bluuebunny/crossref_metadata_2025 huggingface dataset:
Occlusion pressures during the ventilatory response to hypoxemia in the newborn monkey
Authors: LaFramboise W. A. , Standaert T. A. , Woodrum D. E. , Guthrie R. D.
Published: December 2017

End-expiratory airway occlusions were performed in eight unanesthetized premature newborn monkeys during acute hypoxemia to investigate mechanisms involved in the newborn's biphasic ventilatory response to hypoxia. Two-day-old monkeys demonstrated an immediate increase in minute ventilation (VI) and a decrease in PaCO2 followed within 5 min by a return of VI and PaCO2 to base-line levels. The decline in VI was associated with a decrease in tidal volume (VT) and inspiratory flow (VT/TI) and an increase in respiratory frequency. Occlusion pressures (PO.2) remained elevated throughout the hypoxic stimulus, and end-expiratory lung volume increased during the late response. “Effective” impedance (P0.1/V0.1, P0.2/V0.2, etc.) and “effective” elastance (Pmax/VT) were also elevated. At 21 days of age, the monkeys demonstrated a sustained ventilatory response as VI, VT, VT/TI, and P0.2 remained elevated throughout the period of hypoxemia. End-expiratory lung volume increases as on day 2, but effective impedance and effective elastance did not change. These data suggest that the biphasic response to hypoxia in the newborn may result from a change in respiratory timing and an alteration in respiratory mechanics and is not due to a decrease in central respiratory drive.
Steady-state vascular responses to graded hypoxia in isolated lungs of five species
Authors: Peake M. D. , Harabin A. L. , Brennan N. J. , Sylvester J. T.
Published: December 2017

In the isolated pig lung exposed to graded levels of hypoxia, steady-state pulmonary vasomotor tone is maximum at an O2 tension (PO2) of 50 Torr. Below 50-Torr decreases in PO2 cause steady-state tone to fall below this maximum. To determine whether this stimulus-response relation was peculiar to pigs, we measured the steady-state relation between PO2 and vasomotor tone in the isolated lungs of dogs, rabbits, cats, and ferrets, by using identical techniques in each species. Marked species differences were apparent in both the level of PO2 required to elicit responses and the amplitude of the responses. The ferret and the pig had the largest vasoconstrictor responses to hypoxia. No significant responses were obtained in the dog. The cat and rabbit were intermediate responders. In the ferret, cat, and rabbit, the stimulus-response relationship was biphasic, as in the pig. On the average, maximal constriction occurred at an PO2 of 25 Torr. When PO2 was lowered below 25 Torr, steady-state tone fell. Thus pulmonary vasodilation at low PO2 occurs in the isolated lungs of several species.
Autonomic mechanisms of training bradycardia: beta-adrenergic receptors in humans
Authors: Williams R. S. , Eden R. S. , Moll M. E. , Lester R. M. , Wallace A. G.
Published: December 2017

To address the autonomic mechanisms underlying the bradycardia of physical training in human subjects, we performed a cross-sectional study comparing the heart-rate responses to graded doses of isoproterenol in 7 elite marathon runners and 7 age-matched controls, and a longitudinal study in 12 normal volunteers of the effects of 6 wk of intense physical training on lymphocyte beta-adrenergic receptors identified by l-[3H]dihydroalprenolol. We observed no significant differences between marathoners and controls in the dose of isoproterenol that produced a 25-beat/min increment in heart rate, either in the absence (1.9 +/- 0.6 vs. 2.5 +/- 0.6 microgram; P, 0.509) or in the presence of cholinergic blockade (4.4 +/- 1.3 vs. 3.1 +/- 0.4 microgram: P, 0.320). Likewise, we observed no effects of physical training on lymphocyte beta-adrenergic receptors in terms of receptors number (53 +/- 11 vs. 56 +/- 10 fmol/mg protein) or receptor affinity (Kd 4.0 +/- 0.7 vs. 3.6 +/- 0.7 nM) (P, 0.9178). Although our data cannot exclude reduced chronotropic sensitivity to catecholamines as contributing to lowered heart rate in some highly conditioned individuals, these results are consistent with the hypothesis that altered neuronal input to the sinus node is usually a more important mechanism of training bradycardia.
Effects of norepinephrine and alpha-block on O2 uptake and blood flow in dog hindlimb
Authors: Cain S. M. , Chapler C. K.
Published: December 2017

Norepinephrine (NE) may increase skeletal muscle O2 demand at the same time that it restricts O2 transport by vasoconstriction. We prevented vasoconstriction with 3.0 mg/kg phenoxybenzamine (alpha-Bl) in 10 anesthetized, paralyzed dogs ventilated at constant rate. Hindlimb and whole-body O2 uptake (VO2) and blood flow were measured for a 20-min control period, 20 min of NE infusion at 1 micrograms . kg-1 . min-1 either intravenously (iv) or intra-arterially (ia), and 20 min of recovery. The sequence was repeated for the other route of infusion. A second group of 10 without alpha-Bl was treated the same. Cardiac output increased with both ia and iv infusions in the no-block group and was unchanged in the alpha-Bl group. Limb blood flow increased 25% during the first 5 min of iv but decreased 40% with ia infusion in the no-block group. Whole-body VO2 was significantly increased 9% in both groups by both routes of NE. Limb VO2 was significantly decreased in the no-block group at 5 min of NE infusion iv when limb blood flow was increased. Limb VO2 did not change significantly in the alpha-Bl group with NE by either route. Hindlimb skeletal muscle did not participate in or contribute to the calorigenic effect of NE on the whole body, and that lack of effect was not due to any effect of NE on rate or distribution of blood flow in the limb.
Gas mixing by cardiogenic oscillations: a theoretical quantitative analysis
Authors: Slutsky A. S.
Published: December 2017

