Flow-dependent influence of high-O2-affinity erythrocytes on peak VO2 in exercising muscle in situ

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.

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

Journal of Applied Physiology ◽

10.1152/jappl.1990.69.3.830 ◽

1990 ◽

Vol 69 (3) ◽

pp. 830-836 ◽

Cited By ~ 18

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)

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Effects of hyperoxia on leg blood flow and metabolism during exercise

Journal of Applied Physiology ◽

10.1152/jappl.1977.42.3.385 ◽

1977 ◽

Vol 42 (3) ◽

pp. 385-390 ◽

Cited By ~ 77

Author(s):

H. G. Welch ◽

F. Bonde-Petersen ◽

T. Graham ◽

K. Klausen ◽

N. Secher

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Aerobic Capacity ◽

Power Output ◽

Limb Blood Flow ◽

O2 Uptake ◽

Maximal Aerobic Capacity ◽

Leg Blood Flow ◽

O2 Delivery

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.

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Effect of hemoglobin concentration on maximal O2 uptake in canine gastrocnemius muscle in situ

Journal of Applied Physiology ◽

10.1152/jappl.1991.70.3.1105 ◽

1991 ◽

Vol 70 (3) ◽

pp. 1105-1112 ◽

Cited By ~ 44

Author(s):

M. C. Hogan ◽

D. E. Bebout ◽

P. D. Wagner

Keyword(s):

Gastrocnemius Muscle ◽

Random Sequence ◽

Hemoglobin Concentration ◽

Random Order ◽

O2 Uptake ◽

Blood Flows ◽

Hb Concentration ◽

O2 Delivery ◽

The Relationship

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)

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Effects of reduced O2 delivery with anemia, hypoxia, or ischemia on peak VO2 and force in skeletal muscle

Journal of Applied Physiology ◽

10.1152/jappl.1993.74.1.186 ◽

1993 ◽

Vol 74 (1) ◽

pp. 186-191 ◽

Cited By ~ 32

Author(s):

S. L. Dodd ◽

S. K. Powers ◽

E. Brooks ◽

M. P. Crawford

Keyword(s):

Venous Blood ◽

Random Order ◽

O2 Uptake ◽

Plantaris Muscle ◽

Experimental Conditions ◽

Tension Development ◽

O2 Concentration ◽

O2 Delivery ◽

Stimulation Pattern

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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Hypoxic vasodilation does not require nitric oxide (EDRF/NO) synthesis

Journal of Applied Physiology ◽

10.1152/jappl.1994.76.3.1256 ◽

1994 ◽

Vol 76 (3) ◽

pp. 1256-1261 ◽

Cited By ~ 17

Author(s):

B. Vallet ◽

S. E. Curtis ◽

M. J. Winn ◽

C. E. King ◽

C. K. Chapler ◽

...

Keyword(s):

Nitric Oxide ◽

Control Period ◽

Peripheral Resistance ◽

No Production ◽

O2 Uptake ◽

O2 Extraction ◽

Arterial Inflow ◽

Hypoxic Vasodilation ◽

O2 Delivery

Our question was whether inhibition of nitric oxide [endothelium-derived relaxing factor (EDRF)/NO] production in an in situ vascularly isolated but innervated canine hindlimb would prevent hypoxic vasodilation or interfere with O2 extraction during ischemic (IH) or hypoxic hypoxia (HH). After a control period, we gave NG-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg i.v.) to two of four groups of six dogs before a 30-min period of IH or HH. In IH, arterial inflow from a pump-membrane oxygenator system was lowered from 65 to 35 ml.min-1.kg-1 with PO2 maintained at approximately 110 Torr. In HH, PO2 was lowered from 107 to 28 Torr with flow at 78 ml.min-1.kg-1. Total O2 delivery was lowered to approximately 5 ml.min-1.kg-1 in all groups during hypoxia. Hindlimb vascular resistance (LVR) increased from 1.11 +/- 0.09 to 2.21 +/- 0.25 peripheral resistance units (PRU; P < 0.05) after L-NAME infusion and hindlimb O2 uptake increased from 3.9 +/- 0.2 to 4.5 +/- 0.3 ml.min-1.kg-1 (P < 0.05). In controls, LVR decreased from 1.10 +/- 0.06 to 0.63 +/- 0.04 PRU with HH (P < 0.05) and from 1.03 +/- 0.06 to 0.82 +/- 0.02 PRU (P = NS) with IH. In L-NAME-treated dogs, LVR decreased from 2.38 +/- 0.37 to 1.07 +/- 0.13 PRU with HH (P < 0.05) and from 2.04 +/- 0.29 to 1.41 +/- 0.13 PRU (P = NS) with IH. There were no differences in O2 extraction ratio (0.72) or in O2 uptake between groups during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

