Metabolic and circulatory responses of normoxic skeletal muscle to whole-body hypoxia

1988 ◽  
Vol 65 (5) ◽  
pp. 2063-2068 ◽  
Author(s):  
D. L. Bredle ◽  
C. K. Chapler ◽  
S. M. Cain
Keyword(s):  
Perfusion Pressure ◽  
Muscle Blood Flow ◽  
Autologous Blood ◽  
Whole Body ◽  
Membrane Oxygenator ◽  
O2 Uptake ◽  
Ici 118,551 ◽  
Autoregulatory Escape ◽  
Beta 2 ◽  
O2 Supply

Whole-body hypoxia may increase peripheral O2 demand because it increases catecholamine calorigenesis, an effect attributable to beta 2-adrenoceptors. We tested these possibilities by pump-perfusing innervated hindlimbs in eight dogs with autologous blood kept normoxic by a membrane oxygenator while ventilating the animals for 40 min with 9% O2 in N2 (NOB group). Similar periods of normoxic ventilation preceded and followed the hypoxic period. A second group (n = 8, beta B) was pretreated with the specific beta 2 blocker ICI 118,551. Hindlimb O2 uptake was elevated by 25 min of hypoxia in NOB, whereas whole-body O2 uptake was reduced. Limb O2 uptake remained elevated in recovery, but all effects on limb O2 uptake were absent in beta B. Hindlimb resistance and perfusion pressure increased in hypoxia in both groups, and there was little evidence of local escape from reflex vasoconstriction. These results clearly indicated that global hypoxia increased O2 demand in muscle when the local O2 supply was not limited and that beta 2-receptors were necessary for this response. Autoregulatory escape of limb muscle blood flow from centrally mediated vasoconstriction during whole-body hypoxia was also shown to be practically nil, if normoxia was maintained in the limb.

Analysis of oxygen delivery and uptake relationships in the Krogh tissue model

1989 ◽  
Vol 67 (3) ◽  
pp. 1234-1244 ◽  
Author(s):  
P. T. Schumacker ◽  
R. W. Samsel
Keyword(s):  
Blood Flow ◽  
Critical Point ◽  
Real Data ◽  
Whole Body ◽  
O2 Uptake ◽  
Highly Sensitive ◽  
O2 Extraction ◽  
O2 Supply ◽  
Experimental Findings ◽  
O2 Delivery

Normally, tissue O2 uptake (VO2) is set by metabolic activity rather than O2 delivery (QO2 = blood flow X arterial O2 content). However, when QO2 is reduced below a critical level, VO2 becomes limited by O2 supply. Experiments have shown that a similar critical QO2 exists, regardless of whether O2 supply is reduced by progressive anemia, hypoxemia, or reduction in blood flow. This appears inconsistent with the hypothesis that O2 supply limitation must occur by diffusion limitation, since very different mixed venous PO2 values have been seen at the critical point with hypoxic vs. anemic hypoxia. The present study sought to begin clarifying this paradox by studying the theoretical relationship between tissue O2 supply and uptake in the Krogh tissue cylinder model. Steady-state O2 uptake was computed as O2 delivery to tissue representative of whole body was gradually lowered by anemic, hypoxic, or stagnant hypoxia. As diffusion began to limit uptake, the fall in VO2 was computed numerically, yielding a relationship between QO2 and VO2 in both supply-independent and O2 supply-dependent regions. This analysis predicted a similar biphasic relationship between QO2 and VO2 and a linear fall in VO2 at O2 deliveries below a critical point for all three forms of hypoxia, as long as intercapillary distances were less than or equal to 80 microns. However, the analysis also predicted that O2 extraction at the critical point should exceed 90%, whereas real tissues typically extract only 65–75% at that point. When intercapillary distances were larger than approximately 80 microns, critical O2 extraction ratios in the range of 65–75% could be predicted, but the critical point became highly sensitive to the type of hypoxia imposed, contrary to experimental findings. Predicted gas exchange in accord with real data could only be simulated when a postulated 30% functional peripheral O2 shunt (arterial admixture) was combined with a tissue composed of Krogh cylinders with intercapillary distances of less than or equal to 80 microns. The unrealistic efficacy of tissue O2 extraction predicted by the Krogh model (in the absence of postulated shunt) may be a consequence of the assumed homogeneity of tissues, because real tissues exhibit many forms of heterogeneity among capillary units. Alternatively, the failure of the original Krogh model to fully predict tissue O2 supply dependency may arise from basic limitations in the assumptions of that model.

