bluuebunny/crossref_metadata_2025 huggingface dataset:
A model of dynamic exercise: the decerebrate rat locomotor preparation
Authors: Bedford T. G. , Loi P. K. , Crandall C. C.
Published: December 2017

The purpose of this study was to develop a dynamic exercise model in the rat that could be used to study central nervous system control of the cardiovascular system. Rats of both sexes were decerebrated under halothane anesthesia and prepared for induced locomotion on a freely turning wheel. Electrical stimulation of the mesencephalic locomotor region (MLR) elicited locomotion at different speeds and gait patterns and increased heart rate and blood pressure. Two maneuvers were performed to illustrate the potential use of the preparation. The first maneuver consisted of muscular paralysis, which prevents excitation of muscle mechanoreceptors and chemoreceptors resulting from exercise. MLR stimulation still increased blood pressure. The second maneuver was performed to determine whether the blood pressure response obtained during paralysis was an artifact of electrical stimulation of the MLR. After microinjection of gamma-aminobutyric acid into the MLR, electrical current thresholds for blood pressure and locomotion increased in parallel. gamma-Aminobutyric acid injection also reduced the pressor response to suprathreshold electrical stimulation by 76%. The injection results suggest that electrical stimulation of the MLR activates cells rather than fibers of passage. The blood pressure response of the exercise model is probably not an artifact of stimulation. The decerebrate rat locomotor preparation should offer another approach to investigate difficult problems in exercise physiology.
Input impedance and peripheral inhomogeneity of dog lungs
Authors: Hantos Z. , Daroczy B. , Suki B. , Nagy S. , Fredberg J. J.
Published: December 2017

Tracheal pressure, central airflow, and alveolar capsule pressures in cardiac lobes were measured in open-chest dogs during 0.1- to 20-Hz pseudorandom forced oscillations applied at the airway opening. In the interval 0.1–4.15 Hz, the input impedance data were fitted by four-parameter models including frequency-independent airway resistance and inertance and tissue parts featuring a marked negative frequency dependence of resistance and a slight elevation of elastance with frequency. The models gave good fits both in the control state and during histamine infusion. At the same time, the regional transfer impedances (alveolar pressure-to-central airflow ratios) showed intralobar and interlobar variabilities of similar degrees, which increased with frequency and were exaggerated during histamine infusion. Results of simulation studies based on a lung model consisting of a central airway and a number of peripheral units with airway and tissue parameters that were given independent wide distributions were in agreement with the experimental findings and showed that even an extremely inhomogeneous lung structure can produce virtually homogeneous mechanical behavior at the input.
Dextran sulfate and heparin sulfate inhibit platelet-activating factor-induced pulmonary edema
Authors: Hocking D. , Ferro T. J. , Johnson A.
Published: December 2017

We tested the hypothesis that dextran sulfate and heparin sulfate inhibit platelet-activating factor- (PAF) induced pulmonary edema in the isolated perfused guinea pig lung via a charge-dependent mechanism. Dextran sulfate prevented the changes in pulmonary capillary pressure (Ppc, 7.8 +/- 0.9 vs. 14.0 +/- 0.7 cmH2O), lung weight gain (dW, +0.48 +/- 0.29 vs. +8.41 +/- 2.07 g), and pulmonary edema formation or wet-to-dry weight ratio [(W-D)/D, 6.5 +/- 0.3 vs. 13.2 +/- 2.6] occurring 60 min after PAF infusion (10(-11) M) into an isolated lung. The unsulfated form of dextran had no protective effect [Ppc, dW, and (W-D)/D, 11.9 +/- 1.4 cmH2O, +5.33 +/- 2.18 g, and 11.2 +/- 3.2, respectively]. The unrelated anionic compound, heparin sulfate, also inhibited the PAF response [Ppc, dW, and (W-D)/D, 7.0 +/- 0.5 cmH2O, +0.61 +/- 0.32 g, and 6.1 +/- 0.2, respectively], whereas the partially desulfated form of heparin was not effective in inhibiting PAF-induced edema [Ppc, dW, and (W-D)/D, 15.1 +/- 0.7 cmH2O, +6.07 +/- 1.58 g, and 10.0 +/- 1.2, respectively]. When the metachromatic dye crystal violet was used as an indicator of charge interactions, the sulfated compounds interacted with PAF in vitro. The data indicate that PAF-induced pulmonary edema is inhibited by sulfated polysaccharides, possibly via a charge interaction between negatively charged compounds and PAF.
Protamine interaction with the epithelial cell surface
Authors: Peterson M. W. , Gruenhaupt D.
Published: December 2017

We have previously reported that exposing cultured Madin Darby canine kidney (MDCK) cells to the polycation protamine (PRO) results in increased short-circuit current and decreased barrier integrity as measured by mannitol permeability and transepithelial electrical resistance. To further investigate the interaction of PRO with the surface of epithelial cells, we labeled PRO with [14C] with use of reductive alkylation. [14C]PRO bound to the cells in a biphasic pattern. Approximately 10% of the [14C]PRO was bound to the cells in the first 5 min, followed by an additional 10% that was bound over the next 25 min. No additional [14C]PRO bound to the cells after the initial 30 min. Binding of [14C]PRO was inhibited by “cold” PRO, which suggested specificity. Binding was also inhibited by polyanions, serum, and albumin, agents previously found to protect MDCK cells from PRO-induced injury. The binding of PRO to MDCK cells was not inhibited by incubation of the MDCK cells with neuraminidase, to remove surface sialic acid residues, or with heparinase, to remove surface heparan sulfate, even though metabolic labeling experiments demonstrated that neuraminidase decreased cell sialic acid and heparinase decreased cell heparan sulfate. Neuraminidase and heparinase offered no protection from PRO injury and had no effect themselves on mannitol permeability. Incubation of the cells with trypsin, however, blunted both the binding of PRO to the cells and the increase in mannitol permeability after exposure of the cells to PRO.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of perfused capillary density in canine intestinal mucosa during endotoxemia
Authors: Drazenovic R. , Samsel R. W. , Wylam M. E. , Doerschuk C. M. , Schumacker P. T.
Published: December 2017