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Dissociation of maximal O2 uptake from O2 delivery in canine gastrocnemius in situ

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.3.1219 ◽

1989 ◽

Vol 66 (3) ◽

pp. 1219-1226 ◽

Cited By ~ 64

Author(s):

M. C. Hogan ◽

J. Roca ◽

J. B. West ◽

P. D. Wagner

Keyword(s):

Lactate Concentration ◽

High Flow ◽

Peripheral Tissue ◽

Low Flow ◽

O2 Uptake ◽

Muscle Lactate ◽

O2 Partial Pressure ◽

O2 Diffusion ◽

O2 Delivery

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.

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

Journal of Applied Physiology ◽

10.1152/jappl.1988.65.2.815 ◽

1988 ◽

Vol 65 (2) ◽

pp. 815-821 ◽

Cited By ~ 52

Author(s):

M. C. Hogan ◽

J. Roca ◽

P. D. Wagner ◽

J. B. West

Keyword(s):

Acute Hypoxia ◽

Muscle Performance ◽

O2 Uptake ◽

Muscle Lactate ◽

Venous Circulation ◽

O2 Diffusion ◽

Four Levels ◽

And Performance ◽

O2 Delivery

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.

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

Journal of Applied Physiology ◽

10.1152/jappl.1995.79.5.1729 ◽

1995 ◽

Vol 79 (5) ◽

pp. 1729-1735 ◽

Cited By ~ 15

Author(s):

S. S. Kurdak ◽

B. Grassi ◽

P. D. Wagner ◽

M. C. Hogan

Keyword(s):

Blood Flow ◽

Muscle Blood Flow ◽

Flow Distribution ◽

Hemoglobin Concentration ◽

Related Factor ◽

Blood Flow Distribution ◽

O2 Uptake ◽

Cell Spacing ◽

O2 Delivery

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.

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Assessment of Donkey (Equus asinus africanus) Whole Blood Stored in CPDA-1 and CPD/SAG-M Blood Bags

Biology ◽

10.3390/biology10020133 ◽

2021 ◽

Vol 10 (2) ◽

pp. 133

Author(s):

Isabella Oliveira Barros ◽

Rejane Santos Sousa ◽

Marcondes Dias Tavares ◽

Renato Otaviano Rêgo ◽

Paulo Ricardo Firmino ◽

...

Keyword(s):

Blood Cell ◽

Cell Count ◽

Whole Blood ◽

Blood Collection ◽

Blood Gas ◽

Blood Cell Count ◽

Animal Blood ◽

Equus Asinus ◽

Citrate Phosphate Dextrose ◽

Citrate Phosphate

Hemotherapy using whole blood and its components is being increasingly used in veterinary therapy. Since it is important to store animal blood while maintaining acceptable hematological, blood gas, and biochemical characteristics, increasing our knowledge of available technologies for strategic blood storage is imperative. Thus, we aimed to assess the hematological, blood gas, and biochemical changes in donkey whole blood using blood bags with two different types of storage agents. Eight adult healthy male donkeys were used; 900 mL of blood was collected from each, with 450 mL stored in citrate-phosphate-dextrose and adenine bags (CPDA-1) and 450 mL stored in bags containing citrate-phosphate-dextrose, adenine, mannitol, and sodium chloride (CPD/SAG-M). Both bags were kept refrigerated between 1 and 6 °C for 42 days. Blood samples were removed from the bags eight times (T): T0 (immediately after blood collection), T1, T3, T7, T14, T21, T35, and T42 (1, 3, 7, 14, 21, 35 and 42 days after storage). Hematological, blood gas, biochemical, and microbiological parameters were assessed. The CPDA-1 bags had a higher packed cell volume when compared to CPD/ SAG-M. The red blood cell count reduced by around 19% in both the bags due to hemolysis, which was confirmed by an increase in plasma hemoglobin. The white blood cell count; pH; concentrations of glucose, sodium, bicarbonate, and 2,3 diphosphoglycerate were reduced in both bags. Meanwhile, pO2, pCO2, lactate dehydrogenase, and levels of potassium increased in the CPDA-1 and CPD/SAG-M bags. Blood bags were efficient for the storage of donkey blood for up to 42 days.

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