Determinants of maximal exercise VO2 during single leg knee-extensor exercise in humans

1995 ◽  
Vol 268 (4) ◽  
pp. H1453-H1461 ◽  
Author(s):  
R. S. Richardson ◽  
D. R. Knight ◽  
D. C. Poole ◽  
S. S. Kurdak ◽  
M. C. Hogan ◽  
...  
Keyword(s):  
Maximal Exercise ◽  
Muscle Blood Flow ◽  
Knee Extensor ◽  
Quadriceps Muscle ◽  
Diffusion Limitation ◽  
O2 Uptake ◽  
Maximum Work ◽  
O2 Supply ◽  
Exercise In Humans ◽  
Diffusive Capacity

Previously, a reduction in fractional inspired O2 (FIO2) during dynamic exercise of the human quadriceps muscles of one leg resulted in increased muscle blood flow (Q) and a fall in femoral venous O2 tension (PO2) but no change in peak O2 uptake (VO2). These data can be interpreted as reflecting an increase in muscle O2 diffusive capacity (DO2) in hypoxia or, alternatively, that maximum O2 uptake (VO2max) was not reached for these muscles when air was breathed, in which case the theory of diffusion limitation to VO2max is not applicable to these data. Therefore, the primary goal of this study was to test the hypothesis that VO2max would be reduced in hypoxia as a result of the decreased O2 supply and a constant diffusional conductance from blood to exercising muscle. To resolve this, five trained men were studied performing single leg incremental knee-extensor exercise to VO2max while breathing air (N) and again while breathing 12% O2 (H). The maximum work rate (WRmax) was 30–50 W greater and produced even greater associated maximum leg Q (N = 9.1 +/- 0.61 and H = 8.2 +/- 0.65 l/min, P < 0.05) and leg O2 than in previous studies. Hypoxia reduced quadriceps muscle VO2max (N = 1.4 +/- 0.1 and H = 1.1 +/- 0.1 l/min, P < 0.05). In the two conditions the relationships between 1) measured femoral venous PO2 (N = 18 +/- 0.5 and H = 13 +/- 0.5 Torr) and VO2max and 2) calculated mean capillary PO2 (N = 37 +/- 0.4 and H = 28 +/- 0.8 Torr) and VO2max were each one of proportionality.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic and intestinal limits of O2 extraction in the dog

1987 ◽  
Vol 63 (1) ◽  
pp. 387-394 ◽  
Author(s):  
D. P. Nelson ◽  
C. E. King ◽  
S. L. Dodd ◽  
P. T. Schumacker ◽  
S. M. Cain
Keyword(s):  
Extraction Ratio ◽  
Whole Body ◽  
Systemic Delivery ◽  
O2 Uptake ◽  
Critical Limit ◽  
O2 Extraction ◽  
Isolated Segment ◽  
O2 Supply ◽  
O2 Delivery ◽  
Arterial Tone

