bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluid shifts and muscle function in humans during acute simulated weightlessness
Authors: Hargens A. R. , Tipton C. M. , Gollnick P. D. , Mubarak S. J. , Tucker B. J. , Akeson W. H.
Published: December 2017

Head-down tilt is considered an effective experimental model to simulate weightlessness. To determine the acute effects of simulated weightlessness on transcapillary fluid balance, tissue fluid shifts, muscle function, and triceps surae reflex time, eight supine subjects were tilted 5 degrees head down for 8 h. A cephalic fluid shift from the legs was indicated by facial edema, nasal congestion, increased urine flow, decreased creatinine excretion, reduced calf girth, and decreased lower leg volume. As measured by wick catheters inserted under local anesthesia, interstitial fluid pressure in the tibialis anterior muscle (4.6 +/- 0.6 mmHg) and subcutaneous tissue (0.6 +/- 0.5 mmHg) of the lower leg fell significantly to -2.8 +/- 0.5 and -3.8 +/- 0.4 mmHg, respectively. Other transcapillary pressures (capillary and interstitial fluid colloid osmotic pressures) were relatively unchanged. Needle-biopsy specimens, obtained just before and after tilt, indicated that total water content of soleus muscle was unchanged during 8 h of head-down tilt. After head-down tilt, isometric strength and isokinetic strength of the plantar flexors were unchanged. Triceps surae reflex time associated with plantar flexion movement slowed slightly after the tilt maneuver. Collectively these results demonstrated a dehydration effect of head-down tilt on muscle and subcutaneous tissues of the lower leg that may affect muscle function.
Regional lung function in erect humans after lobectomy
Authors: Fleetham J. A. , Clarke H. , Anthonisen N. R.
Published: December 2017

By using the 133Xe technique, we studied five erect adult subjects who had undergone lobectomy at least 2 mo previously and were otherwise normal, to allow comparison between operated and unoperated lungs; four subjects had undergone upper lobectomy, and one had undergone lower lobectomy. In addition we studied a sixth subject who had undergone lower lobectomy and had residual disease in the contralateral lung, and results from the diseased lung were discarded. At the same overall volume, lungs that had undergone lobectomy were more expanded than contralateral control lungs, and their washout half times were prolonged more than could be accounted for by their increased functional residual capacity-to-total lung capacity ratio. In subjects with upper lobectomy, apex-to-base gradients of regional lung volume were normal on the operated side when lung expansion was accounted for. In subjects with lower lobectomy, apex-to-base volume gradients were reduced on the side that had undergone resection, suggesting relative overexpansion of basal regions. These interpretations were supported by distributions of regional washout half times and of boluses inhaled at residual volume. We interpreted these results as indicating that both lung weight and lung-chest wall shape interaction determine the distribution of regional lung volumes.
Ventilation-perfusion relationships during hemorrhagic hypotension and reinfusion in the dog
Authors: Fortune J. B. , Mazzone R. W. , Wagner P. D.
Published: December 2017

The inert gas elimination technique was used to estimate pulmonary ventilation-perfusion (VA/Q) mismatching in heparinized, ventilated, anesthetized dogs during a 90-min period of hemorrhagic hypotension (mean arterial pressure 40 Torr) and subsequent reinfusion of the shed blood. Systemic and pulmonary arterial pressures, as well as cardiac output, were similar to those in previously reported studies using this protocol. Mean arterial O2 partial pressure (PO2) fell from 86 to 75 Torr after hemorrhage and rose to a mean value of 78 Torr after reinfusion. The VA/Q distributions showed that a mean of 56.7% of the ventilation was associated with unperfused or poorly perfused (VA/Q greater than 10) regions during hypotension (control 33.7%). After reinfusion, a mean of 47.8% of the ventilation was still directed to lung with little or no perfusion. This could not be explained on a hydrostatic basis, since pulmonary arterial pressure after reinfusion was greater than the control value. Shunt or blood flow to low VA/Q regions did not increase at any time during hemorrhagic hypotension or reinfusion. Microscopic examination of lung tissue revealed extensive leukocyte aggregation that was not seen in control animals. The mean diameter of obstructed pulmonary vessels was 35 microns (range 13.8–59.8 microns). Storing the shed blood in acid-citrate-dextrose instead of heparin had no significant effect on the extent of leukocyte aggregation. We suggest that leukocyte aggregation and margination may be related to the high VA/Q regions seen in these animals.
Surfactant dysfunction in diabetic offspring: inhibitors and fatty acid lecithin content
Authors: Sosenko I. R. , Werthammer J. , Cunningham M. D. , Frantz I. D.
Published: December 2017

We have previously demonstrated that the lungs of fetuses of alloxan-diabetic rabbits are functionally immature when compared with controls. In this study we have examined pulmonary lavage fluid from fetuses of diabetic and control does for the presence of a surfactant inhibitor, cholesterol content, and phosphatidylcholine (lecithin) fatty acid content. When lavage fluids from fetuses of control and diabetic does were mixed and examined on the surface balance, the measured surfactant content corresponded to the arithmetic average of the surfactant content of the individual fluids, thus ruling out the presence of an excess of a surfactant inhibitor. We were able to demonstrate inhibition of surfactant function when exogenous cholesterol was added to lavage samples, but cholesterol content of lavage fluid from fetuses of diabetic and control does was not significantly different. Finally, the fatty acid composition of surfactant phosphatidylcholine was not different between the two groups. These studies indicate that mechanisms other than the presence of a surfactant inhibitor or altered fatty acid composition must explain the functional immaturity seen in offspring of the diabetic pregnancy.
Ventilation-perfusion relationships after hemorrhage and resuscitation: an inert gas analysis
Authors: Robinson N. B. , Chi E. Y. , Robertson H. T.
Published: December 2017

