Effect of [Hb] on blood flow distribution and O2 transport in maximally working skeletal muscle

1995 ◽  
Vol 79 (5) ◽  
pp. 1729-1735 ◽  
Author(s):  
S. S. Kurdak ◽  
B. Grassi ◽  
P. D. Wagner ◽  
M. C. Hogan

We investigated whether the reduction in calculated muscle diffusion capacity for O2 (DmO2) previously shown to occur with lowered hemoglobin concentration ([Hb]) perfusion of maximally working muscle is related to changes in the blood flow distribution. If blood flow distribution is altered during low [Hb] conditions, the reduction in the calculated DmO2 may in fact be due to increasing heterogeneity and not to some other hemoglobin-related factor. Color-stained (15-microns-diam) microspheres were injected into the artery supplying maximally working isolated in situ dog gastrocnemius muscle (n = 6) while it was being perfused (flow controlled by pump perfusion) with whole blood at three different levels of [Hb] (14.1 +/- 0.5, 8.9 +/- 0.4, and 5.7 +/- 0.4 (SE) g/100 ml] in a blocked-order design. Muscle blood flow and arterial PO2 were not changed as [Hb] was altered. Maximal O2 uptake (11.8 +/- 1.3, 8.2 +/- 0.8, and 6.0 +/- 0.9 ml.100 g-1 min-1 for those [Hb] values, respectively) and the associated estimate of DmO2 (0.25 +/- 0.03, 0.18 +/- 0.03, and 0.15 +/- 0.03 ml.100 g-1.min-1.Torr-1) declined significantly (P < 0.05) with [Hb]. However, the dispersion of the blood flow distribution did not change significantly and, if anything, indicated less heterogeneity at lower [Hb] (coefficient of variation - 0.52 +/- 0.06, 0.46 +/- 0.05, and 0.43 +/- 0.03). These results suggest that in maximally working canine muscle in situ, when O2 delivery is reduced by lowering [Hb] (at constant blood flow), changes in blood flow distribution play no significant role in the reduction of maximal O2 uptake and calculated DmO2. The apparent increase in the resistance to O2 diffusion (i.e., reduction in the DmO2) during anemia may therefore be a result of increased red blood cell spacing in the capillary, slow chemical off-loading kinetics of O2 from Hb, or some other effect that remains to be determined.

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)


1996 ◽  
Vol 80 (6) ◽  
pp. 1978-1983 ◽  
Author(s):  
S. S. Kurdak ◽  
B. Grassi ◽  
P. D. Wagner ◽  
M. C. Hogan

The purpose of this study was to determine whether reduction in apparent muscle O2 diffusing capacity (Dmo2) calculated during reduced blood flow conditions in maximally working muscle is a reflection of alterations in blood flow distribution. Isolated dog gastrocnemius muscle (n = 6) was stimulated for 3 min to achieve peak O2 uptake (VO2) at two levels of blood flow (controlled by pump perfusion): control (C) conditions at normal perfusion pressure (blood flow = 111 +/- 10 ml.100 g-1.min-1) and reduced blood flow treatment [ischemia (I); 52 +/- 6 ml.100 g-1.min-1]. In addition, maximal vasodilation was achieved by adenosine (A) infusion (10(-2)M) at both levels of blood flow, so that each muscle was subjected randomly to a total of four conditions (C, CA, I, and IA; each separated by 45 min of rest). Muscle blood flow distribution was measured with 15-microns-diameter colored microspheres. A numerical integration technique was used to calculate Dmo2 for each treatment with use of a model that calculates O2 loss along a capillary on the basis of Fick's law of diffusion. Peak VO2 was reduced significantly (P < 0.01) with ischemia and was unchanged by adenosine infusion at either flow rate (10.6 +/- 0.9, 9.7 +/- 1.0, 6.7 +/- 0.2, and 5.9 +/- 0.8 ml.100 g-1.min-1 for C, CA, I, and IA, respectively). Dmo2 was significantly lower by 30-35% (P < 0.01) when flow was reduced (except for CA vs. I; 0.23 +/- 0.03, 0.20 +/- 0.02, 0.16 +/- 0.01, and 0.13 +/- 0.01 ml.100 g-1.min-1.Torr-1 for C, CA, I, and IA, respectively). As expressed by the coefficient of variation (0.45 +/- 0.04, 0.47 +/- 0.04, 0.55 +/- 0.03, and 0.53 +/- 0.04 for C, CA, I, and IA, respectively), blood flow heterogeneity per se was not significantly different among the four conditions when examined by analysis of variance. However, there was a strong negative correlation (r = 0.89, P < 0.05) between Dmo2 and blood flow heterogeneity among the four conditions, suggesting that blood flow redistribution (likely a result of a decrease in the number of perfused capillaries) becomes an increasingly important factor in the determination of Dmo2 as blood flow is diminished.