When systemic delivery of O2 (QO2 = QT X CaO2, where QT is cardiac output and CaO2 is arterial O2 content) is reduced by bleeding, the systemic O2 extraction ratio [ER = (CaO2 - CVO2)/CaO2, where CVO2 is venous O2 content] increases until a critical limit is reached below which O2 uptake (VO2) becomes limited by O2 delivery. During hypovolemia, reflex increases in mesenteric arterial tone may preferentially reduce gut blood flow so that the onset of O2 supply dependence occurs in the gut before other regions. We compared the critical O2 delivery (QO2c) and critical extraction ratio (ERc) of whole body and an isolated segment (30–50 g) of small bowel in seven anesthetized paralyzed dogs ventilated with room air. Systemic QO2 was reduced in stages by controlled hemorrhage as arterial O2 content was maintained, and systemic and gut VO2 and QO2 were measured at each stage. Body QO2c was 7.9 +/- 1.9 ml X kg-1 X min-1 (ERc = 0.69 +/- 0.12), whereas gut O2 supply dependency occurred when gut QO2 was 34.3 +/- 11.3 ml X min-1 X kg gut wt-1 (ERc = 0.63 +/- 0.09). O2 supply dependency in the gut occurred at a higher systemic QO2 (9.7 +/- 2.7) than whole-body QO2c (P less than 0.05). The extraction ratio at the final stage (maximal ER) was less in the gut (0.80 +/- 0.05) than whole body (0.87 +/- 0.06). Thus during reductions in systemic QO2, gut VO2 was maintained by increases in gut extraction of O2.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscle perfusion and oxygenation during local hyperoxia

1988 ◽  
Vol 65 (5) ◽  
pp. 2057-2062 ◽  
Author(s):  
D. L. Bredle ◽  
W. E. Bradley ◽  
C. K. Chapler ◽  
S. M. Cain
Keyword(s):  
Constant Pressure ◽  
Autologous Blood ◽  
Local Effect ◽  
Whole Body ◽  
Constant Flow ◽  
O2 Uptake ◽  
Flow Restriction ◽  
Hindlimb Muscles ◽  
Hindlimb Muscle ◽  
Anesthetized Dogs

Ventilation with O2 was previously shown to decrease whole-body and hindlimb muscle O2 uptake (VO2) in anesthetized dogs, particularly during anemia. To determine whether this was a purely local effect of hyperoxia (HiOx), we pump perfused isolated dog hindlimb muscles with autologous blood made hyperoxic (PO2 greater than 500 Torr) in a membrane oxygenator while the animals were ventilated with room air. Both constant-flow and constant-pressure protocols were used, and half the dogs were made anemic by exchange transfusion of dextran to hematocrit (Hct) approximately 15%. Thus there were four groups of n = 6 dogs each. A 30-min period of HiOx was preceded and followed by similar periods of perfusion with normoxic blood. In HiOx all four groups showed increased leg hindrance, increased leg venous PO2, and no significant changes in leg O2 inflow. Limb blood flow and VO2 decreased approximately 20% in HiOx with constant-pressure perfusion, regardless of Hct. In the constant-flow protocol, leg VO2 in HiOx was maintained by the anemic animals and actually increased in the normocythemic group. We conclude that HiOx directly affected vascular smooth muscle to cause flow restriction and maldistribution. Constant flow offset these effects, but the increased limb VO2 may have been a toxic effect. Anemia appeared to exaggerate the microcirculatory maldistribution caused by HiOx.

Effects of hyperthermia and hypothermia on oxygen extraction by tissues during hypovolemia

1987 ◽  
Vol 63 (3) ◽  
pp. 1246-1252 ◽  
Author(s):  
P. T. Schumacker ◽  
J. Rowland ◽  
S. Saltz ◽  
D. P. Nelson ◽  
L. D. Wood
Keyword(s):  
Extraction Ratio ◽  
Whole Body ◽  
Lower Body ◽  
Body Temperatures ◽  
Systemic Delivery ◽  
O2 Uptake ◽  
Mechanically Ventilated ◽  
O2 Extraction ◽  
Stepwise Reduction ◽  
O2 Supply

