Coronary constrictor effect of stroma-free hemoglobin solutions

Abstract

A coronary vasoconstrictor effect of human stroma-free hemoglobin (SFH) was identified in isolated rabbit hearts perfused with Krebs-Henseleit buffer or whole rabbit blood at a constant coronary flow rate. In buffer-perfused hearts, SFH in concentrations of 5 to 200 mg/dl produced dose-related increases of coronary perfusion pressure. At a concentration of 150 mg/dl, SFH, equilibrated with CO to form carboxyhemoglobin, caused an increase in perfusion pressure (55 +/- 7 mmHg), similar to that observed with oxyhemoglobin (57 +/- 6 mmHg); addition of potassium ferricyanide to form methemoglobin reduced the increase of perfusion pressure to 34 +/- 5 mmHg (P less than 0.05). The vasoconstrictor activity could not be eliminated by dialyzing against the perfusion buffer. Human SFH prepared by different methods had similar vasoconstrictor activity. Rabbit SFH and human SFH were equi-effective in the rabbit heart. Less constrictor activity of SFH was evident in rat and guinea pig heart. Polymerized, pyridoxalated SFH had greatly reduced constrictor effect compared with unmodified or pyridoxalated tetramer SFH. In blood-perfused hearts, increasing plasma hemoglobin to 1.6 +/- 0.1 g/dl, without changing total hemoglobin or arterial O2 content, increased coronary perfusion pressure by 36 +/- 13 mmHg (P less than 0.05). We conclude that stroma-free hemoglobin solutions exert a coronary vasoconstrictor effect that is unrelated to O2 delivery.

Inhaled Nitric Oxide Enables Artificial Blood Transfusion Without Hypertension

“…21 A major limitation to the clinical application of artificial blood transfusion has been the concern that some HBOC have caused coronary vasoconstriction that would reduce coronary perfusion and result in myocardial ischemia. [22][23][24][25] Several hemoglobin modifications have been attempted to limit vasoconstriction after HBOC administration. One strategy has been to genetically engineer the heme pocket of hemoglobin to reduce its NO affinity.…”

Control of coronary vascular tone by nitric oxide.

“…There are good reasons to assume that the NO-mediated control is not restricted to the saline-perfused isolated heart: Increasing plasma hemoglobin in blood-perfused rabbit hearts, while keeping total hemoglobin and arterial oxygen content constant, exerted a pronounced coronary vasoconstrictory effect. 53 …”

The potential of Angeli's salt to decrease nitric oxide scavenging by plasma hemoglobin

“…The increased ability of cell-free Hb to scavenge NO has been widely attributed to the hypertension, increased systemic and pulmonary vascular resistance, and morbidity and mortality associated with administration of hemoglobin-based oxygen carriers (HBOCs or "blood substitutes") [53][54][55][56][57][58][59][60][61][62][63][64][65][66][67]. More recently, the importance of intravascular hemolysis on NO bioavailability in diseased states including hemolytic anemias like sickle cell disease and paroxysmal nocturnal hemoglobinuria (PNH), thalassemia intermedia, malaria, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome and cardiopulmonary bypass has been elucidated [17][18][19][68][69][70][71][72][73].…”