Biomedical subjects

P M Young

Publications and source records attributed to P M Young.

At least 19 recordsLinked to original sources

PubMed1992

Operation Everest II: metabolic and hormonal responses to incremental exercise to exhaustion.

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

Adult↗

PubMed1991

Effect of beta-adrenergic blockade on plasma lactate concentration during exercise at high altitude.

When unacclimatized lowlanders exercise at high altitude, blood lactate concentration rises higher than at sea level, but lactate accumulation is attenuated after acclimatization. These responses could result from the effects of acute and chronic hypoxia on beta-adrenergic stimulation. In this investigation, the effects of beta-adrenergic blockade on blood lactate and other metabolites were studied in lowland residents during 30 min of steady-state exercise at sea level and on days 3, 8, and 20 of residence at 4300 m. Starting 3 days before ascent and through day 15 at high altitude, six men received propranolol (80 mg three times daily) and six received placebo. Plasma lactate accumulation was reduced in propranolol- but not placebo-treated subjects during exercise on day 3 at high altitude compared to sea-level exercise of the same percentage maximal oxygen uptake (VO2max). Plasma lactate accumulation exercise on day 20 at high altitude was reduced in both placebo- and propranolol-treated subjects compared to exercise of the same percentage VO2max performed at sea level. The blunted lactate accumulation during exercise on day 20 at high altitude was associated with reduced muscle glycogen utilization. Thus, increased plasma lactate accumulation in unacclimatized lowlanders exercising at high altitude appears to be due to increased beta-adrenergic stimulation. However, acclimatization-induced changes in muscle glycogen utilization and plasma lactate accumulation are not adaptations to chronically increased beta-adrenergic activity.

Adrenergic beta-Antagonists↗

PubMed1991

Estimating impacts on developing countries of the decrease in U.S. training opportunities for foreign medical graduates.

Between 1973 and 1983, the number of foreign nationals from developing nations who entered the United States for graduate medical education decreased by approximately 90%. Many of those who would have studied in the United States if this decrease had not occurred would have returned home to serve their countries. To estimate the impact of this loss, a survey was conducted in six major cities in Latin America between 1983 and 1989. Selected local medical students interviewed 554 physicians who had returned home after U.S. training and 60 of their classmates who had not trained there. The findings indicate that the returned physicians had given approximately twice as much time to teaching, research, and medical administration as did those who had not left home. The authors maintain that this and related findings show how the curtailment of opportunities for training foreign nationals in the United States is detrimental to both the aspirations of developing nations and the influence of the United States in world affairs.

Adult↗

PubMed1991

Alternative mobile phases for enhanced chromatographic selectivity and increased sensitivity in peptide separations.

The standard method for separating peptide mixtures is reversed-phase high-performance liquid chromatography with gradients of increasing concentrations of acetonitrile in the presence of trifluoroacetic acid. With modern instruments and columns, complex peptide mixtures can be separated, and low picomole amounts can be collected in tens of microliters. Difficult separations are addressed by modifying the gradient slope or organic eluant composition. Further improvements in resolution are often needed, requiring fundamental changes in mobile phase composition or selection of complementary chromatographic separation mechanisms. For the present study, tryptic digests of cytochrome c from various species were separated in the presence of dilute hydrochloric acid by reversed phase on a Waters Delta-PakTM C18 high-performance insert column and by strong cation exchange on a Waters Protein-PakTM SP 8HR. Different and enhanced reversed-phase selectivity was obtained by replacing trifluoroacetic acid with dilute hydrochloric acid at the same pH. The increased optical clarity of hydrochloric acid-based mobile phases in the low ultraviolet wavelengths yielded increased sensitivity. Very different selectivity was observed with the cation-exchange chromatography. These data expand the options for peptide mapping by providing additional selectivity combined with increased mass sensitivity and spectral information in the low ultraviolet.

Amino Acid Sequence↗

PubMed1990

Optimization of high-performance liquid chromatographic peptide separations with alternative mobile and stationary phases.