As systemic delivery of O2 (QO2 = QT X CaO2) is reduced during progressive hemorrhage, the O2 extraction ratio [(CaO2 - CVO2)/CaO2] increases until a critical delivery is reached below which O2 uptake (VO2) becomes limited by delivery (O2 supply dependence). When tissue metabolic activity and O2 demand are increased or reduced, the critical QO2 required to maintain VO2 should rise or fall accordingly, unless other changes in the distribution of a limited QO2 precipitate the onset of O2 supply dependence at a different critical extraction ratio. We compared the critical QO2 and critical extraction ratio in 23 normothermic (38 degrees C), hyperthermic (41 degrees C), or hypothermic (34 decrees C) dogs during stepwise reduction in delivery produced by bleeding, as arterial O2 content was maintained. Dogs were anesthetized, paralyzed, and mechanically ventilated. Hypothermia reduced whole-body VO2 by 31%, whereas hyperthermia increased VO2 by 20%. The critical QO2 was significantly reduced during hypothermia (5.6 +/- 0.95 ml.min-1.kg-1) (P less than 0.05) and increased during hyperthermia (8.9 +/- 1.1) (P approximately equal to 0.06) compared with normothermic controls (7.4 +/- 1.2). The extraction ratio at the onset of supply dependency was significantly increased in hyperthermia (0.76 +/- 0.05) compared with hypothermia (0.65 +/- 0.10) (P less than 0.05), and the normothermic critical extraction was 0.71 +/- 0.1. These results suggest that higher body temperatures are associated with an improved ability to maintain a VO2 independent of QO2, since a higher fraction of the delivered O2 can be extracted before the onset of O2 supply dependence, relative to lower body temperatures.

Responses of innervated and denervated gut to whole-body hypoxia

1987 ◽  
Vol 62 (2) ◽  
pp. 651-657 ◽  
Author(s):  
S. L. Dodd ◽  
C. E. King ◽  
S. M. Cain
Keyword(s):  
Blood Flow ◽  
Neural Activity ◽  
Whole Body ◽  
O2 Uptake ◽  
Severe Limitation ◽  
Energy Stores ◽  
Anesthetized Dogs ◽  
Extrinsic Innervation ◽  
O2 Supply ◽  
O2 Deficit

As a significant user of O2 at rest (20% of whole body), the gut may be subject to more severe limitation of O2 supply during global hypoxia than more vital areas because of preferential redistribution of blood flow. Accordingly, its accumulation of O2 deficit during hypoxia and its excess O2 use during normoxic recovery might be altered by extrinsic neural activity. We measured blood flow and O2 uptake in whole body (WB) and gut segments while anesthetized dogs were ventilated with 9% O2–91% N2 for 30 min followed by 30-min normoxic recovery. In six dogs extrinsic innervation to the gut segment was left intact and it was severed in another six animals. O2 deficit and excess were the accumulated differences from the normoxic O2 uptake for both gut and WB corrected for O2 stores changes. The intact gut, although only 4% body wt, incurred 22% of WB O2 deficit but contributed only 8% to WB O2 excess. The imbalance (gut excess was only 44% of gut deficit) implied that O2 using functions were curtailed during hypoxia without obligating an energy stores deficit. Denervation did not alter these quantitative relationships. Blood flow responses to transition between normoxia and hypoxia were only transiently altered. Extrinsic innervation apparently plays no major role in gut responses to WB hypoxia.

Circulatory and metabolic responses to carbon monoxide hypoxia during beta-adrenergic blockade

1988 ◽  
Vol 255 (1) ◽  
pp. H77-H84
Author(s):  
M. J. Melinyshyn ◽  
S. M. Cain ◽  
S. M. Villeneuve ◽  
C. K. Chapler
Keyword(s):  
Carbon Monoxide ◽  
Cardiac Output ◽  
Sampling Period ◽  
Whole Body ◽  
Metabolic Responses ◽  
Control Group ◽  
Adrenergic Blockade ◽  
Control Series ◽  
Ici 118,551 ◽  
Beta 2

The role(s) of beta-adrenoceptors in whole body and hindlimb skeletal muscle cardiovascular and metabolic responses during carbon monoxide hypoxia (COH) was studied in anesthetized dogs. One group of animals was beta-blocked with propranolol (beta 1- and beta 2-blockade), a second was given ICI 118,551 (beta 2-blockade), and a third served as a time control. Immediately after a control-sampling period, COH was induced (about a 63% decrease in arterial O2 content), and additional measurements were then obtained at 30 and 60 min of hypoxia. Cardiac output values were not different between the three series at control; an increase (P less than 0.05) occurred in all groups during COH. This rise was greatest in the COH group; the values for the propranolol- and ICI 118,551-blocked groups were not different from each other during COH. Hindlimb blood flow rose (P less than 0.05) during COH only in the control group. Both whole body (30 min) and hindlimb (30 and 60 min) resistance values were greater during hypoxia in the beta-blocked groups (P less than 0.05) than in the control series. Furthermore, whole body oxygen uptake decreased (P less than 0.05) in both beta-blocked groups during COH. We conclude that approximately 35% of the rise in cardiac output occurring during COH depended on peripheral vasodilation mediated through beta 2-adrenoceptors.