Previous investigations suggest that ventilation-perfusion (VA/Q) relationships after hemorrhagic shock are primarily dependent on regional distribution of pulmonary blood flow and implicated early VA/Q heterogeneity secondary to disproportionate redistribution of pulmonary blood flow to dependent lung regions. Multiple inert gas elimination analysis, as described by Wagner et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 36: 588–599, 1974), was applied to a standard hemorrhagic shock preparation to test this hypothesis. Soon after hemorrhage, VA/Q distributions shifted homogeneously into high VA/Q compartments, preserving base-line VA/Q relationships around a new mean VA/Q ratio. Although the mean VA/Q and VA/Q distribution returned to base line after resuscitation with autologous blood, absolute dead space ventilation persisted. Gas exchange defects included increased Bohr dead space ventilation, which could be attributed to 1) a homogeneous shift of VA/Q distributions into high VA/Q compartments, and 2) new absolute dead space ventilation associated with observed intravascular leukostasis and vascular occlusion. In contrast to previous investigations, these data suggest that VA/Q heterogeneity does not occur after hemorrhage, but rather pulmonary blood flow decreases proportionately throughout all lung regions, preserving base-line VA/Q patterns around a new mean VA/Q ratio.
Gravity dependence of phases III, IV, and V in single-breath washout curves
Authors: Verhamme M. , Roelandts J. , De Roo M. , Demedts M.
Published: December 2017

The gravity dependence of phases III (IIIa and IIIb), IV, and V of simultaneously performed He-bolus and N2-resident gas single-breath washout curves was studied in different body positions by the technique of 180 degrees body inversion between inspiration and expiration. Phase IIIa was mainly determined by nongravitational factors. Phase IIIb was influenced by gravitational, as well as nongravitational, factors. The former were more important with the bolus method in both lateral decubitus positions and the latter with the N2 method in the prone and supine positions. Phases IV and V were mainly gravity dependent. The difference in gravity dependence between the He and N2 methods appeared to be correlated with the vertical interregional concentration gradients of both gases; indeed the vertical gradient was larger for the 133Xe bolus inhaled at residual volume (which is comparable to the He-bolus distribution) than for the 133Xe residual volume-to-total lung capacity ratio (which is comparable to the N2-resident gas distribution). The greater gravity dependence in the lateral decubitus positions than in the supine or prone postures was related to the larger vertical interregional concentration difference as well as to the more pronounced sequential ventilation in the former positions. Finally the negligible effect of gravity on phase IIIa, its moderate effect on phase IIIb, and its predominant effect on phases IV and V were in agreement with the increased sequential filling and emptying due to gravity near residual volume.
Human sinus arrhythmia as an index of vagal cardiac outflow
Authors: Eckberg D. L.
Published: December 2017

Since changes of heart period follow changes of cardiac vagal efferent activity quantitatively with nearly fixed latencies, measurements of respiratory sinus arrhythmia may provide insights into human central vagal mechanisms. Accordingly, I measured intervals between heartbeats during controlled breathing (at breathing intervals of 2.5–10 s and nominal tidal volumes of 1,000 and 1,500 ml) in six healthy young men and women. As breathing interval increased, the longest heart periods became longer, the shortest heart periods became shorter, and the peak-valley P-P intervals increased asymptotically. Peak-valley P-P intervals also increased in proportion to tidal volume. However, this influence was small: a 50% increase of tidal volume increased the average peak-valley P-P interval by only about 15%. The phase angles between heart period changes and respiration varied as linear functions of breathing interval. Heart period shortening (cardioacceleration) began in inspiration at short breathing intervals and in expiration at long breathing intervals. Heart period lengthening, however, began in early expiration at all breathing intervals studied. These results point toward a close relationship between variations of respiratory depth and interval and the quantity, periodicity, and timing of vagal cardiac outflow in conscious humans. They suggest that, at usual breathing rates, phasic respiration-related changes of vagal motoneuron activity began in expiration, progress slowly, and are incompletely expressed at fast breathing rates.
Effects of histamine on lung water and hemodynamics after beta-blockade
Authors: Olson N. C. , Robinson N. E. , Scott J. B.
Published: December 2017

The effects of 90 min intravenous histamine (10 micrograms base . kg-1 . min-1) with and without beta (propranolol)-receptor blockade on lung water and hemodynamics were studied. In anesthetized dogs cold 3% saline was used as the indicator to determine cardiac index, central blood volume, and lung extravascular thermal volume. Propranolol alone decreased stroke volume and cardiac index but increased central blood volume, total peripheral resistance, and mean pulmonary arterial and pulmonary arterial wedge pressures. Pulmonary vascular resistance, mean arterial pressure, and lung extravascular thermal volume were not changed. Histamine with propranolol further reduced stroke volume and cardiac index, whereas mean pulmonary arterial and pulmonary arterial wedge pressures returned to control values. Mean arterial pressure, central blood volume, and total peripheral resistance decreased, pulmonary vascular resistance increased, and lung extravascular thermal volume remained unchanged. In all experiments postmortem extravascular lung water-to-dry weight ratio was unchanged. We conclude that histamine does not increase lung water content and that beta-receptor blockade does not modify this response.
Barometric pressures at extreme altitudes on Mt. Everest: physiological significance
Authors: West J. B. , Lahiri S. , Maret K. H. , Peters R. M. , Pizzo C. J.
Published: December 2017