A quantitative theoretical model of the enhanced gas mixing secondary to cardiogenic oscillations is presented based on the concept of augmented gas transport within the tracheobronchial tree (Science 209: 609, 1980). The model assumes “well-mixed” flow in the upper airways with the enhanced mixing described by Deff = Dmol + K . ud, where Deff is the effective diffusivity; Dmol, the molecular diffusivity: K, a constant; u, the root-mean-square flow; and d, the airway diameter. In the smaller airways on analysis based on Taylor laminar dispersion is used described by Deff = Dmol + (1/192) (ud)2/Dmol. The model predicts that, in dogs, cardiogenic oscillations should enhance gas mixing about 10-fold depending on the flow rates generated by the heart. Other predictions are that the augmentation of gas mixing should be greater 1) at lower lung volumes, 2) with sulfur hexafluoride vs. helium or air, 3) after peripheral airway dilation, and 4) after central airways constriction. Theoretical predictions are very close to published experimental results where available. This model should help in the development of mathematical models of gas mixing within the lungs that will include the contribution of cardiogenic oscillations.
Hypoxic arousal in intact and carotid chemodenervated sleeping cats
Authors: Neubauer J. A. , Santiago T. V. , Edelman N. H.
Published: December 2017

To determine whether the carotid chemoreceptors or hyperpnea are required for arousal from sleep by hypoxia, 14 sleep-deprived cats were studied during slow-wave (SWS) and rapid-eye-movement (REM) sleep. Rapid hypoxia was produced by inhalation of 5% O2 in N2 or 6% CO in 40% O2 by intact cats and 5% O2 in N2 after carotid body denervation. Preliminary studies identified a period of SWS unassociated with spontaneous arousals. In 69 studies during SWS unassociated with spontaneous arousals, arterial O2 saturation (SaO2) values at arousal were: 47.1 +/- 1.5% (mean +/- SE) (5% O2, intact); 48.9 +/- 1.4% (6% CO, intact); and 49.9 +/- 2.0% (5% O2, denervated). During SWS associated with spontaneous arousals, SaO2 values at arousal were 71.6 +/- 1.8% (5% O2, intact). Arousal from REM occurred at significantly lower values: 31.7 +/- 3.9% (6% CO, intact) and 43.5 +/- 2.3% (5% O2, intact). During both SWS and REM, inhalation of 5% O2 by intact animals caused a substantial increase in ventilation while 6% CO did not. We conclude that more severe hypoxia is required for arousal from SWS when studies are done in a period unassociated with spontaneous arousals than from SWS associated with spontaneous arousals. Hypoxic arousal does not appear to require activation of the carotid bodies or hyperpnea.
Conduction velocity and EMG power spectrum changes in fatigue of sustained maximal efforts
Authors: Bigland-Ritchie B. , Donovan E. F. , Roussos C. S.
Published: December 2017

The relationship between the electromyographic (EMG) power spectrum and muscle conduction velocity was investigated during both fatiguing and nonfatiguing contractions of the adductor pollicis muscle. Changes in the EMG power spectrum were measured by Fourier transform analysis and by comparing the power in the high (130–238 Hz) and low (20--40 Hz) frequency bands. Changes in conduction velocity were measured during voluntary activity from changes in the muscle mass action potential evoked by periodic maximal shocks to the nerve. This was varied independently either by maintaining a 60-s fatiguing maximal voluntary contraction involving 30--50% loss of force or by changing muscle temperature in the absence of fatigue. Both procedures resulted in similar changes in the power spectrum. However, the change in conduction velocity required to generate equal changes in the EMG was about 10 times greater in the absence of fatigue than those observed during a 60-s maximum contraction initiated at any initial muscle temperature. This suggests that during fatigue of maximal voluntary contractions, factors other than changes in the wave form of individual muscle fiber action potentials must contribute to the observed shift in the total surface EMG frequency components.
Improved accuracy and precision of single-breath CO diffusing capacity measurements
Authors: Graham B. L. , Mink J. T. , Cotton D. J.
Published: December 2017

Using three conventional methods and a new method we measured the single-breath diffusing capacity for carbon monoxide [DLCO(SB)] in a group of normal subjects. Whereas the conventional methods calculated DLCO(SB) from a single equation valid only for breath holding, the new method used three equations, one for each phase of the single-breath maneuver, i.e., inhalation, breath holding, and exhalation. We found that while the conventional methods of calculating DLCO(SB) were greatly affected by variations in the way in which the single-breath maneuver was performed and/or the way in which the alveolar gas sample was collected, these variations had little effect on the calculations of DLCO(SB) using the new method. These results were in close agreement with results from a computerized mathematical lung model in which the diffusing capacity did not change with lung volume. We concluded that the new method significantly improves the accuracy and precision of DLCO(SB) measurements while reducing the effects of maneuver variability. For these reasons comparisons of DLCO(SB) values between patients and normal subjects or between two groups with different pulmonary function may be more valid using the new method than using conventional methods.
Variability of oxygen affinity of blood: human subjects native to high altitude
Authors: Winslow R. M. , Monge C. C. , Statham N. J. , Gibson C. G. , Charache S. , Whittembury J. , Moran O. , Berger R. L.
Published: December 2017