Pulmonary and Critical Care Medicine, University of Chicago, Illinois 60637.
Exercise training improves left ventricular contractile response to beta-adrenergic agonist
Authors: Spina R. J. , Ogawa T. , Coggan A. R. , Holloszy J. O. , Ehsani A. A.
Published: December 2017

To determine whether endurance exercise training can improve left ventricular function in response to beta-adrenergic stimulation, young healthy sedentary subjects (10 women and 6 men) were studied before and after 12 wk of endurance exercise training. Training consisted of 3 days/wk of interval training (running and cycling) and 3 days/wk of continuous running for 40 min. The training resulted in an increase in maximal O2 uptake from 41.0 +/- 2 to 49.3 +/- 2 ml.kg-1.min-1 (P less than 0.01). Left ventricular function was evaluated by two-dimensional echocardiography under basal conditions and during beta-adrenergic stimulation induced by isoproterenol infusion. Fractional shortening (FS) under basal conditions was unchanged after training (36 +/- 1 vs. 36 +/- 2%). During the highest dose of isoproterenol, FS was 52 +/- 1% before and 56 +/- 1% after training (P less than 0.05). At comparable changes in end-systolic wall stress (sigma es), the increase in FS induced by isoproterenol was significantly larger after training (13 +/- 1 vs. 17 +/- 2%, P less than 0.01). Furthermore there was a greater decrease in end-systolic dimension at similar changes in sigma es in the trained state during isoproterenol infusion (-4.6 +/- 0.1 mm before vs. -7.0 +/- 0.1 mm after training, P less than 0.01). There were no concurrent changes in end-diastolic dimension between the trained and untrained states during isoproterenol infusion, suggesting no significant changes in preload at comparable levels of sigma es.(ABSTRACT TRUNCATED AT 250 WORDS)
PGE1 inhibited PMN attachment to air emboli in vivo during infusion of ZAP without preventing lung injury
Authors: Doerr T. A. , Rosolia D. L. , Peters S. P. , Gee M. H. , Albertine K. H.
Published: December 2017

Prostaglandin E1 (PGE1) treatment of neutrophils inhibits their adherence to substrates in vitro, including endothelial cell monolayers. Demonstration that PGE1 inhibits neutrophil adherence in vivo in the lung, however, is complicated by PGE1 effects on cells other than neutrophils, such as endothelial cells. To determine whether PGE1 inhibits neutrophil adherence properties in vivo, we used air emboli as intravascular targets for neutrophil attachment. Four experimental conditions were studied in anesthetized and awake sheep that were treated with 1) PGE1 and air emboli, 2) saline and air emboli, 3) PGE1 and zymosan-activated plasma (ZAP) + air emboli, and 4) saline and ZAP + air emboli. PGE1 (30 ng.kg-1.min-1) or saline was infused continuously 1 h before and 1 h during the infusion of air emboli (group 1; n = 13 sheep) or ZAP + air emboli (group 2; n = 13 sheep). The number of neutrophils (PMNs) attached to air emboli in four anesthetized sheep per condition was significantly less in sheep given PGE1 and ZAP + air emboli [8 +/- 3 (SD) PMNs/mm of embolus perimeter] than in the other three conditions (14–21 PMNs/mm; P less than 0.05). Repeated experiments in five awake sheep per group showed that PGE1 treatment did not prevent increased lung lymph protein clearance in either group compared with saline treatment. We conclude that PGE1 specifically inhibited attachment of ZAP-activated neutrophils to air emboli in vivo. The lack of pathophysiological protection suggests that PGE1-induced alterations in neutrophil attachment properties were independent of other cellular activation responses.
Influence of diet and carnitine palmitoyltransferase I inhibition on myosin and sarcoplasmic reticulum
Authors: Rupp H. , Wahl R. , Hansen M.
Published: December 2017

To examine the role of metabolic signals for ventricular myosin expression and activity of the sarcoplasmic reticulum Ca2+ pump, Wistar rats were treated for 7–8 wk with 5 or 50 mg/kg etomoxir, which inhibits fatty acid utilization. The proportion of myosin V1 was increased (P less than 0.05) with 50 mg/kg etomoxir (75 +/- 5% vs. 62 +/- 6% of control rats), whereas both doses increased the rate of Ca2+ uptake. A carbohydrate-rich fat-free diet or 8% sucrose drinking solutions, however, had no effect on myosin and sarcoplasmic reticulum. When rats were fed diets with an increased content (10 or 20%) of sunflower oil, the calorie intake and myosin V1 increased (56 +/- 8 or 64 +/- 8% vs. 44 +/- 6% of control rats). Isocaloric 10% fat diets of varying fatty acid composition (coconut fat, olive oil, or mackerel oil) also induced a higher calorie intake and increased V1 (64 +/- 6, 60 +/- 9, or 65 +/- 8% for the respective oils vs. 44 +/- 6% of control rats) but did not significantly increase rate of Ca2+ uptake. We concluded that calorie-rich diets changed the myosin expression not by affecting the ratio of fatty acid to glucose utilization but via the increased calorie intake.
Increased negativity of interstitial fluid pressure in rat trachea in dextran anaphylaxis
Authors: Koller M. E. , Reed R. K.
Published: December 2017

