Coronary vasoconstrictor activity of purified and modified human hemoglobin

Unpurified stroma-free hemoglobin (SFH) from water-lysed human red blood cells, hemoglobin Ao (HbAo), and hemoglobin cross-linked between alpha chains with 3,5-bis-dibromosalicyl-fumarate (HbXLDBBF) were infused into isolated perfused rabbit hearts. Vasoactivity and myocardial performance were determined using an isovolumic Langendorff preparation. With constant coronary flow, infusion of SFH (55 mg/dl) resulted in a 56% increase in aortic pressure as opposed to 29% and 11% increases with HbAo and HbXLDBBF, respectively. Rates of aortic pressure increase were over 6 times greater with SFH than with either HbAo or HbXLDBBF and exhibited concentration dependence only with SFH. Myocardial function remained normal. With constant coronary pressure, coronary flow decreased by 36% with SFH accompanied by a 23% decline in left ventricular developed pressure indicative of ischemia. With HbAo or HbXLDBBF, coronary flow decreased by only 1/3 that with SFH, while developed pressure declined by 4% and 2% with HbAo and HbXLDBBF, respectively. These data suggest that purification of HbAo to a single component can eliminate the dominant of at least two distinct vasoactive factors normally found in SFH. Furthermore, the physiological significance of the vascular response to HbAo is minimal. Preparations of HbXLDBBF accomplish this same result.