Whole blood O2 equilibrium curves (OEC) were measured in 46 Peruvians native to high altitude (4,540 m) and in 25 sea-level controls. A method was employed that records the entire OEC from 0 to 150 Torr with constant pH and PCO2. The data were analyzed by fitting the Adair equation describing the successive oxygenation of hemoglobin. At pH 7.4 the PO2 at which hemoglobin is half-saturated with O2 (P50) was significantly higher in the high-altitude population (31.2 +/- 1.9 Torr) than in controls (29.2 +/- 1.8 Torr, P less than 0.001). The acid-base status of the high-altitude subjects, however, was that of compensated respiratory alkalosis (plasma pH 7.439 +/- 0.065), and when the P50's were corrected to the subjects' plasma pH the values (30.1 +/- 2.2 Torr) could no longer be distinguished from the controls. We conclude that, on the average, increased P50 resulting from increased red cell 2,3-diphosphyoglycerate concentration at high altitude is offset by compensated respiratory alkalosis with the net result that the position of the OEC more closely approaches that of sea-level humans than has hitherto been thought. Considerable variation exists in P50, both at sea level and high altitude. This variation might have important consequences for acclimatization and survival under adverse environmental conditions.
Specificity of power improvements through slow and fast isokinetic training
Authors: Coyle E. F. , Feiring D. C. , Rotkis T. C. , Cote R. W. , Roby F. B. , Lee W. , Wilmore J. H.
Published: December 2017

College age males performed maximal two-legged isokinetic knee extensions three times per week for 6 wk at either 60 degrees/s (slow) or 300 degrees/s (fast) or both 60 and 300 degrees/s (mixed). The velocity specific and action specific (two-leg vs. one leg) improvements in peak torque (PT) were compared to a placebo group receiving low-level muscle stimulation. The slow group improved PT significantly (P less than 0.05) more than the placebo group only at its training velocity (60 degrees/s) and more so when the specific two-legged training action was mimicked (+32% with two legs vs. +19% with one leg). The mixed group enhanced PT by 24 and 16% at their respective training velocities of 60 and 300 degrees/s. These improvements were significantly larger than placebo and also significantly larger than the 9% improvement observed at the midvelocity of 180 degrees/s. The training specificity demonstrated by the slow and mixed groups suggest that neural mechanisms contributed to their improvements in power. This is supported by their unchanging muscle morphology. Training solely at 300 degrees/s (fast) however improved PT significantly more than placebo not only at the training velocity (+18%), but also at a slower velocity of 180 degrees/s (+17%). The fast group demonstrated a significant enlargement (+11%) of type II muscle fibers. These data suggest type II fiber hypertrophy to be a plausible mechanism for the nonspecific improvement of the fast group; however, a neurological adaptation that enhances power at and below the training velocity cannot be excluded.
Lung tissue volume changes induced by hypertonic NaCl: morphometric evaluation
Authors: Wangensteen D. , Bachofen H. , Weibel E. R.
Published: December 2017

Lung tissue was examined to determine how the volumes of alveolar septum components change when NaCl is added to the vascular perfusate, increasing the osmolarity by 70 mosM. Isolated rabbit lungs were perfused with Ringer solution containing dextran, either with or without added NaCl, and fixed by vascular perfusion. Tissue samples from both “control” and “hypertonic” lungs, prepared for electron microscopy, were examined using established morphometric procedures. Volumes of septal cells, interstitial space, capillary lumen, surface-lining layer, and endothelial and epithelial areas were measured, all normalized against the endothelium basement-membrane area. Results showed that hypertonic NaCl caused a reduction in total cell and surface-lining layer volumes but no change in interstitial or capillary lumen volumes. This supports the hypothesis that small molecules have no osmotic effect across the pulmonary capillary endothelium but do cause a fluid flux from cells and across the alveolar epithelium. Areas and volume measurements for different septal cell types suggest a heterogeneous response: epithelial cells showed significant decreases and endothelial cells changed little, if at all.
Measurement of respiratory gas exchange during artificial respiration
Authors: Abdul-Rasool I. H. , Chamberlain J. H. , Swan P. C. , Mitchell F. T.
Published: December 2017

This paper reports a new system for the continuous measurements of respiratory gas exchange in ventilated subjects. It involves mixing some of the inspired gas with all of the expired gas and withdrawing the mixture at a constant rate through a dry gas meter that measures the flow. The inspired gas and expired gas mixtures are sampled and O2 and CO2 concentrations measured with a paramagnetic gas analyzer and a capnograph, respectively, to an accuracy of 0.01%. Evidence is presented to confirm the necessary stability and sensitivity of these instruments. It is possible to use the system with high inspired O2 concentrations, with ventilators where there is incomplete separation of inspired and expired gas, and in the presence of intermittent mandatory ventilation, positive end-expiratory pressure, and continuous airway pressure. The system was compared with the N2-dilution method and with the collection of expired gas in a Douglas bag in dog experiments and with patients in the intensive therapy unit. Excellent correlation between these methods was found in all circumstances.
Deficiencies in pore-membrane models of microvascular fluid and solute transudation
Authors: Winn R. , Nadir B. , Gleisner J. , Stothert J. , Hildebrandt J.
Published: December 2017

