Limitation of maximal O2 uptake and performance by acute hypoxia in dog muscle in situ

1988 ◽  
Vol 65 (2) ◽  
pp. 815-821 ◽  
Author(s):  
M. C. Hogan ◽  
J. Roca ◽  
P. D. Wagner ◽  
J. B. West

The factors that determine maximal O2 uptake (VO2max) and muscle performance during severe, acute hypoxemia were studied in isolated, in situ dog gastrocnemius muscle. Our hypothesis that VO2max is limited by O2 diffusion in muscle predicts that decreases in VO2max, caused by hypoxemia, will be accompanied by proportional decreases in muscle effluent venous PO2 (PvO2). By altering the fraction of inspired O2, four levels of arterial PO2 (PaO2) [21 +/- 2, 28 +/- 1, 44 +/- 1, and 80 +/- 2 (SE) Torr] were induced in each of eight dogs. Muscle arterial and venous circulation was isolated and arterial pressure held constant by pump perfusion. Each muscle worked maximally (3 min at 5-6 Hz, isometric twitches) at each PaO2. Arterial and venous samples were taken to measure lactate, [H+], PO2, PCO2, and muscle VO2. Muscle biopsies were taken to measure [H+] (homogenate method) and lactate. VO2max decreased with PaO2 and was linearly (R = 0.99) related to both PVO2 and O2 delivery. As PaO2 fell, fatigue increased while muscle lactate and [H+] increased. Lactate release from the muscle did not change with PaO2. This suggests a barrier to lactate efflux from muscle and a possible cause of the greater fatigue seen in hypoxemia. The gas exchange data are consistent with the hypothesis that VO2max is limited by peripheral tissue diffusion of O2.

1989 ◽  
Vol 66 (3) ◽  
pp. 1219-1226 ◽  
Author(s):  
M. C. Hogan ◽  
J. Roca ◽  
J. B. West ◽  
P. D. Wagner

To test the hypothesis that maximal O2 uptake (VO2max) can be limited by O2 diffusion in the peripheral tissue, we kept O2 delivery [blood flow X arterial O2 content (CaO2)] to maximally contracting muscle equal between 1) low flow-high CaO2 and 2) high flow-low CaO2 conditions. The hypothesis predicts, because of differences in the capillary PO2 profile, that the former condition will result in both a higher VO2max and muscle effluent venous PO2 (PVO2). We studied the relations among VO2max, PVO2, and O2 delivery during maximal isometric contractions in isolated, in situ dog gastrocnemius muscle (n = 6) during these two conditions. O2 delivery was matched by varying arterial O2 partial pressure and adjusting flow to the muscle accordingly. A total of 18 matched O2 delivery pairs were obtained. As planned, O2 delivery was not significantly different between the two treatments. In contrast, VO2max was significantly higher [10.4 +/- 0.5 (SE) ml.100 g-1.min-1; P = 0.01], as was PVO2 (25 +/- 1 Torr; P less than 0.01) in the low flow-high CaO2 treatment compared with the high flow-low CaO2 treatment (9.1 +/- 0.4 ml.100 g-1.min-1 and 20 +/- 1 Torr, respectively). The rate of fatigue was greater in the high flow-low CaO2 condition, as was lactate output from the muscle and muscle lactate concentration. The results of this study show that VO2max is not uniquely dependent on O2 delivery and support the hypothesis that VO2max can be limited by peripheral tissue O2 diffusion.


1990 ◽  
Vol 69 (3) ◽  
pp. 830-836 ◽  
Author(s):  
M. C. Hogan ◽  
D. E. Bebout ◽  
A. T. Gray ◽  
P. D. Wagner ◽  
J. B. West ◽  
...  

