Search

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)

We previously showed that stress failure of pulmonary capillaries occurs at transmural pressures of approximately 50 cmH2O (40 mmHg) and above in rabbit lung. In this study, we examined whether pulmonary capillaries are more resistant to failure in dogs than in rabbits. This might be expected because of the greater athletic ability of dogs and therefore their presumably greater tolerance to large cardiac outputs and higher pulmonary vascular pressures. The lungs of 12 anesthetized mongrel dogs [22.1 +/- 5.2 (SD) kg] were perfused in situ with autologous blood and then with saline-dextran (5 min) and glutaraldehyde solution (10 min), all three perfusions at the same preset transmural pressure of 32.5, 72.5, 92.5, or 112.5 cmH2O. In dogs, the stress failure curves relating break number per millimeter of epithelium and endothelium were right shifted by approximately 40 cmH2O compared with rabbits. Blood-gas barrier thickness was significantly greater than in rabbits at 32.5 cmH2O, and unlike in rabbits, neither total nor interstitial thickness increased significantly with increasing pressure. These results indicate that pulmonary capillaries are more resistant to stress failure in dogs than rabbits.

Federspiel et al.1 have suggested that the plasma space between red blood cells in capillaries does not contribute significantly to diffusive O2 transport out of the muscle vasculature due to the low plasma solubility of O2. To test this, we pump-perfused in situ isolated canine gastrocnemius muscle stimulated electrically to produce VO2 max under two conditions [with blood flow 120 ml 100 gm−1 min−1, [Hb] 8.7 gm dl−1 and PaO2 ~ 500 torr in each case]: A) control, and B) with Oxygent (perflubron emulsion, Alliance) added at 6 gm perflubron/70 ml. Total plasma O2 solubility was taken to be 0.003 ml 100 ml−1 torr−1 in A) and computed to be 0.005 ml 100 ml−1 torr−1 in B) from the increase in total [O2] in B) compared to A).

During induced hypothermia with cardiopulmonary bypass, acid-base management usually follows one of two strategies: the so-called ectothermic or alpha-stat strategy, in which the pH of the arterial blood increases 0.015 pH units for every degree Celsius decrease in body temperature, or the pH-stat strategy, in which pH remains 7.4 at all temperatures. It has been assumed that oxygen consumption decreases approximately equally during hypothermia with either strategy, although there are biochemical reasons to hypothesize that oxygen consumption would be better maintained with the alpha-stat strategy. We also hypothesized that venous oxygen tension would be lower with the more alkaline alpha-stat strategy than with the pH-stat acid-base strategy, because of the Bohr effect. We tested these hypotheses by placing 10 anesthetized immature domestic pigs on cardiopulmonary bypass. We measured whole body oxygen consumption and myocardial oxygen consumption. Control measurements were made at 37 degrees C. Then the animals were cooled to 27 degrees C and the measurements were repeated. The alpha-stat strategy (pH 7.554 +/- 0.020 at 27 degrees C) was used in five animals and five animals received pH-stat management (pH 7.409 +/- 0.012 at 27 degrees C). Whole body and myocardial oxygen consumption rate decreased in both groups, but more so in the alpha-stat animals than in the pH-stat animals. The unexpectedly high oxygen consumption in the pH-stat animals also resulted in a lower than expected venous oxygen tension. Thus the effect of hypothermia in reducing oxygen consumption was less pronounced with pH-stat acid-base management.

Previous studies on normal subjects and patients with polycythemia have given conflicting results of the effect of polycythemia on pulmonary gas exchange. We studied acutely induced normovolemic polycythemia in the dog and measured arterial blood gases and ventilation-perfusion (VA/Q) relationships using the multiple inert gas elimination technique. The mean base-line hematocrit of 43 +/- 5% was increased to 57 +/- 4 and 68 +/- 8%, respectively, after two exchange transfusions of packed erythrocytes. Subsequent plasma exchange transfusions returned the mean hematocrit to 44 +/- 4%. Polycythemia caused no significant arterial hypoxemia; indeed there was a slight improvement in the alveolar-arterial PO2 difference. The multiple inert gas elimination measurements showed no increase in VA/Q inhomogeneity with no increase in log SD ventilation (V) or log SD blood flow (Q). There was a shift of mean V and mean Q to high VA/Q areas because of a decrease in cardiac output, presumably caused by increased blood viscosity. This study showed no deleterious effects on pulmonary gas exchange within the hematocrit range of 36-76%.

A simple expression is derived to describe the partial pressure at 50% hemoglobin saturation with oxygen (P50) that maximizes venous oxygen tension (PO2) for a given arterial PO2 and oxygen consumption. That “optimal P50” also maximizes arteriovenous saturation differences for given arterial and venous PO2 values. The optimal P50 can be expressed as the square root of the product of arterial and venous PO2 values. Alternatively, it can be expressed as a simple function of the arterial PO2 and the arteriovenous saturation difference. Nomograms summarize the relationships between the variables, and published observations that suggest an observational basis for our theoretical analysis are reviewed. We conclude that for normoxia or moderate hypoxia a high P50 is advantageous, whereas for more severe hypoxia or increased metabolic demands, a low P50 is advantageous.

Two chronic animal models and one acute animal model were used to evaluate exchange transfusion with stroma-free hemoglobin solutions. A direct comparison was made between stroma-free hemoglobin solutions having differing oxygen offloading characteristics as well as a colloid solution consisting of 7% bovine albumin. These studies involved a partial exchange involving approximately 50% of the animal's blood volume to simulate a clinically more appropriate partial blood replacement situation. We noted a consistent increase in the arterial oxygen content of animals exchanged with the stroma-free hemoglobin solutions and some modest improvement in oxygen dynamics. Our studies examining myocardial contractility, especially those carried out in the right heart bypass swine preparation failed to substantiate any difference between an exchange with albumin or stroma-free hemoglobin solutions. The conscious animal models examined both at rest and at exercise demonstrated marked differences in exercise response. Animals exchanged transfused with stroma-free hemoglobin solutions often had an almost normal exercise response while those animals exchanged with non-oxygen carrying albumin solution frequently failed to exercise on a treadmill. Blood flow measurements using radiolabeled microspheres were performed in chronically instrumented swine. These animals had a normal variation in organ blood flow during exercise which was noted both during the control period as well as following exchange with stroma-free hemoglobin solutions. Animals exchanged transfused with albumin had a marked derangement in organ blood flow apparently reflecting the decreased oxygen availability. Results from these three studies substantiate a significant benefit to animals undergoing a 50% exchange when that exchange is done with an oxygen carrying solution such as stroma-free hemoglobin solutions as opposed to a non-oxygen carrying but oncotically active solution such as albumin solution. These studies seem to offer encouragement to the continued investigation and ultimate clinical utilization of hemoglobin solutions as an appropriate blood substitute.