Exponential and diphasic ventilatory response to hypoxia in conscious lambs

This study was undertaken to test the hypothesis that in the neonate the hypoxic chemoreflex drive adapts to steady-state hypoxia but not to progressive hypoxia. First we have compared the ventilatory (VE) response of 2-day-old conscious lambs to steady-state hypoxia with their response to progressive hypoxia. Second, we have quantified the chemoreceptor excitatory function operating at the end of each period of hypoxia by studying the immediate VE response to the withdrawal of the hypoxic stimulus. Lambs responded to steady-state hypoxia [fractional concentration of inspired O2 (FIO2) = 0.08] by a diphasic VE response but responded to progressive hypoxia (FIO2 0.21-0.08) by an exponential VE increase. Hyperventilation in steady-state hypoxia was transient; VE increased immediately from 532 to a mean peak response of 712 ml X kg-1 X min-1 and decreased to 595 ml X kg-1. min-1 within 10 min. With progressive hypoxia, VE increased within 13 min from 514 to 705 ml X kg-1 X min-1. At the end of steady-state and progressive hypoxia the abrupt withdrawal of the hypoxic drive caused an instantaneous VE decrease to 390 and 399 ml X kg-1 X min-1, respectively; the VE decrease was respectively 306 and 205 ml X kg-1 X min-1 (P less than 0.05). This demonstrates that during steady-state hypoxia the lambs had suffered a loss of one third of the chemoreceptor excitatory function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of adenosine on ventilatory responses to hypoxia and hypercapnia in humans

Adenosine infusion (100 micrograms X kg-1 X min-1) in humans stimulates ventilation but also causes abdominal and chest discomfort. To exclude the effects of symptoms and to differentiate between a central and peripheral site of action, we measured the effect of adenosine infused at a level (70-80 micrograms X kg-1 X min-1) below the threshold for symptoms. Resting ventilation (VE) and progressive ventilatory responses to isocapnic hypoxia and hyperoxic hypercapnia were measured in six normal men. Compared with a control saline infusion given single blind on the same day, adenosine stimulated VE [mean increase: 1.3 +/- 0.8 (SD) l/min; P less than 0.02], lowered resting end-tidal PCO2 (PETCO2) (mean fall: -3.9 +/- 0.9 Torr), and increased heart rate (mean increase: 16.1 +/- 8.1 beats/min) without changing systemic blood pressure. Adenosine increased the hypoxic ventilatory response (control: -0.68 +/- 0.4 l X min-1 X %SaO2-1, where %SaO2 is percent of arterial O2 saturation; adenosine: -2.40 +/- 1.2 l X min-1 X %SaO2-1; P less than 0.01) measured at a mean PETCO2 of 38.3 +/- 0.6 Torr but did not alter the hypercapnic response. This differential effect suggests that adenosine may stimulate ventilation by a peripheral rather than a central action and therefore may be involved in the mechanism of peripheral chemoreception.     