This study shows that, in rat trachea, dextran anaphylaxis is associated with increased negativity of interstitial fluid pressure (Pif) as measured with sharpened glass capillaries (tip diameter 3–7 microns) connected to a servo-controlled counterpressure system. Experiments were carried out in pentobarbital-anesthetized Wistar-Moller rats. Pif in the control situation was -2.5 +/- 0.38 (SD) mmHg. The mean pressure in animals killed 2 min after initiation of the anaphylactic reaction by injection of 1 ml of 10% Dextran 70 in 0.9% NaCl was -10.3 +/- 2.6 mmHg. In another experimental series, interstitial fluid volume was measured after dextran administration but without inducing circulatory arrest. Interstitial fluid volume increased from 0.94 +/- 0.16 to 1.56 +/- 0.42 ml/g dry wt after 10 min to 1.57 +/- 0.30 and 1.10 +/- 0.27 ml/g dry wt after 30 and 60 min, respectively. The increased negativity in Pif in tracheal mucosa in the early phase of dextran anaphylaxis will markedly increase the transcapillary net filtration pressure in the initial phase of edema development.
Modulation of NK cell activity by moderate intensity endurance training and chronic ethanol consumption
Authors: Blank S. E. , Johansson J. O. , Origines M. M. , Meadows G. G.
Published: December 2017

Chronic ethanol consumption can suppress natural killer (NK) cell activity. Exercise after ethanol administration may enhance blood ethanol clearance, which may benefit the immune response. This study examined the effects of moderate intensity endurance training and chronic ethanol consumption (20% wt/vol) on splenic NK cell activity. Mice were assigned to one of four groups: sedentary, water drinking (SED-H2O); sedentary, ethanol consuming (SED-EtOH); trained, water drinking (TR-H2O), and trained, ethanol consuming (TR-EtOH). TR groups ran 60 min/day, 5 days/wk, at 12 m/min for 10 wk. Mice were killed 48 h after exercise. Baseline NK cell activity was suppressed 30% in TR and EtOH groups compared with SED-H2O controls. Activation with recombinant human interleukin-2 increased cytolytic activity in all groups four- to fivefold. These results indicate that training did not abrogate the effects of chronic ethanol consumption on NK cell activity. Furthermore, moderate endurance training may contribute to suppressed nylon wool-enriched NK cell activity in murine splenocytes for as long as 48 h after exercise.
Effect of bolus fluid intake on energy expenditure values as determined by the doubly labeled water method
Authors: Drews D. , Stein T. P.
Published: December 2017

The doubly labeled water (DLW, 2H(2)18O) method is a highly accurate method for measuring energy expenditure (EE). A possible source of error is bolus fluid intake before body water sampling. If there is bolus fluid intake immediately before body water sampling, the saliva may reflect the ingested water disproportionately, because the ingested water may not have had time to mix fully with the body water pool. To ascertain the magnitude of this problem, EE was measured over a 5-day period by the DLW method. Six subjects were dosed with 2H2(18)O. After the reference salivas for the two-point determination were obtained, subjects drank water (700–1,000 ml), and serial saliva samples were collected for the next 3 h. Expressing the postbolus saliva enrichments as a percentage of the prebolus value, we found 1) a minimum in the saliva isotopic enrichments were reached at approximately 30 min with the minimum for 2H (95.48 +/- 0.43%) being significantly lower than the minimum for 18O (97.55 +/- 0.44, P less than 0.05) and 2) EE values calculated using the postbolus isotopic enrichments are appreciably higher (19.9 +/- 7.5%) than the prebolus reference values. In conclusion, it is not advisable to collect saliva samples for DLW measurements within approximately 1 h of bolus fluid intake.
No evidence for brain stem cooling during face fanning in humans
Authors: Jessen C. , Kuhnen G.
Published: December 2017

The interpeak latencies (IPLs) of the acoustically evoked brain stem potentials depend on brain stem temperature. This was used to see whether face fanning during hyperthermia lowers brain stem temperature. In 15 subjects, three thermally stable conditions were maintained by a water bath. In each condition the IPLs were determined in 10 separate trials. In condition A esophageal temperature (Tes) was 36.9 +/- 0.3 degrees C and increased to 38.6 +/- 0.2 degrees C in condition B. In conditions A and B the head was enclosed in a ventilated hood (air temperature 38 degrees C, relative humidity 100%) to suppress any direct heat loss from the head. From conditions A to B the IPL at peaks I-V decreased by 0.146 ms/degrees C change in Tes, reflecting a change in brain stem temperature. In condition C the hood was removed and the face was fanned by a cold air-stream (8–15 degrees C, 4–10 m/s) to maximize direct heat loss from the head. Skin temperature at the sweating forehead decreased from 38 to 23 degrees C, whereas Tes in condition C was maintained at the same level as in condition B (38.5 +/- 0.2 degrees C). The IPL at peaks I-V showed no difference between conditions B and C. It is concluded that face fanning in hyperthermic subjects does not dissociate brain stem temperature from Tes.
Regional differences in interstitial fluid albumin concentration in edematous lamb lungs
Authors: Raj J. U. , Anderson J.
Published: December 2017

