Why is V˙o 2 max after altitude acclimatization still reduced despite normalization of arterial O2 content?

2003 ◽  
Vol 284 (2) ◽  
pp. R304-R316 ◽  
Author(s):  
J. A. L. Calbet ◽  
R. Boushel ◽  
G. Rådegran ◽  
H. Søndergaard ◽  
P. D. Wagner ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Sea Level ◽  
Chronic Hypoxia ◽  
Maximal Exercise ◽  
Acute Hypoxia ◽  
Hemoglobin Concentration ◽  
Cycle Ergometry ◽  
The Other ◽  
Circulatory Effects

Acute hypoxia (AH) reduces maximal O2 consumption (V˙o 2 max), but after acclimatization, and despite increases in both hemoglobin concentration and arterial O2 saturation that can normalize arterial O2 concentration ([O2]),V˙o 2 max remains low. To determine why, seven lowlanders were studied at V˙o 2 max(cycle ergometry) at sea level (SL), after 9–10 wk at 5,260 m [chronic hypoxia (CH)], and 6 mo later at SL in AH (Fi O2 = 0.105) equivalent to 5,260 m. Pulmonary and leg indexes of O2 transport were measured in each condition. Both cardiac output and leg blood flow were reduced by ∼15% in both AH and CH ( P < 0.05). At maximal exercise, arterial [O2] in AH was 31% lower than at SL ( P < 0.05), whereas in CH it was the same as at SL due to both polycythemia and hyperventilation. O2extraction by the legs, however, remained at SL values in both AH and CH. Although at both SL and in AH, 76% of the cardiac output perfused the legs, in CH the legs received only 67%. PulmonaryV˙o 2 max (4.1 ± 0.3 l/min at SL) fell to 2.2 ± 0.1 l/min in AH ( P < 0.05) and was only 2.4 ± 0.2 l/min in CH ( P < 0.05). These data suggest that the failure to recoverV˙o 2 max after acclimatization despite normalization of arterial [O2] is explained by two circulatory effects of altitude: 1) failure of cardiac output to normalize and 2) preferential redistribution of cardiac output to nonexercising tissues. Oxygen transport from blood to muscle mitochondria, on the other hand, appears unaffected by CH.

Oxygen transport to exercising leg in chronic hypoxia

1988 ◽  
Vol 65 (6) ◽  
pp. 2592-2597 ◽  
Author(s):  
P. R. Bender ◽  
B. M. Groves ◽  
R. E. McCullough ◽  
R. G. McCullough ◽  
S. Y. Huang ◽  
...  
Keyword(s):  
Blood Flow ◽  
Sea Level ◽  
Chronic Hypoxia ◽  
Peripheral Resistance ◽  
Hemoglobin Concentration ◽  
Barometric Pressure ◽  
Ambient Air ◽  
Leg Blood Flow ◽  
State Cycle ◽  
O2 Delivery

Residence at high altitude could be accompanied by adaptations that alter the mechanisms of O2 delivery to exercising muscle. Seven sea level resident males, aged 22 +/- 1 yr, performed moderate to near-maximal steady-state cycle exercise at sea level in normoxia [inspired PO2 (PIO2) 150 Torr] and acute hypobaric hypoxia (barometric pressure, 445 Torr; PIO2, 83 Torr), and after 18 days' residence on Pikes Peak (4,300 m) while breathing ambient air (PIO2, 86 Torr) and air similar to that at sea level (35% O2, PIO2, 144 Torr). In both hypoxia and normoxia, after acclimatization the femoral arterial-iliac venous O2 content difference, hemoglobin concentration, and arterial O2 content, were higher than before acclimatization, but the venous PO2 (PVO2) was unchanged. Thermodilution leg blood flow was lower but calculated arterial O2 delivery and leg VO2 similar in hypoxia after vs. before acclimatization. Mean arterial pressure (MAP) and total peripheral resistance in hypoxia were greater after, than before, acclimatization. We concluded that acclimatization did not increase O2 delivery but rather maintained delivery via increased arterial oxygenation and decreased leg blood flow. The maintenance of PVO2 and the higher MAP after acclimatization suggested matching of O2 delivery to tissue O2 demands, with vasoconstriction possibly contributing to the decreased flow.