Effect of hematocrit reduction on hormonal and metabolic responses to exercise

We wished to determine the effect of a 25% hematocrit reduction on glucoregulatory hormone release and glucose fluxes during exercise. In five anemic dogs, plasma glucose fell by 21 mg/dl and in five controls by 7 mg/dl by the end of the 90-min exercise period. After 50 min of exercise, hepatic glucose production (Ra) and glucose metabolic clearance rate (MCR) began to rise disproportionately in anemics compared with controls. By the end of exercise, the increase in Ra was almost threefold higher (delta 15.1 +/- 3.4 vs. delta 5.2 +/- 1.3 mg X kg-1 X min-1) and MCR nearly fourfold (delta 24.6 +/- 8.8 vs. delta 6.5 +/- 1.3 ml X kg-1 X min-1). Exercise with anemia, in relation to controls resulted in elevated levels of glucagon [immunoreactive glucagon (IRG) delta 1,283 +/- 507 vs delta 514 +/- 99 pg/ml], norepinephrine (delta 1,592 +/- 280 vs. delta 590 +/- 155 pg/ml), epinephrine (delta 2,293 +/- 994 vs. delta 385 +/- 186 pg/ml), cortisol (delta 6.7 +/- 2.2 vs. delta 2.1 +/- 1.0 micrograms/dl) and lactate (delta 12.1 +/- 2.2 vs. delta 4.2 +/- 1.8 mg/dl) after 90 min. Immunoreactive insulin and free fatty acids were similar in both groups. In conclusion, exercise with a 25% hematocrit reduction results in 1) elevated lactate, norepinephrine, epinephrine, cortisol, and IRG levels, 2) an increased Ra which is likely related to the increased counterregulatory response, and 3) we speculate that a near fourfold increase in MCR is related to metabolic changes due to hypoxia in working muscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Somatostatin inhibits the ventilatory response to hypoxia in humans

The effects of a 90-min infusion of somatostatin (1 mg/h) on ventilation and the ventilatory responses to hypoxia and hypercapnia were studied in six normal adult males. Minute ventilation (VE) was measured with inductance plethysmography, arterial 02 saturation (SaO2) was measured with ear oximetry, and arterial PCO2 (Paco2) was estimated with a transcutaneous CO2 electrode. The steady-state ventilatory response to hypoxia (delta VE/delta SaO2) was measured in subjects breathing 10.5% O2 in an open circuit while isocapnia was maintained by the addition of CO2. The hypercapnic response (delta VE/delta PaCO2) was measured in subjects breathing first 5% and then 7.5% CO2 (in 52-55% O2). Somatostatin greatly attenuated the hypoxic response (control mean -790 ml x min-1.%SaO2 -1, somatostatin mean -120 ml x min-1.%SaO2 -1; P less than 0.01), caused a small fall in resting ventilation (mean % fall - 11%), but did not affect the hypercapnic response. In three of the subjects progressive ventilatory responses (using rebreathing techniques, dry gas meter, and end-tidal Pco2 analysis) and overall metabolism were measured. Somatostatin caused similar changes (mean fall in hypoxic response -73%; no change in hypercapnic response) and did not alter overall O2 consumption nor CO2 production. These results show an hitherto-unsuspected inhibitory potential of this neuropeptide on the control of breathing; the sparing of the hypercapnic response is suggestive of an action on the carotid body but does not exclude a central effect.     

Augmented hypoxic ventilatory response in men at altitude.

To test the hypothesis that the hypoxic ventilatory response (HVR) of an individual is a constant unaffected by acclimatization, isocapnic 5-min step HVR, as delta VI/delta SaO2 (l.min-1.%-1, where VI is inspired ventilation and SaO2 is arterial O2 saturation), was tested in six normal males at sea level (SL), after 1-5 days at 3,810-m altitude (AL1-3), and three times over 1 wk after altitude exposure (PAL1-3). Equal medullary central ventilatory drive was sought at both altitudes by testing HVR after greater than 15 min of hyperoxia to eliminate possible ambient hypoxic ventilatory depression (HVD), choosing for isocapnia a P'CO2 (end tidal) elevated sufficiently to drive hyperoxic VI to 140 ml.kg-1.min-1. Mean P'CO2 was 45.4 +/- 1.7 Torr at SL and 33.3 +/- 1.8 Torr on AL3, compared with the respective resting control end-tidal PCO2 of 42.3 +/- 2.0 and 30.8 +/- 2.6 Torr. SL HVR of 0.91 +/- 0.38 was unchanged on AL1 (30 +/- 18 h) at 1.04 +/- 0.37 but rose (P less than 0.05) to 1.27 +/- 0.57 on AL2 (3.2 +/- 0.8 days) and 1.46 +/- 0.59 on AL3 (4.8 +/- 0.4 days) and remained high on PAL1 at 1.44 +/- 0.54 and PAL2 at 1.37 +/- 0.78 but not on PAL3 (days 4-7). HVR was independent of test SaO2 (range 60-90%). Hyperoxic HCVR (CO2 response) was increased on AL3 and PAL1. Arterial pH at congruent to 65% SaO2 was 7.378 +/- 0.019 at SL, 7.44 +/- 0.018 on AL2, and 7.412 +/- 0.023 on AL3.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute and chronic hypoxic pulmonary hypertension in guinea pigs