Barometric pressures were measured on Mt. Everest from altitudes of 5,400 (base camp) to 8,848 m (summit) during the American Medical Research Expedition to Everest. Measurements at 5,400 m were made with a mercury barometer, and above this most of the pressures were obtained with an accurate crystal-sensor barometer. The mean daily pressures were 400.4 +/- 2.7 (SD) Torr (n = 35) at 5,400 m, 351.0 +/- 1.0 Torr (n = 16) at 6,300 m, 283.6 +/- 1.5 Torr (n = 6) at 8,050 m, and 253.0 Torr (n = 1) at 8,848 m. All these pressures are considerably higher than those predicted from the ICAO Standard Atmosphere. The chief reason is that pressures at altitudes between 2 and 16 km are latitude dependent, being higher near the equator because of the large mass of cold air in the stratosphere of that region. Data from weather balloons show that the pressure at the altitude of the summit of Mt. Everest varies considerably with season, being about 11.5 Torr higher in midsummer than in midwinter. Although the mountain has been climbed without supplementary O2, the very low O2 partial pressure at the summit means that it is at the limit of man's tolerance, and even day-by-day variations in barometric pressure apparently affect maximal O2 uptake.
Lactic acid infusion in dogs: effects of varying infusate pH
Authors: Gladden L. B. , Yates J. W.
Published: December 2017

This study had two purposes: 1) to determine the effects of varying the pH of lactic acid infusion solutions on the acid-base status of anesthetized dogs, and 2) to determine the effect of elevated blood lactate concentration on muscle lactate concentration. The experiments were performed on the in situ gastro cnemius-plantaris muscle group in 14 mongrel dogs. The infusions increased the arterial blood lactate concentration to 11.0 +/- 0.5 (SE) mM after 20 min. Above an infusate pH of 4.4, the arterial pH increased by 0.118–0.167 during infusion; the arterial pH was unchanged when the infusate pH was between 3.4 and 4.0; and the arterial pH decreased as infusate pH decreased below 3.0. The effect of lactic acid infusion on blood pH appears to be the result of two opposing effects: 1) an acidifying effect due to its weak acid properties, and 2) an alkalinizing effect due to the metabolism of sodium lactate. The estimated ratio between intracellular muscle lactate and venous plasma water lactate averaged 0.647 +/- 0.038, indicative of a substantial gradient between blood and muscle. The infusion produced a significant change from lactate output to lactate uptake by the muscles. The infusion also transiently increased muscle blood flow and oxygen uptake.
Effect of diaphragm contraction on canine heart and pericardium
Authors: Lloyd T. C. , Cooper J. A.
Published: December 2017

Pericardiophrenic attachments transmit diaphragm contraction to the pericardium. We investigated this in two ways. 1) We replaced the hearts of externally perfused dogs with a balloon from which we measured pressure changes. Diaphragm contraction increased pressure from 4.6 to 5.5 Torr, equivalent to an isobaric volume decrease of 1.5%, and decreased volumetric compliance by 3%. 2) We selectively servo controlled right atrial pressure, left atrial pressure, or cardiac output in open-chest dogs and monitored the effect of diaphragm contraction on cardiovascular and abdominal pressures, cardiac output, and the volume of blood added to or withdrawn from the circulation to achieve servo control. Diaphragm contraction decreased left atrial pressure 0.4 Torr when right atrial pressure was controlled and right atrial pressure increased 0.2 Torr while controlling left atrial pressure, but there were no significant changes in cardiac output. Atrial pressure did not change significantly when output was controlled. Servo control required removal of approximately 50 ml of blood, presumably reflecting a decreased splanchnic vascular capacity at the higher abdominal pressure. We conclude that the diaphragm may slightly tense the pericardium, but this has no important primary effect on the heart.
Effect of caffeine on skeletal muscle function before and after fatigue
Authors: Lopes J. M. , Aubier M. , Jardim J. , Aranda J. V. , Macklem P. T.
Published: December 2017

We studied the effect of caffeine on voluntary and electrically stimulated contractions of the adductor pollicis muscle in five adult volunteers. Caffeine (500 mg) was administered orally in a double-blind fashion. Electrical stimulation of the ulnar nerve was performed at 10, 20, 30, 50, and 100 Hz before and after a sustained voluntary contraction held at 50% of the maximal voluntary contraction (MVC). A brief tetanus at 30 Hz was also performed to calculate relaxation rate in the fresh muscle. Contractile properties, relaxation rate, and endurance were then assessed after caffeine and placebo, as well as the response of the fatigued muscle to different frequencies of stimulation. There was no difference in the maximal tension obtained with electrical stimulation (T100) or in the MVC between placebo and caffeine. The tensions developed with electrical stimulation at lower frequencies increased significantly with caffeine ingestion, shifting the frequency-force curve to the left, both before and after fatigue. Mean plasma caffeine concentration associated with these responses was 12.2 +/- 4.9 mg/l. We conclude that caffeine has a direct effect on skeletal muscle contractile properties both before and after fatigue as demonstrated by electrical stimulation.
Effects of beta-adrenergic blockade on ventilation and gas exchange during exercise in humans
Authors: Petersen E. S. , Whipp B. J. , Davis J. A. , Huntsman D. J. , Brown H. V. , Wasserman K.
Published: December 2017