We have determined regional lung interstitial fluid albumin concentration in lambs with hydrostatic pulmonary edema and correlated it with lung lymph and plasma albumin concentrations. In anesthetized lambs, we raised left atrial pressure to 25–30 cmH2O by obstructing the aorta and volume overloading the lambs with infusions of Ringer lactate solution (group I, n = 10) or sheep's blood (group II, n = 9). We measured lung lymph flow and concentrations of total protein and albumin in plasma and lymph. With micropipettes we also collected interstitial fluid from interlobular septal pools and peribronchial, periarterial, and perivenous liquid cuffs near the hilum for measurement of albumin concentration by the gel immunoelectrophoresis method. In both groups, lung lymph flow increased with left atrial hypertension, and the ratio of lymph to plasma protein concentration fell. For group I, plasma and lymph albumin concentrations during the phase of hydrostatic edema were 1.97 +/- 0.49 and 1.15 +/- 0.36, respectively; for group II, they were 3.77 +/- 0.42 and 2.43 +/- 0.39 g/dl, respectively. Lung wet-to-dry weight ratio averaged 6.0 in both groups. Albumin concentration was always lower in interstitial fluid than in plasma. In both groups, albumin concentration was similar in periarterial and peribronchial fluid cuffs (group I 1.19 +/- 0.6 and 1.36 +/- 0.79 g/dl, respectively; group II 2.87 +/- 1.05 and 2.33 +/- 0.58 g/dl, respectively) but was always greater than that in perivenous and interlobular septal pools (group I 0.61 +/- 0.21 and 0.67 +/- 0.23 g/dl, respectively; group II 1.76 +/- 0.49 and 1.55 +/- 0.52 g/dl, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in respiratory activity induced by mastication in humans
Authors: Fontana G. A. , Pantaleo T. , Bongianni F. , Cresci F. , Viroli L. , Sarago G.
Published: December 2017

We studied the influence of mastication on respiratory activity in nine healthy volunteers who were requested to masticate a 5-g chewing gum bolus at a spontaneous rate (SR) for 5 min and “at the maximum possible rate” (MPR) for 1 min. Significant increases in respiratory frequency were induced by SR mastication due to a decrease in both the inspiratory and expiratory time. Tidal volume displayed slight nonsignificant decreases, but minute ventilation and mean inspiratory flow significantly increased. The duty cycle (TI/TT) did not change significantly. Total airway resistance significantly increased. Both peak and rate of rise of the integrated electromyographic activity of inspiratory muscles presented marked increases, accompanied by the appearance of a low level of tonic muscular activity. Similar but more intense effects on respiratory activity were induced by MPR mastication; in addition, a significant decrease in tidal volume and a significant increase in TI/TT were observed. Rhythmic handgrip exercise performed at metabolic rates comparable to those attained during SR or MPR mastication induced similar changes in the drive and time components of the breathing pattern, although accompanied respectively by nonsignificant or significant increases in tidal volume. Furthermore, the frequency of SR mastication significantly entrained the respiratory rhythm. The results suggest that mastication-induced hyperpnea does not merely represent a ventilatory response to exercise but also reflects complex interactions between respiratory and nonrespiratory functions of the upper airway and chest wall muscles.
A comparison of the oxygen drift in downhill vs. level running
Authors: Westerlind K. C. , Byrnes W. C. , Mazzeo R. S.
Published: December 2017

This investigation explored the recent theory that muscle damage causes the drift in oxygen consumption (VO2) during low-intensity downhill running. Seven subjects participated in a maximal VO2 (VO2max) test and three submaximal bouts [one level (Level) and two downhill runs (Down 1, Down 2) at 40% peak VO2]. Two downhill runs (30 min at -10% grade) were performed to vary the extent of muscle damage. Creatine kinase (CK) increased more after Down 1 (61%) than after Down 2 (11%), as did soreness ratings, indicating reduced muscle damage during Down 2. Significantly greater increases in VO2 over time were noted for Down 1 (15.6%) and Down 2 (14.7%) than for Level (1.2%). Heart rate increased 8 beats/min for Level but 29 and 25 beats/min for Down 1 and Down 2, respectively. Expired ventilation increased more for Down 1 (20.5%) and Down 2 (24%) than for Level (3.5%). Rectal temperature increased approximately 0.8 degree C for all bouts. Because the magnitude of the drift was similar in the two downhill bouts, the findings suggest that muscle damage does not cause the drift in VO2 during low-intensity downhill running.
Pulmonary and leg VO2 during submaximal exercise: implications for muscular efficiency
Authors: Poole D. C. , Gaesser G. A. , Hogan M. C. , Knight D. R. , Wagner P. D.
Published: December 2017

Insights into muscle energetics during exercise (e.g., muscular efficiency) are often inferred from measurements of pulmonary gas exchange. This procedure presupposes that changes of pulmonary O2 (VO2) associated with increases of external work reflect accurately the increased muscle VO2. The present investigation addressed this issue directly by making simultaneous determinations of pulmonary and leg VO2 over a range of work rates calculated to elicit 20–90% of maximum VO2 on the basis of prior incremental (25 or 30 W/min) cycle ergometry. VO2 for both legs was calculated as the product of twice one-leg blood flow (constant-infusion thermodilution) and arteriovenous O2 content difference across the leg. Measurements were made 3–5 min after each work rate imposition to avoid incorporation of the VO2 slow component above the lactate threshold. For all 17 subjects, the slope of pulmonary VO2 (9.9 +/- 0.2 ml O2.W-1.min-1) was not different (P greater than 0.05) from that for leg VO2 (9.2 +/- 0.6 ml O2.W-1.min-1). Estimation of “delta” efficiency (i.e., delta work accomplished divided by delta energy expended, calculated from slope of VO2 vs. work rate and a caloric equivalent for O2 of 4.985 cal/ml) using pulmonary VO2 measurements (29.1 +/- 0.6%) was likewise not significantly different (P greater than 0.05) from that made using leg VO2 measurements (33.7 +/- 2.4%). These data suggest that the net VO2 cost of metabolic “support” processes outside the exercising legs changes little over a relatively broad range of exercise intensities. Thus, under the conditions of this investigation, changes of VO2 measured from expired gas reflected closely those occurring within the exercising legs.
Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure
Authors: Yanai M. , Sekizawa K. , Ohrui T. , Sasaki H. , Takishima T.
Published: December 2017