Regional blood flow and cardiac output during acute hypoxia in the anesthetized dog

1963 ◽  
Vol 204 (6) ◽  
pp. 963-968 ◽  
Author(s):  
John F. Murray ◽  
I. Maureen Young
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Regional Blood Flow ◽  
Acute Hypoxia ◽  
Arterial Oxygen Saturation ◽  
Head Kidney ◽  
Arterial Oxygen ◽  
Circulatory Effects ◽  
Low Concentrations ◽  
Anesthetized Dogs

The circulatory effects of breathing low concentrations of oxygen were studied in ten anesthetized dogs. Simultaneous measurements were made of cardiac output (indicator dilution technique) and blood flow to the head, kidney, and hind limb (electromagnetic flowmeters). Four experiments were performed with the addition of succinylcholine to inhibit the ventilatory response to hypoxia and maintain pCO2 constant. A rise in cardiac output and mean arterial pressure occurred which was significantly correlated to the decrease in arterial oxygen saturation. No threshold for these responses was found. Blood flow tended to increase during hypoxia in the regions studied but the responses were variable and only the change in renal blood flow had a significant correlation to arterial oxygen unsaturation. Systemic and regional vascular resistances during hypoxia varied both in direction and magnitude of change. The preponderant effects of hypoxia influence cardiac output more than peripheral vascular resistance.

Costal vs. crural diaphragmatic blood flow during submaximal and near-maximal exercise in ponies

1988 ◽  
Vol 65 (4) ◽  
pp. 1514-1519 ◽  
Author(s):  
M. Manohar
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Left Atrium ◽  
Maximal Exercise ◽  
Muscle Blood Flow ◽  
Intercostal Muscle ◽  
Quiet Breathing ◽  
Blood Flows ◽  
Graded Exercise ◽  
Crural Diaphragm

The present study was carried out 1) to compare blood flow in the costal and crural regions of the equine diaphragm during quiet breathing at rest and during graded exercise and 2) to determine the fraction of cardiac output needed to perfuse the diaphragm during near-maximal exercise. By the use of radionuclide-labeled 15-micron-diam microspheres injected into the left atrium, diaphragmatic and intercostal muscle blood flow was studied in 10 healthy ponies at rest and during three levels of exercise (moderate: 12 mph, heavy: 15 mph, and near-maximal: 19-20 mph) performed on a treadmill. At rest, in eucapnic ponies, costal (13 +/- 3 ml.min-1.100 g-1) and crural (13 +/- 2 ml.min-1.100 g-1) phrenic blood flows were similar, but the costal diaphragm received a much larger percentage of cardiac output (0.51 +/- 0.12% vs. 0.15 +/- 0.03% for crural diaphragm). Intercostal muscle perfusion at rest was significantly less than in either phrenic region. Graded exercise resulted in significant progressive increments in perfusion to these tissues. Although during exercise, crural diaphragmatic blood flow was not different from intercostal muscle blood flow, these values remained significantly less (P less than 0.01) than in the costal diaphragm. At moderate, heavy, and near-maximal exercise, costal diaphragmatic blood flow (123 +/- 12, 190 +/- 12, and 245 +/- 18 ml.min-1.100 g-1) was 143%, 162%, and 162%, respectively, of that for the crural diaphragm (86 +/- 10, 117 +/- 8, and 151 +/- 14 ml.min-1.100 g-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Pushmi-Pullyu and the Right Atrium

2011 ◽  
pp. 55-62
Author(s):  
James R. Munis
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Right Ventricle ◽  
Flow Rate ◽  
Blood Flow Rate ◽  
The Other ◽  
Right Atrial ◽  
The One ◽  
The Right ◽  
Point Of Intersection

What does right atrial pressure (PRA) do to cardiac output (CO)? On the one hand, we've been taught that PRA represents preload for the right ventricle. That is, the higher the PRA, the greater the right ventricular output (and, therefore, CO). This is simply an application of Starling's law to the right side of the heart. On the other hand, we've been taught that PRA represents the downstream impedance to venous return (VR) from the periphery. That is, the higher the PRA, the lower the VR, and therefore, the lower the CO. The point of intersection between the 2 curves defines a unique blood flow rate, which is both CO and VR at the same time.

Circulatory effects of acute or chronic endotoxemia in rats

1981 ◽  
Vol 59 (2) ◽  
pp. 204-208 ◽  
Author(s):  
R. Keeler ◽  
Anamaria Barrientos ◽  
K. Lee
Keyword(s):  
Escherichia Coli ◽  
Blood Pressure ◽  
Blood Flow ◽  
Cardiac Output ◽  
Gastrointestinal Tract ◽  
Peripheral Resistance ◽  
Circulatory Effects ◽  
Arterial Blood ◽  
Flow Changes ◽  
Fractional Distribution

A study was made of the effects of acute (4 h) or chronic (4 days) infusion of Escherichia coli endotoxin on cardiovascular function in rats. Rats with acute endotoxemia had a reduced cardiac output but maintained their arterial blood pressure. Fractional distribution of the cardiac output was increased to the liver and reduced to the gastrointestinal tract and skin. No changes in fractional distribution to the kidneys, lungs, or heart were observed although absolute blood flow to these areas was reduced.Rats with chronic endotoxemia had a reduced cardiac output and hypotension with no change in peripheral resistance. Other changes resembled those seen in acute endotoxemia apart from a low renal fraction of the cardiac output. Calculation and interpretation of blood flow changes in these animals was difficult because of a large fall in hematocrit and changes in organ weight.