The effects of beta-adrenergic blockade induced by intravenous propranolol hydrochloride (0.2 mg/kg) on ventilatory and gas exchange responses to exercise were studied during tests in which the work rate was either increased progressively or maintained at a constant load in six healthy young male subjects. Heart rate during exercise decreased by about 20% and cardiac output, as estimated by a modification of the method of Kim et al. (J. Appl. Physiol. 21: 1338–1344, 1966), by about 15%. The relation between work rate and O2 uptake (VO2) was unaffected by propranolol, whereas maximal O2 uptake (VO2max) decreased by 5% and the anaerobic threshold, estimated noninvasively, was lowered by 23%. The relations between CO2 output (VCO2) and end-tidal CO2 partial pressure (PCO2) and between VCO2 and minute ventilation (VE) were both unaffected. The time constants for changes of VO2, VCO2, and VE during on-transients from unloaded pedaling to either a moderate (ca. 50% VO2max) or a heavy (ca. 67% VO2max) work rate in the control studies were in agreement with previously reported values, i.e., 42, 60, and 69 s, respectively. beta-Blockade was associated with a significantly increased time constant for VO2 of 61 s but with less consistent and insignificant changes for VCO2 and VE. There was a small but significant increase of the time constant for heart rate from 40 to 45 s. It is concluded that propranolol exerts its primary influence during exercise on the cardiovascular system without any discernible effect on ventilatory control.
Effect of ethanol on ion transport and electrical properties of dog trachea in vitro
Authors: McCool F. D. , Zorn J. P. , Marin M. G.
Published: December 2017

We studied the effect of ethanol on the electrical and ion transport properties of dog tracheal epithelium using Ussing's short-circuit technique. There was a significant reduction of short-circuit current and electrical potential difference and a tendency of electrical resistance to increase in response to increasing concentrations of ethanol in the bathing solutions. Threshold changes in the electrical properties were noted at an ethanol concentration of 3.3 microliter/ml (260 mg/100 ml). Ethanol did not produce these changes in electrical properties when Cl- and Na+ were substituted in the bathing media with either choline or SO2-(4). In five paired tissue preparations, ethanol (13.3 microliters/ml) significantly reduced the net flux of Cl- toward the lumen from 2.68 +/- 0.62 to 1.00 +/- 0.69 (SE) mu eq X cm-2 X h-1, due primarily to a reduced unidirectional flux of Cl- from submucosa to lumen. These observations demonstrate that ethanol has an effect on the ion transport and electrical properties of dog tracheal epithelium at concentrations that may be of clinical relevance.
Changes in relaxation rate with diaphragmatic fatigue in humans
Authors: Esau S. A. , Bellemare F. , Grassino A. , Permutt S. , Roussos C. , Pardy R. L.
Published: December 2017

Maximum relaxation rate (MRR) and the time constant of relaxation (tau) of transdiaphragmatic pressure (Pdi) was measured in four male subjects and compared with the high-to-low frequency ratio (H/L) of the diaphragmatic electromyogram (EMG) as a predictor of diaphragmatic fatigue. Pdi and inspiratory time-to-total breath duration ratios (TI/TT) were varied, and TT and tidal volume were held constant; inspiratory resistances were used to increase Pdi. Studies were performed at various tension-time indices (TTdi = Pdi/Pdimax X TI/TT). Base-line MRR/Pdi was 0.0100 +/- 0.0004 (SE) ms-1, and baseline tau was 53.2 +/- 3.2 ms. At TTdi greater than 0.20, MRR and H/L decreased and tau increased, with maximum changes at the highest TTdi. At TTdi less than 0.20, there was no change in H/L, MRR, or tau. The time course of changes in H/L correlated with those of MRR and tau under fatiguing conditions. In this experimental setting, change in relaxation rate was as useful a predictor of diaphragmatic fatigue as fall in H/L of the diaphragmatic EMG.
Calorimetry with heat flux transducers: comparison with a suit calorimeter
Authors: Layton R. P. , Mints W. H. , Annis J. F. , Rack M. J. , Webb P.
Published: December 2017

Regional and total body heat loss rates of human subjects at rest were measured simultaneously by means of an array of heat flux transducers and with a tube suit calorimeter. Conditions ranged from thermal comfort to strong cooling. A high degree of correlation was found between heat loss rates determined by the two independent techniques. For the head and arms, the transducer array system measured less heat loss than the suit. For the torso and legs, measurements by the two methods were equivalent. For the whole body, the transducer system yielded a heat loss rate 87% of the suit calorimeter value.
Esophageal elastance in anesthetized humans
Authors: Hedenstierna G. , Jarnberg P. O. , Torsell L. , Gottlieb I.
Published: December 2017

Esophageal elastance (Ees) was measured in 13 human subjects, awake and anesthetized by halothane, in the supine and left lateral postures. Static esophageal pressure was measured by an esophageal balloon catheter, respiratory volumes by pneumotachography, and functional residual capacity (FRC) by body plethysmography. In the supine awake subject, Ees averaged 3 cmH2O/ml at FRC and increased significantly with lung volume. Ees remained unaltered at FRC during anesthesia in the supine position, but lung volume dependence was no longer observed. In the left lateral position the awake subject displayed the same Ees at FRC as in the supine position and lung volume exerted only a small influence on Ees. The latter was reduced during anesthesia and tended to diminish with increasing lung volume. All variations in Ees caused by posture, anesthesia, and lung volume were small and affected the shape of the pressure-volume curve of the lung to only a minor degree.
Hyperpnea of exercise at various PIO2 in normal and carotid body-denervated ponies
Authors: Forster H. V. , Pan L. G. , Bisgard G. E. , Kaminski R. P. , Dorsey S. M. , Busch M. A.
Published: December 2017

