The aim of this study was to test whether oxygenation in acutely ischemic, collateralized tissue may be improved by normovolemic hemodilution with a solution containing liposome-encapsulated human Hb (HbV). A skin flap model in anesthetized hamsters was used, which consisted of two parts receiving either anatomic or collateral perfusion. Microhemodynamics were investigated with intravital microscopy. Partial tissue oxygen tension was measured with a Clark-type microprobe. Hemodilution was obtained by exchanging 50% of the total blood volume with HbV suspended in 8% human serum albumin (HSA8) or 6% Dextran 70 (Dx70). The size of the vesicles was 276 nm, the P50 was 22 mmHg, and the Hb concentration of the solutions was 7.5 g/dl. Colloid osmotic pressure and viscosity were 49.9 mmHg and 8.7 cP for HbV-Dx70 and 40.0 mmHg and 2.9 cP for HbV-HSA8, respectively. Hemodilution with HbV-Dx70 led to an increase in microvascular blood flow in the ischemic microvessels to maximally 158% (median, P < 0.01), whereas blood flow remained virtually unchanged after hemodilution with HbV-HSA8. In the ischemic tissue, oxygen tension was improved from 11.9 to 17.0 mmHg ( P < 0.01) after hemodilution with HbV-Dx70 but remained virtually unchanged after hemodilution with HbV-HSA8. Our study suggests that the oxygenation in acutely ischemic, collateralized tissue may be improved by normovolemic hemodilution with HbV suspended in Dx70. The effect was achieved by an increase in microcirculatory blood flow related to the rheological properties of the suspending medium.
. Improved oxygenation in ischemic hamster flap tissue is correlated with increasing hemodilution with Hb vesicles and their O 2 affinity. Am J Physiol Heart Circ Physiol 285: H1140-H1147, 2003. First published May 8, 2003 10.1152/ ajpheart.00285.2003.-The aim of this study was to test the influence of oxygen affinity of Hb vesicles (HbVs) and level of blood exchange on the oxygenation in collateralized, ischemic, and hypoxic hamster flap tissue during normovolemic hemodilution. Microhemodynamics were investigated with intravital microscopy. Tissue PO 2 was measured with Clarktype microprobes. HbVs with a P 50 of 15 mmHg (HbV15) and 30 mmHg (HbV30) were suspended in 6% Dextran 70 (Dx70). The Hb concentration of the solutions was 7.5 g/dl. A stepwise replacement of 15%, 30%, and 50% of total blood volume was performed, which resulted in a gradual decrease in total Hb concentration. In the ischemic tissue, hemodilution led to an increase in microvascular blood flow to maximally 141-166% of baseline in all groups (median; P Ͻ 0.01 vs. baseline, not significant between groups). Oxygen tension was transiently raised to 121 Ϯ 17% after the 30% blood exchange with Dx70 (P Ͻ 0.05), whereas it was increased after each step of hemodilution with HbV15-Dx70 and HbV30-Dx70, reaching 217 Ϯ 67% (P Ͻ 0.01) and 164 Ϯ 33% (P Ͻ 0.01 vs. baseline and other groups), respectively, after the 50% blood exchange. We conclude that despite a decrease in total Hb concentration, the oxygenation in the ischemic, hypoxic tissue could be improved with increasing blood exchange with HbV solutions. Furthermore, better oxygenation was obtained with the left-shifted HbVs. blood substitutes; artificial red blood cells; microhemodynamics; hypoxia; collateral circulation MAINTAINING ADEQUATE OXYGENATION is crucial for functional recovery and survival of cerebral, myocardial, mesenteric, or peripheral tissues rendered ischemic due to acute obstruction of their anatomic blood supply. In this scenario, oxygenation is determined by the amount of oxygen that is transported into the infarcted tissue via a collateral vasculature as well as by the potential of the oxygen carrier to deliver oxygen to this tissue.Oxygenation and survival of ischemic myocardial (7, 19), cerebral (3, 18, 29), and peripheral tissues (2) could successfully be improved after the infusion of solutions containing artificial oxygen carriers, such as perfluorocarbons and chemically modified Hbs. These solutions have initially been developed with the scope of reducing the need of allogeneic blood transfusions, and at least four compounds are currently in advanced clinical trials to evaluate their potential as red blood cell (RBC) substitutes in blood loss (1, 10).In a recent study (6), we were able to demonstrate that hypoxia in ischemic, collateralized hamster flap tissue was attenuated by a 50% blood exchange with a solution containing Hb vesicles (HbVs) suspended in 6% Dextran 70 (Dx70). The effect was associated with an increased capacity to transport oxygen to the ischemic tissue...
Our results suggest that the oxygenation in ischemic and hypoxic flap tissue may be improved by normovolemic hemodilution. The maximal benefit may be expected at a hemoglobin concentration at or slightly less than 9 g/dl.
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