We have attempted to determine the membrane parameters, permeability-surface area product (PS) and reflection coefficient (sigma), necessary to describe solute exchange in the pulmonary circulation. Experimental lymph-to-plasma ratios were obtained for total protein (Rtot) and albumin (Ralb) using lung lymph collected from goats with chronic lung lymph fistulae. Lymph flow (QL) and solute flow (QS) were varied by increasing microvascular pressure in a stepwise manner by inflating a balloon in the left atrium. The increased QL and decreased Ralb from multiple experiments in four goats were used to plot PS vs. sigma using the equation of Patlak et al. (J. Theor. Biol. 5: 426–442, 1963). The region of intersection of two or more such curves should identify the two membrane constants. However, these curves rarely intersected suggesting that perhaps the lung barrier was not adequately represented by a single homoporous membrane. To evaluate heteroporosity, the three-pore model of Blake and Staub (Microvasc. Res. 12: 197–220, 1976) was investigated. By use of their pore sizes and relative pore distributions, values for the fluid filtration coefficient, PS, and sigma of each pore type were calculated, and finally QL and R were predicted at various microvascular pressures. When these calculated values of QL and R were plotted using the equation of Patlak et al., an equivalent homoporous PS and sigma could still be found. Therefore, a heteroporous membrane does not appear to explain the failure of our data plots to intersect. Possible alternative models are suggested.
Pattern of breathing and ventilatory response to CO2 in subjects practicing hatha-yoga
Authors: Stanescu D. C. , Nemery B. , Veriter C. , Marechal C.
Published: December 2017

WE studied eight Belgian subjects well advanced in the practice of hatha-yoga and compared them with eight sex-, age-, and height-matched control subjects. Practice of yoga (range 4–12 yr) involves control of posture and manipulation of breathing, including slow near-vital capacity maneuvers accompanied by apnea at end inspiration and end expiration. Average values for the yoga and the control group (in parentheses) are as follows: ventilation (VE) 5.53 1 X min-1 (7.07); tidal volume (VT), 1.03 liters (0.56); rate of breathing, 5.5 min-1 (13.4); end-tidal PCO2, 39.0 Torr (35.3). All differences are significant (P less than 0.05). Ventilatory response to CO2 (rebreathing technique) was significantly lower in the yoga group (P less than 0.01). The regression relating VE to VT during rebreathing of CO2 was VE = 8.1 (VT - 0.23) for the yoga group and VE = 15.8 (VT - 0.16) for the control group (P less than 0.005). We attribute these changes to chronic manipulation of respiration.
Effect of body temperature on ventilatory control in the alligator
Authors: Davies D. G. , Thomas J. L. , Smith E. N.
Published: December 2017

Pulmonary ventilation and arterial blood acid-base balance were measured in six unanesthetized alligators, Alligator mississipiensis, at 15, 25, and 35 degree C. The animals exhibited pronounced ventilatory responses to hypercapnia at all temperatures studied. Arterial PCO2 increased and pH decreased with increases in body temperature during both normocapnia and hypercapnia. The fractional dissociation of imidazole (alpha Pr) remained constant with changes in body temperature during normocapnia, but increased with temperature during hypercapnia. Ventilatory sensitivity, defined as delta (VE/VO2/delta (alpha Pr), was independent of body temperature. We conclude that the control of breathing in the alligator is a physiological defense of alpha Pr and that ventilatory responses occur following nontemperature-induced changes in blood acid-base balance, which tend to return alpha Pr to a normal value.
Ventilatory effects of kainic acid injection of the ventrolateral solitary nucleus
Authors: Berger A. J. , Cooney K. A.
Published: December 2017

We studied in cats the long-term effects upon resting ventilation and the ventilatory responses to CO2 breathing of destruction of neuronal cell bodies within the ventrolateral nucleus of the tractus solitarius (vl-NTS) by kainic acid (KA) injection (KAI). Animals were studied in the awake state and under pentobarbital anesthesia both before and 8 wk after stereotaxic bilateral microinjection of the vl-NTS with mock cerebrospinal fluid (CSF) (controls, n = 2) or with KA in mock CSF (KAI, n = 5). KA reduced the number of cell bodies within the vl-NTS by 75%. Under anesthesia minute ventilation (VI) was reduced by 49% after KAI, due primarily to a 54% reduction in breathing frequency (f). Four of five anesthetized KAI animals exhibited a significantly reduced (P less than 0.01) ventilatory sensitivity to inspired CO2 under anesthesia. In the awake state some KAI animals had significant changes (P less than 0.01) in ventilation; VI reduced (2 of 5), tidal volume reduced (1 of 5), f reduced (3 of 5), and inspiratory and expiratory times increased (2 of 5). Decreases in the awake ventilatory CO2 sensitivity were not significant within individual KAI animals but were significant (P less than 0.05) when considered as a group. Thus following 75% neuronal loss within the vl-NTS, rhythmic ventilation was sustained during both anesthesia and wakefulness, although f was reduced in the former state. The vl-NTS may function to set most but not all of the ventilatory sensitivity to CO2 during anesthesia and to a lesser extent during wakefulness.
Erythrocyte indices during a competitive marathon
Authors: Kolka M. A. , Stephenson L. A. , Wilkerson J. E.
Published: December 2017

