Chronic administration of sodium cyanate decreases O2 extraction ratio in dogs

It has been proposed that an increase in the affinity of hemoglobin for O2 may be beneficial in severe hypoxemia. To test this hypothesis, we compared the response to progressive hypoxemia in dogs with normal hemoglobin affinity (P50 = 32.4 +/- 0.7 Torr) to dogs with a left shift of the oxyhemoglobin dissociation curve (P50 = 21.9 +/- 0.5 Torr) induced by chronic oral administration of sodium cyanate. Animals were anesthetized, paralyzed, and mechanically ventilated. The inspired O2 fraction was progressively lowered by increasing the inspired fraction of N2. The lowest level of O2 transport required to maintain base-line O2 consumption (VO2) was 9.3 +/- 0.8 ml.min-1.kg-1 for control and 16.5 +/- 1.1 ml.min-1.kg-1 for the sodium cyanate-treated dogs (P less than 0.01). Other measured parameters at this level of O2 transport were, for experimental vs. control: arterial PO2 19.3 +/- 2.4 (SE) Torr vs. 21.8 +/- 1.6 Torr (NS); arterial O2 content 10.0 +/- 1.2 ml/dl vs. 4.9 +/- 0.4 ml/dl (P less than 0.01); mixed venous PO2 14.0 +/- 1.5 Torr vs. 13.8 +/- 1.0 Torr (NS); mixed venous O2 content 6.8 +/- 1.0 ml/dl vs. 2.3 +/- 0.2 ml/dl (P less than 0.01); and O2 extraction ratio 32.7 +/- 2.8% vs. 51.2 +/- 3.8% (P less than 0.01). We conclude that chronic administration of sodium cyanate appears to be detrimental to O2 transport, since the experimental dogs were unable to increase their O2 extraction ratios to the same level as control, thus requiring a higher level of O2 transport to maintain their base-line VO2 values.     

Effect of increased Hb-O2 affinity on VO2max at constant O2 delivery in dog muscle in situ

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)     

Effect of pentoxiphylline on oxygen transport during hypothermia

At least two investigators have demonstrated a reduction in O2 extraction during induced hypothermia (Cain and Bradley, J. Appl. Physiol. 55: 1713-1717, 1983; Schumacker et al., J. Appl. Physiol. 63: 1246-1252, 1987). We hypothesized that administration of pentoxiphylline (PTX), a theobromine that lowers blood viscosity and has vasodilator effects, would increase O2 extraction during hypothermia. To test this hypothesis, we studied O2 transport in anesthetized, paralyzed, mechanically ventilated beagles exposed to hypoxic hypoxia during either 1) normothermia (38 degrees C), 2) hypothermia (30 degrees C), or 3) hypothermia + PTX (30 degrees C and PTX, 20 mg.kg-1.h-1). Measurements included arterial and mixed venous PO2, hemoglobin concentration and saturation, cardiac output, systemic vascular resistance (SVR), blood viscosity, and O2 consumption (VO2). Critical levels of O2 delivery (DO2, the product of arterial O2 content and cardiac output) were determined by a system of linear regression. Hypothermia significantly decreased base line cardiac output (-35%), DO2 (-37%), and VO2 (-45%), while increasing SVR and blood viscosity. Addition of PTX increased cardiac output (35%) and VO2 (14%), and returned SVR and blood viscosity to normothermic levels. Hypothermia alone failed to significantly reduce the critical level of DO2, but addition of PTX did [normothermia, 11.4 +/- 4.2 (SD) ml.kg-1.min-1; hypothermia, 9.3 +/- 3.6; hypothermia + PTX, 6.6 +/- 1.3; P less than 0.05, analysis of variance]. The O2 extraction ratio (VO2/DO2) at the critical level of DO2 was decreased during hypothermia alone (normothermia, 0.60 +/- 0.13; hypothermia, 0.42 +/- 0.16; hypothermia + PTX, 0.62 +/- 0.19; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Tissue oxygen extraction during hypovolemia: role of hemoglobin P50