To partition the central and peripheral airway resistance in awake humans, a catheter-tipped micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a 3-mm-ID bronchus in 5 normal subjects, 7 patients with chronic bronchitis, 8 patients with emphysema, and 20 patients with bronchial asthma. We simultaneously measured mouth flow, transpulmonary pressure, and intra-airway lateral pressure during quiet tidal breathing. Total pulmonary resistance (RL) was calculated from transpulmonary pressure and mouth flow and central airway resistance (Rc) from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by the subtraction of Rc from RL. The technique permitted identification of the site of airway resistance changes. In normal subjects, RL was 3.2 +/- 0.2 (SE) cmH2O.l-1.s and the ratio of Rp to RL was 0.24 during inspiration. Patients with bronchial asthma without airflow obstruction showed values of Rc and Rp similar to those of normal subjects. Although Rc showed a tendency to increase, only Rp significantly increased in those patients with bronchial asthma with airflow obstruction and patients with chronic bronchitis and emphysema. The ratio of Rp to RL significantly increased in three groups of patients with airflow obstruction (P less than 0.01). These observations suggest that peripheral airways are the predominant site of airflow obstruction, irrespective of the different pathogenesis of chronic airflow obstruction.
An apparatus to measure in vivo biomechanical behavior of dorsi- and plantarflexors of mouse ankle
Authors: Ashton-Miller J. A. , He Y. , Kadhiresan V. A. , McCubbrey D. A. , Faulkner J. A.
Published: December 2017

We developed an apparatus to quantify the biomechanical behavior of the dorsi- and plantarflexor muscles of the ankle of an anesthetized mouse. When the dorsi- or plantarflexor muscle group is activated by electrical stimulation of either the peroneal or tibial nerve, the apparatus measures the moment developed about the ankle during isometric, isovelocity shortening, or isovelocity lengthening contractions. Displacements may be performed over the full 105 degrees range of ankle motion with an angular resolution of 0.09 degrees. Bidirectional isovelocity ramps in ankle angle up to 1,100 degrees/s are possible and are equivalent to maximum velocities of 2.3 fiber lengths/s (Lf/s) for the fibers in tibialis anterior muscle and 11.9 Lf/s for those in gastrocnemius muscle. During single contractions of the dorsi- and plantarflexor muscle groups at 37 degrees C and with both knee and ankle joint at 90 degrees neutral position, the isometric tetanic force developed was 1.4 and 3.3 N, power output at 2.2 Lf/s was 3.1 and 5.9 mW, and power absorption at 0.5 Lf/s was 4.9 and 9.0 mW, respectively. These values are in reasonable agreement with data from the same muscle groups tested in situ. We conclude that the apparatus provides valid measurements of force and power of the dorsi- and plantarflexor muscle groups.
Repetitive apneas induce periodic hypertension in normal subjects through hypoxia
Authors: van den Aardweg J. G. , Karemaker J. M.
Published: December 2017

Periodic increases in blood pressure (BP) can occur in the sleep apnea syndrome (SAS) during recurrent apneas. To investigate the mechanisms causing this periodic hypertension, we simulated SAS by imposing a matching breathing pattern on seven healthy awake male volunteers. Continuous finger arterial BP, electrocardiogram, arterial O2 saturation (SaO2), end-tidal CO2, and tidal volume were measured. The role of hypoxia was studied by comparing apneas during depletion of O2 in the spirometer with those during 100% O2 breathing. In all subjects, BP periodically reached values greater than 150/95 mmHg in the hypoxic series. During the hyperoxic apnea series, however, BP remained stable. End-apneic mean BP was shown to be inversely correlated to SaO2 in six subjects in the SaO2 range from 60 to 100%. Although the hypoxic BP pattern closely mimicked that in SAS, the heart rate pattern in four of our subjects remained distinct from that in patients. Atropine could not prevent large BP swings in the hypoxic series. We conclude that SaO2 is a major determinant of periodic hypertension in recurrent apneas. Its effect probably results from chemoreflex modulation of peripheral resistance.
Changes in canine latissimus dorsi muscle during 24 wk of continuous electrical stimulation
Authors: Lucas C. M. , Havenith M. G. , van der Veen F. H. , Habets J. , van der Nagel T. , Schrijvers-Van Schendel J. M. , Penn O. C. , Wellens H. J.
Published: December 2017

To study functional, structural, and biochemical adaptations to electrical stimulation of striated muscle in a large animal, the canine latissimus dorsi (LD) muscle was conditioned continuously for 24 wk with an increasing number of pulse bursts (burst duration 250 ms, burst frequency 30 Hz). Force measurements in vivo after 12 wk showed a significant decrease in the ripple, the ratio of interstimulus to peak force amplitude, from 0.94 +/- 0.03 to 0.13 +/- 0.08 (SE; n = 8, P less than 0.05), indicating reduction in contractile speed. Also the steep part of the force-frequency relation shifted to lower frequencies. A significant change in fiber-type composition was seen with both enzyme- and immunohistochemistry, manifested by an increase of type I fibers from 29.5 +/- 2.9 to 83 +/- 8% (SE; n = 8, P less than 0.05). During this period a transient rise in the number of type IIc/Ic fibers (from 3 to 10%) was seen. In the stimulated muscle, capillary-to-fiber ratio increased from 1.9 +/- 0.4 to 2.7 +/- 0.1 (P less than 0.05). A significant increase in mitochondrial volume was also seen, especially in the peripheral part of the fiber. Both creatine kinase and lactate dehydrogenase revealed a significant decline in activity within 12 wk. At the same time a shift in lactate dehydrogenase-isozyme pattern was observed toward the cardiac composition. No additional changes occurred after 12 wk of stimulation, indicating that conversion of the canine LD muscle was complete within this period.
Transient changes in blood pressure during spontaneous deep breaths in rats with sinoaortic deafferentation
Authors: Machado B. H. , Mauad H. , Glass M. L.
Published: December 2017

