Exercise In Acute Hypoxia Research Articles

Is pulmonary gas exchange during exercise in hypoxia impaired with the increase of cardiac output?

During exercise in humans, the alveolar-arterial O(2) tension difference ((A-a)DO(2)) increases with exercise intensity and is an important factor determining the absolute level of oxygen binding to hemoglobin and therefore the level of systemic oxygen transport. During exercise in hypoxia, the (A-a)DO(2) is accentuated. Using the multiple inert gas elimination technique it has been shown that during exercise in acute hypoxia the contribution of ventilation-perfusion inequality to (A-a)DO(2) is rather small and in the absence of pulmonary edema intrapulmonary shunts can be ruled out. This implies that the main mechanism limiting pulmonary gas exchange is diffusion limitation. It is presumed that an elevation of cardiac output during exercise in acute hypoxia should increase the (A-a)DO(2). However, no studies have examined how variations in cardiac output independently affect pulmonary diffusion with increases in exercise intensity. We have consistently observed that during steady-state, submaximal (100-120 W) exercise on the cycle ergometer in hypoxia the lung can accommodate an increase in cardiac output of approximately 2 L x min(-1) without any significant effect on pulmonary gas exchange. This result contrasts with the predicted effect of cardiac output on (A-a)DO(2) using the model of Piiper and Scheid, and thus indicates that an elevation of cardiac output is not necessarily accompanied by a reduction of mean transit time and (or) diffusion limitation during submaximal exercise in acute hypoxia. It remains to be determined what is the influence of changes in cardiac output per se on pulmonary gas exchange during high-intensity exercise.

Inspiratory muscle work in acute hypoxia influences locomotor muscle fatigue and exercise performance of healthy humans

Our aim was to isolate the independent effects of 1) inspiratory muscle work (W(b)) and 2) arterial hypoxemia during heavy-intensity exercise in acute hypoxia on locomotor muscle fatigue. Eight cyclists exercised to exhaustion in hypoxia [inspired O(2) fraction (Fi(O(2))) = 0.15, arterial hemoglobin saturation (Sa(O(2))) = 81 +/- 1%; 8.6 +/- 0.5 min, 273 +/- 6 W; Hypoxia-control (Ctrl)] and at the same work rate and duration in normoxia (Sa(O(2)) = 95 +/- 1%; Normoxia-Ctrl). These trials were repeated, but with a 35-80% reduction in W(b) achieved via proportional assist ventilation (PAV). Quadriceps twitch force was assessed via magnetic femoral nerve stimulation before and 2 min after exercise. The isolated effects of W(b) in hypoxia on quadriceps fatigue, independent of reductions in Sa(O(2)), were revealed by comparing Hypoxia-Ctrl and Hypoxia-PAV at equal levels of Sa(O(2)) (P = 0.10). Immediately after hypoxic exercise potentiated twitch force of the quadriceps (Q(tw,pot)) decreased by 30 +/- 3% below preexercise baseline, and this reduction was attenuated by about one-third after PAV exercise (21 +/- 4%; P = 0.0007). This effect of W(b) on quadriceps fatigue occurred at exercise work rates during which, in normoxia, reducing W(b) had no significant effect on fatigue. The isolated effects of reduced Sa(O(2)) on quadriceps fatigue, independent of changes in W(b), were revealed by comparing Hypoxia-PAV and Normoxia-PAV at equal levels of W(b). Q(tw,pot) decreased by 15 +/- 2% below preexercise baseline after Normoxia-PAV, and this reduction was exacerbated by about one-third after Hypoxia-PAV (-22 +/- 3%; P = 0.034). We conclude that both arterial hypoxemia and W(b) contribute significantly to the rate of development of locomotor muscle fatigue during exercise in acute hypoxia; this occurs at work rates during which, in normoxia, W(b) has no effect on peripheral fatigue.