In the present study we investigated the effects of carboxyhemoglobinemia (HbCO) on muscle maximal O2 uptake (VO2max) during hypoxia. O2 uptake (VO2) was measured in isolated in situ canine gastrocnemius (n = 12) working maximally (isometric twitch contractions at 5 Hz for 3 min). The muscles were pump perfused at identical blood flow, arterial PO2 (PaO2) and total hemoglobin concentration [( Hb]) with blood containing either 1% (control) or 30% HbCO. In both conditions PaO2 was set at 30 Torr, which produced the same arterial O2 contents, and muscle blood flow was set at 120 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. To minimize CO diffusion into the tissues, perfusion with HbCO-containing blood was limited to the time of the contraction period. VO2max was 8.8 +/- 0.6 (SE) ml.min-1.100 g-1 (n = 12) with hypoxemia alone and was reduced by 26% to 6.5 +/- 0.4 ml.min-1.100 g-1 when HbCO was present (n = 12; P less than 0.01). In both cases, mean muscle effluent venous PO2 (PVO2) was the same (16 +/- 1 Torr). Because PaO2 and PVO2 were the same for both conditions, the mean capillary PO2 (estimate of mean O2 driving pressure) was probably not much different for the two conditions, even though the O2 dissociation curve was shifted to the left by HbCO. Consequently the blood-to-mitochondria O2 diffusive conductance was likely reduced by HbCO.(ABSTRACT TRUNCATED AT 250 WORDS)


1990 ◽  
Vol 69 (2) ◽  
pp. 570-576 ◽  
Author(s):  
M. C. Hogan ◽  
D. E. Bebout ◽  
P. D. Wagner ◽  
J. B. West

We investigated the relationships among maximal O2 uptake (VO2max), effluent venous PO2 (PvO2), and calculated mean capillary PO2 (PCO2) in isolated dog gastrocnemius in situ as arterial PO2 (PaO2) was progressively reduced with muscle blood flow held constant. The hypothesis that VO2max is determined in part by peripheral tissue O2 diffusion predicts proportional declines in VO2max and PCO2 if the diffusing capacity of the muscle remains constant. The inspired O2 fraction was altered in each of six dogs to produce four different levels of PaO2 [22 +/- 2, 29 +/- 1, 38 +/- 1, and 79 +/- 4 (SE) Torr]. Muscle blood flow, with the circulation isolated, was held constant at 122 +/- 15 ml.100 g-1.min-1 while the muscle worked maximally (isometric twitches at 5-7 Hz) at each of the four different values of PaO2. Arterial and venous samples were taken to measure lactate, pH, PO2, PCO2, and muscle VO2. PCO2 was calculated using Fick's law of diffusion and a Bohr integration procedure. VO2max fell progressively (P less than 0.01) with decreasing PaO2. The decline in VO2max was proportional (R = 0.99) to the fall in both muscle PvO2 and calculated PCO2 while the calculated muscle diffusing capacity was not different among the four conditions. Fatigue developed more rapidly with lower PaO2, although lactate output from the muscle was not different among conditions. These results are consistent with the hypothesis that resistance to O2 diffusion in the peripheral tissue may be a principal determinant of VO2max.


1984 ◽  
Vol 57 (2) ◽  
pp. 321-325 ◽  
Author(s):  
W. N. Stainsby ◽  
C. Sumners ◽  
G. M. Andrew

This study was designed to test the hypothesis that epinephrine (E) and norepinephrine (NE) increase net muscle lactate output (L) of in situ gastrocnemius-plantaris muscle group during contractions. Plasma [E] and [NE] were measured before and after the surgical isolation of the muscle and at 10-min intervals during the 60-min experiments. Plasma [E] and [NE] were increased threefold by intravenous infusions of E (n = 3) or NE (n = 3) at a rate of 1.5 micrograms X kg body wt-1 X min-1. Arterial and muscle venous blood samples for O2 and lactate concentrations were also obtained. The infusions began at min 11 and repetitive isometric contractions (4 tw/s) began at min 31. The presurgery plasma [E] and [NE] averaged 0.34 and 0.52 ng/ml, respectively, and rose to 1.12 and 1.19 ng/ml 10 min after surgery. Arterial and venous lactate concentrations (CaL and CvL) increased continuously during E infusion but remained constant during NE infusion. Maximal L during the first 10 min of contractions was significantly increased compared with an identical earlier study without infusions. O2 uptake was not changed by the infusions. It is concluded that E causes CaL to rise and that both E and NE increase maximal net lactate output during contractions.