Sinoaortic deafferentation (SAD) in rats produces moderate increases in mean arterial pressure (MAP) along with a large augmentation of arterial pressure lability (APL). The mechanisms generating this APL are incompletely understood. To study the possible influence of breathing activity on APL in conscious SAD rats, we simultaneously recorded pulmonary ventilation and arterial blood pressure. The general pattern of pulmonary ventilation was the same in normal, sham-operated, and SAD rats. In all groups single large tidal volumes were regularly interposed in 1- to 2-min periods of shallower breathing. In SAD rats these single large inspirations were consistently accompanied by substantial and abrupt reductions of MAP, whereas this effect was markedly smaller or absent in normal and sham-operated rats. The data reflect the lack of fast moment-to-moment control of arterial pressure normally exerted by the aortic and carotid baroreceptors. In this context, effects of ventilatory changes must be considered along with humoral and neurogenic factors to explain APL after SAD.
In vitro effects of pH and hemoglobin-oxygen saturation on plasma and erythrocyte K+ levels in blood from trout
Authors: Nielsen O. B. , Lykkeboe G.
Published: December 2017

Plasma and erythrocyte K+ were monitored during storage and tonometry of blood samples taken from resting rainbow trout, Oncorhynchus mykiss. During storage of arterial blood samples, plasma K+ concentration increased by 38% in 12 min. During extended tonometry of blood with a pH near 7.9 and full hemoglobin-bound oxygen (HbO2) saturation the erythrocytes showed a net loss of K+. Plasma K+ concentration increased from 2.9 mM to a near steady-state value of 5.6 mM. When tonometered at a pH near 7.2 and a HbO2 saturation at approximately 4% the erythrocytes took up K+, leading to a dramatic reduction in plasma K+ concentration to 0.2 mM. This net uptake was stimulated by isoprenaline and was inhibited by ouabain. It is concluded that net erythrocyte K+ uptake and loss can be induced in trout by changes in blood pH or HbO2 saturation in vitro.
Mechanical implications of in vivo human diaphragm shape
Authors: Paiva M. , Verbanck S. , Estenne M. , Poncelet B. , Segebarth C. , Macklem P. T.
Published: December 2017

Using magnetic resonance imaging, we measured the three-dimensional form of the diaphragm in vivo in four supine relaxed subjects at functional residual capacity and calculated its total surface area, the right and left surface areas in the zone of apposition, and the principal radii of curvature as a function of height. The area of apposition comprised 45 +/- 1.5% (SE) of the total surface area of the diaphragm. Available data on the area of the central tendon indicate that a considerable part of the muscular part of the diaphragm is lung apposed. The curvature was linearly related to height over 7 cm of the posterior half of each hemidiaphragm. From the linear portion of this graph and assuming a vertical gradient of transdiaphragmatic pressure of 0.75 cmH2O/cm, we applied the Laplace law and calculated tensions of 54 and 32 g/cm for right and left sides, respectively. We conclude that the shape of at least part of the posterior half of the relaxed human diaphragm in the supine position at functional residual capacity can be explained by the Laplace law, suggesting that both the lung and abdominal contents behave sufficiently as fluids so that they do not impose their shape on the diaphragm. Because diaphragm muscle is partly lung apposed, it is unlikely that the diaphragm functions simply as a piston.
Nasal effects of bradykinin and capsaicin: influence on plasma protein leakage and role of sensory neurons
Authors: Rajakulasingam K. , Polosa R. , Lau L. C. , Church M. K. , Holgate S. T. , Howarth P. H.
Published: December 2017

Nasal insufflation with bradykinin induces nasal discomfort, rhinorrhea, and nasal blockage, all features of rhinitis. We recently showed these effects to be mediated by the B2-receptor subtype, which has been identified at neural and vascular sites. To investigate the relative contribution of capsaicin-sensitive sensory neural stimulation to the action(s) of bradykinin, two randomized double-blind placebo-controlled studies have been undertaken comparing the nasal effects of single-dose administrations of bradykinin (1.88 x 10(-3) M) and capsaicin (3.28 x 10(-5) M). In comparison with placebo, both bradykinin and capsaicin induced nasal pain/discomfort (P less than 0.01) and rhinorrhea (P less than 0.02). Bradykinin significantly increased nasal airways resistance (P less than 0.005) and plasma protein exudation (P less than 0.02). No such changes were identified after nasal challenge with capsaicin. These findings suggest that bradykinin-induced nasal discomfort and rhinorrhea are neurally mediated, whereas the effects on nasal airways resistance and plasma protein exudation are due to a direct vascular action. In addition, these findings question the role of capsaicin-sensitive sensory neurons in nasal vasculature responses, because no vascular effects of capsaicin could be identified in the human nasal mucosa.
Endothelin-3 is a potent pulmonary vasodilator in the rat
Authors: Crawley D. E. , Liu S. F. , Barnes P. J. , Evans T. W.
Published: December 2017