Three adult male volunteers ran a competitive marathon (42.2 km) during which there was an average ambient air (dry bulb) temperature of 19.4 degree C, with an average ambient water vapor pressure of 9.5 Toor. Prior to and at 4.8-km (3-mi) intervals throughout the race, venous blood samples were drawn from an indwelling catheter in a peripheral arm vein. In each blood sample the total erythrocyte count (EC) was made, and whole blood hemoglobin concentration, hematocrit, and plasma osmolality were determined. From these measurements, the standard red blood cell (RBC) indices of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were calculated. The three subjects completed the race in 191, 240, and 310 min, with weight losses averaging 5.4% of prerace body weight. EC linearly decreased below the prerace control levels of 5.69 X 10(6) RBC/mm3 for the first 14.5 km of the race, so that EC was 4.7% below control levels by this point. Subsequently, EC rose back to control levels by 19.3 km, where it remained for the rest of the race. MCHC, MCH, and calculated total RBC volume did not significantly change during the race. Plasma osmolality related to plasma osmolality. These data indicate the dynamic nature of erythrocyte number and volume during long-duration submaximal exercise, and the extraordinary ability of the human body to maintain RBC indices within narrow limits when confronted with a severe stress such as the marathon.
Interrelationships among airway CO2, airway pressure, and breathing frequency
Authors: Nilsestuen J. O. , Coon R. L. , Zuperku E. J. , Kampine J. P.
Published: December 2017

The breathing frequency response to changes in airway CO2 of a vascularly isolated lobe of the canine lung has previously been shown to be primarily dependent on CO2-mediated changes in airway pressure. This study was carried out to determine what contribution changes in airway pressure make in the whole lung airway CO2-mediated breathing frequency response. Mongrel dogs were anesthetized and placed on cardiopulmonary bypass. Diaphragm electromyogram (EMG) was used to monitor respiratory center output and to trigger ventilation of the lungs. Isoproterenol administered to the lungs prevented hypocapnic airway constriction but only partially blocked the decrease in breathing frequency, suggesting that in the whole lung preparation, airway CO2 in part alters breathing frequency through a direct effect on pulmonary receptors. At constant positive end-expired pressures (1–6 Torr), 0% airway CO2 produced greater increases in expiratory time than 10% CO2. Thus airway CO2 can affect breathing frequency in the absence of CO2-related changes in airway pressure at pressures that would produce lung volumes similar to those observed at end expiration in the intact animal. An argument is presented that the receptors directly affected by CO2 are probably not located in the airways constricted by hypocapnia.
Phase V of the single-breath washout test
Authors: Nichol G. M. , Michels D. B. , Guy H. J.
Published: December 2017

A downward-deflecting phase V is often seen following the phase IV terminal rise in the single-breath N2 washout test (SB N2). This phase V was studied in eight normal nonsmoking subjects aged 27–41, using both the SB N2 test and single-breath washouts of boluses of inert tracer gas slowly inhaled from residual volume (RV). All of the subjects showed a distinct phase V in both tests. Expiratory flow rates between 0.1 and 2.0 1/s were used; at each flow rate phase V appeared shortly after expiration became flow limited. Thus the volume above RV at which phase V began increased with increasing expiratory flow rate. The difference between the exhaled volumes at which flow became limited and phase V appeared was shown to be approximately equal to the anatomic dead space. This behavior is predicted by a model of lung emptying in a gravitational field. As expiration proceeds, flow limitation occurs first in the (tracer-poor) lower lung regions and then progresses toward the (tracer-rich) upper lung regions causing phase IV. When all lung regions have finally become flow limited, the amount of flow from the upper regions decreases relative to that of the lower regions, thereby causing phase V.
Regulation of PaCO2 and ventilation in humans inspiring low levels of CO2
Authors: Forster H. V. , Klein J. P. , Hamilton L. H. , Kampine J. P.
Published: December 2017

This study was designed to determine whether 1) arterial PCO2 (PaCO2) increases when inspired PCO2 (PICO2) is increased from less than 0.4 Torr (eupnea) to 7 or 14 Torr, and 2) ventilatory sensitivity to CO2 (delta VE/ delta PaCO2) is greater at low levels of PICO2 (7–21 Torr) than it is at higher levels (28–42 Torr). Human subjects were studied while seated in an environmental chamber that permitted alteration of PICO2 by changing the chamber PCO2. In study 1, arterial blood was sampled over the final 5 min of a eupneic period and again 10–15 min later when PICO2 was 7 or 14 Torr. With this protocol, PACO2 was increased above eupnea by 0.7 (P less than 0.02) and 0.9 Torr (P less than 0.01) when PICO2 was 7 and 14 Torr, respectively. In study 2, arterial blood was sampled every 5 min during two 1-h periods of eupnea that were separated by 3 h during which PICO2 was increased by 7 Torr each 0.5 h. With this protocol there was no consistent difference in PACO2 between eupneic periods and periods when PICO2 was 7–14 Torr. There was a progressively increased hypercapnia as PICO2 was increased from 7 to 42 Torr. The delta VE/ delta PaCO2 was less than half for data obtained at low relative to high PICO2. The two studies demonstrated that measurement error and physiologic variation necessitate using a “powerful” experimental design (study 1) to detect small increases in PaCO2. On the basis of these results, we have concluded that there is no apparent reason to postulate a sensory mechanism other than the carotid and intracranial chemoreceptors to account for the hyperpnea during CO2 inhalation. Specifically, isocapnic hyperpnea probably does not occur.
Renin, aldosterone, and converting enzyme during exercise and acute hypoxia in humans
Authors: Milledge J. S. , Catley D. M.
Published: December 2017