We studied the effect of changes in inspired [O2] on partial pressure of CO2 in arterial blood (PaCO2) during treadmill exercise (3 mph, 3% grade) in normal, acute (+2–2 wk), and chronic (+1–2 yr) carotid body-denervated (CBD) ponies. In all studies, PaCO2 decreased (P less than 0.01) from rest during exercise, reaching a nadir usually between 15 and 30 s of exercise. During normoxia [partial pressure of O2 in arterial blood (PaO2) approximately 95 Torr], the PaCO2 nadir was 2.3 +/- 0.6 Torr below resting level in normal ponies, but the nadir was greater (P less than -0.01) in acute (delta = 6.4 +/- 0.8 Torr) and chronic (delta = -4.7 +/- 1.1 Torr) CBD ponies. Hyperoxia (PaO2 approximately 180 Torr) accentuated (P less than 0.01) the hypocapnia only in the normal ponies (delta = -6.3 +/- 1.0 Torr). In contrast, hypoxia (PaO2 48 Torr) attenuated (P less than 0.01) the exercise-induced hypocapnia by 3–5 Torr in all ponies. Usually PaCO2 gradually increased after 30 s of exercise, reaching a stable level 1–3 Torr below rest by about 2 min (P less than 0.05). Tidal volume (VT) increased from rest during the first 15 s of exercise only when there was a large decrease in PaCO2. Recovery of PaCO2 after 30 s of exercise was associated with a decrease in VT toward rest. We concluded the following. 1) The accentuated hypocapnia caused by eliminating (CBD) or reducing (hyperoxia) carotid chemoreceptor activity suggests that the chemoreceptors normally dampen alveolar ventilation (VA) at the onset of exercise. 2) Attenuation of the hypocapnia at the onset of exercise by hypoxia in CBD ponies suggests that a direct CNS effect of hypoxia dampens VA. 3) Mechanisms tending to minimize the hypocapnia during exercise appear to adjust VA by modulating VT.
Effect of hypoxia and hypercapnia on catecholamine content in cat carotid body
Authors: Fitzgerald R. S. , Garger P. , Hauer M. C. , Raff H. , Fechter L.
Published: December 2017

The purpose of this study was to determine the content of catecholamines (CA) in the cat carotid body before and after 0.5 h exposures to normoxic normocapnia [arterial O2 partial pressure (Pao2) 126 +/- 28 Torr, arterial CO2 partial pressure (Paco2) 36.4 +/- 1.5 Torr], hypoxic normocapnia (Pao2 25 +/- 3 Torr, Paco2 36.7 +/- 3.3 Torr), and normoxic hypercapnia (Pao2 132 +/- 13 Torr, Paco2 = 98.2 +/- 7.6 Torr). CA synthesis was blocked using alpha-methylparatyrosine methyl ester (AMPT) prior to alterations in the inspired air. There was a significant decrease in carotid body content of dopamine (DA), norepinephrine (NE), and epinephrine (E) 1 h after AMPT administration. Analysis of variance and Duncan new multiple range procedures revealed that during the subsequent 0.5-h exposures to normoxia, hypoxia, or hypercapnia, only the decrease in DA during hypoxia was significantly greater than that during normoxia; the loss during hypercapnia was not. The decreases in NE during the three exposures were indistinguishable among themselves as were the decreases in E. The decrease in CA content is probably attributable to increased release. The data reveal that the release of CAs during the chemoreception of hypoxia is different from that during the chemoreception of hypercapnia and support the concept of different mechanisms for the chemoreception of hypoxia and hypercapnia.
Transient ventilatory response to CO2 as a function of sleep state in full-term infants
Authors: Anderson J. V. , Martin R. J. , Abboud E. F. , Dyme I. Z. , Bruce E. N.
Published: December 2017

The influence of sleep state on the transient (i.e., initial 60 s) and steady-state ventilatory responses to 2% CO2 inhalation was studied in 19 healthy full-term infants. A nasal mask pneumotachometer was used to measure ventilation and end-tidal CO2 partial pressure (PCO2) and enabled abrupt changes in the inspired gas concentration to be made. The magnitude of the change in minute ventilation for both the transient and steady-state responses to CO2 was not statistically different between active (AS) and quiet (QS) sleep. Nonetheless the greater variability in minute ventilation during AS compared with QS continued throughout the period of CO2 inhalation and was associated with a more variable change in ventilation in the individual infants during AS. There was a greater increase in end-tidal PCO2 over the first 60 s during AS (3.3 +/- 0.3 vs. 2.6 +/- 0.2 Torr, in AS and QS, respectively, P less than 0.03). This may indicate a smaller initial increase in alveolar ventilation, relative to CO2 delivery to the lungs, in response to CO2 inhalation during AS. Asynchronous chest wall movements were more common during AS than QS (P less than 0.005) and did not change with CO2. The inconsistent transient ventilatory response to CO2 during AS compared with QS may be important in the behavior of infants to spontaneous episodes of hypercapnia occurring during AS.
Granulocytes mediate the increase in pulmonary vascular permeability after thrombin embolism
Authors: Tahamont M. V. , Malik A. B.
Published: December 2017