The properties of endothelin-3 (ET-3) were investigated in isolated pulmonary artery rings and isolated blood-perfused lungs of the rat. ET-3 elicited a concentration-dependent relaxation of pulmonary artery rings, and effect inhibited by the nitric oxide synthesis inhibitor L-NG-monomethyl-L-arginine. At 0.1 microM, the response to ET-3 was biphasic, resulting in a sustained contraction. In the isolated lung, ET-3 caused a dose-dependent increase in pulmonary arterial pressure. In lungs ventilated with 3% oxygen, 10 nM ET-3 completely reversed the resultant hypoxic vasoconstriction (HPV) by 100 +/- 8%, an effect unchanged by either indomethacin (1 microM) or glibenclamide (10 microM). L-NG-monomethyl-L-arginine attenuated both the ET-3 dilation in prostaglandin F2 alpha-constricted lungs and the dose-dependent vasodilation of HPV by acetylcholine. ET-3 (10 nM) showed the response time to peak pulmonary arterial pressure generation by hypoxia, the size of the response being unchanged. These results demonstrate that ET-3 has both vasodilator and constrictor actions in the rat lung and that, like acetylcholine, the former is mediated in part via the release of nitric oxide. ET-3 also has the ability to modulate HPV.
Triangularis sterni and phrenic nerve responses to progressive brain hypoxia
Authors: Chae L. O. , Melton J. E. , Neubauer J. A. , Edelman N. H.
Published: December 2017

Activity of the respiratory muscles that are not normally active during eupnea (genioglossal and abdominal) has been shown to be more vulnerable to hypoxic depression than inspiratory diaphragmatic activity. We hypothesized that respiratory muscles that are active at eupnea would be equally vulnerable to isocapnic progressive brain hypoxia (PBH). Phrenic (PHR) and triangularis sterni nerve (TSN) activity were recorded in anesthetized peripherally chemodenervated vagotomized ventilated cats. Hypercapnia [arterial PCO2 (PaCO2) = 57 +/- 3 (SE) Torr] produced parallel increases in peak PHR and TSN activity. PBH [0.5% CO–40% O2–59.5% N2, arterial O2 content (CaO2) reduced from 13.1 +/- 1.0 to 3.7 +/- 0.3 vol%] resulted in parallel decreases of peak PHR and TSN activity to neural apnea. PBH was continued until PHR gasping ensued (CaO2 = 2.9 +/- 0.2 vol%); TSN activity remained silent during gasping. After 6–12 min of recovery (95% O2–5% CO2; CaO2 = 7.8 +/- 0.8 vol%; PaCO2 = 55 +/- 2 Torr), peak PHR activity was increased to 110 +/- 18% (% of activity at 9% CO2) whereas peak TSN activity was augmented to 269 +/- 89%. The greater augmentation of TSN activity during the recovery period could not be explained solely by hypercapnia. In conclusion, we found that 1) TSN expiratory and PHR inspiratory activities are equally vulnerable to hypoxic depression and 2) recovery from severe hypoxia is characterized by a profound augmentation of TSN expiratory activity.
Convective and diffusive gas transport in canine intrapulmonary airways
Authors: Schulz H. , Heilmann P. , Hillebrecht A. , Gebhart J. , Meyer M. , Piiper J. , Heyder J.
Published: December 2017

The significance of convective and diffusive gas transport in the respiratory system was assessed from the response of combined inert gas and particle boluses inhaled into the conducting airways. Particles, considered as “nondiffusing gas,” served as tracers for convection and two inert gases with widely different diffusive characteristics (He and SF6) as tracers for convection and diffusion. Six-milliliter boluses labeled with monodisperse di-2-ethylhexyl sebacate droplets of 0.86-microns aerodynamic diameter, 2% He, and 2% SF6 were inspired by three anesthetized mechanically ventilated beagle dogs to volumetric lung depths up to 170 ml. Mixing between inspired and residual air caused dispersion of the inspired bolus, which was quantified in terms of the bolus half-width. Dispersion of particles increased with increasing lung depth to which the boluses were inhaled. The increase followed a power law with exponents less than 0.5 (mean 0.39), indicating that the effect of convective mixing per unit volume was reduced with depth. Within the pulmonary dead space, the behavior of the inert gases He and SF6 was similar to that of the particles, suggesting that gas transport was almost solely due to convection. Beyond the dead space, dispersion of He and SF6 increased more rapidly than dispersion of particles, indicating that diffusion became significant. The gas and particle bolus technique offers a suitable approach to differential analysis of gas transport in intrapulmonary airways of lungs.
Fiber-optic transmission catheter for regional venous oxygen saturation and blood flow
Authors: Iwasaki H. , Yoshizaki K. , Koyano H.
Published: December 2017

We have developed a method for monitoring regional venous oxygen saturation. The key feature of this system is the use of highly flexible polymer fiber optics, and this flexibility allowed the production of a new fiber-optic transmission catheter. The space between the “face-to-face” positioned fiber-optic tips forms a remote catheter-based transmission cell. Our method applies Twersky's theory, in which absorption and scattering can be treated independently. Fresh rabbit blood was pumped through a disk oxygenator in which gas exchange occurred and passed the catheter. Simultaneous results obtained by the catheter and a cuvette oximeter were excellent (r = 0.99, SD = 1.1%). Oxygen saturation measured by this catheter was independent of vessel wall artifacts, blood pH, and flow velocity. Another application of this method is measurement of blood flow by the dye- (indocyanine green) dilution technique. The results of flow measurements by the catheter appeared to be satisfactory (r = 0.99, SD = 1.7%). This study concludes that our method is effective for monitoring the balance between regional oxygen supply and demand.
Microvascular and macrovascular endothelial cells produce different constrictor substances
Authors: Glassberg M. K. , Nolop K. B. , Jackowski J. T. , Abraham W. M. , Wanner A. , Ryan U. S.
Published: December 2017