The possibility that hypoxia might inhibit the secretion of angiotension-converting enzyme (ACE) would explain the low concentrations of aldosterone reported in humans at high altitude. To observe the effect of such a reduction in ACE concentration on the plasma aldosterone concentration (PAC) four subjects performed mild exercise throughout a 2-h study so as to elevate their plasma renin activity (PRA). After the first 60 min breathing air they were switched to breathing 12.8% O2 (4,000 an altitude equivalent). Venous samples were taken at intervals for hormone analysis. Results showed the expected rise of PRA and PAC both tending toward a plateau after about 45 min. There was no significant change in ACE activity (F = 0.065). Hypoxia produced a further 50% rise in PRA but a fall in PAC and a 30% reduction in ACE activity. Angiotensin I concentrations closely followed PRA throughout (r = 0.984). These results indicate that during exercise acute hypoxia changes the usual close relationship between PAC and PRA by reducing ACE activity.
Heart contractility at pressure loads induced by ischemia of exercised muscle in humans
Authors: Bonde-Petersen F. , Suzuki Y.
Published: December 2017

During one- or two-leg bicycle exercise in three subjects the exercised limb(s) were made ischemic by occlusion cuffs inflated to 300 Torr immediately at, or 30 s before, end of 7-min exercise and kept inflated for 3 min of recovery. Mean arterial pressure (MAP) remained elevated during occluded recovery, whereas heart rate (HR) and forearm blood flow tended to recover at the same rate as in the control situation without occlusion. Systolic time intervals (STI) were negatively correlated to HR in the interval 60–120 beats/min. In spite of a variation in afterload of 30 Torr induced by occlusion the correlation between HR and STI fitted the same equations. The involvement of different size of muscle mass did not change these relationships. The elevation of MAP during ischemia of exercised muscles is due to an increased vascular tone reflexly induced from muscle chemoreceptors and not cardiac in origin. The results also demonstrate that heart contractility adapts well to the induced afterload.
Pulmonary carbonic anhydrase in the human, monkey, and rat
Authors: Lonnerholm G.
Published: December 2017

The distribution of carbonic anhydrase in the human, monkey, and rat lung was studied by the histochemical method of Hansson. High activity of this enzyme was demonstrated in the endothelium of pulmonary capillaries. In the human and the monkey lung enzyme activity was exhibited in the whole circumference of the capillaries, but in the rat enzyme activity is confined to capillary segments having close contact with alveolar epithelium forming the blood-air barrier. Staining was inhibited by 10 microM acetazolamide, but was not affected by 10 microM Cl 13,850, an inactive acetazolamide analogue. The location of carbonic anhydrase in the lung supports the idea that pulmonary carbonic anhydrase promotes CO2 elimination from the blood into the alveolar space. Its possible functions may be to act upon plasma to accelerate the conversion of HCO-3 to CO2 and to facilitate CO2 transport through the lung tissue.
Strain difference in thermoregulation of rats surviving extreme heat
Authors: Furuyama F.
Published: December 2017

The survival times of unanesthetized rats in 42.5 degree C. 48% rh were studied in 12 different strains. In males, Sprague-Dawley rats (P less than 0.01) and Fisher 344/MK (P less than 0.05) showed significantly higher heat tolerance than the other 9 strains. Among Sprague-Dawley rats, females tolerated heat longer than males (P less than 0.05). There was no difference in lethal body temperature according to strains and exposure temperatures (38.5–48.5 degree C). Maximum survivable body temperature was 43.1 degree C in males and 43.3 degree C in females. The body weight loss in heat was greater in Sprague-Dawley, Fisher 344/MK, and JCL:Wistar strains. The degree of saliva spreading during the equilibrium period just below the maximum survivable body temperature correlated significantly with heat tolerance and was found to be the index of strain difference in heat tolerance. These findings demonstrated that the thermoregulatory system of rats is controlled genetically, though survival times of individuals in different strains sometimes overlap.
Control of breathing in young twins
Authors: Kawakami Y. , Yoshikawa T. , Shida A. , Asanuma Y. , Murao M.
Published: December 2017

To clarify the role of genetics in determining chemical and behavioral control of breathing, an age-, body size-, and sex ratio-matched study was conducted in 62 twins (mean age 16.4 yr, 20 pairs of monozygotic twins (MZ) and 11 pairs of dizygotic twins (DZ)] for ventilatory responses to hypoxia (A) and hypercapnia (S) along with thresholds for perception of added inspiratory resistance. A and S were determined by a dual-control system developed to regulate arterial blood gases at predetermined levels. Mean values for A, S, thresholds for added resistance, and mouth pressure at the threshold were not different between MZ and DZ. Within-pair variances for A, S, and mouth pressure at the threshold were significantly smaller in MZ than DZ. Neither A nor S correlated with thresholds for resistance and mouth pressure in either MZ or DZ. These results indicate that in adolescent twins sensitivity to added inspiratory resistance and chemosensitivity to hypoxia and hypercapnia involve genetically determined factors, and perception of added inspiratory resistance is not directly related to chemical control of breathing.
Effect of breathing patterns on the perceived magnitude of added loads to breathing
Authors: Killian K. J. , Bucens D. D. , Campbell E. J.
Published: December 2017