To determine whether the strength of acute hypoxic vasoconstriction predicts the magnitude of chronic hypoxic pulmonary hypertension, we performed serial studies on guinea pigs. Unanesthetized, chronically catheterized guinea pigs increased mean pulmonary arterial pressure (PAP) from 11 +/- 0.5 to 13 +/- 0.7 Torr in acute hypoxia (10% O2 for 65 min). The response was maximal at 5 min, remained stable for 1 h, and was reversible on return to room air. Cardiac index did not change with acute hypoxia or recovery. Guinea pigs exposed to chronic hypoxia increased PAP, measured in room air 1 h after removal from the hypoxic chamber, to 18 +/- 1 Torr by 5 days with little further increase in PAP to 20 +/- 1 Torr after 21 days. Cardiac index fell from 273 +/- 12 to 206 +/- 7 ml.kg-1.min-1 (P less than 0.05) after 21 days of hypoxia. Medial thickness of pulmonary arteries adjacent to terminal bronchioles and alveolar ducts increased significantly by 10 days. The magnitude of the pulmonary vasoconstriction to acute hypoxia persisted and was unabated during the development and apparent stabilization of chronic hypoxic pulmonary hypertension, suggesting that if vasoconstriction is the stimulus for remodeling, then the importance of the stimulus lessens with duration of hypoxia. In individual animals followed serially, we found no correlation between the magnitude of the acute vasoconstrictor response before chronic hypoxia and the severity of chronic pulmonary hypertension that subsequently developed either because the initial response was small and variable or because vasoconstriction may not be the sole stimulus for vascular remodeling in the guinea pig.     

Dopaminergic modulation of ventilation in obese Zucker rats.

To investigate the hypothesis that the impaired respiratory drive noted in morbid obesity was attributable to altered dopaminergic mechanisms acting on peripheral and/or central chemoreflex sensitivity, seven obese and seven lean Zucker rats were studied at 11 wk of age. Ventilation (VE) was measured by the barometric technique during hyperoxic (100% O(2)), normoxic (21% O(2)), hypoxic (10% O(2)), and hypercapnic (7% CO(2)) exposures after the administration of vehicle (control), haloperidol [Hal, 1 mg/kg, a central and peripheral dopamine (Da) receptor antagonist], or domperidone (Dom, 0.5 mg/kg, a peripheral Da receptor antagonist). In both lean and obese rats, Hal increased tidal volume and decreased respiratory frequency during hyperoxia or normoxia, resulting in an unchanged VE. In contrast, Dom did not affect tidal volume, frequency, or VE during hyperoxia or normoxia. During hypoxia, however, VE significantly increased from 1,132 +/- 136 to 1,348 +/- 98 ml. kg(-1). min(-1) (P < 0.01) after the administration of Dom in obese rats, whereas no change was observed in lean rats. Hal significantly decreased VE during hypoxia compared with control in lean but not obese rats. In both lean and obese rats, Hal decreased VE in response to hypercapnia, whereas Dom had no effect. Our major findings suggest that peripheral chemosensitivity to hypoxia in obese Zucker rats is reduced as a result of an increased dopaminergic receptor modulation in the carotid body.     