The media from cultured microvascular and macrovascular endothelial cells (conditioned media, CM) were collected and tested for constrictor activity in sheep coronary artery rings and tracheal smooth muscle strips in vitro (isometric force), expressed as percentage of contraction produced by 80 mM KCl. Both microvascular (micro) and macrovascular (macro) CM caused a sustained slow-onset contraction (P less than 0.05) of the coronary artery rings by 71 +/- 10% (micro; n = 7) and 67 +/- 8% (macro; n = 6) and tracheal smooth muscle strips by 33 +/- 14% (micro; n = 6) and 34 +/- 6% (macro; n = 11); the calcium antagonist gallopamil (10(-7) M) attenuated these effects by 25–55%. Unconditioned medium and medium conditioned by cultured tracheal smooth muscle cells had no constrictor activity on coronary artery rings or tracheal smooth muscle strips. Synthetic endothelin (ET-1) also produced contraction of coronary artery rings and tracheal smooth muscle strips. The mean levels of ET-1 measured by radioimmunoassay were 1,200 pg/ml in the macro CM and 33 pg/ml in the micro CM. Depleting macro CM of ET-1 by affinity columns constructed with protein A agarose and anti-ET-1 antibody removed the contractile activity for coronary artery rings and tracheal smooth muscle strips. Thus ET-1 did not appear to be the contractile substance in the micro CM. Preliminary characterization of the contractile substance in micro CM revealed that it was heat stable, had a molecular weight of less than 10,000, was inactivated by trypsin, and retained its activity after two cycles of freeze-thawing.(ABSTRACT TRUNCATED AT 250 WORDS)
Vagal function impairment after exercise training
Authors: Negrao C. E. , Moreira E. D. , Santos M. C. , Farah V. M. , Krieger E. M.
Published: December 2017

The present investigation was undertaken to evaluate the vagal function of trained (T) and sedentary (S) rats by use of different approaches in the same animal. After 13 wk of exercise training (treadmill for 1 h 5 times/wk at 26.8 m/min and 15% grade), T rats had a resting heart rate (HR) slightly but significantly lower than S rats (299 +/- 3 vs. 308 +/- 3 beats/min). T rats had marked reduction of the intrinsic HR (329 +/- 4 vs. 369 +/- 5 beats/min) after blockade by methylatropine and propranolol. They also exhibited depressed vagal and sympathetic tonus. Baroreflex bradycardia (phenylephrine injections) was reduced, bradycardic responses produced by electrical stimulation of the vagus were depressed, and responses to methacholine injection were decreased in T rats. Therefore several evidences of vagal function impairment were observed in T rats. The resting bradycardia after exercise training is more likely to be dependent on alterations of the pacemaker cells, inasmuch as the intrinsic HR was markedly reduced.
Effects of acid-base status on acute hypoxic pulmonary vasoconstriction and gas exchange
Authors: Loeppky J. A. , Scotto P. , Riedel C. E. , Roach R. C. , Chick T. W.
Published: December 2017

To investigate the relationship between hypoxic pulmonary vasoconstriction and respiratory and metabolic acidosis and respiratory alkalosis, the pulmonary gas exchange and pulmonary hemodynamic responses were measured in anesthetized, paralyzed, and mechanically ventilated dogs in two sets of experiments (series A, n = 6; series B, n = 10). The animals were treated with acute hypoxia, CO2 inhalation, hyperventilation, and dinitrophenol in various combinations. Multiple regression analysis indicated that mean pulmonary arterial pressure (Ppa) was significantly correlated with end-tidal PO2, mixed venous PO2, and the mean pulmonary capillary pH (average of arterial and mixed venous pH) as independent variables [series A: r = +0.999, standard error of estimate (SEE) = 0.4 mmHg; series B: r = +0.98, SEE = 1.4 mmHg]. Similar analyses of mean values published by other authors from an acute study on humans with exercise at sea level and simulated altitudes of 10,000 and 15,000 ft also indicated a good relationship (n = 14, r = +0.98, SEE = 2.1 mmHg). The mean data (n = 19) obtained in Operation Everest II at various exercise loads and simulated altitudes gave a correlation of r = +0.87, SEE = 6.1 mmHg. These empirical analyses suggest that variations in the rise of Ppa with hypoxia can be accounted for in vivo by the superimposed acid-base status. Furthermore, ventilation-perfusion inhomogeneity, as estimated in the dogs from end-tidal and arterial O2 and CO2 differences and assuming no true shunt or diffusion impairment, was highly correlated with Ppa and mean pulmonary capillary pH (r = +0.999 in series A, r = +0.77 in series B). The human data from the above studies also showed significant correlations between Ppa and directly measured ventilation-perfusion (standard deviation of perfusion obtained from inert gas measurements). These observations indicate that the beneficial effects of hyperventilation during hypoxia may be related to the marked alkalosis that serves to reduce Ppa and improve pulmonary gas exchange efficiency.
Effect of nocturnal atrial demand cardiac pacing on diurnal hemodynamic patterns
Authors: Engel B. T. , Talan M. I. , Chew P. H.
Published: December 2017

Heart rate (HR), stroke volume (SV), intra-arterial blood pressure, and central venous pressure were recorded on a beat-to-beat basis, 18 h/day (1800–1200 h the following day), for approximately 2 mo in four monkeys (Macaca mulatta). Cardiac output, left ventricular work, and total peripheral resistance were derived from these primary measurements. During the 1st mo we measured these parameters under control conditions, and during the 2nd mo the animals were studied while HR was paced by atrial demand pacing sufficient to prevent the normal nocturnal fall in HR (approximately 10 beats/min above the fastest hourly average rate recorded during the control condition). The main hypothesis of this study was that when HR is prevented from falling, SV, which normally does not fall overnight, would fall; this hypothesis was confirmed. In addition, we observed that, during the period of pacing, relative to the control period, SV was approximately 14% greater during the early evening and 4% lower during the early morning; total peripheral resistance was similar during the early evening but was 13% higher by morning. Throughout the night, systolic pressure was approximately 4% greater, diastolic pressure was 17% higher, central venous pressure was 43% greater, and left ventricular work was 27% higher. These findings show that when HR is prevented from falling overnight by atrial demand pacing, even to a relatively modest degree, there can be very significant sustained changes in cardiovascular function.