We have studied the perceived magnitude (psi) of a range of externally added resistive (delta R) and elastic (delta E) loads to breathing while varying the flow rate, tidal volume, and inspiratory duration. The sensory magnitude of an added resistive load increased with both the inspiratory flow rate (P less than 0.001) and the magnitude of the added resistance (P less than 0.01). Similarly, the perceived magnitude of an added elastic load increased with both the tidal volume (P less than 0.001) and the magnitude of the added elastance (P less than 0.01). When inspiratory duration was not controlled, a single relationship was found to hold for both types of load when analyzed as a function of inspiratory airway pressure (P): psi = K . P1.15 (r = 0.94 for delta R); psi = K . p1.10 (r = 0.98 for delta E). When inspiratory duration was controlled, the perceived magnitude of both resistive and elastic loads also increased as the inspiratory duration increased (P less than 0.05). Again, the sensory magnitude was closely related to the airway pressure; but for any given airway pressure the perceptual magnitude also increased as inspiratory duration increased: psi = K . t0.6 (for delta R); psi = K . t0.52 (for delta E). When resistive, elastic, and mixed resistive and elastic loads were presented while keeping inspiratory duration constant, the sensory magnitude was directly related to the airway pressure (r = 0.99) and there was no discernible difference between the types of load. The results suggest that the perceived magnitude of added loads to breathing is directly related to the inspiratory muscle force and its duration (psi = K . P1.3 . t0.56) and indirectly to the added load.
Interaction of chemoreceptor effects and its dependence on the intensity of stimuli
Authors: Adams J. M. , Severns M. L.
Published: December 2017

We have studied the way in which carotid and medullary chemoreceptor effects combine to control respiration in pentobarbital anesthetized dogs. The carotid sinuses were autoperfused from a membrane oxygenator system to produce either normoxic or hypoxic-hypercapnic blood without producing brain stem hypoxia. The dogs breathed CO2 in O2, N2 mixtures regulated to produce isocapnic levels of arterial partial pressure of CO2 (PaCO2) of 36, 54, and 68 Torr at PaO2 = 87. Tidal volume (VT) increased (P less than 0.05) from a control value of 317 ml to 545 at PaCO2 = 54 but did not increase further at PaCO2 = 68. Carotid chemoreceptor stimulation increased VT to 432 ml at PaCO2 = 36 (P less than 0.05) but did not increase VT at the higher levels of PaCO2. Thus, VT has reached a maximum at PaCO2 = 54 Torr and was not increased further by either chemoreceptor drive. Breathing frequency (f) increased (P less than 0.05) from an eupnic value of 20.2 breaths/min to 35.5 and 41.3 at PaCO2 = 54 and 68, respectively. Carotid chemoreceptor stimulation increased (P less than 0.05) f by 7.7, 5.2, and 5.0 breaths/min at each of the levels of PaCO2. Tidal volume exhibited a less-than-additive (P less than 0.05) combination of chemoreceptor effects but f was not significantly different from additive. We conclude that, in pentobarbital-anesthetized dogs, f continues to increase at chemoreceptor drives beyond those at which VT reaches a maximum. This VT nonlinearity may be responsible for the different interactions found in these experiments.
Respiratory and inert gas exchange during high-frequency ventilation
Authors: Robertson H. T. , Coffey R. L. , Standaert T. A. , Truog W. E.
Published: December 2017

Pulmonary gas exchange during high-frequency low-tidal volume ventilation (HFV) (10 Hz, 4.8 ml/kg) was compared with conventional ventilation (CV) and an identical inspired fresh gas flow in pentobarbital-anesthetized dogs. Comparing respiratory and infused inert gas exchange (Wagner et al., J. Appl. Physiol. 36: 585--599, 1974) during HFV and CV, the efficiency of oxygenation was not different, but the Bohr physiological dead space ratio was greater on HFV (61.5 +/- 2.2% vs. 50.6 +/- 1.4%). However, the elimination of the most soluble inert gas (acetone) was markedly enhanced by HFV. The increased elimination of the soluble infused inert gases during HFV compared with CV may be related to the extensive intraregional gas mixing that allows the conducting airways to serve as a capacitance for the soluble inert gases. Comparing as exchange during HFV with three different density carrier gases (He, N2, and Ar), the efficiency of elimination of Co2 or the intravenously infused inert gases was greatest with He-O2. However, the alveolar-arterial partial pressure difference for O2 on He-O2 exceeded that on N2-O2 by 5.4 Torr during HFV. The finding agrees with similar observations during CV, suggesting that this aspect of gas exchange is not substantially altered by HFV.
Onset of respiration in infants delivered by cesarean section
Authors: Mortola J. P. , Fisher J. T. , Smith J. B. , Fox G. S. , Weeks S. , Willis D.
Published: December 2017

We studied the ventilatory parameters and the pattern of breathing including the onset of respiration in 20 healthy infants immediately after cesarean-section delivery. In eight of the infants further measurements were obtained at 60 min of life. The pattern of breathing immediately after delivery is very irregular with a marked tendency to keep the lung inflated mainly through interruptions of expiration. After the first expiration some air remains in the lung representing the formation of functional residual capacity (FRC). FRC obtained with the first breath is proportional to the previous inspired volume and is the largest contribution towards the full establishment of FRC. Tidal volume and FRC of the first breath are similar to that reported in babies delivered vaginally, which suggests that the forces required for lung inflation are similar in the two groups of infants. The first breath tends to be deeper and slower and has a longer expiratory time than subsequent breaths. At 60 min of life the respiratory pattern becomes more regular, tidal volume is further decreased, and respiratory frequency is increased through a reduction of expiratory time.
Effect of acid-base status on the kinetics of the ventilatory response to moderate exercise
Authors: Oren A. , Whipp B. J. , Wasserman K.
Published: December 2017