When the delivery of O2 to tissues (QO2 = blood flow X O2 content) falls below a critical threshold, tissue O2 uptake (VO2) becomes limited by QO2. The mechanism responsible for this extraction limitation is not understood but may involve molecular diffusion limitation as mean capillary PO2 drops below a critical minimum level in some capillaries. We tested this hypothesis by measuring the critical QO2 necessary to maintain VO2 independent of QO2 in anesthetized, paralyzed normal dogs (n = 7) and in a second group in which PO2 at 50% saturation of hemoglobin (P50) was reduced by exchange transfusion with low-P50 erythrocytes (n = 7). QO2 was reduced in stages by removing blood volume to reduce blood flow while VO2 was measured by spirometry at each step. To the extent that O2 extraction was limited by a critical capillary PO2, we reasoned that the onset of diffusion limitation should occur at a higher QO2 with low P50, since a lower end-capillary PO2 is required to achieve the same O2 extraction. The critical QO2 (7.8 +/- 1.2 ml X min-1 X kg-1) and extraction ratio (0.63 +/- 0.06) in dogs with reduced P50 were not different from controls. At the critical delivery, mixed venous PO2 was lower in low P50 (16.1 +/- 2.9 Torr) than controls (29.9 +/- 2.3 Torr). We concluded that diffusion limitation does not initiate the early fall in VO2 below the critical QO2 and offer an alternative model to explain the onset of supply dependency.(ABSTRACT TRUNCATED AT 250 WORDS)     

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

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.     

Arterial blood gases and acid-base status of dogs during graded dynamic exercise

The objective of this study was to determine whether arterial PCO2 (PaCO2) decreases or remains unchanged from resting levels during mild to moderate steady-state exercise in the dog. To accomplish this, O2 consumption (VO2) arterial blood gases and acid-base status, arterial lactate concentration ([LA-]a), and rectal temperature (Tr) were measured in 27 chronically instrumented dogs at rest, during different levels of submaximal exercise, and during maximal exercise on a motor-driven treadmill. During mild exercise [35% of maximal O2 consumption (VO2 max)], PaCO2 decreased 5.3 +/- 0.4 Torr and resulted in a respiratory alkalosis (delta pHa = +0.029 +/- 0.005). Arterial PO2 (PaO2) increased 5.9 +/- 1.5 Torr and Tr increased 0.5 +/- 0.1 degree C. As the exercise levels progressed from mild to moderate exercise (64% of VO2 max) the magnitude of the hypocapnia and the resultant respiratory alkalosis remained unchanged as PaCO2 remained 5.9 +/- 0.7 Torr below and delta pHa remained 0.029 +/- 0.008 above resting values. When the exercise work rate was increased to elicit VO2 max (96 +/- 2 ml X kg-1 X min-1) the amount of hypocapnia again remained unchanged from submaximal exercise levels and PaCO2 remained 6.0 +/- 0.6 Torr below resting values; however, this response occurred despite continued increases in Tr (delta Tr = 1.7 +/- 0.1 degree C), significant increases in [LA-]a (delta [LA-]a = 2.5 +/- 0.4), and a resultant metabolic acidosis (delta pHa = -0.031 +/- 0.011). The dog, like other nonhuman vertebrates, responded to mild and moderate steady-state exercise with a significant hyperventilation and respiratory alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of chronic sodium cyanate administration on O2 transport and uptake in hypoxic and normoxic exercise.

Systemic O2 transport during maximal exercise at different inspired PO2 (PIO2) values was studied in sodium cyanate-treated (CY) and nontreated (NT) rats. CY rats exhibited increased O2 affinity of Hb (exercise O2 half-saturation pressure of Hb = 27.5 vs. 42.5 Torr), elevated blood Hb concentration, pulmonary hypertension, blunted hypoxic pulmonary vasoconstriction, and normal ventilatory response to exercise. Maximal rate of convective O2 transport was higher and tissue O2 extraction was lower in CY than in NT rats. The relative magnitude of these opposing changes, which determined the net effect of cyanate on maximal O2 uptake (VO2 max), varied at different PIO2: VO2 max (ml. min-1. kg-1) was lower in normoxia (72.8 +/- 1.9 vs. 81. 1 +/- 1.2), the same at 70 Torr PIO2 (55.4 +/- 1.4 vs. 54.1 +/- 1.4), and higher at 55 Torr PIO2 (48 +/- 0.7 vs. 40.4 +/- 1.9) in CY than in NT rats. The beneficial effect of cyanate on VO2 max at 55 Torr PIO2 disappeared when Hb concentration was lowered to normal. It is concluded that the effect of cyanate on VO2 max depends on the relative changes in blood O2 convection and tissue O2 extraction, which vary at different PIO2. Although uptake of O2 by the blood in the lungs is enhanced by cyanate, its release at the tissues is limited, probably because of a reduction in the capillary-to-tissue PO2 diffusion gradient secondary to the increased O2 affinity of Hb.     