Peptides are routinely separated with reversed-phase high-performance liquid chromatography using increasing concentrations of acetonitrile in the presence of trifluoroacetic acid. While these separations may be improved by adjustments of gradient slope or substitutions of different solid-phase chemistries, many mixtures would benefit from systematic optimization of mobile phase components. Tryptic digests of cytochrome c from various species were separated on Waters Delta-Pak C18. The effects of varying pH as well as the concentration and type of ion-pair reagent were examined. In addition, low pH, ion-suppression/ion-pairing chromatography was inverted using a polymeric reversed-phase column at high pH with alkyl amine ion pairing. Finally, a tryptic digest of cytochrome c was resolved by ion-exchange chromatography with a strong cation-exchange high-performance liquid chromatography column. These data suggest a framework for dramatically changing the selectivity of peptide separations, leading to more satisfactory peptide mapping.

Amino Acid Sequence↗

PubMed1990

Lack of diurnal variation in the onset of non-Q wave infarction.

Data concerning the time of onset of myocardial infarction were obtained for 540 of the 544 patients with creatinine kinase (CK)-MB-confirmed non-Q wave myocardial infarction enrolled in the multicenter Diltiazem Reinfarction Study. Data were also collected for 627 patients who were screened but excluded. Among the 1,167 patients, no diurnal pattern of onset could be found at either 2- or 6-hour intervals. Among the 540 patients enrolled in the trial, no pattern could be found at these intervals either, although at 8-hour intervals, 27% of infarctions occurred between midnight and 8:00 AM, compared with 37% between 8:00 AM and 4:00 PM and 36% between 4:00 PM and 12:00 AM (p = 0.02). In contrast to the patterns previously noted for Q wave myocardial infarction, there was no preponderance of non-Q wave infarction in the late morning. Circadian rhythm was also absent among patients not treated with beta-blockers as well as among patients presenting with ST segment elevation on their enrollment electrocardiograms. Diabetics, women, and patients with first infarction were more likely to present during the afternoon hours. We conclude that the late morning preponderance seen for Q-wave myocardial infarction is not discernable in patients with non-Q wave myocardial infarction. This observation suggests that the pathogenesis of these two infarct subtypes is different or that the process of thrombotic coronary occlusion in Q wave infarction (sustained) differs from that in non-Q wave infarction (nonsustained).

Adrenergic beta-Antagonists↗

PubMed1989

Operation Everest II: plasma lipid and hormonal responses during a simulated ascent of Mt. Everest.

To examine the effect of hypobaric hypoxia on plasma lipid profiles, fasting blood samples were collected from six men (21-31 yr) at 760 Torr and periodically during a 40-day exposure to decreasing barometric pressure culminating in a final ambient pressure of 282 Torr. Preascent plasma total cholesterol concentration ([TC]) was decreased by 25% after the 40-day exposure (P less than 0.01). High-density lipoprotein concentrations ([HDL-C]) decreased 32% (P less than 0.001) with no alteration in the TC-to-HDL-C weight ratio. Plasma triglyceride concentration increased twofold during this period (P less than 0.01). There were no significant differences in fasting plasma free fatty acid concentrations or free fatty acid-to-albumin molar ratio throughout the study. Fasting plasma insulin levels were increased approximately twofold with no significant changes in glucagon concentration or the insulin-to-glucagon molar ratio. Plasma norepinephrine concentrations were increased threefold on reaching 282 Torr (P less than 0.01), with no significant changes in plasma epinephrine concentrations. Mean energy intake (kcal/day) decreased 42%, whereas mean body weights decreased by 8.9 +/- 0.8% (P less than 0.01) with exposure. Increased concentrations of insulin may lead to increased hepatic production of triglyceride-rich lipoproteins, thus eliciting metabolic changes independent of weight loss and dietary intake.

Adult↗

PubMed1989

Operation Everest II: maximal oxygen uptake at extreme altitude.