Hypoxia in vivo inhibits aldosterone synthesis and aldosterone synthase mRNA in rats

1996 ◽  
Vol 81 (2) ◽  
pp. 604-610 ◽  
Author(s):  
H. Raff ◽  
B. M. Jankowski ◽  
W. C. Engeland ◽  
M. K. Oaks
Keyword(s):  
Chronic Hypoxia ◽  
Acute Hypoxia ◽  
The Other ◽  
Severe Hypoxia ◽  
Mrna Levels ◽  
Mitochondrial Cytochrome ◽  
Moderate Hypoxia ◽  
Adrenal Cells ◽  
Cytochrome P 450

Hypoxia leads to a decrease in aldosterone that cannot be entirely explained by extrinsic controllers of adrenal function. We have shown that acute hypoxia attenuates aldosterone synthesis via a direct inhibition of the function of the aldosterone enzyme pathway. The mechanism of the sustained decrease in aldosterone during chronic hypoxia is unknown. The present study evaluated the hypothesis that chronic hypoxia leads to a decrease in the expression of the steroidogenic enzyme P-450c11AS unique to the aldosterone pathway. Rats were exposed to 3 days of normoxia, moderate hypoxia (12% O2), or severe hypoxia (10% O2). Adrenal glands were removed and prepared for biochemical analysis of steroidogenesis in vitro (dispersed capsular cells) and for measurement of steady-state enzyme mRNA levels by reverse-transcription competitive polymerase-chain reaction (RT-cPCR) and by in situ hybridization histochemistry (ISHH). Moderate hypoxia had no effect on steroidogenesis. Adrenal cells from rats exposed to severe hypoxia demonstrated a decreased conversion of corticosterone to aldosterone (late pathway catalyzed by P-450c11AS) without a change in the other mitochondrial cytochrome P-450 enzyme activities. Adrenal cells from rats exposed to hypoxia also demonstrated a three- to fourfold decrease in P-450c11AS mRNA without a change in the other mitochondrial cytochrome P-450 enzymes mRNAs, as determined by either RT-cPCR or ISHH. We conclude that relatively short-term chronic hypoxia in rats leads to a decrease in aldosteronogenesis by decreasing the expression of the gene for the late-pathway enzyme unique to the aldosterone pathway (P-450c11AS).

Cardiac and respiratory effects of digitalis during chronic hypoxia in intact conscious dogs

1975 ◽  
Vol 229 (2) ◽  
pp. 270-274 ◽  
Author(s):  
GA Beller ◽  
SR Giamber ◽  
SB Saltz ◽  
TW Smith
Keyword(s):  
Sea Level ◽  
Chronic Hypoxia ◽  
Acute Hypoxia ◽  
Left Ventricular ◽  
Control Group ◽  
Continuous Exposure ◽  
Ventricular Performance ◽  
Toxic Dose ◽  
Respiratory Effects ◽  
Significant Difference

The arrhythmogenic and respiratory effects of ouabain during chronic hypoxia were studied in 10 unanesthetized dogs in a hypobaric chamber (446 mmHg) following 7-19 (mean 14.7) days of continuous exposure at this altitude. Another 15 dogs studied at sea level comprised the normoxic control group. In both groups, a 7.5-mug/kg loading dose of ouabain was followed by infusion of ouabain at 3.0 mug/kg per min to ECG evidence of toxicity. Mean arterial Po2 was 46 +/- 5 mmHg in chronically hypoxic dogs as compared to 86 +/- 7 mmHg in normoxic animals (P less than 0.001). Mean hematocrit was 54 +/- 1% in hypoxic and 43 +/- 2% in normoxic groups (P less than 0.001). In five dogs studied first at sea level and subsequently under conditions of chronic hypoxia, mean maximum left ventricular dP/dt and peak (dP/dt)P-1 were unchanged. Marked hyperventilation during ouabain infusion was observed. In normoxic dogs mean arterial pH rose from 7.43 +/- 0.05 to 7.70 +/- 0.02 U, and Pco2 fell from 41 +/- 4 to 15 +/- 1 mmHg during ouabain administration (P less than 0.001). Similar changes were observed in hypoxic dogs. There was no significant difference in the mean toxic dose of ouabain in chronically hypoxic (71 +/- 11 mug/kg) versus normoxic (78 +/- 12 mug/kg) animals. Thus, in contrast to acute hypoxia, chronic hypoxia in unanesthetized dogs was not associated with a significant reduction in the dose of ouabain required to produce toxic arrhythmias. Chronic hypoxia was also not associated with alterations in left ventricular performance.