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

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)     

Effects of moderate hypothermia on O2 consumption at various O2 deliveries in a sheep model.

The effects of modest hypothermia on oxygen consumption (VO2) were studied at various levels of oxygen delivery (DO2) in six sheep. Each animal was placed on cardiopulmonary bypass by extrathoracic cannulations. DO2 was varied by changing blood flow through an extracorporeal circuit. VO2 was measured spirometrically across a membrane lung. VO2 was initially measured at various levels of DO2 at normothermic temperatures (39 degrees C). The animals were then cooled to 33 degrees C. DO2 was varied, and the corresponding VO2's were determined. The data at both temperatures demonstrated the biphasic relationship of VO2 to various levels of DO2. A critical level of DO2 (DO2 crit) was defined to reflect the transition area between the dependent and independent portions of the consumption-delivery curve. The average baseline VO2's on the delivery independent portion of the curve were calculated to be 5.33 and 3.17 ml O2.kg-1.min-1 at 39 and 33 degrees C, respectively (P less than 0.001). The corresponding DO2 crit's were 6.17 and 4.57 ml O2.kg-1.min-1 (P less than 0.05). The oxygen extraction ratios at DO2 crit for each of these temperatures did not differ significantly. We conclude that hypothermia, by lowering baseline VO2, reduces DO2 crit. Hypothermia may therefore reduce or eliminate the anaerobic metabolism and subsequent acidosis that would otherwise occur during normothermia at low levels of DO2.     

Effect of endotoxin on systemic and skeletal muscle O2 extraction

Patients with the adult respiratory distress syndrome (ARDS) show a pathological dependence of O2 consumption (VO2) on O2 delivery (QO2, blood flow X arterial O2 content). In these patients, a defect in tissues' ability to extract O2 from blood can leave tissue O2 needs unmet, even at a normal QO2. Endotoxin administration produces a similar state in dogs, and we used this model to study mechanisms that may contribute to human pathology. We measured systemic and hindlimb VO2 and QO2 while reducing cardiac output by blood withdrawal. At the onset of supply dependence, the systemic QO2 was 11.4 +/- 2.7 ml.kg-1.min-1 in the endotoxin group vs. 8.0 +/- 0.7 in controls (P less than 0.05). At this point, the endotoxin-treated animals extracted only 61 +/- 11% of the arterial O2, whereas control animals extracted 70 +/- 7% (P less than 0.05). Systemic VO2 rose by 15% after endotoxin (P less than 0.05) but did not change in controls. Despite this poorer systemic ability to extract O2 by the endotoxin-treated dogs, isolated hindlimb O2 extraction at the onset of supply dependence was the same in endotoxin-treated and control dogs. At normal levels of QO2, hindlimb VO2 in endotoxin-treated dogs was 23% higher than in controls (P less than 0.05). Fractional blood flow to skeletal muscle did not differ between control and endotoxin-treated dogs. Thus skeletal muscle was not overperfused in endotoxemia and did not contribute to a systemic extraction defect by stealing blood flow from other tissues. Skeletal muscle in endotoxin-treated dogs demonstrated an increase in VO2 but no defect in O2 extraction, differing in both respects from the intestine.     

Intrapulmonary oxygen consumption in experimental pneumococcal pneumonia

To test the hypothesis that lung affected by acute bacterial pneumonia consumes significant amounts of O2, whole-body O2 consumption (VO2) was measured simultaneously by collection of expired gas (VO2exp) and by the Fick principle (VO2Fick) in five dogs with acute experimental pneumococcal pneumonia and in five uninfected controls. This approach is based on the premise that VO2Fick will not detect lung VO2, whereas the expired gas measurement represents the true whole-body VO2, including the lung. In controls VO2 exp averaged 110 +/- 20 ml/min (4.78 +/- 0.78 ml.min-1.kg-1), and VO2Fick was nearly identical at 114 +/- 21 ml/min (4.96 +/- 0.79 ml.min-1.kg-1). The VO2Fick in the pneumonia group was 127 ml/min, similar to both control group values when indexed for body weight (4.91 +/- 1.17 ml.min-1.kg-1). VO2exp, however, was 146 +/- 46 ml/min (5.74 +/- 1.57 ml.min-1.kg-1), exceeding VO2Fick by an average of 20 +/- 9 ml/min (P less than 0.01). This between-method difference of 20 +/- 9 ml/min (or 24 ml/min if the difference in the control group is assumed to apply to the pneumonia group) amounted to 13-15% of whole-body VO2 and can be attributed to VO2 in the lung, presumably by cells involved in the acute inflammatory response. Implications include the potential for significant underestimate of whole-body VO2 by the Fick method when used in the presence of lung inflammation and overestimate of blood flow to shunting or low ventilation-perfusion ratio lung units by the O2 method of measuring venous admixture-like perfusion. This observation may also explain the disproportionate hypoxemia sometimes seen in patients with severe pneumonia.     