We examined the effect of pulmonary embolization with microthrombi on the lung vascular permeability to proteins and the role of platelets and granulocytes as putative cellular factors in mediating the alterations in permeability. Anesthetized artificially ventilated sheep were prepared with lung lymph fistulas. Pulmonary embolization was induced using thrombin. Pulmonary vascular resistance (PVR) was increased approximately threefold from baseline. Pulmonary lymph flow (Qlym) increased 2 h after thrombin, but the lymph-to-plasma protein ratio (L/P) did not change significantly from base line. Raising the pulmonary capillary pressure (Pc) by inflating a left atrial balloon produced a large increase in Qlym but no change in L/P, indicating a permeability-increasing effect of thrombin. Reduction of platelet count with antiplatelet serum before thrombin also produced an increase in Qlym without a change in L/P. Raising Pc in this group resulted in changes comparable with those in the control group, i.e., increased Qlym without a change in L/P. In contrast to both control and platelet-depleted groups, reduction of the granulocyte count with hydroxyurea did not affect Qlym or L/P after thrombin. Raising Pc in this group increased Qlym but decreased L/P, indicating normal capillary sieving of proteins. Therefore embolization of pulmonary vessels with microthrombi increases pulmonary vascular permeability, and the increase is mediated by granulocytes.
Opposing effects of dopamine receptor blockade on ventilation and carotid chemoreceptor activity
Authors: Smatresk N. J. , Pokorski M. , Lahiri S.
Published: December 2017

To determine the effects of dopamine receptor blockade on the ventilatory responses to hypoxia and hypercapnia we simultaneously measured ventilation and carotid chemoreceptor activity in eight anesthetized cats. During normoxia, haloperidol (1 mg . kg-1 iv) stimulated carotid chemoreceptor activity within 15 s of its administration from a control level of 5.3 +/- 1.1 to 10.4 +/- 2.0 impulses . s-1. Minute ventilation (VI) also rose from 1.00 +/- 0.20 to 1.66 +/- 0.34 l . min-1. Chemoreceptor activity remained elevated, but in the next 15 min VI fell back to or below control levels. Thus haloperidol produced a transient stimulation of ventilation. In the steady state, after haloperidol, carotid chemoreceptor activity was also elevated significantly at all levels of arterial O2 and CO2 partial pressures (PaO2 and PaCO2, respectively). Steady-state ventilation, however, was not significantly different in normoxia (PaO2 82 Torr) after haloperidol despite the elevated chemoreceptor activity. Haloperidol also greatly attenuated the ventilatory response to hypoxia, despite the stimulated carotid chemoreceptor activity. The ventilatory response to hypercapnia was not significantly affected by haloperidol, indicating that its effect was specific for the chemoreflex responses to hypoxia. We conclude that dopamine antagonism by haloperidol blocks the central integration of peripheral chemoreceptor activity, thus attenuating the ventilatory chemoreflex responses to hypoxia while augmenting the carotid chemoreceptor response.
Power spectral analysis of the diaphragm electromyogram
Authors: Aldrich T. K. , Adams J. M. , Arora N. S. , Rochester D. F.
Published: December 2017

We studied the power spectrum of the diaphragm electromyogram (EMG) at frequencies between 31 and 246 Hz in four young normal subjects and five patients with chronic obstructive lung disease (COPD). Diaphragm EMGs were analyzed during spontaneous breathing and maximum inspiratory efforts to determine the effect of signal-to-noise ratio on the power spectrum and if treadmill exercise to dyspnea was associated with diaphragm fatigue. We found that the centroid frequencies of the power spectra (fc) were strongly correlated (r = 0.93) with ratios of power at high frequencies to power at low frequencies (H/L) for all subjects. Of the two indices, H/L had the largest standard deviation expressed as a percentage of the mean. The mean values of both of these decreased significantly after exercise, fc from 100.2 to 97.3 and H/L from 1.07 to 0.97. Signal-to-noise ratios were higher in maximal inspiratory efforts and after exercise in normal subjects and higher in COPD patients. The signal-to-noise ratio was correlated negatively with fc and H/L, indicating that these indices of the shape of the power spectrum are influenced by signal strength and noise levels as well as muscle function. We conclude that the fc and H/L index similar qualities of the power spectrum, that they are partially determined by the signal-to-noise ratio, and that, in some cases, exercise to dyspnea is associated with apparently mild diaphragm fatigue.
Relaxant action of VIP on cat pulmonary artery: comparison with acetylcholine, isoproterenol, and PGE1
Authors: Hamasaki Y. , Mojarad M. , Said S. I.
Published: December 2017

Vasoactive intestinal peptide (VIP), a potent systemic vasodilator, was recently identified in nerve fibers within the pulmonary arterial wall of cats and other mammals. We have investigated the smooth muscle relaxant action of VIP on isolated strips of kitten pulmonary artery that were placed in a 5-ml bath and precontracted with prostaglandin endoperoxide (PGH2) analogue. The action of VIP was compared with that of acetylcholine, isoproterenol, and prostaglandin E1 (PGE1). The effectiveness of VIP as a relaxant of pulmonary artery, measured as maximal relaxation and expressed in weight equivalents, was 29.9 +/- 2.0 X 10(-2) g in the presence of adrenergic and cholinergic blockers, or 28.8 +/- 4.5 X 10(-2) g in the absence of blockers. This relaxation was similar to that of acetylcholine (30.4 +/- 4.0 X 10(-2) g) and isoproterenol (26.4 +/- 2.2 X 10(-2) g), but smaller than that of PGE1 (41.1 +/- 3.7 X 10(-2) g). Judging by the EC50 or EC10 (effective concentration needed to develop 50 or 10%, respectively, of maximal relaxation), VIP was at least 40 times as potent as acetylcholine, 2,770 times as potent as isoproterenol, and 120 times as potent as PGE1, on a molar basis. The effect of VIP was unaltered in the presence of atropine, propranolol, or phenoxybenzamine in the incubation medium. The findings demonstrate the potent relaxant action of VIP in isolated pulmonary arterial strips and the independence of this action from cholinergic and adrenergic receptors. The results support the possibility that VIP may play an important role in regulating pulmonary vascular tone in kittens.
Length-tension relationship of mammalian diaphragm muscles
Authors: McCully K. K. , Faulkner J. A.
Published: December 2017