Respiratory muscle blood flow in oleic acid-induced pulmonary edema

If respiratory muscle blood flow (RMBF) demands in pulmonary edema are large enough, an imbalance between supply and demand could lead to respiratory muscle failure. Therefore, to determine the magnitude of RMBF in this condition we produced pulmonary edema by injecting oleic acid into the pulmonary circulation and measured RMBF with radiolabeled microspheres injected into the left atrium. We then related changes in muscle blood flow to changes in respiratory variables including frequency of breathing (fb, breaths/min), tidal volume (VT, ml), ventilation (VE, ml . kg-1 . min-1), pleural pressure-time index (PTI, cmH2O), and dynamic compliance (Cdyn, 1/cmH2O) at 0 (control), 30, 60, and 120 min. Cardiac output and blood pressure did not change throughout the experiment, but hypoxia became progressively more severe with a final PO2 of 37 +/- 10 Torr. With pulmonary edema, fb rose from a control value of 32 +/- 13 to 111 +/- 33 at peak, VE rose from 237 +/- 90 to 806 +/- 188, but VT did not change. PTI rose from 54 +/- 16 to 180 +/- 48, and Cdyn decreased from 0.06 +/- 0.02 to 2.02 +/- 0.01. Diaphragmatic blood flow (Qdi) rose from 16.0 +/- 6.26 to 120.1 +/- 54.5 ml . min-1 X 100 g-1 and accounted for 55% of the total RMBF of 217 +/- 100 ml/min. The RMBF accounted for 11.4 +/- 4.7% of the cardiac output at peak affect. The rise in Qdi was best predicted by PTI and to a smaller extent by PO2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Locus of hypoxic vasoconstriction in isolated ferret lungs

To determine whether hypoxic pulmonary vasoconstriction (HPV) occurs mainly in alveolar or extra-alveolar vessels in ferrets, we used two groups of isolated lungs perfused with autologous blood and a constant left atrial pressure (-5 Torr). In the first group, flow (Q) was held constant at 50, 100, and 150 ml.kg-1 X min-1, and changes in pulmonary arterial pressure (Ppa) were recorded as alveolar pressure (Palv) was lowered from 25 to 0 Torr during control [inspired partial pressure of O2 (PIO2) = 200 Torr] and hypoxic (PIO2 = 25 Torr) conditions. From these data, pressure-flow relationships were constructed at several levels of Palv. In the control state, lung inflation did not affect the slope of the pressure-flow relationships (delta Ppa/delta Q), but caused the extrapolated pressure-axis intercept (Ppa0), representing the mean backpressure to flow, to increase when Palv was greater than or equal to 5 Torr. Hypoxia increased delta Ppa/delta Q and Ppa0 at all levels of Palv. In contrast to its effects under control condition, lung inflation during hypoxia caused a progressive decrease in delta Ppa/delta Q, and did not alter Ppa0 until Palv was greater than or equal to 10 Torr. In the second group of experiments flow was maintained at 100 ml.kg-1 X min-1, and changes in lung blood volume (LBV) were recorded as Palv was varied between 20 and 0 Torr. In the control state, inflation increased LBV over the entire range of Palv. In the hypoxic state inflation decreased LBV until Palv reached 8 Torr; at Palv 8-20 Torr, inflation increased LBV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Peak oxygen uptake during arm cranking for men and women