Low-dose dopamine hastens onset of gut ischemia in a porcine model of hemorrhagic shock.

Gut metabolism may become anaerobic before the whole body during progressive phlebotomy in dogs. Because dopamine has selective mesenteric vasodilator effects, we asked whether dopamine could delay onset of bowel ischemia during hemorrhagic shock. We studied whole body and gut O2 consumption (VO2) and O2 delivery (QO2) using progressive phlebotomy in anesthetized pigs. Nine pigs received a dopamine infusion of 2 micrograms.kg-1.min-1, whereas a control group of seven pigs received equivalent saline infusion. Onset of ischemia in whole body and gut was determined as critical O2 delivery (QO2c), the intersection point of biphasic regression on plots of VO2-QO2 relationships. Blood flow and O2 extraction were measured as mechanisms of gut ischemia for entire in situ small and large gut using a superior mesenteric venous fistula. Dopamine hastened onset of gut ischemia relative to onset of whole body ischemia (gut critical point in terms of whole body QO2 9.9 +/- 2.1 ml O2.kg-1.min-1, whole body QO2c 7.8 +/- 0.7 ml O2.kg-1.min-1, P less than 0.01). In contrast, onset of gut ischemia in control animals occurred at same time as onset of whole body ischemia (gut critical point in terms of whole body QO2 7.4 +/- 2.3 ml O2.kg-1.min-1, whole body QO2c 7.1 +/- 2.7 ml O2.kg-1.min-1, P = not significant). Hastening of onset of gut ischemia in dopamine-treated animals was associated with decreased ability of gut to extract O2. Low-dose dopamine was not protective against gut ischemia during shock but rather caused earlier onset of gut ischemia during hemorrhagic shock.     

Role of hemoglobin P50 in O2 transport during normoxic and hypoxic exercise in the dog

High hemoglobin affinity for O2 [low PO2 at 50% saturation of hemoglobin (P50)] could degrade exercise performance in normoxia by lowering mean tissue PO2 but could enhance O2 transport in hypoxic exercise by increasing arterial O2 saturation. We measured O2 transport at rest and at graded levels of steady-state exercise in tracheostomized dogs with normal P50 (28.8 +/- 1.8 Torr) and again after P50 was lowered (19.5 +/- 0.7 Torr) by sodium cyanate infusions. Measurements were made during ventilation with room air (RA), 12% O2 in N2, or 10% O2 in N2. Cardiac output (QT) as a function of O2 consumption (VO2) was not altered by low P50 at any inspired O2 fraction (P greater than 0.05). With RA exercise, arterial content (CaO2) and O2 delivery (QT X CaO2) were unchanged at low P50, whereas mixed venous PO2 was reduced at each level of VO2. With exercise in hypoxia, CaO2 and O2 delivery were significantly improved at low P50 (P less than 0.05). Mixed venous PO2 was lower than control during 12% O2 (P less than 0.05) but not different from control during 10% O2 exercise at low P50. Despite a presumed decrease in tissue PO2 during RA and 12% O2 exercise, exercise performance and base excess decline were not significantly worse than control levels. We conclude that, in canine steady-state exercise, hemoglobin P50 is not an important determinant of tissue O2-extraction capacity during normoxia or moderate hypoxia. In extreme hypoxia, low P50 may help to maintain tissue PO2 by enhancing systemic O2 delivery at each level of QT.     

Flow redistribution during progressive hemorrhage is a determinant of critical O2 delivery