To determine the influence of altered carotid body drive on exercise ventilatory kinetics, five subjects performed four repetitions of constant-load cycle ergometer exercise during air and O2 breathing under each of the following conditions: 1) metabolic acidosis, (NH4Cl, 0.3 g . kg-1 . day-1); 2) metabolic alkalosis (NaHCO3, 0.7 g . kg-1 . day-1); and 3) control (CaCO3, 0.1 g . kg-1 . day-1). Ventilatory and gas exchange variables were computed, breath-by-breath, and the time constant of the ventilatory response in each condition was determined by a least-squares technique. While breathing air, metabolic acidosis caused the magnitude of the ventilatory response to increase and the time constant of the ventilatory kinetics to decrease. With metabolic alkalosis the increase in ventilation caused by exercise tended to be smaller and time constant larger although these changes were not statistically significant. Hyperoxia slowed the ventilatory response in the three acid-base conditions to a similar value. Thus hyperoxia slowed the ventilatory kinetics to a greater degree during acidosis than during control or alkalosis. We conclude that ventilatory dynamics during moderate exercise can be appreciably influenced by the acid-base status with acidosis significantly speeding the response dynamics. And, as these effects are abolished by hyperoxia, they appear to be mediated via the carotid bodies, in the human.
Theoretical analysis of optimal P50
Authors: Willford D. C. , Hill E. P. , Moores W. Y.
Published: December 2017

A simple expression is derived to describe the partial pressure at 50% hemoglobin saturation with oxygen (P50) that maximizes venous oxygen tension (PO2) for a given arterial PO2 and oxygen consumption. That “optimal P50” also maximizes arteriovenous saturation differences for given arterial and venous PO2 values. The optimal P50 can be expressed as the square root of the product of arterial and venous PO2 values. Alternatively, it can be expressed as a simple function of the arterial PO2 and the arteriovenous saturation difference. Nomograms summarize the relationships between the variables, and published observations that suggest an observational basis for our theoretical analysis are reviewed. We conclude that for normoxia or moderate hypoxia a high P50 is advantageous, whereas for more severe hypoxia or increased metabolic demands, a low P50 is advantageous.
Adjustments in metabolic heat production by squirrel monkeys exposed to microwaves
Authors: Adair E. R. , Adams B. W.
Published: December 2017

Squirrel monkeys (Saimiri sciureus) were exposed in the far field of a horn antenna to both brief (10-min) and prolonged (90-min) periods of 2,450-MHz continuous microwaves. Ambient temperature (Ta) was constant at 15, 20, or 25 degrees C. Microwave power density ranged from 2.5 to 10 mW/cm2, representing a range of whole-body energy absorption from 0.4 to 1.5 W/kg. Reliable reductions in metabolic heat production (M), calculated from oxygen deficit in the monkey's expired air, were initiated at all Ta by 10-min whole-body exposures to power densities of 4 mW/cm2 (2 monkeys) or 6 mW/cm2 (1 monkey) and above. The magnitude of M reduction was linearly related to microwave intensity above the threshold level. Termination of microwaves was followed by a rapid M rebound. The change in M produced by a given power density was nearly the same in Ta = 15 and 20 degrees C. During 90-min exposures at Ta = 20 degrees C, the vigorous M reduction to microwave onset adapted slowly, ensuring continual precise regulation of internal body temperature. Thus cold-exposed endotherms readily compensate for microwave-induced body heating by reducing endogenous heat production.
Lipoprotein lipase hydrolyzes endogenous triacylglycerols in muscle of exercised rats
Authors: Oscai L. B. , Caruso R. A. , Wergeles A. C.
Published: December 2017

A strenuous program of treadmill running increased endogenous lipoprotein lipase (LPL) activity 2.7-fold in the soleus and 2.8-fold in fast-red fibers of the quadriceps. Under these conditions, intracellular triacylglycerols (TG) decreased 25% in the soleus and 44% in fast-red muscle fibers. Free fatty acids (FFA) increased 2.1-fold (soleus) and 2.7-fold (fast-red). In the heart, a 2-h bout of swimming in untrained rats increased intracellular LPL activity 64% measured 24 h after work. The magnitude of the increase in endogenous LPL activity in heart was dependent on the intensity of the exercise. With elevated levels of intracellular LPL activity in the myocardium, TG was reduced 49% and FFA increased 3.4-fold. These results provide evidence that exercise may result in an increased capacity to hydrolyze intramuscular TG. Further, they suggest that LPL may be the enzyme responsible for intracellular TG hydrolysis in heart and skeletal muscle.
Comparative physiological responses to exercise stress
Authors: Hastings A. B. , White F. C. , Sanders T. M. , Bloor C. M.
Published: December 2017

We determined the effect of exhaustive exercise on the acid-base balance, O2 consumption, and cardiac output in dogs and pigs to examine which species was comparable with humans in its physiological response to exercise. We ran 11 dogs and 11 pigs on a motor-driven treadmill at steady-state (heart rate 75% maximum) and exhaustive (maximum heart rate) exercise levels. Measuring heart rate, cardiac output, and aortic pressure via implanted probes we obtained arterial and venous blood samples before, during, and after exercise to determine hematocrit, blood gas tensions, pH, and lactic acid levels. Dogs had a twofold greater work capacity than the pigs, but the dogs could not run at maximal heart rate as long as the pigs did. Although O2 consumption correlated well with cardiac output and total work in both species, dogs were capable of a greater range of values. The acid-base studies showed that exhaustive exercise in the pigs resulted in a severe metabolic acidosis, whereas this did not occur in dogs. Respiratory alkalosis was noted in dogs. This suggested that the supply of O2 to the working muscles of the pig was insufficient to maintain aerobic metabolism. The pigs' responses to exercise conformed to those found by others in the human, suggesting that the pig is a more appropriate model for some exercise studies.