Neural control of glucose uptake by skeletal muscle after central administration of NMDA

1995 ◽  
Vol 268 (2) ◽  
pp. R492-R497 ◽  
Author(s):  
C. H. Lang ◽  
M. Ajmal ◽  
A. G. Baillie
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Neural Control ◽  
Plasma Insulin ◽  
Regional Blood Flow ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Glucose Disposal ◽  
Central Administration

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow.

Muscle maximal O2 uptake at constant O2 delivery with and without CO in the blood

1990 ◽  
Vol 69 (3) ◽  
pp. 830-836 ◽  
Author(s):  
M. C. Hogan ◽  
D. E. Bebout ◽  
A. T. Gray ◽  
P. D. Wagner ◽  
J. B. West ◽  
...  
Keyword(s):  
Blood Flow ◽  
Muscle Blood Flow ◽  
Hemoglobin Concentration ◽  
O2 Uptake ◽  
Isometric Twitch ◽  
O2 Delivery ◽  
Arterial Po2 ◽  
O2 Dissociation Curve ◽  
Total Hemoglobin Concentration

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)

Effect of changes in myocardial epinephrine stores on plasma norepinephrine gradient across the dog heart

1994 ◽  
Vol 266 (6) ◽  
pp. H2404-H2409 ◽  
Author(s):  
F. Peronnet ◽  
G. Boudreau ◽  
J. de Champlain ◽  
R. Nadeau
Keyword(s):  
Electrical Stimulation ◽  
Adrenal Medulla ◽  
Pulse Width ◽  
Stellate Ganglion ◽  
Plasma Norepinephrine ◽  
Direct Support ◽  
Left Stellate Ganglion ◽  
Ici 118,551 ◽  
Beta 2 ◽  
Stimulation Of

Plasma norepinephrine (NE) concentration ([NE]) gradient across the heart was measured under electrical stimulation of the left stellate ganglion (LSG; 4 Hz, 4 V, 2 ms pulse width, 1 min) in control (Ctrl) and in adrenalectomized (Adrx) dogs, without and with a 10-min epinephrine (Epi) infusion (92 ng.kg-1.min-1), which partly restored myocardial Epi stores in Adrx dogs (2.9 +/- 0.7 ng/g vs. 6.4 +/- 0.7 ng/g in Ctrl dogs) and slightly increased tissue Epi stores in Ctrl dogs (10.5 +/- 1.3 pg/g). Compared with Ctrl dogs (1,069 +/- 172 pg/ml), the [NE] gradient across the heart under stimulation of the LSG was not modified 1 wk after bilateral adrenalectomy (1,190 +/- 122 pg/ml) or after Epi infusion in Ctrl (1,134 +/- 276 pg/ml) and Adrx (1,259 +/- 279 pg/ml) dogs. The beta 2-antagonist ICI-118,551 significantly reduced the stimulation-induced [NE] gradient across the heart in Ctrl dogs (621 +/- 190 and 603 +/- 86 pg/ml without and with a 10-min Epi infusion, respectively) but not in Adrx dogs deprived of tissue Epi (1,345 +/- 345 pg/ml). Partial repletion of myocardial Epi stores in Adrx dogs restored the effect of ICI-118,551 on the stimulation-induced [NE] gradient (776 +/- 121 pg/ml). These results provide direct support of the hypothesis that tissue Epi, which originates from the adrenal medulla and which is released locally along with NE, is the endogenous agonist for presynaptic beta 2-receptors and potentiates NE release.

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