To determine upper body peak O2 uptake (VO2) in a group of young females and to obtain information on possible sex differences, 40 subjects, 20 females and 20 males, mean age 26 +/- 4 (SD) and 31 +/- 6 yr, respectively, were studied during maximal arm-cranking exercise. Peak values for power output, VO2, minute ventilation (VE), and heart rate (HR) were determined for each subject. In addition, arm-shoulder volume (A-SV) was measured before exercise. Significant differences between males and females (P less than 0.05) were found for peak power output (134 +/- 18 vs. 86 +/- 13 W), peak VO2 expressed in liters per minute (2.55 +/- 0.45 vs. 1.81 +/- 0.36) and milliliters per kilogram per minute (34.2 +/- 5.3 vs. 29.2 +/- 4.9), peak VE (95.4 +/- 14.5 vs. 70.1 +/- 19.2 1 X min-1), and A-SV (3,126 +/- 550 vs. 2,234 +/- 349 ml), whereas peak HR was not significantly different between the two groups (174 +/- 14 vs. 174 +/- 36 beats X min-1). However, when peak VO2 was corrected for arm and shoulder size there was no significant difference between the groups (0.82 +/- 0.13 vs. 0.78 +/- 0.13 ml X ml A-SV-1 X min-1). These results suggest that the observed differences between men and women for peak VO2 elicited during arm cranking when expressed in traditional terms (1 X min-1 and ml X kg-1 X min-1) are a function of the size of the contracting muscle mass and are not due to sex-related differences in either O2 delivery or the O2 utilization capacity of the muscle itself.     

Atrial natriuretic factor attenuates the pulmonary pressor response to hypoxia

The influence of endogenous and exogenous atrial natriuretic factor (ANF) on pulmonary hemodynamics was investigated in anesthetized pigs during both normoxia and hypoxia. Continuous hypoxic ventilation with 11% O2 was associated with a uniform but transient increase of plasma immunoreactive (ir) ANF that peaked at 15 min. Plasma irANF was inversely related to pulmonary arterial pressure (Ppa; r = -0.66, P less than 0.01) and pulmonary vascular resistance (PVR; r = -0.56, P less than 0.05) at 30 min of hypoxia in 14 animals; no such relationship was found during normoxia. ANF infusion after 60 min of hypoxia in seven pigs reduced the 156 +/- 20% increase in PVR to 124 +/- 18% (P less than 0.01) at 0.01 microgram.kg-1.min-1 and to 101 +/- 15% (P less than 0.001) at 0.05 microgram.kg-1.min-1. Cardiac output (CO) and systemic arterial pressure (Psa) remained unchanged, whereas mean Ppa decreased from 25.5 +/- 1.5 to 20.5 +/- 15 mmHg (P less than 0.001) and plasma irANF increased two- to nine-fold. ANF infused at 0.1 microgram.kg-1.min-1 (resulting in a 50-fold plasma irANF increase) decreased Psa (-14%) and reduced CO (-10%); systemic vascular resistance (SVR) was not changed, nor was a further decrease in PVR induced. No change in PVR or SVR occurred in normoxic animals at any ANF infusion rate. These results suggest that ANF may act as an endogenous pulmonary vasodilator that could modulate the pulmonary pressor response to hypoxia.     

Peripheral chemoreceptor function after carbonic anhydrase inhibition during moderate-intensity exercise.

The effect of carbonic anhydrase inhibition with acetazolamide (Acz, 10 mg/kg) on the ventilatory response to an abrupt switch into hyperoxia (end-tidal PO2 = 450 Torr) and hypoxia (end-tidal PO2 = 50 Torr) was examined in five male subjects [30 +/- 3 (SE) yr]. Subjects exercised at a work rate chosen to elicit an O2 uptake equivalent to 80% of the ventilatory threshold. Ventilation (VE) was measured breath by breath. Arterial oxyhemoglobin saturation (%SaO2) was determined by ear oximetry. After the switch into hyperoxia, VE remained unchanged from the steady-state exercise prehyperoxic value (60.6 +/- 6.5 l/min) during Acz. During control studies (Con), VE decreased from the prehyperoxic value (52.4 +/- 5.5 l/min) by approximately 20% (VE nadir = 42.4 +/- 6.3 l/min) within 20 s after the switch into hyperoxia. VE increased during Acz and Con after the switch into hypoxia; the hypoxic ventilatory response was significantly lower after Acz compared with Con [Acz, change (Delta) in VE/DeltaSaO2 = 1.54 +/- 0.10 l. min-1. SaO2-1; Con, DeltaVE/DeltaSaO2 = 2.22 +/- 0.28 l. min-1. SaO2-1]. The peripheral chemoreceptor contribution to the ventilatory drive after acute Acz-induced carbonic anhydrase inhibition is not apparent in the steady state of moderate-intensity exercise. However, Acz administration did not completely attenuate the peripheral chemoreceptor response to hypoxia.     