Effect of Arterial Oxygenation on Fatigability of Isolated Quadriceps Muscle

PURPOSE: The aim of the present study was to clarify the effect of various levels of inspired oxygen fractions (FIO2) on quadriceps muscle fatigability during isolated muscle exercise. METHODS: Six healthy males were participated in this study. Quadriceps twitch force (Qtw) was determined using supra-maximal magnetic femoral nerve stimulation. In Experiment I, maximal voluntary contraction (MVC) and Qtw of resting quadriceps muscle were assessed in normoxia (FIO2 = 0.21), acute-hypoxia (FIO2 = 0.11), and acute-hyperoxia (FIO2 = 1.0). In Experiment II, the subjects performed three sets of nine, intermittent, unilateral, isometric, submaximal quadriceps muscle contractions (62+/−3.7% MVC followed by one MVC in each set) while breathing hypoxic, normoxic or hyperoxic gas. Myoelectrical activity of the vastus lateralis was measured during exercise, and Qtw was assessed before and after exercise. RESULTS: There were no significant differences in MVC and Qtw of the resting quadriceps muscle among the three FIO2s (Experiment I). These results indicated that changes in FIO2 had no effect on maximal quadriceps contractility pre-exercise conditions, and thus quadriceps muscle contractions performed at the same absolute intensity were conducted at the same relative exercise intensity (Experiment II below). The increase in integrated electromyogram during intermittent submaximal contractions in hypoxia (15.4+/−1.3%) was larger (P<0.05) than in normoxia (7.2+/−1.7%) or hyperoxia (6.7+/−1.1%). The percent reduction of twitch force (potentiated Qtw) in hypoxia (−27.0+/−2.0%) was significantly (P<0.05) greater than those in normoxia (−21.4+/−3.0%) and hyperoxia (−19.9+/−2.7%); as were the changes in intra-twitch indices of contractile properties. CONCLUSIONS: These findings suggest that quadriceps muscle fatigability is exaggerated during isolated muscle exercise in acute-hypoxia, and that a significant portion of hypoxic effect on exercise induced peripheral muscle fatigue is independent of the relative exercise intensity.

Importance of hemoglobin concentration to exercise: Acute manipulations

An acute reduction of blood hemoglobin concentration ([Hb]), even when the circulating blood volume is maintained, results in lower (.)V(O(2)(max) and endurance performance, due to the reduction of the oxygen carrying capacity of blood. Conversely, an increase of [Hb] is associated with enhanced (.)V(O(2)(max) and endurance capacity, that is also proportional to the increase in the oxygen carrying capacity of blood. The effects on endurance capacity appear more pronounced and prolonged than on (.)V(O(2)(max). During submaximal exercise, there is a tight coupling between O(2) demand and O(2) delivery, such that if [Hb] is acutely decreased muscle blood flow is increased proportionally and vice versa. During maximal exercise with either a small or a large muscle mass, neither peak cardiac output nor peak leg blood flow are affected by reduced [Hb]. An acute increase of [Hb] has no effect on maximal exercise capacity or (.)V(O(2)(max) during exercise in acute hypoxia. Likewise, reducing [Hb] in altitude-acclimatized humans to pre-acclimatization values has no effect on (.)V(O(2)(max) during exercise in hypoxia.

Sildenafil improves cardiac output and exercise performance during acute hypoxia, but not normoxia

Sildenafil causes pulmonary vasodilation, thus potentially reducing impairments of hypoxia-induced pulmonary hypertension on exercise performance at altitude. The purpose of this study was to determine the effects of sildenafil during normoxic and hypoxic exercise. We hypothesized that 1) sildenafil would have no significant effects on normoxic exercise, and 2) sildenafil would improve cardiac output, arterial oxygen saturation (SaO2), and performance during hypoxic exercise. Ten trained men performed one practice and three experimental trials at sea level (SL) and simulated high altitude (HA) of 3,874 m. Each cycling test consisted of a set-work-rate portion (55% work capacity: 1 h SL, 30 min HA) followed immediately by a time trial (10 km SL, 6 km HA). Double-blinded capsules (placebo, 50, or 100 mg) were taken 1 h before exercise in a randomly counterbalanced order. For HA, subjects also began breathing hypoxic gas (12.8% oxygen) 1 h before exercise. At SL, sildenafil had no effects on any cardiovascular or performance measures. At HA, sildenafil increased stroke volume (measured by impedance cardiography), cardiac output, and SaO2 during set-work-rate exercise. Sildenafil lowered 6-km time-trial time by 15% (P<0.05). SaO2 was also higher during the time trial (P<0.05) in response to sildenafil, despite higher work rates. Post hoc analyses revealed two subject groups, sildenafil responders and nonresponders, who improved time-trial performance by 39% (P<0.05) and 1.0%, respectively. No dose-response effects were observed. During cycling exercise in acute hypoxia, sildenafil can greatly improve cardiovascular function, SaO2, and performance for certain individuals.

