Exchange transfusion with albumin-heme as an artificial O-2-infusion into anesthetized rats: Physiological responses, O-2-delivery, and reduction of the oxidized hemin sites by red blood cells

Human serum albumin (HSA) incorporating synthetic hemes, the tetrakis(o-piv alamido)phenyl-porphinatoiron(II) derivative (FeP), is an artificial hemopr otein (HSA-FeP) which is able to reversibly bind and release dioxygen under physiological conditions (in aqueous media, pH 7.4, 37 degrees C) like hem oglobin and myoglobin. Physiological responses to exchange transfusion with HSA-FeP solution [[HSA], 5 g/dL; FeP/HSA, 4 (mol/mol)] into rats after hem odilution and hemorrhage (Hct, about 10%) has been evaluated. The declined mean arterial pressure (MAP) and blood flow after a 70% exchange with HSA a nd the further 40% bleeding of blood were significantly recovered up to abo ut 90% of the baseline values by the injection of HSA-FeP. Furthermore, the renal cortical O-2-tensions and skeletal. tissue O-2-tensions were also in creased, indicating the in vivo O-2-delivery of HSA-FeP. Autoxidation of fe rrous Fe(II)P to ferric Fe(III)P was retarded in the blood stream; the half -lifetime of the dioxygenated FeP [tau(1/2)(O-2)] in vivo was 4.1 h [cf. 1. 0 h (in vitro)]. It has been found that autooxidized Fe(III)P was certainly reduced in the whole blood suspension. Physiological concentrations of asc orbic acid continuously provided by red blood cells probably rereduces Fe(I II)P, leading to the apparent long lifetime of the dioxygenated species of FeP.