increased during consecutive theta breaths. These changes were due to the influence of the relative hyperventilation of the alpha state and the relative hypoventilation of the theta state on metabolic drive.
Increased thrombin-antithrombin III complexes after 1 h of physical exercise
Authors: Herren T. , Bartsch P. , Haeberli A. , Straub P. W.
Published: December 2017

Concentrations of thrombin-antithrombin III (TAT) complexes in plasma were previously reported to be increased after a 100-km run, while fibrinopeptide A (FPA) concentration remained unchanged. Thus, antithrombin III appears to neutralize thrombin generated during running and prevents fibrin formation. To determine the clinical relevance of these findings, we compared the effects of exhaustive running (1 h, n = 10) on the plasma concentrations of prothrombin fragments F1 and F2, TAT, FPA, and beta-thromboglobulin with the effects of recreational jogging (1 h, n = 10) and exhaustive bicycling on an ergometer (1 h, n = 8). Prothrombin fragments F1 and F2 and TAT concentrations increased significantly in each group. The most significant increase in TAT concentration was measured in the running group (from 1.72 +/- 0.49 to 3.61 +/- 1.03 ng/ml, P < 0.001). The best correlation was found between the postexercise TAT and lactate concentrations (r = 0.62, n = 28, P < 0.001). Mean FPA concentrations after exercise did not exceed normal values in any of the three groups analyzed. An increase in beta-thromboglobulin concentration was measured in the running and in the cycling group. Thus, thrombin is formed, in particular, when associated with anaerobic metabolism, and platelets are activated during high-intensity exercise.
Training can improve muscle strength and endurance in 78- to 84-yr-old men
Authors: Grimby G. , Aniansson A. , Hedberg M. , Henning G. B. , Grangard U. , Kvist H.
Published: December 2017

Nine men, 78–84 yr of age, participated in a dynamometer training program 2–3 times/wk, totaling 25 sessions, using voluntary maximal isometric, concentric, and eccentric right knee–extension actions (30 and 180 degrees/s). Measurements of muscle strength with a Kin-Com dynamometer and simultaneous electromyograms (EMG) were performed of both sides before and after the training period. Muscle biopsies were taken from the right vastus lateralis muscle. The total quadriceps cross-sectional area was measured with computerized tomography. Training led to an increase in maximal torque for concentric (10% at 30 degrees/s) and eccentric (13–19%) actions in the trained leg. The EMG activity increased at maximal eccentric activities. The total cross-sectional quadriceps area of the trained leg increased by 3%, but no changes were recorded in muscle fiber areas in these subjects, who already had large mean fiber areas (5.15 microns 2 x 10(3)). The fatigue index measured from 50 consecutive concentric contractions at 180 degrees/s decreased and the citrate synthase activity increased in all but one subject. The results demonstrate that increased neural activation accompanies an increase in muscle strength at least during eccentric action in already rather active elderly men and that muscle endurance may also be improved with training.
Gamma irradiation prevents compensatory hypertrophy of overloaded mouse extensor digitorum longus muscle
Authors: Rosenblatt J. D. , Parry D. J.
Published: December 2017

Mouse extensor digitorum longus (EDL) muscle was subjected to a dose of gamma irradiation that causes reproductive death of satellite cells and/or to chronic compensatory overload, achieved by removal of the distal portion of the tibialis anterior muscle. Four weeks later the mass, fiber type percentage, and fiber size of the EDL muscle were measured. Both the irradiated + overloaded and the irradiated only EDL muscles were significantly lighter and contained significantly smaller fibers than untreated muscle or muscle subjected to chronic overload only. Overload muscle, whether irradiated or not, had a larger percentage of type IIx fibers and a smaller percentage of type IIb fibers than muscle that had not been overloaded. The results confirm that satellite cell proliferation is a prerequisite for muscle hypertrophy induced by synergist incapacitation, but it appears not to be required for the maintenance of, or change in, normal muscle fiber myosin heavy chain phenotype expression.
Operation Everest II: metabolic and hormonal responses to incremental exercise to exhaustion
Authors: Young P. M. , Sutton J. R. , Green H. J. , Reeves J. T. , Rock P. B. , Houston C. S. , Cymerman A.
Published: December 2017

The reasons for the reduced exercise capacities observed at high altitudes are not completely known. Substrate availability or accumulations of lactate and ammonium could have significant roles. As part of Operation Everest II, peak oxygen uptakes were determined in five normal male volunteers with use of progressively increasing cycling work loads at ambient barometric pressures of 760, 380, and 282 Torr. Decrements from sea level (SL) to 380 and 282 Torr occurred in peak power output (19 and 47%), time to exhaustion (19 and 48%), and oxygen uptake (41 and 61%), respectively. Arterial saturations after exhaustive exercise were decreased to 63% at 380 Torr and 39% at 282 Torr. At 380 and 282 Torr, postexercise plasma concentrations of glucose and free fatty acids were not increased, whereas plasma glycerol concentrations were decreased relative to SL (145 +/- 24 microM at 380 Torr and 77 +/- 10 microM at 282 Torr vs. 213 +/- 24 microM at SL). Preexercise plasma insulin concentrations were elevated at both 380 and 282 Torr (87 +/- 16 pM at 380 Torr and 85 +/- 18 pM at 282 Torr vs. 41 +/- 30 pM at SL). In general, postexercise concentrations of plasma catecholamines were decreased at altitude compared with SL. Preexercise lactate and ammonium concentrations were not different at any simulated altitude. From these data neither substrate availability nor metabolic product accumulation limited exercise capacity at extreme simulated altitude.
Nitrogen tensions in brachial vein blood of Korean ama divers
Authors: Radermacher P. , Falke K. J. , Park Y. S. , Ahn D. W. , Hong S. K. , Qvist J. , Zapol W. M.
Published: December 2017

Intravascular bubble formation and symptoms of decompression sickness have been reported during repetitive deep breath-hold diving. Therefore we examined the pattern of blood N2 kinetics during and after repetitive breath-hold diving. To study muscle N2 uptake and release, we measured brachial venous N2 partial pressure (PN2) in nine professional Korean breath-hold divers (ama) during a 3-h diving shift at approximately 4 m seawater depth and up to 4 h after diving. PN2 was determined with the manometric Van Slyke method. Diving time and depth were recorded using a backpack computer-assisted dive longer that allowed calculating the surface-to-depth time ratio to derive the effective depth. With the assumption that forearm muscle N2 kinetics follow the general Haldanian principles of compression and decompression, i.e., forearm muscle is a single compartment with a uniform tissue PN2 equal to venous PN2, PN2 data were fitted to monoexponential functions of time. In the early phase of the diving shift, PN2 rapidly increased to 640 Torr (half time = 6 min) and then slowly declined to baseline levels (half time = 36 min) after the work shift. Peak PN2 levels approximated the alveolar PN2 derived from the effective depth. We conclude that forearm muscle N2 kinetics are well described by a Haldanian single-compartment model. Decompression sickness is theoretically possible in the ama; it did not occur because the absolute PN2 remained low due to the shallow working depth of the ama we studied.