Pulmonary hypertension and pulmonary vascular reactivity in beagles at high altitude

1988 ◽  
Vol 65 (6) ◽  
pp. 2632-2640 ◽  
Author(s):  
R. F. Grover ◽  
R. L. Johnson ◽  
R. G. McCullough ◽  
R. E. McCullough ◽  
S. E. Hofmeister ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
High Altitude ◽  
Sea Level ◽  
Vascular Reactivity ◽  
Chronic Hypoxia ◽  
Acute Hypoxia ◽  
Prostaglandin Synthesis ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Pulmonary Arterial ◽  
Low Altitude

It is unclear whether dogs develop pulmonary hypertension (PH) at high altitude. Beagles from sea level were exposed to an altitude of 3,100 m (PB 525 Torr) for 12-19 mo and compared with age-matched controls remaining at low altitude of 130 m (PB 750 Torr). In beagles taken to high altitude as adults, pulmonary arterial pressures (PAP) at 3,100 m were 21.6 +/- 2.6 vs. 13.2 +/- 1.2 Torr in controls. Likewise, in beagles taken to 3,100 m as puppies 2.5 mo old, PAP was 23.2 +/- 2.1 vs. 13.8 +/- 0.4 Torr in controls. This PH reflected a doubling of pulmonary vascular resistance and showed no progression with time at altitude. Pulmonary vascular reactivity to acute hypoxia was also enhanced at 3,100 m. Inhibition of prostaglandin synthesis did not attenuate the PH or the enhanced reactivity. Once established, the PH was only partially reversed by acute relief of chronic hypoxia, but reversal was virtually complete after return to low altitude. Hence, beagles do develop PH at 3,100 m of a severity comparable to that observed in humans at the same or even higher altitudes.

Role of the autonomic nervous system in the reduced maximal cardiac output at altitude

2002 ◽  
Vol 93 (1) ◽  
pp. 271-279 ◽  
Author(s):  
Harm J. Bogaard ◽  
Susan R. Hopkins ◽  
Yoshiki Yamaya ◽  
Kyuichi Niizeki ◽  
Michael G. Ziegler ◽  
...  
Keyword(s):  
Nervous System ◽  
Cardiac Output ◽  
Autonomic Nervous System ◽  
Sea Level ◽  
Maximal Exercise ◽  
Maximal Heart Rate ◽  
Contributing Factors ◽  
Volume Depletion ◽  
Autonomic Nervous

After acclimatization to high altitude, maximal exercise cardiac output (Q˙t) is reduced. Possible contributing factors include 1) blood volume depletion, 2) increased blood viscosity, 3) myocardial hypoxia, 4) altered autonomic nervous system (ANS) function affecting maximal heart rate (HR), and 5) reduced flow demand from reduced muscle work capability. We tested the role of the ANS reduction of HR in this phenomenon in five normal subjects by separately blocking the sympathetic and parasympathetic arms of the ANS during maximal exercise after 2-wk acclimatization at 3,800 m to alter maximal HR. We used intravenous doses of 8.0 mg of propranolol and 0.8 mg of glycopyrrolate, respectively. At altitude, peak HR was 170 ± 6 beats/min, reduced from 186 ± 3 beats/min ( P = 0.012) at sea level. Propranolol further reduced peak HR to 139 ± 2 beats/min ( P = 0.001), whereas glycopyrrolate increased peak HR to sea level values, 184 ± 3 beats/min, confirming adequate dosing with each drug. In contrast, peak O2 consumption, work rate, and Q˙t were similar at altitude under all drug treatments [peak Q˙t = 16.2 ± 1.2 (control), 15.5 ± 1.3 (propranolol), and 16.2 ± 1.1 l/min (glycopyrrolate)]. All Q˙t results at altitude were lower than those at sea level (20.0 ± 1.8 l/min in air). Therefore, this study suggests that, whereas the ANS may affect HR at altitude, peak Q˙t is unaffected by ANS blockade. We conclude that the effect of altered ANS function on HR is not the cause of the reduced maximal Q˙t at altitude.

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