We tested the hypothesis that the length-tension relationship of diaphragm muscle is different from that of other skeletal muscle. Isometric contractile properties of small bundles of diaphragm muscle from rats, cats, rhesus monkeys, dogs, and pigs were measured in vitro at 37 degrees C. For diaphragm muscles from all species, twitch contraction and relaxation times and histochemical myofibrillar ATPase indicated a mixture of fast and slow muscle fiber types. By use of tetanic stimulations of 400-ms duration, isometric tension was recorded from bundles of diaphragm muscle at lengths between 50 and 130% of the muscle fiber length at which active tension was maximal (Lo). At lengths below 60–70% of Lo, tetanic tension did not reach a plateau within 400 ms. With longer stimulation durations, active tension could be recorded between 30 and 40% of Lo. The length-tension curves for bundles of fibers from the diaphragm muscle were not different among species and were consistent with results reported for intact limb muscles.
Elastic characteristics of the lung perivascular interstitial space
Authors: Smith J. C. , Mitzner W.
Published: December 2017

An analysis of the elastic behavior of the lung perivascular interstitial space during interstitial fluid accumulation is presented. Fluid accumulation must deform the lung parenchyma and vascular walls that form the interstitial space boundaries. The deformations of these boundaries are predicted from previously published data on the elastic properties of the boundary materials. The analysis gives the relationships among the elastic properties of the boundaries, the compliance of the interstitium, the lung volume, and the lung elastic recoil pressure. Values of the interstitial compliance are predicted to decrease with increasing lung recoil pressure and are dependent on the lung pressure-volume history. At low recoil pressures over 70% of the interstitial compliance results from deformation of the parenchyma. As the recoil pressure increases, either with increasing lung volume or due to the lung pressure-volume history, the contributions of the parenchymal and vascular wall deformations become similar. The predictions are generally consistent with published data on interstitial compliance obtained from measurements of isolated lung weight gain during vascular fluid transudation. This correlation suggests that the elastic behavior of the interstitial space can be accounted for by the known elastic properties of the boundary materials.
Role of the larynx in control of pattern of breathing during CO2 inhalation in humans
Authors: Gardner W. N.
Published: December 2017

To determine whether change of laryngeal resistance causes shortening of expiratory time (TE) and hence increase of respiratory frequency with CO2 inhalation in conscious humans, 11 fit male subjects with permanent tracheostomies after laryngectomy for cancer (L group) and 8 matched control subjects (C group) inhaled CO2 in mild hyperoxia to produce various levels of steady-state hyperpnea within “nonvagal” range 1. Breathing pattern was averaged at the end of each steady state and behaved similarly in both groups. As end-tidal PCO2 (PACO2) increased, TE significantly shortened in both groups, whereas inspiratory time (TI) remained roughly constant (slightly increasing in the L group), suggesting that the larynx, at least in range 1, has no major role in determining this pattern. Quantitative comparison between the two groups showed that in the L group TE was significantly longer, whereas expiratory flow peaked and declined significantly earlier, resulting in a greater tendency to form end-expiratory pauses. All differences were greatest in eucapnia and decreased as PACO2 increased. Despite matched mean PACO2 values, mean tidal volume (VT) ventilation and mean inspiratory flow (VT/TI) were significantly less in the L group, and the slope of VT/TI vs. PACO2 was significantly depressed.
Respiratory effects of stimulation of intercostal muscles and saphenous nerve in kittens
Authors: Trippenbach T. , Kelly G. , Marlot D.
Published: December 2017

Effects of intercostal muscle stimulation were studied in 2- to 7-day-old kittens under ketamine-acepromazine anesthesia. Animals were vagotomized, paralyzed, and artificially ventilated. Stimuli applied during inspiration (TI) inhibited this phase. Stimulus strength necessary for TI inhibition decreased with time. However, an all-or-nothing effect was not always observed. Stimulation during expiration (TE) prolonged this phase. The responsiveness increased with increasing stimulus delay. The effects of intercostal muscle stimulation were compared with those recorded during saphenous nerve stimulation. Stimulation during TI prolonged this phase. Phrenic activity increased after a short-lasting decrease in the on-going activity. Stimulation during the first 50% of TE had variable effects, whereas stimulation with longer delay shortened this phase. Our results indicated that the pattern of breathing in newborns can be affected by both intercostal muscle and other somatic efferents. However, the mechanisms controlling respiratory timing may differ in newborns and in adults. Different effects of respiratory muscle and saphenous nerve stimulation suggest different transmitters involved or different sites of interaction of these inputs with the medullary respiratory rhythm generator.
Sampling and analysis of cerebrospinal fluid for chronic studies in awake rats
Authors: Lai Y. L. , Smith P. M. , Lamm W. J. , Hildebrandt J.
Published: December 2017