Pulmonary venous pressure increases during alveolar hypoxia in isolated lungs of newborn pigs.

The purpose of this study was to determine whether pulmonary venous pressure increases during alveolar hypoxia in lungs of newborn pigs. We isolated and perfused with blood the lungs from seven newborn pigs, 6-7 days old. We maintained blood flow constant at 50 ml.min-1.kg-1 and continuously monitored pulmonary arterial and left atrial pressures. Using the micropuncture technique, we measured pressures in 10 to 60-microns-diam venules during inflation with normoxic (21% O2-69-74% N2-5-10% CO2) and hypoxic (90-95% N2-5-10% CO2) gas mixtures. PO2 was 142 +/- 21 Torr during normoxia and 20 +/- 4 Torr during hypoxia. During micropuncture we inflated the lungs to a constant airway pressure of 5 cmH2O and kept left atrial pressure greater than airway pressure (zone 3). During hypoxia, pulmonary arterial pressure increased by 69 +/- 24% and pressure in small venules increased by 40 +/- 23%. These results are similar to those obtained with newborn lambs and ferrets but differ from results with newborn rabbits. The site of hypoxic vasoconstriction in newborn lungs is species dependent.     

Increased oxygen consumption associated with breathing activity in fetal lambs

To examine the relationship between fetal O2 consumption and fetal breathing movements, we measured O2 consumption, umbilical blood flow, and cardiovascular and blood gas data before, during, and after fetal breathing movements in conscious chronically catheterized fetal lambs. During fetal breathing movements, O2 consumption increased by 30% from a control value of 7.7 +/- 0.7 (SE) ml X min-1 X kg-1. Umbilical blood flow was 210 +/- 21 ml X min-1 X kg-1 before fetal breathing movements; in 9 of 16 samples it increased by 52 +/- 12 ml X min-1 X kg-1, while in the other 7 it decreased by 23 +/- 9 ml X min-1 X kg-1. Umbilical arterial and venous O2 partial pressures and pH fell during fetal breathing movements, and the fall was greater when umbilical blood flow was decreased. Partial CO2 pressure rose in both vessels, and again the increase was greatest when umbilical blood flow fell during fetal breathing movements. Also associated with a fall in umbilical blood flow was the transition from low-amplitude irregular to large-amplitude regular fetal breathing movements. It is concluded that fetal breathing movements increase fetal O2 demands and are associated with a transient deterioration in fetal blood gas status, which is most severe during large-amplitude breathing movements.     

Development of CO2 sensitivity: effects of gestational age, postnatal age, and sleep state

To determine the independent effects of sleep state, gestational age, and postnatal age on eucapnic ventilation and steady-state CO2 sensitivity, nine premature (146 +/- 3 days) and eight full-term (168 +/- 2 days) monkeys, Macaca nemestrina, from accurately timed conceptions were studied serially over the first 3 wk of life. Minute volume (VE)/kg,tidal volume (VT)/kg, and respiratory frequency were quantitated during rapid-eye-movement sleep (REM) and nonrapid-eye-movement sleep (NREM)in room air and when animals were breathing varied concentrations of cO2 in 21% O2. Eucapnic VE/kg and CO2 sensitivity [(deltaVE/kg)/delta PaCO2] increased progressively with advancing postnatal age during NREM sleep in grouped term and premature animals. CO2 sensitivity was not significantly different between REM and NREM sleep except in full-term animals at the highest postconceptual age studied (189 +/- 2 days) when [(delta VE/kg)/delta PaCO2] was lower in REM sleep than in NREM sleep (209 +/- 54 vs. 301 +/- 71 ml.min-1.kg-1.Torr-1; P less than 0.05, paired-t test). Gestational age had no measurable effect on eucapnic ventilation or CO2 sensitivity. These results support the hypothesis that REM sleep-induced depression of CO2 sensitivity develops in the neonatal monkey with advancing postconceptual age.     