Chronic exposure to high altitude reduces maximal O2 uptake (VO2max). At extreme altitudes approaching the summit of Mt. Everest [inspiratory PO2(PIO2) = 43 Torr], mean VO2max have been determined to be 15.3 ml.kg-1.min-1 in two subjects who breathed 14% O2 at 6,300 m on Mt. Everest (West et al., J. Appl. Physiol. 54: 1188-1194, 1983). To provide a more complete description of performance near the limits of human tolerance to chronic hypoxia, we measured VO2max in volunteers in an altitude chamber before, during, and after a 40-day decompression to a barometric pressure (PB) of 240 Torr (PIO2 = 43 Torr). In five of eight subjects studied at sea level and PB of 464, 347, 289, and 240 Torr, VO2max was reduced from 4.13 to 1.17 l/min (49.1-15.3 ml.kg-1.min-1) in agreement with the prior study. Although the range decreased, the rank order among the subjects was preserved. Arterial O2 saturation at maximum effort decreased (46% by ear oximetry), but minute ventilation, respiratory frequency, and tidal volume did not. The highest minute ventilation (201 l/min BTPS) was observed at PB of 464 Torr. Arterial PCO2 in three subjects at PB of 240 Torr, at rest, and with maximum effort, averaged 10.3 and 9.6 Torr, respectively. Sustained hyperventilation was crucial to exercise performance during chronic, severe hypoxemia. VO2max was lower after altitude exposure compared with initial sea level values, indicating that exposure had not improved sea level exercise capacity.

Adult↗

PubMed1989

Operation Everest II: adaptations in human skeletal muscle.

Adaptations in skeletal muscle in response to progressive hypobaria were investigated in eight male subjects [maximal O2 uptake = 51.2 +/- 3.0 (SE) ml.kg-1.min-1] over 40 days of progressive decompression to the stimulated altitude of the summit of Mt. Everest. Samples of the vastus lateralis muscle extracted before decompression (SL-1), at 380 and 282 Torr, and on return to sea level (SL-2) indicated that maximal activities of enzymes representative of the citric acid cycle, beta-oxidation, glycogenolysis, glycolysis, glucose phosphorylation, and high-energy phosphate transfer were unchanged (P greater than 0.05) at 380 and 282 Torr over initial SL-1 values. After exposure to 282 Torr, however, representing an additional period of approximately 7 days, reductions (P less than 0.05) were noted in succinic dehydrogenase (21%), citrate synthetase (37%), and hexokinase (53%) between SL-2 and 380 Torr. No changes were found in the other enzymes. Capillarization as measured by the number of capillaries per cross-sectional area (CC/FA) was increased (P less than 0.05) in both type I (0.94 +/- 0.8 vs. 1.16 +/- 0.05) and type II (0.84 +/- 0.07 vs. 1.05 +/- 0.08) fibers between SL-1 and SL-2. This increase was mediated by a reduction in fiber area. No changes were found in fiber-type distribution (type I vs. type II). These findings do not support the hypothesis, at least in humans, that, at the level of the muscle cell, extreme hypobaric hypoxia elicits adaptations directed toward maximizing oxidative function.

Acclimatization↗

PubMed1989

Operation Everest II: comparison of four instruments for measuring blood O2 saturation.

The bias and precision of four different methods for determining O2 saturation (SO2) were evaluated during a study of hypobaric hypoxia conducted with seven male subjects exposed progressively over a 40-day period to simulated altitudes from sea level (760 Torr) to 8,840 m (240 Torr). SO2 of arterial and mixed venous blood samples were measured with the Instrumentation Laboratory 282 CO-oximeter (CO-OX), the Radiometer ABL-300 (ABL), and the Lex-O2-Con-K (LEX). Noninvasive measurements of arterial SO2 were made with a Hewlett-Packard 47201A ear oximeter (EAR-OX). The CO-OX method was used as a secondary standard for comparison with the other methods because it has been validated against the classical Van Slyke method over a wide physiological range (Maas et al., Clin. Chim. Acta 29: 303-309, 1970). The LEX results most closely approximated but consistently underestimated those of the CO-OX: LEX = 0.93 CO-OX -0.86, standard error of the estimate (SEE) = 5.17, r = 0.98, n = 670. The ABL method appeared to combine two linear trends: for SO2 greater than 75%, ABL = 0.84 CO-OX +14.4, SEE = 1.77, r = 0.97, n = 369; less than 75%, ABL = 0.98 CO-OX +5.9, SEE = 4.44, r = 0.97, n = 486. The EAR-OX results were found to approximate those of the CO-OX at SO2 values only greater than 65%: EAR-OX = 1.07 CO-OX -6.12, SEE = 7.71, r = 0.98, n = 326.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Risk stratification of patients with non-Q wave myocardial infarction. The critical role of ST segment depression. The Diltiazem Reinfarction Study Research Group.