1993 ◽  
Vol 74 (4) ◽  
pp. 1742-1747 ◽  
Author(s):  
M. C. Hogan ◽  
D. E. Bebout ◽  
P. D. Wagner

The purpose of this study was to decrease O2 delivery to maximally working muscle by reductions in muscle blood flow (Q), while maintaining hemoglobin concentration and the arterial PO2 (PaO2) constant, to investigate how the decreases in maximal O2 uptake (VO2max) that occur with ischemia are related to changes in the estimated effective muscle O2 diffusing capacity (DO2). Additionally, the relationships among Q, DO2, O2 uptake (VO2), and effluent venous PO2 (PVO2) were used to infer whether the reductions in Q occur uniformly throughout the muscle or whether a nonuniform (greater heterogeneity of Q to VO2) pattern develops. Isolated dog gastrocnemius muscle (n = 6) was stimulated maximally at three levels of muscle blood flow (controlled by pump perfusion): control [C; 119 +/- 3 ml.100 g-1.min-1 (SE)], moderate ischemia (MI; 80 +/- 6), and severe ischemia (SI; 45 +/- 6) in random order. Arterial and venous samples were taken to measure blood gases, O2 concentration, and lactate concentration, whereas a Bohr integration technique using a model based on Fick's law of diffusion was used to estimate mean capillary PO2 and DO2 for each Q condition. VO2max fell progressively (P < 0.05) with Q, even though the O2 extraction ratio (VO2/O2 delivery) increased significantly (C = 67%, MI = 84%, SI = 90%). PVO2 and VO2max fell in proportion to each other from C to MI, but there was not a significant fall in PVO2 from MI to SI. Thus the calculated DO2 did not change between C and MI but fell in proportion to Q between MI and SI. These results suggest that with moderate Q reduction, perfusion falls relatively uniformly throughout the muscle, whereas more severe ischemia leads to nonuniform changes in Q distribution with some areas being poorly perfused to allow more adequate perfusion to other areas.


1992 ◽  
Vol 73 (6) ◽  
pp. 2470-2475 ◽  
Author(s):  
M. C. Hogan ◽  
D. C. Willford ◽  
P. E. Keipert ◽  
N. S. Faithfull ◽  
P. D. Wagner

A perfluorocarbon emulsion [formulation containing 90% wt/vol perflubron (perfluorooctylbromide); Alliance Pharmaceutical] was used to increase O2 solubility in the plasma compartment during hyperoxic low hemoglobin concentration ([Hb]) perfusion of a maximally working dog muscle in situ. Our hypothesis was that the increased plasma O2 solubility would increase the muscle O2 diffusing capacity (DO2) by augmenting the capillary surface area in contact with high [O2]. Oxygen uptake (VO2) was measured in isolated in situ canine gastrocnemius (n = 4) while working for 6 min at a maximal stimulation rate of 1 Hz (isometric tetanic contractions) on three to four separate occasions for each muscle. On each occasion, the last 4 min of the 6-min work period was split into 2 min of a control treatment (only emulsifying agent mixed into blood) and 2 min of perflubron treatment (6 g/kg body wt), reversing the order for each subsequent work bout. Before contractions, the [Hb] of the dog was decreased to 8–9 g/100 ml and arterial PO2 was increased to 500–600 Torr by having the dog breathe 100% O2 to maximize the effect of the perflubron. Muscle blood flow was held constant between the two experimental conditions. Plasma O2 solubility was almost doubled to 0.005 ml O2 x 100 ml blood-1 x Torr-1 by the addition of the perflubron. Muscle O2 delivery and maximal VO2 were significantly improved (at the same blood flow and [Hb]) by 11 and 12.6%, respectively (P < 0.05), during the perflubron treatment compared with the control. O2 extraction by the muscle remained the same between the two treatments, as did the estimate of DO2.(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.


2000 ◽  
Vol 89 (4) ◽  
pp. 1293-1301 ◽  
Author(s):  
Bruno Grassi ◽  
Michael C. Hogan ◽  
Kevin M. Kelley ◽  
William G. Aschenbach ◽  
Jason J. Hamann ◽  
...  