Substrate utilization in sea level residents during exercise in acute hypoxia and after 4 weeks of acclimatization to 4100 m.

To investigate the effect of acclimatization to hypoxia on substrate utilization, eight sea level residents were studied during exercise at the same relative (rel) and absolute (abs) work rate as at sea level (SL), under acute (AH), and after 4 weeks exposure to 4100 m altitude (CH). Carbohydrate (CHO) and fat oxidation during exercise at SL were 2.0 +/- 0.2 and 0.3 +/- 0.0 g min(-1), respectively. At AHabs and CHabs CHO oxidation increased (P < 0.05) to 2.5 +/- 0.2 and 2.3 +/- 0.1 for CHO, and fat oxidation decreased (P < 0.05) to 0.2 +/- 0.01 and 0.2 +/- 0.01 g min(-1), respectively. Exercise in AHrel and CHrel did not cause a change in the relative CHO and fat oxidation compared with SL, the absolute rate of CHO oxidized being 1.7 +/- 0.1 and 1.7 +/- 0.02 g min(-1), respectively, and fat oxidation was 0.2 +/- 0.02 g min(-1) in ACrel and 0.3 +/- 0.02 g min(-1) in CHrel. In conclusion, substrate utilization is unaffected by AH and CH, when the work rate is matched to the same relative intensity as at SL.

Peak heart rate decreases with increasing severity of acute hypoxia.

The purpose of the present study was to investigate the degree to which peak heart rate is reduced during exhaustive exercise in acute hypoxia. Five sea-level lowlanders performed maximal exercise at normobaric normoxia and at three different levels of hypobaric hypoxia (barometric pressures of 518, 459, and 404 mmHg) in a hypobaric chamber and while breathing 9% O(2) in N(2). These conditions were equivalent to altitudes of 3300, 4300, 5300, and 6300 m above sea level, respectively. At 4300 m, maximal exercise was also repeated after 4 and 8 h. Peak heart rate (HR) decreased from 191 (182-202) (mean and range) at sea level to 189 (179-200), 182 (172-189), 175 (166-183), and 165 (162-169) in the acute hypoxic conditions. Peak HR did not decrease further after 4 and 8 h at 4300 m compared to the acute exposure at this altitude. Between barometric pressures of 518 and 355 mmHg (approximately 3300 and 6300 m), peak HR decreased linearly: peak HR(hypobaria) = peak HR(sea level) - 0.135 x [hypobaria(3100) - hypobaria (mmHg)]; or peak HR(altitude) = peak HR(sea level) - 0.15 x (altitude - 3100 m). This corresponds to approximately 1-beat x min(-1) reduction in peak HR for every 7-mmHg decrease in barometric pressure below 530 mmHg (approximately 130 m of altitude gained above 3100 m). At termination of exercise, maximal plasma lactate and norepinephrine concentrations were similar to those observed during maximal exercise in normobaric normoxia. This study clearly demonstrates a progressive decrease in peak HR with increasing altitude, despite evidence of similar exercise effort and unchanged sympathetic excitation.

Cardiorespiratory responses to exercise in acute hypoxia, hyperoxia and normoxia.