1996 ◽  
Vol 80 (3) ◽  
pp. 832-838 ◽  
Author(s):  
H. Kohzuki ◽  
Y. Enoki ◽  
K. Matsumura ◽  
S. Sakata ◽  
S. Shimizu

To evaluate the influence of a high-O2 affinity of the erythrocyte and of flow rate on muscle's ability to extract O2 and develop force, we perfused dog gastrocnemius contracting isometrically at 4 Hz with normal-O2-affinity perfusate or high-O2-affinity perfusate at high and moderate flows (200 and 100 ml . min-1 . 100g-1, respectively). High-O2-affinity perfusate was prepared by incubating human citrate-phosphate-dextrose-stored erythrocytes with buffered saline containing cyanate (4 degrees C, 18 h) and normal-affinity perfusate by storing 2,3-diphosphoglycerate-rejuvenated erythrocytes in the same solution without cyanate. PO2 when blood is half oxygenated was 30.6 Torr for normal perfusate and 18.1 Torr for high-affinity perfusate. During 4-Hz stimulation, the tension developed by the muscle increased incrementally (positive staircase) to reach a peak value after 1.2-1.6 min for the normal perfusate and 0.6-0.7 min for the high-affinity perfusate (P < 0.05). The rate of decline during the early fatigue (measured from the onset of tension decline to 3 min) with high-affinity perfusate was significantly faster than it was with normal perfusate (P < 0.05). These findings suggest that both the staircase effect and the early fatigue are related to O2 availability, which is restricted when erythrocytes have a high O2 affinity. The peak O2 uptake values measured at 3 and 5 min were significantly lower (by 14-24%) with high-affinity perfusate than with normal perfusate at a given level of O2 delivery (arterial O2 content x flow) (P < 0.05). PO2 of venous effluent was proportionally related to peak O2 uptake. The present results indicate that neither blood flow nor O2 delivery is the sole determinant of the muscle's ability to extract O2.


1991 ◽  
Vol 70 (6) ◽  
pp. 2656-2662 ◽  
Author(s):  
M. C. Hogan ◽  
D. E. Bebout ◽  
P. D. Wagner

We investigated the effect of increasing hemoglobin- (Hb) O2 affinity on muscle maximal O2 uptake (VO2max) while muscle blood flow, [Hb], HbO2 saturation, and thus O2 delivery (muscle blood flow X arterial O2 content) to the working muscle were kept unchanged from control. VO2max was measured in isolated in situ canine gastrocnemius working maximally (isometric tetanic contractions). The muscles were pump perfused, in alternating order, with either normal blood [O2 half-saturation pressure of hemoglobin (P50) = 32.1 +/- 0.5 (SE) Torr] or blood from dogs that had been fed sodium cyanate (150 mg.kg-1.day-1) for 3-4 wk (P50 = 23.2 +/- 0.9). In both conditions (n = 8) arterial PO2 was set at approximately 200 Torr to fully saturate arterial blood, which thereby produced the same arterial O2 contents, and muscle blood flow was set at 106 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. VO2max was 11.8 +/- 1.0 ml.min-1.100 g-1 when perfused with the normal blood (control) and was reduced by 17% to 9.8 +/- 0.7 ml.min-1.100 g-1 when perfused with the low-P50 blood (P less than 0.01). Mean muscle effluent venous PO2 was also significantly less (26 +/- 3 vs. 30 +/- 2 Torr; P less than 0.01) in the low-P50 condition, as was an estimate of the capillary driving pressure for O2 diffusion, the mean capillary PO2 (45 +/- 3 vs. 51 +/- 2 Torr). However, the estimated muscle O2 diffusing capacity was not different between conditions.(ABSTRACT TRUNCATED AT 250 WORDS)


1977 ◽  
Vol 42 (3) ◽  
pp. 385-390 ◽  
Author(s):  
H. G. Welch ◽  
F. Bonde-Petersen ◽  
T. Graham ◽  
K. Klausen ◽  
N. Secher