Effect of hyperoxia on substrate utilization during intense submaximal exercise

Six trained males [mean maximal O2 uptake (VO2max) = 66 ml X kg-1 X min-1] performed 30 min of cycling (mean = 76.8% VO2max) during normoxia (21.35 +/- 0.16% O2) and hyperoxia (61.34 +/- 1.0% O2). Values for VO2, CO2 output (VCO2), minute ventilation (VE), respiratory exchange ratio (RER), venous lactate, glycerol, free fatty acids, glucose, and alanine were obtained before, during, and after the exercise bout to investigate the possibility that a substrate shift is responsible for the previously observed enhanced performance and decreased RER during exercise with hyperoxia. VO2, free fatty acids, glucose, and alanine values were not significantly different in hyperoxia compared with normoxia. VCO2, RER, VE, and glycerol and lactate levels were all lower during hyperoxia. These results are interpreted to support the possibility of a substrate shift during hyperoxia.     

Metabolic habituation following repeated resting cold-water immersion is not apparent during low-intensity cold-water exercise.

This project examined the effects of repeated, resting cold-water immersion on metabolic heat production and core temperature defence during subsequent rest and exercising immersions. Seven males undertook 15 days of cold-water adaptation, immersed to the fourth intercostal space, with cold-water stress tests (CWST) on days 1, 8 and 15 (18.1 SD 0.1 degree C: 60 min seated, followed by 30 min cycling (1 W.kg-1)), and 90-min resting immersions (18.4 SD 0.4 degree C) on each of the intervening days. Adaptation elicited an habituated thermogenic response during the rest phase of CWST3 beyond 20 min, compared to CWST1 (P < 0.05), with oxygen consumption averaging 11.15 (+/- 0.25) ml.kg-1.min-1 and 8.61 (+/- 0.90) ml.kg-1.min-1 by 50 min, for CWST1 and CWST3, respectively. During exercise, this metabolic blunting was only apparent over the first 10-min period (60-70 min). No significant differences were observed during either the rest or exercise phases of the CWSTs for oesophageal temperature (Tes). While repeated cold-water exposures produced an habituated-thermogenic response, for an equivalent drop in Tes during rest, neither this response, nor an elevated thermogenesis, were apparent during subsequent cold-water exercise.     

Effect of high-frequency ventilation on gas exchange and pulmonary vascular resistance in lambs

We studied the effects of conventional mechanical ventilation (CMV) (15 ml/kg tidal volume delivered at 18-25 breaths/min) and high-frequency oscillatory ventilation (HFOV) (less than or equal to 2 ml/kg delivered at 10 Hz) on pulmonary hemodynamics and gas exchange during ambient air breathing and hypoxic gas breathing in 10 4-day-old lambs. After instrumentation and randomization to either HFOV or CMV the animals breathed first ambient air and then hypoxic gas (inspired O2 fraction = 0.13) for 20 min. The mode of ventilation was then changed, and the normoxic and hypoxic gas challenges were repeated. The multiple inert gas elimination technique was utilized to assess gas exchange. There was a significant increase with HFOV in mean pulmonary arterial pressure (Ppa) (20.1 +/- 4.2 vs. 22 +/- 3.8 Torr, CMV vs. HFOV, P less than 0.05) during ambient air breathing. During hypoxic gas breathing Ppa was also greater with HFOV than with CMV (29.5 +/- 5.7 vs. 34 +/- 3.1 Torr, CMV vs. HFOV, P less than 0.05). HFOV reduced pulmonary blood flow (Qp) during ambient air breathing (0.33 +/- 0.11 vs. 0.28 +/- 0.09 l . kg-1 . min-1, CMV vs. HFOV, P less than 0.05) and during hypoxic gas breathing (0.38 +/- 0.11 vs. 0.29 +/- 0.09 l . kg-1 . min-1, P less than 0.05). There was no significant difference in calculated venous admixture for sulfur hexafluoride or in the index of low ventilation-perfusion lung regions with HFOV compared with CMV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interactive effect of hypoxia and otolith organ engagement on cardiovascular regulation in humans.