O2 consumption (VO2) of anesthetized whole mammals is independent of O2 delivery (DO2) until DO2 declines to a critical value (DO2c). Below this value, VO2 becomes O2 supply dependent. We assessed the influence of whole body DO2 redistribution among organs with respect to the commencement of O2 supply dependency. We measured DO2, VO2, and DO2c of whole body, liver, intestine, kidney, and remaining carcass in eight mongrel dogs during graded progressive hemorrhage. Whole body DO2 was redistributed such that the organ-to-whole body DO2 ratio declined for liver and kidney and increased for carcass. We then created a mathematical model wherein each organ-to-whole body DO2 ratio remained approximately constant at all values of whole body DO2 and assigned organ VO2 to predicted organ DO2 by interpolation and extrapolation of observed VO2-DO2 plots. The model predicted that O2 supply dependency without redistribution would have commenced at a higher value of whole body DO2 for whole body (8.11 +/- 0.89 vs. 6.98 +/- 1.16 ml.kg-1.min-1, P less than 0.05) and carcass (6.83 +/- 1.16 vs. 5.06 +/- 1.15 ml.kg-1.min-1, P less than 0.01) and at a lower value of whole body DO2 for liver (6.33 +/- 1.86 vs. 7.59 +/- 1.95, ml.kg-1.min-1, P less than 0.02) and kidney (1.25 +/- 0.64 vs. 4.54 +/- 1.29 ml.kg-1.min-1, P less than 0.01). We conclude that redistribution of whole body DO2 among organs facilitates whole body O2 regulation.     

Critical O2 transport values at lowered body temperatures in rats

Whole-body O2 uptake (VO2) in rats was reported not to increase when total O2 transport (TOT = cardiac output X arterial O2 concentration) was increased above normal ranges when body temperature was kept at 38 degrees C (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 53: 660-664, 1982). Similar experiments were performed to see if hypothermic rats at 34 degrees C would increase VO2 with an increased TOT in an effort to generate heat. Anesthetized rats were ventilated with 9 or 12% O2 (hypoxia), room air (normoxia), and O2 (hyperoxia) to vary TOT from 52.6 to 6.6 ml X kg-1 X min-1. VO2 was measured in a closed-circuit, double servospirometer system. Although VO2 was significantly lower at 34 degrees C than the values previously found at 38 degrees C with normoxia and hyperoxia, there was no increase with increasing values of TOT. In spite of a lower plateau value of VO2 at 34 degrees C, the critical value of TOT below which VO2 could not be maintained was nearly the same as at 38 degrees C (22 ml X kg-1 X min-1). The reason for this was that O2 was less completely extracted as TOT was lowered below the critical value in the hypothermic animal. Some of the difficulty in extracting O2 at the tissues was probably due to the decrease in P50 (PO2 at 50% saturation) that occurs with decreased body temperature.     

Oxygen delivery rate and sufficiency of oxygenation during ECMO in newborn baboons

Minimum acceptable O2 delivery (DO2) during extracorporeal membrane oxygenation (ECMO) remains to be defined in a newborn primate model. The right atrium, carotid artery, and femoral artery were cannulated, and the ductus arteriosus, aorta, and pulmonary artery ligated in neonatal baboons (Papio cynocephalus) under a combination of ketamine, diazepam, and pancuronium. The internal jugular vein was also cannulated retrograde to the level of the occipital ridge. We measured hemoglobin, pH, arterial and venous PO2 (both from the pump circuit and from the cerebral venous site), serum lactate and bicarbonate concentrations, and pump flow, and we calculated hemoglobin saturations, (DO2), O2 consumption (VO2), systemic O2 extraction, and cerebral O2 extraction. Six baboons were studied during each of two phases of the experiment. In the first, flow rates were varied sequentially from 200 to 50 ml.kg-1.min-1 with saturation maximized. In the second, flow was maintained at 200 ml.kg-1.min-1 and saturation was reduced sequentially from 100 to 38%. VO2 fell significantly below baseline at a flow rate of 50 ml.kg-1.min-1 and a DO2 of 8 +/- 2 (SE) ml.kg-1.min-1 in phase 1 and at DO2 of 12 +/- 5 in phase 2. Both systemic and cerebral O2 extraction rose significantly at a flow of 100 ml.kg-1.min-1 and DO2 of 17 +/- 4 ml.kg-1.min-1 in phase 1, whereas neither rose with decreasing DO2 in phase 2. In fact, cerebral extraction fell significantly DO2 of 16 +/- 6 ml.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

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

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.     

Effect of alkalosis on maximum oxygen uptake in rats acclimated to simulated altitude.