One-year follow-up data on 515 patients who survived hospitalization with MB-creatine kinase-confirmed, acute non-Q wave myocardial infarction were analyzed for factors related to mortality (n = 57) and late reinfarction (n = 64). Twelve of 24 analyzed variables were significantly associated with mortality. Those factors, which were independently predictive of mortality by Cox regression analysis, were persistent ST depression (p = 0.0009), a history of congestive heart failure (CHF) (p = 0.0069), older age (p = 0.0128), and ST elevation at hospital discharge (p = 0.0173). In-hospital reinfarction achieved borderline significance (p = 0.0512). Mortality during the follow-up period was 5.5% in patients with no ST depression, 10.1% in those with ST depression at baseline or discharge, and 22.2% in patients with ST depression at baseline and discharge (i.e., "persistent" ST depression). The age-adjusted risk of mortality for patients with persistent ST depression, discharge-ST elevation, and CHF was 13.99 times as high as was the risk for patients with no ST depression, no discharge-ST elevation, and no CHF. Of the 483 patients with complete electrocardiographic data at both baseline and discharge, 203 (42%) could be stratified into a high risk population with a risk ratio for 1-year mortality more than sevenfold that of patients with no risk factors. Although persistent ST depression was significantly associated with several measures of structural left ventricular damage, the independent significance of ST depression persisted even after adjusting for these factors. The independent predictors of late reinfarction (persistent ST depression, p = 0.0058; Killip class II or III, p = 0.0106; and left ventricular hypertrophy, p = 0.0470) permitted a similar risk stratification. We conclude that 1) easily identified clinical and electrocardiographic factors permit stratification of patients with non-Q wave infarction into high-risk subsets who may benefit from aggressive therapy; 2) ST depression is a highly significant and independent predictor of poor prognosis; and 3) the powerful predictive value of persistent ST depression suggests that non-Q wave myocardial infarction patients with this depression should be viewed as potentially high-risk patients who may be candidates for additional noninvasive testing or early coronary angiography.

Diltiazem↗

PubMed1989

Effects of propranolol on acute mountain sickness (AMS) and well-being at 4,300 meters of altitude.

A number of physiological responses and adjustments occur at high altitude to compensate for hypoxia. We hypothesized that interference with one component of the normal compensatory process, the sympathetic nervous system, would hinder altitude acclimatization and thereby exacerbate acute mountain sickness (AMS) and compromise well-being. Twelve young males (21.2 +/- 0.4 years) received either 80 mg propranolol (PRO; n = 6) or placebo (PLA; n = 6), t.i.d. at sea level (SL) and during the first 15 d of a 19-d residence at 4,300 m (HA). Individuals were randomly assigned to each group. The Environmental Symptoms Questionnaire (ESQ) was administered at SL and twice daily (AM and PM) during the entire altitude exposure in order to assess AMS symptoms and subjective feelings of well-being. Supine heart rate (HR) was determined at rest twice at SL and four times at HA. HR in the PLA group increased 40% over SL values (57 +/- 3 to 80 +/- 4 beats/min) by day 7 at HA (p less than 0.01). HR in the PRO group did not increase above SL values during medication at HA. By 4 d after the medication administration was terminated, HR in the PRO group had increased and did not differ from the PLA group. Throughout the entire altitude exposure, ESQ scores for the PRO group were lower than or similar to the PLA group. Furthermore, cessation of PRO treatment did not result in a change in well-being. These findings suggested that interference with the normal acclimatization process by beta-adrenergic blockade did not exacerbate AMS or reduce feelings of well-being.

Acute Disease↗

PubMed1989

Propranolol and the compensatory circulatory responses to orthostasis at high altitude.