A previous study (Grassi B, Gladden LB, Samaja M, Stary CM, and Hogan MC, J Appl Physiol 85: 1394–1403, 1998) showed that convective O2 delivery to muscle did not limit O2 uptake (V˙o 2) on-kinetics during transitions from rest to contractions at ∼60% of peakV˙o 2. The present study aimed to determine whether this finding is also true for transitions involving contractions of higher metabolic intensities.V˙o 2 on-kinetics were determined in isolated canine gastrocnemius muscles in situ ( n = 5) during transitions from rest to 4 min of electrically stimulated isometric tetanic contractions corresponding to the muscle peakV˙o 2. Two conditions were compared: 1) spontaneous adjustment of muscle blood flow (Q˙) (Control) and 2) pump-perfused Q˙, adjusted ∼15–30 s before contractions at a constant level corresponding to the steady-state value during contractions in Control (Fast O2 Delivery). In Fast O2 Delivery, adenosine was infused intra-arterially. Q˙ was measured continuously in the popliteal vein; arterial and popliteal venous O2 contents were measured at rest and at 5- to 7-s intervals during the transition. Muscle V˙o 2 was determined as Q˙times the arteriovenous blood O2 content difference. The time to reach 63% of the V˙o 2 difference between resting baseline and steady-state values during contractions was 24.9 ± 1.6 (SE) s in Control and 18.5 ± 1.8 s in Fast O2 Delivery ( P < 0.05). FasterV˙o 2 on-kinetics in Fast O2Delivery was associated with an ∼30% reduction in the calculated O2 deficit and with less muscle fatigue. During transitions involving contractions at peak V˙o 2, convective O2 delivery to muscle, together with an inertia of oxidative metabolism, contributes in determining theV˙o 2 on-kinetics.


1995 ◽  
Vol 79 (5) ◽  
pp. 1762-1768 ◽  
Author(s):  
C. R. Woodman ◽  
L. A. Sebastian ◽  
C. M. Tipton

Rats exposed to simulated conditions of microgravity by head-down suspension (HDS) exhibit reductions in aerobic capacity. This may be due to an impaired ability to augment cardiac output and to redistribute blood flow during exercise. The purpose of this investigation was to measure cardiac output and blood flow distribution in rats that were exposed to 14 days of HDS or cage control conditions. Measurements were obtained at rest and during light-intensity (15 m/min) and heavy-intensity (25 m/min; 10% grade) treadmill exercise. Cardiac output was similar in HDS and cage control rats at rest and light exercise but was significantly lower in HDS rats (-33%) during heavy exercise. Soleus muscle blood flow (ml/min) was lower at rest and during exercise in HDS rats; however, when expressed relative to muscle mass (ml.min-1.100 g-1), soleus blood flow was lower only during light exercise. Plantaris muscle blood flow was lower in HDS rats during heavy exercise. Blood flow to the ankle flexor, knee extensor, and knee flexor muscles was not altered by HDS. Blood flow to the spleen and kidney was significantly higher in HDS rats. It was concluded that the reduction in aerobic capacity associated with HDS is due in part to an impaired ability to augment cardiac output during exercise.


1992 ◽  
Vol 73 (2) ◽  
pp. 728-736 ◽  
Author(s):  
M. C. Hogan ◽  
P. G. Arthur ◽  
D. E. Bebout ◽  
P. W. Hochachka ◽  
P. D. Wagner

This study was designed to investigate the role of tissue oxygenation in some of the factors that are thought to regulate muscle respiration and metabolism. Tissue oxygenation was altered by reductions in O2 delivery (muscle blood flow x arterial O2 content), induced by decreases in arterial PO2 (PaO2). O2 uptake (VO2) was measured in isolated in situ canine gastrocnemius at rest and while working at two stimulation intensities (isometric tetanic contractions at 0.5 and 1 contractions/s) on three separate occasions, with only the level of PaO2 (78, 30, and 21 Torr) being different for each occasion. Muscle blood flow was held constant (pump perfusion) at each work intensity for the three different levels of PaO2. Muscle biopsies were obtained at the end of each rest and work period. Muscle VO2 was significantly less (P less than 0.05) at both stimulation intensities for the hypoxemic conditions, whereas [ATP] was reduced only during the highest work intensity during both hypoxemic conditions (31% reduction at 21 Torr PaO2 and 17% at 30 Torr). For each level of PaO2, the relationships between the changes that occurred in VO2 and levels of phosphocreatine, ADP, and ATP/ADP.P(i) as the stimulation intensity was increased were significantly correlated; however, the slopes and intercepts of these lines were significantly different for each PaO2. Thus a greater change in any of the proposed regulators of tissue respiration (e.g., phosphocreatine, ADP) was required to achieve a given VO2 as PaO2 was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)


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)


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