There is a prevailing hypothesis that an acute change in the fraction of oxygen in inspired air (F(I)O2) has no effect on maximal cardiac output (Qcmax), although maximal oxygen uptake (VO2max) and exercise performance do vary along with F(I)O2. We tested this hypothesis in six endurance athletes during progressive cycle ergometer exercise in conditions of hypoxia (FI(O)2 = 0.150), normoxia (F(I)O2 = 0.209) and hyperoxia (F(I)O2=0.320). As expected, VO2max decreased in hypoxia [mean (SD) 3.58 (0.45)l.min(-1), P<0.05] and increased in hyperoxia [5.17 (0.34) l.min(-1), P<0.05] in comparison with normoxia [4.55 (0.32)l.min(-1)]. Similarly, maximal power (Wmax) decreased in hypoxia [334 (41) W, P< 0.05] and tended to increase in hyperoxia [404 (58) W] in comparison with normoxia [383 (46) W]. Contrary to the hypothesis, Qcmax was 25.99 (3.37) l.min(-1) in hypoxia (P<0.05 compared to normoxia and hyperoxia), 28.51 (2.36) l.min(-1) in normoxia and 30.13 (2.06)l.min(-1) in hyperoxia. Our results can be interpreted to indicate that (1) the reduction in VO2max in acute hypoxia is explained both by the narrowing of the arterio-venous oxygen difference and reduced Qcmax, (2) reduced Qcmax in acute hypoxia may be beneficial by preventing a further decrease in pulmonary and peripheral oxygen diffusion, and (3) reduced Qcmax and VO2max in acute hypoxia may be the result rather than the cause of the reduced Wmax and skeletal muscle recruitment, thus supporting the existence of a central governor.

Acute hypoxia and hypoxic exercise induce DNA strand breaks and oxidative DNA damage in humans.

The present study investigated the effect of a single bout of exhaustive exercise on the generation of DNA strand breaks and oxidative DNA damage under normal conditions and at high-altitude hypoxia (4559 meters for 3 days). Twelve healthy subjects performed a maximal bicycle exercise test; lymphocytes were isolated for analysis of DNA strand breaks and oxidatively altered nucleotides, detected by endonuclease III and formamidipyridine glycosylase (FPG) enzymes. Urine was collected for 24 h periods for analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of oxidative DNA damage. Urinary excretion of 8-oxodG increased during the first day in altitude hypoxia, and there were more endonuclease III-sensitive sites on day 3 at high altitude. The subjects had more DNA strand breaks in altitude hypoxia than at sea level. The level of DNA strand breaks further increased immediately after exercise in altitude hypoxia. Exercise-induced generation of DNA strand breaks was not seen at sea level. In both environments, the level of FPG and endonuclease III-sensitive sites remained unchanged immediately after exercise. DNA strand breaks and oxidative DNA damage are probably produced by reactive oxygen species, generated by leakage of the mitochondrial respiration or during a hypoxia-induced inflammation. Furthermore, the presence of DNA strand breaks may play an important role in maintaining hypoxia-induced inflammation processes. Hypoxia seems to deplete the antioxidant system of its capacity to withstand oxidative stress produced by exhaustive exercise.

Human VEGF gene expression in skeletal muscle: effect of acute normoxic and hypoxic exercise.

Vascular endothelial growth factor (VEGF) is involved in extracellular matrix changes and endothelial cell proliferation, both of which are precursors to new capillary growth. Angiogenesis is a vital adaptation to exercise training, and the exercise-induced reduction in intracellular PO2 has been proposed as a stimulus for this process. Thus we studied muscle cell PO2 [myoglobin PO2 (MbPO2)] during exercise in normoxia and in hypoxia (12% O2) and studied the mRNA levels of VEGF in six untrained subjects after a single bout of exercise by quantitative Northern analysis. Single-leg knee extension provided the acute exercise stimulus: a maximal test followed by 30 min at 50% of the peak work rate achieved in this graded test. Because peak work rate was not affected by hypoxia, the absolute and relative work rates were identical in hypoxia and normoxia. Three pericutaneous needle biopsies were collected from the vastus lateralis muscle, one at rest and then the others at 1 h after exercise in normoxia or hypoxia. At rest (control), VEGF mRNA levels were very low (0.38 +/- 0.04 VEGF/18S). After exercise in normoxia or hypoxia, VEGF mRNA levels were much greater (16.9 +/- 6.7 or 7.1 +/- 1.8 VEGF/18S, respectively). In contrast, there was no measurable basic fibroblast growth factor mRNA response to exercise at this 1-h postexercise time point. Magnetic resonance spectroscopy of myoglobin confirmed a reduction in MbPO2 in hypoxia (3.8 +/- 0.3 mmHg) compared with normoxia (7.2 +/- 0.6 mmHg) but failed to reveal a relationship between MbPO2 during exercise and VEGF expression. This VEGF mRNA increase in response to acute exercise supports the concept that VEGF is involved in exercise-induced skeletal muscle angiogenesis but questions the importance of a reduced cellular PO2 as a stimulus for this response.

