Vasoconstrictive response of rat mesenteric arterioles following infusion of cross-linked, polymerized, and conjugated hemoglobin solutions.
Infusion of hemoglobin-based oxygen-carrying solutions (HBOCs) produce an immediate rise in blood pressure with most solutions, both in animals and humans, as a result of systemic and pulmonary vasoconstriction. Autoregulation of the O2 supply by the microvasculature has been proposed as a phenomenon involved in the vasoconstriction elicited by HBOCs. Nevertheless, little is known about the ability of various HBOCs to induce constriction in the microcirculation according to their specific physicochemical properties (viscosity, molecular weight, P50, etc.). This study was therefore designed to assess the effects of three HBOCs, that is, bis(3.5-dibromosalicyl) fumarate-crosslinked hemoglobin (alphaalpha-Hb), dextran-benzene-tetracarboxylate-conjugated hemoglobin (Hb-Dex-BTC) and o-raffinose-oligomerized hemoglobin (o-raffinose-Hb), on the vascular tone of rat mesenteric arterioles (diameter, 15-25 microm) viewed microscopically in moderate hemodilution conditions. The effects of HBOCs were compared to those elicited by a reference solution of hydroxyethyl starch (HES-200) infused in the same conditions. In each experimental group, a fall in arteriolar diameter was observed 2 min and 5 min after infusion of the solution. The maximum changes were observed in Hb-Dex-BTC and o-raffinose-Hb groups, in which diameter decreased from 6.9 +/- 0.5% and 5.2 +/- 0.7%, respectively, 2 min after infusion. The changes in arteriolar diameter induced by Hb-Dex-BTC and o-raffinose-Hb were significantly higher than those elicited by HES-200 and alphaalpha-Hb. In conclusion, our data indicate that moderate hemodilution with HBOCs induces instantaneous constriction in rat mesenteric arterioles, with amplitudes depending on both pharmacological and physicochemical properties of the hemoglobin solution infused.
Department of Hematology and Physiology, Faculty of Pharmacy, University Henri Poincaré-Nancy 1, France.
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Caron
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Malfatti
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Aguejouf
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Faivre-Fiorina
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D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001802:Blood Substitutes / Q000008:administration & dosage / Q000494:pharmacology*; D003911:Dextrans / Q000008:administration & dosage / Q000494:pharmacology; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008643:Mesentery / Q000098:blood supply*; D011887:Raffinose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*
D001802:Blood Substitutes; D003911:Dextrans; D006454:Hemoglobins; C097124:O-raffinose cross-linked human hemoglobin; C053936:hemoglobin XL99alpha; C095659:hemoglobin-dextran 10-benzene-tetracarboxylate; D011887:Raffinose; D001241:Aspirin