A method is described whereby cerebrospinal fluid (CSF) may be sampled repeatedly from awake rats over a period of 1 to 10 wk. Stainless steel or Teflon catheters (22-gauge) were implanted in the cisterna magna of anesthetized rats (n = 19) via a midline hole immediately rostral to the interparietal-occipital suture. Several days later almost simultaneous CSF and blood samples from the same air-breathing animals were slowly drawn into glass capillary tubes. pH was determined immediately by electrode and total CO2 by microgasometer. Because sampling via Tygon microbore tubing attached to the implanted catheters allowed part of CSF CO2 content to be lost through the tube wall, stainless steel tube is preferred to make this connection. For mock CSF, total CO2 calculated from pH and PCO2 values was closely comparable to that directly measured by microgasometer. CSF pH, PCO2, and [HCO-3] in five awake rats were found to be similar to those reported in the literature for the briefly anesthetized rat. The sampling procedure did not of itself significantly alter breathing patterns (n = 14). Thus, chronic CSF sampling is feasible in awake rats for purposes of studies of ventilatory control.
Effects of static muscular contraction on impulse activity of groups III and IV afferents in cats
Authors: Kaufman M. P. , Longhurst J. C. , Rybicki K. J. , Wallach J. H. , Mitchell J. H.
Published: December 2017

Static contraction of the hindlimb muscles, induced by electrical stimulation of the ventral roots, reflexly increases arterial blood pressure and heart rate. Although stimulation of groups III and IV muscle afferents is believed to cause these reflex increases, the responses of these afferents to a level of static contraction that increases arterial pressure have not yet been determined. Therefore, in barbiturate-anesthetized cats, afferent impulses arising from endings in the gastrocnemius muscle were recorded from the L7 or S1 dorsal roots, while the cut peripheral end of the L7 ventral root was stimulated. In addition, the effects of capsaicin (100-200 micrograms) and bradykinin (25 micrograms) on the activity of the groups III and IV afferents stimulated by contraction were examined. Contraction of the gastrocnemius muscle to a level equal to or greater than that needed to cause a pressor response stimulated 12 of 19 (63%) group III afferents and 13 of 19 (68%) group IV afferents. However, the discharge patterns of the group III afferents stimulated by contraction were very different from those of the group IV fibers. No relationship was found between those fibers stimulated by contraction and those stimulated by chemicals. Our results suggest that although both groups III and IV muscle afferents contribute to the reflex cardiovascular increases evoked by static exercise, group III fibers were likely to be stimulated by the mechanical effects of muscular contraction, whereas at least some group IV fibers were likely to be stimulated by the metabolic products of muscular contraction.
Permeability of the canine visceral pleura
Authors: Kinasewitz G. T. , Groome L. J. , Marshall R. P. , Diana J. N.
Published: December 2017

Fluid and protein movement across the pulmonary endothelial membrane (PEM) and adjacent mesothelial layer of the visceral pleura was quantitatively analyzed in terms of a two-compartment model of fluid exchange. The left lungs of 13 spontaneously breathing anesthetized dogs were enclosed in a water-impermeable membrane, creating a visceral pleural space; fluid flux was determined as the filtration or reabsorption of water and protein in the visceral pleural space. Aortic, pulmonary arterial, left atrial, and pleural pressures were monitored; oncotic pressure was calculated from the protein concentration of plasma and pleural fluid. To determine the hydraulic conductivity (Lp), diffusional permeability (Pd), and the solute and solvent drag reflection coefficients for protein (sigma d and sigma f, respectively), fluid exchange was monitored during two or more experimental periods during which the visceral pleural space contained saline and plasma. The permeability coefficients determined for the PEM of the visceral pleura, Lp = 7.7 (+/- 0.3) X 10(-7) ml X s-1 X mmHg-1 X cm-2, sigma d = 0.93, sigma f = 0.61, and Pd = 2.4 (+/- 1.0) X 10(-6) cm/s, are more restrictive than those previously reported for the devascularized visceral pleura in vitro. We conclude that it is the pulmonary endothelial membrane that determines the rate and composition of visceral pleural fluid flux in response to hydrostatic and oncotic gradients in the intact animal.
Effect of temperature on the contractile properties and muscle power of triceps surae in humans
Authors: Davies C. T. , Young K.
Published: December 2017

In five spontaneously breathing kittens (12-13 days old), anesthetized with pentobarbital sodium, we measured the passive and active elastances and resistances of the respiratory system and the decay of inspiratory muscle pressure (PmusI) during expiration. When normalized for body weight (BW), passive resistance (Rrs . BW) was smaller in kittens than in adult cats, whereas passive elastance (Ers . BW) did not differ significantly. As a result, passive time constant (tau rs = Rrs/Ers) was shorter in kittens (mean +/- SE: 0.073 +/- 0.011 s) than in cats (0.121 +/- 0.008 s). This, associated with a faster decay in PmusI in kittens, results in 2-3 times higher flows per kilogram body weight during spontaneous tidal expirations in kittens than in cats. As in the adult cats, the average values of active elastance and resistance were higher than the passive, the average percentage increase amounting to 59 and 49%, respectively. The greater active impedance reflects force-length and force-velocity properties of inspiratory muscles. Its price is higher work of breathing; its advantage is greater intrinsic load compensation.
Changes in total body calcium balance with exercise in the rat
Authors: LeBlanc A. D. , Evans H. J. , Johnson P. C. , Jhingran S.
Published: December 2017

The purpose of this study was to evaluate the effect of deconditioning on the total body calcium in rats. Two separate experiments were performed using female Sprague-Dawley rats, 187-266 days of age. Total body calcium was measured in experimental and control rats during and following several weeks of voluntary exercise. The slope from the least-squares fit of total body calcium with time was used to obtain an average calcium balance for each animal during each study period. In both groups the exercised rats had a significantly decreased calcium balance after cessation of exercise, whereas no significant change was seen in nonexercised controls. In both groups, the exercised animals gained calcium at a significantly greater rate than controls. Our findings indicate that while exercised rats may gain calcium at a faster rate compared with nonexercising controls, the rate of gain following cessation of exercise is less than the controls.