Ventilation's role in the decline in ??VO2maxand SaO2 in acute hypoxic exercise

The role of ventilation in the response in aerobic capacity and arterial oxygen saturation (SaO2) to acute hypoxic exercise was studied in 13 healthy active men divided into two groups based on their normoxic maximal exercise VE/VO2 (LOW < or =27.7; HIGH > or = 30.2) and PAO2 estimates (LOW < or = 107 mm Hg; HIGH > or = 110 mm Hg). Groups performed two incremental progressive maximal cycle exercise (VO2max) tests: normoxia (FIO2 = 20.9%) and acute hypoxia (FIO2 = 13.3%). To evaluate the influence of hypoxic ventilatory drive on ventilation, resting hypoxic ventilatory response (rHVR) was measured. LOW demonstrated lower ventilatory responses (VE, VE/VO2, and VE/VCO2) during both normoxic and hypoxic exercise (P < or = 0.05). During maximal hypoxic exercise, LOW had a greater decline in both VO2max (21.6 mL x kg(-1) x min(-1) vs 16.6 mL x kg(-1) x min[-1]) and SaO2 (31.9% vs 22.1%). Modest but significant correlations were identified between normoxic VE/VO2 and the decline in both VO2max (r = -0.62) and SaO2 (r = -0.60). No correlations were identified between rHVR and any ventilatory response or SaO2. In summary, the results from this study suggest that a low exercise-induced hyperventilatory response is a significant mechanism in the arterial desaturation observed during hypoxic exercise and the decline in aerobic capacity associated with this desaturation. However, the ventilatory response to hypoxic exercise is not dependent upon hypoxic ventilatory drive.

Influence of hypoxic ventilatory response on arterial O2 saturation during maximal exercise in acute hypoxia

The aim of this study was to evaluate the influence of peripheral chemosensitivity estimated by hypoxic ventilatory response (HVR) on arterial oxygen saturation (SaO2) during maximal exercise in acute hypoxia. A group of 16 healthy men performed maximal exercise in two conditions of partial pressure of inspired oxygen (PIO2/149 and 70 mm Hg, 19.8 and 9.3 kPa). Measurements of maximal oxygen uptake (VO2max) and SaO2 using an ear-oximeter were carried out in both conditions of PIO2. The HVR was measured at rest by progressive isocapnic hypoxia and evaluated by the slope of the linear regression between the ventilatory flow (VE) and the SaO2 (delta VE/delta SaO2). The absolute value of HVR (in litres per minute per percentage saturation per kilogram) was correlated to maximal expired VE (r = 0.85, P < 0.001), ventilatory equivalent for CO2 (r = 0.83, P < 0.001) and SaO2 (r = 0.60, P < 0.05) determined during maximal exercise in hypoxia: a significant decrease in VO2max (37%) and SaO2 (32%) for PIO2 of 70 mm Hg (9.3 Pa) was observed (P < 0.001). The correlation between the decline of VO2max and arterial oxygen desaturation failed to reach statistical significance (r = 0.47, P = 0.1). The present findings indicated that the peripheral ventilatory chemosensitivity contributed to the interindividual variability of VE and SaO2 during maximal exercise in acute hypoxia.

The effects of D/Q̇ and D/V̇ a inequalities on pulmonary oxygen diffusing capacity estimates

Bohr-integrated estimates of steady-state pulmonary diffusing capacity for oxygen (D l O 2 ) were calculated using lung compartments with different V̇ a/Q̇ rations. Compartmental diffusing capacity was distributed in proportion to either ventilation or blood flow. This method was applied to 115 gas exchange data sets previously collected from healthy human subjects during normoxic ( P i O 2 = 148 Torr ) or acute hypoxic ( P i O 2 = 80 Torr ) exercise. Ventilation-weighted estimates of oxygen diffusing capacity exceeded blood flow-weighted estimates by 10 and 78% during hypoxia and normoxia, respectively. While blood flow-weighted D l O 2 estimates during heavy exercise were greater in hypoxia than in normoxia (mean ± SEM of 87.1 ± 4.4 vs 53.0 ± 3.1 ml·min −1·Torr −1), ventilation-weighted estimates were not significantly different (93.2 ± 5.5 vs 96.3 ± 9.4 ml·min −1·Torr −1). These results show that the effect of D/Q̇ inequality on D l O 2 estimates is greater at higher levels of inspired oxygen. Furthermore, a D/Q̇ mismatch of similar magnitude as the V̇ a/Q̇ mismatch that is observed during heavy exercise can account for a previously observed discrepancy between normoxic and hypoxic oxygen diffusing capacity estimates.