Tachycardia has been shown to be an important response involved in the maintenance of cardiac output during orthostasis at high altitude. This study was undertaken to determine if tachycardia, mediated by beta-adrenergic sympathetic stimulation, actually represents an essential response. Twelve young, healthy male subjects were administered either 80 mg propranolol (n = 6) or placebo (n = 6), t.i.d. at sea level and for 3 days (d) prior to and during the first 15 d of a 19-d altitude sojourn (On Treatment). Individuals were randomly assigned to each group. Upright tilt tests were performed at sea level and at high altitude during days 2, 7, and 15 On Treatment. Subjects were also tilt-tested at sea level and on day 19 of the altitude exposure without placebo or propranolol administration (Off Treatment). Heart rate, stroke volume, calf blood flow, and blood pressure were obtained during supine rest and after 12 min of 60 degrees tilt. We found no differences between groups in any of the circulatory measurements at sea level and altitude while Off Treatment. During the On Treatment phases at sea level and altitude, propranolol caused reductions in heart rate and blood pressure values in each position (p less than 0.05). Supine and upright cardiac output, however, were found not altered due to compensatory increases in stroke volume (p less than 0.05). We concluded that tachycardia, both at rest and during upright tilt at high altitude is important, but not essential to maintain cardiac output.

Adult↗

PubMed1988

Operation Everest II: oxygen transport during exercise at extreme simulated altitude.

A decrease in maximal O2 uptake has been demonstrated with increasing altitude. However, direct measurements of individual links in the O2 transport chain at extreme altitude have not been obtained previously. In this study we examined eight healthy males, aged 21-31 yr, at rest and during steady-state exercise at sea level and the following inspired O2 pressures (PIO2): 80, 63, 49, and 43 Torr, during a 40-day simulated ascent of Mt. Everest. The subjects exercised on a cycle ergometer, and heart rate was recorded by an electrocardiograph; ventilation, O2 uptake, and CO2 output were measured by open circuit. Arterial and mixed venous blood samples were collected from indwelling radial or brachial and pulmonary arterial catheters for analysis of blood gases, O2 saturation and content, and lactate. As PIO2 decreased, maximal O2 uptake decreased from 3.98 +/- 0.20 l/min at sea level to 1.17 +/- 0.08 l/min at PIO2 43 Torr. This was associated with profound hypoxemia and hypocapnia; at 60 W of exercise at PIO2 43 Torr, arterial PO2 = 28 +/- 1 Torr and PCO2 = 11 +/- 1 Torr, with a marked reduction in mixed venous PO2 [14.8 +/- 1 (SE) Torr]. Considering the major factors responsible for transfer of O2 from the atmosphere to the tissues, the most important adaptations occurred in ventilation where a fourfold increase in alveolar ventilation was observed. Diffusion from alveolus to end-capillary blood was unchanged with altitude. The mass circulatory transport of O2 to the tissue capillaries was also unaffected by altitude except at PIO2 43 Torr where cardiac output was increased for a given O2 uptake. Diffusion from the capillary to the tissue mitochondria, reflected by mixed venous PO2, was also increased with altitude. With increasing altitude, blood lactate was progressively reduced at maximal exercise, whereas at any absolute and relative submaximal work load, blood lactate was higher. These findings suggest that although glycogenolysis may be accentuated at low work loads, it may not be maximally activated at exhaustion.

2,3-Diphosphoglycerate↗

PubMed1987

Prognostic significance and beneficial effect of diltiazem on the incidence of early recurrent ischemia after non-Q-wave myocardial infarction: results from the Multicenter Diltiazem Reinfarction Study.

Of 576 patients with non-Q-wave acute myocardial infarction enrolled in the Diltiazem Reinfarction Study, 246 (43%) had 1 or more episodes of angina at rest or with minimal effort during 10.5 days of treatment with either diltiazem (90 mg every 6 hours) or placebo. Reinfarction (12.2% vs 3.6%, p less than 0.0001) or death (6.1% vs 1.5%, p = 0.003) was more likely to occur within 2 weeks of randomization in patients with postinfarction angina than in those without angina. Based on serial electrocardiographic data, 115 of the 246 patients with angina had transient ST-T changes and 131 did not. Comparison of the 14-day event rates in these 2 groups showed that the 115 patients with electrocardiographic evidence of ischemia had a higher frequency of reinfarction (20% vs 5.3%, p less than 0.001), more extensive damage as assessed by peak MB-creatine kinase levels (91 +/- 76 vs 37 +/- 19 IU/liter, p = 0.059 [Wilcoxon rank sum]) and a higher mortality rate (11.3% vs 1.5%, p = 0.001). Angina associated with transient ST-T changes occurred in 70 of the 289 patients in the placebo group but in only 45 of the 287 patients in the diltiazem group--a 28% reduction in cumulative life-table incidence (p = 0.0103 [2-tail, log rank]; 95% confidence interval, 9.3 to 53.8%). It is concluded that patients with early postinfarction angina are at increased risk of reinfarction and death, and angina associated with transient electrocardiographic changes identified a very high risk subset. This subset appeared to have a larger area of viable but jeopardized myocardium and benefited from prophylactic therapy with diltiazem.