We determined the interaction between the vestibulosympathetic reflex and the arterial chemoreflex in 12 healthy subjects. Subjects performed three trials in which continuous recordings of muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), heart rate (HR), and arterial oxygen saturation were obtained. First, in prone subjects the otolith organs were engaged by use of head-down rotation (HDR). Second, the arterial chemoreflex was activated by inspiration of hypoxic gas (10% O2 and 90% N2) for 7 min with HDR being performed during minute 6. Third, hypoxia was repeated (15 min) with HDR being performed during minute 14. HDR [means +/- SE; increase (Delta)7 +/- 1 bursts/min and Delta50 +/- 11% for burst frequency and total MSNA, respectively; P < 0.05] and hypoxia (Delta6 +/- 2 bursts/min and Delta62 +/- 29%; P < 0.05) increased MSNA. Additionally, MSNA increased when HDR was performed during hypoxia (Delta11 +/- 2 bursts/min and Delta127 +/- 57% change from normoxia; P < 0.05). These increases in MSNA were similar to the algebraic sum of the individual increase in MSNA elicited by HDR and hypoxia (Delta13 +/- 1 bursts/min and Delta115 +/- 36%). Increases in MAP (Delta3 +/- 1 mmHg) and HR (Delta19 +/- 1 beats/min) during combined HDR and hypoxia generally were smaller (P < 0.05) than the algebraic sum of the individual responses (Delta5 +/- 1 mmHg and Delta24 +/- 2 beats/min for MAP and HR, respectively; P < 0.05). These findings indicate an additive interaction between the vestibulosympathetic reflex and arterial chemoreflex for MSNA. Therefore, it appears that MSNA outputs between the vestibulosympathetic reflex and arterial chemoreflex are independent of one another in humans.     

Linear relationship between VO2max and VO2max decrement during exposure to acute hypoxia

The purpose of these experiments is to test the hypothesis that exercise-induced hypoxemia at sea level in highly trained athletes might be exacerbated during acute hypoxia and therefore result in correspondingly larger decrements in maximal O2 uptake (VO2max) compared with less trained individuals. Thirteen healthy male volunteers were divided into two groups according to their level of fitness: 1) trained endurance athletes (T) (n = 7), with a VO2max range of 56-75 ml.kg-1.min-1 and 2) untrained individuals (UT) (n = 6), with a VO2max range of 33-49 ml.kg-1.min-1. Subjects performed two incremental cycle ergometry tests to determine VO2max under hypoxic conditions [14% O2-86% N2, barometric pressure (PB) = 760 Torr] and normoxic conditions (21% O2-79% N2, PB = 760 Torr). Tests were single blind, randomly administered, and separated by at least 72 h. Mean percent oxyhemoglobin saturation (%SaO2) during maximal exercise under hypoxic conditions was significantly (P less than 0.05) lower in the T group (77%) compared with the UT group (86%). Furthermore, the T group exhibited larger decrements (P less than 0.05) in VO2max (normoxic-hypoxic) compared with the UT group. Finally, a significant linear correlation (r = 0.94) existed between normoxic VO2max (ml.kg-1.min-1) and delta VO2max (normoxic-hypoxic). These data suggest that highly T endurance athletes suffer more severe gas exchange impairments during acute exposure to hypoxia than UT individuals, and this may explain a portion of the observed variance in delta VO2max among individuals during acute altitude or hypoxia exposure.