Cardiac performance during graded exercise in acute hypoxia

To evaluate the cardiocirculatory changes induced by acute hypoxic stress, rate corrected electro-mechanical systole (QS2)) left ventricular ejection time (LVET), and preejection period (PEP) were determined in 11 healthy males at sea level (SL) and after 2 h at a simulated altitude (HA) of 4,300 m. Recordings were made at rest and at 15 min of upright bicycle exercise at light and moderately heavy loads (40 and 75% of Vo2 max, respectively). Venous blood was withdrawn simultaneously for estimation of total plasma catecholamines (CATS). Exposure to HA produced a significant decrease in each interval at rest with differences narrowing progressively with exercise of increasing intensity. PEP/LVET ratio decreased progressively with graded exercise at SL indicating an enhancement of left ventricular performance that was directly related to the elevation in plasma CATS. Cardiac performance was augmented at rest during HA exposure, despite a normal level of CATS. However, during moderately heavy exercise at HA, when the plasma CATS were increased to twice the SL values, cardiac performance, as reflected by the PEP/LVET ratio, did not increase proportionately. It is postulated that the depressant effect of increased hypoxemia and acidosis during moderately heavy exercise in HA may override the cardiostimulatory influence of circulating CATS.

Efferent components of the cardioaccelerator responses to oxygen lack and cyanide

ARTICLESEfferent components of the cardioaccelerator responses to oxygen lack and cyanideJA KrasneyJA KrasneyPublished Online:01 Dec 1967https://doi.org/10.1152/ajplegacy.1967.213.6.1475MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByRegulation of heart rate in vertebrates during hypoxia: A comparative overview19 January 2022 | Acta Physiologica, Vol. 234, No. 3Hypoxia-induced vagal withdrawal is independent of the hypoxic ventilatory response in menChristoph Siebenmann, Camilla K. Ryrsø, Laura Oberholzer, James P. Fisher, Linda M. Hilsted, Peter Rasmussen, Niels H. Secher, and Carsten Lundby23 January 2019 | Journal of Applied Physiology, Vol. 126, No. 1Experimental, Clinical, Occupational Toxicology, and Forensic Aspects of Hydrogen Cyanide with Particular Reference to Vapor Exposure25 November 2009β‐Adrenergic or parasympathetic inhibition, heart rate and cardiac output during normoxic and acute hypoxic exercise in humans1 July 2003 | The Journal of Physiology, Vol. 550, No. 2Exercise in hypoxic environments: the mechanism remains elusive1 July 2003 | The Journal of Physiology, Vol. 550, No. 2Mechanisms mediating the heart rate response to hypoxemia.Circulation, Vol. 77, No. 2Neural Control of the Circulation during HypoxiaI. Thoracic Epidural Analgesia An Experimental Study in Sheep of the Effects on Central Circulation, Regional Perfusion and Myocardial Performance during Normoxia, Hypoxia and Isoproterenol AdministrationActa Anaesthesiologica Scandinavica, Vol. 22Adrenalectomy-Produced Facilitation of Pavlovian Conditioned Cardiodecelerations in Immobilized RatsPsychophysiology, Vol. 14, No. 2Hypoxemia, atelectasis, and the elevation of arterial pressure and heart rate in paralyzed artificially ventilated ratLife Sciences, Vol. 16, No. 7Cardiovascular and respiratory responses to severe hypoxaemia under anaesthesiaCanadian Anaesthetists’ Society Journal, Vol. 20, No. 5 More from this issue > Volume 213Issue 6December 1967Pages 1475-1479 Copyright & PermissionsCopyright © 1967 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1967.213.6.1475PubMed6075748History Published online 1 December 1967 Published in print 1 December 1967 Metrics