The objective of the present experiments was to determine whether prevention or moderation of exercise acidosis would influence arterial blood oxygenation and exercise capacity in hypoxia. The effect of administration of 0.3 M NaHCO3 (3 ml/100 g) on maximum O2 uptake (VO2max) and arterial blood oxygenation was determined in rats acclimated to simulated altitude (370-380 Torr barometric pressure) for 3 wk (HxBic) and in normoxic littermates (NxBic). Controls were simulated-altitude (HxNaCl) and normoxic rats (NxNaCl) given 0.3 M NaCl. Inspiratory PO2 during treadmill exercise was approximately 70 Torr for hypoxic rats and 140-145 Torr for normoxic rats. VO2max was 18% higher in HxBic than in HxNaCl (62.8 + 1.6 vs. 53.1 + 1.0 ml STPD.min-1.kg-1, respectively, P less than 0.05) and only 8% higher in NxBic than in NxNaCl (74.0 + 1.1 vs. 68.7 + 1.5 ml STPD.min-1.kg-1, respectively, P less than 0.05). Exercise in HxNaCl resulted in a decrease in arterial O2 concentration (CaO2), which was largely due to a pH-induced decrease in O2 saturation of arterial blood, and occurred despite an increase in arterial PO2. NaHCO3 moderated the acidosis of exercise and largely attenuated the decrease in CaO2. The effects of acidosis and bicarbonate on CaO2 were much less evident in the normoxic controls. There was an almost linear relationship between VO2max and the corresponding CaO2 for all four groups, suggesting that the effect of NaHCO3 on VO2max may be related to moderation of the decrease in CaO2.     

Effects of increased pulmonary vascular tone on gas exchange in canine oleic acid pulmonary edema

Pulmonary gas exchange was investigated before and after an increase in pulmonary vascular tone induced by administration of acetylsalicylic acid (ASA), indomethacin, or almitrine in 32 pentobarbital-anesthetized and ventilated (fraction of inspired O2 0.4) dogs with oleic acid lung injury. Pulmonary vascular tone was evaluated by five-point pulmonary arterial pressure (PAP)/cardiac index (Q) plots and intrapulmonary shunt was measured using a SF6 infusion. PAP/Q plots were rectilinear in all experimental conditions. In control dogs (n = 8), oleic acid (0.09 ml/kg iv) increased PAP over the range of Q studied (1-5 l.min-1.m-2). At the same Q, arterial PO2 fell from 186 +/- 11 to 65 +/- 8 (SE) Torr and intrapulmonary shunt rose from 5 +/- 1 to 50 +/- 6% 90 min after oleic acid injection. These changes remained stable during the generation of two consecutive PAP/Q plots. ASA (1 g iv, n = 8), indomethacin (2 mg/kg iv, n = 8), and almitrine (8 micrograms.kg-1.min-1 iv, n = 8) produced a further increase in PAP at each level of Q. ASA and indomethacin, respectively, increased arterial PO2 from 61 +/- 4 to 70 +/- 3 Torr (P less than 0.05) and from 70 +/- 6 to 86 +/- 6 Torr (P less than 0.05) and decreased intrapulmonary shunt from 61 +/- 5 to 44 +/- 4% (P less than 0.05) and from 44 +/- 5 to 29 +/- 4% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Maximum oxygen uptake and arterial blood oxygenation during hypoxic exercise in rats.

The objectives of these experiments were 1) to describe the effect of maximum treadmill exercise on gas exchange, arterial blood gases, and arterial blood oxygenation in rats acclimated for 3 wk to simulated altitude (SA, barometric pressure 370-380 Torr) and 2) to determine the contribution of acid-base changes to the changes in arterial blood oxygenation of hypoxic exercise. Maximum O2 uptake (VO2max) was measured in four groups of rats: 1) normoxic controls run in normoxia (Nx), 2) normoxic controls run in acute hypoxia [AHx inspiratory PO2 (PIO2) approximately 70 Torr], 3) SA rats run in hypoxia (3WHx, PIO2 approximately 70 Torr), and 4) SA rats run in normoxia (ANx). VO2max (ml STPD.min-1.kg-1) was 70.8 +/- 0.9 in Nx, 46.4 +/- 1.9 in AHx, 52.6 +/- 1.1 in 3WHx, and 70.0 +/- 2.4 in ANx. Exercise resulted in acidosis, hypocapnia, and elevated blood lactate in all groups. Although blood lactate increased less in 3WHx and ANx, pH was the same or lower than in Nx and AHx, reflecting the low buffer capacity of SA. In AHx and 3WHx, arterial PO2 increased with exercise; however, O2 saturation of hemoglobin in arterial blood (SaO2) decreased. In vitro measurements of the Bohr shift suggest that SaO2 decreased as a result of a decrease in hemoglobin O2 affinity. The data indicate that several features of hypoxic exercise in this model are similar to those seen in humans, with the exception of the mechanism of decrease in SaO2, which, in humans, appears to be due to incomplete alveolar-capillary equilibration.