Actuarial Analysis↗

PubMed1987

Oxygen transport during exercise at extreme altitude: Operation Everest II.

Eight male volunteers had rest and exercise measurement to determine the mechanisms of oxygen transport during a 40-day chamber decompression simulating high-altitude exposure equivalent to the summit of Mt Everest. Five subjects completing the study decreased their maximum oxygen uptake by 72%. During maximal or near-maximal exercise, arterial PCO2 fell as low as 8 mm Hg, defending the alveolar PO2 and confirming marked hyperventilation. Alveolar-arterial diffusion did not improve and V/Q worsened. Cardiac function was unimpaired. Circulatory oxygen transport resembled that at sea level. The decrease in mixed venous PO2 was not enough to preserve fractional oxygen utilization "on the summit." The PO2 gradients from atmosphere to alveolus, alveolus to arterial blood, arterial to venous blood, and from venous (capillary) blood to mitochondria all decreased. However, hyperventilation appeared to be the primary adaptation that defended the maximum oxygen uptake.

Adult↗

PubMed1987

Operation Everest II: elevated high-altitude pulmonary resistance unresponsive to oxygen.

High altitude increases pulmonary arterial pressure (PAP), but no measurements have been made in humans above 4,500 m. Eight male athletic volunteers were decompressed in a hypobaric chamber for 40 days to a barometric pressure (PB) of 240 Torr, equivalent to the summit of Mt. Everest. Serial hemodynamic measurements were made at PB 760 (sea level), 347 (6,100 m), and 282/240 Torr (7,620/8,840 m). Resting PAP and pulmonary vascular resistance (PVR) increased from sea level to maximal values at PB 282 Torr from 15 +/- 0.9 to 34 +/- 3.0 mmHg and from 1.2 +/- 0.1 to 4.3 +/- 0.3 mmHg.l-1 X min, respectively. During near maximal exercise PAP increased from 33 +/- 1 mmHg at sea level to 54 +/- 2 mmHg at PB 282 Torr. Right atrial and wedge pressures were not increased with altitude. Acute 100% O2 breathing lowered cardiac output and PAP but not PVR. Systemic arterial pressure and resistance did not rise with altitude but did increase with O2 breathing, indicating systemic control differed from the lung circulation. We concluded that severe chronic hypoxia caused elevated pulmonary resistance not accompanied by right heart failure nor immediately reversed by O2 breathing.

Adult↗

PubMed1987

Operation Everest II: preservation of cardiac function at extreme altitude.

Hypoxia at high altitude could depress cardiac function and decrease exercise capacity. If so, impaired cardiac function should occur with the extreme, chronic hypoxemia of the 40-day simulated climb of Mt. Everest (8,840 m, barometric pressure of 240 Torr, inspiratory O2 pressure of 43 Torr). In the five of eight subjects having resting and exercise measurements at the barometric pressures of 760 Torr (sea level), 347 Torr (6,100 m), 282 Torr (7,620 m), and 240 Torr, heart rate for a given O2 uptake was higher with more severe hypoxia. Slight (6 beats/min) slowing of the heart rate occurred only during exercise at the lowest barometric pressure when arterial blood O2 saturations were less than 50%. O2 breathing reversed hypoxemia but never increased heart rate, suggesting that hypoxic depression of rate, if present, was slight. For a given O2 uptake, cardiac output was maintained. The decrease in stroke volume appeared to reflect decreased ventricular filling (i.e., decreased right atrial and wedge pressures). O2 breathing did not increase stroke volume for a given filling pressure. We concluded that extreme, chronic hypoxemia caused little or no impairment of cardiac rate and pump functions.

Adult↗