These experiments were designed to investigate the effects of O2 breathing on limb blood flow and metabolism during exercise. Six subjects took part in the study. Four subjects breathed air or 100% O2 while pedaling a Krogh bicycle at 150 W (55–70% of maximal aerobic capacity). Two subjects breathed either 60% or 100% O2 while working at a power output at or slightly in excess of their maximal aerobic capacities. The major findings of the study were 1) leg blood flow is reduced during exercise when comparing hyperoxia with normoxia; 2) VO2 of the exercising limb is not different during hyperoxia; 3) O2 delivery to the leg (the product of blood flow and arteriovenous O2 difference) is not significantly different in the two conditions; and 4) blood pressure is not markedly affected in the experiments at 150 W. Since BP was not different during hyperoxia, at a time when flow was reduced by 11%, this suggests an increased resistance to flow in the exercising limb. In general, these findings are consistent with those reported for the in situ dog muscle but are at variance with results of experiments with humans, especially the reports indicating substantial increases in O2 uptake during hypertoxic conditions.


1991 ◽  
Vol 70 (3) ◽  
pp. 1105-1112 ◽  
Author(s):  
M. C. Hogan ◽  
D. E. Bebout ◽  
P. D. Wagner

O2 delivery to maximally working muscle was decreased by altering hemoglobin (Hb) concentration and arterial PO2 (PaO2) to investigate whether the reductions in maximal O2 uptake (VO2max) that occur with lowered [Hb] are in part related to changes in the effective muscle O2 diffusing capacity (DmO2). Two sets of experiments were conducted. In the initial set (n = 8), three levels of Hb [5.8 +/- 0.3, 9.4 +/- 0.1, and 14.4 +/- 0.6 (SE) g/100 ml] in the blood were used in random order to pump perfuse, at equal muscle blood flows and PaO2, maximally working isolated dog gastrocnemius muscle. VO2max declined with decreasing [Hb], but the relationship between VO2max and both the effluent venous PO2 (PvO2) and the calculated mean capillary PO2 (PcO2) was not linear through the origin and, therefore, not compatible with a single value of DmO2 (as calculated by Bohr integration using a model based on Fick's law of diffusion). To clarify these results, a second set of experiments (n = 6) was conducted in which two levels of Hb (14.0 +/- 0.6 and 6.9 +/- 0.6 g/100 ml) were each combined with two levels of oxygenation (PaO2 79 +/- 8 and 29 +/- 2 Torr) and applied in random sequence to again pump perfuse maximally working dog gastrocnemius muscle at constant blood flow. In these experiments, the relationship between VO2max and both PvO2 and calculated PcO2 for each [Hb] was consistent with a constant estimate of DmO2 as PaO2 was reduced, but the calculated DmO2 for the lower [Hb] was 33% less than that at the higher [Hb] (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


1993 ◽  
Vol 74 (1) ◽  
pp. 186-191 ◽  
Author(s):  
S. L. Dodd ◽  
S. K. Powers ◽  
E. Brooks ◽  
M. P. Crawford

This investigation was designed to describe alterations in O2 uptake (VO2) and tension development in a contracting in situ gastrocnemious-plantaris muscle preparation during three conditions of reduced O2 delivery [arterial O2 concentration X blood flow (Q)]. The three conditions, hypoxemia (H), ischemia (I), and anemia (A), were matched for O2 delivery. A normoxic normal flow condition was also utilized for comparison. H was produced by respiring the animals with 9% O2 in N2; I was produced by lowering Q, and A was produced by hemodilution with 6% dextran. The stimulation pattern for the isometric tetanic contractions used was 1 train/s, and each train was 200 ms, 70 Hz, and 6 V. The muscle was maximally contracted during each of the experimental conditions, and the conditions were administered in random order. In each bout the contractions continued for 5 min with 30 min of rest between bouts. Samples of arterial and muscle venous blood were obtained during the last 30 s of each bout. VO2 during I (125 ml.kg-1.min-1) was less than during N (145 ml.kg-1.min-1; P < 0.05) and greater than during H or A (104 and 101 ml.kg-1.min-1, respectively; P < 0.05). Venous PO2 (PVO2) was significantly lower during H (17.1 Torr) compared with the other conditions; no differences existed between N, I, and A (26.8, 26.0, and 28.1 Torr, respectively). Tension development was reduced by the reduction of O2 delivery during I, H, and A compared with N. Tension developed among the reduced O2 delivery groups was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)


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