Studies on Blood Substitutes Based on Hemoglobin and Perfluorocarbon

Abstract

Unmodified, and to a lesser extent, modified stromafree hemoglobin preparations have been reported to exhibit coronary and renal vasoconstrictor activity in isolated perfused hearts and kidneys. The physiological significance in vivo of such ex vivo demonstrated vasoconstriction has not yet been established. We have conducted a number of in vivo dog experiments designed to elucidate (a) whether free hemoglobin in the plasma phase contributes to diffusive oxygen supply to the tissues and (b) whether excessive vasoconstriction results in functional impairment. Our findings indicate that (a) the infusion of unmodified SFHS does not cause a significant disturbance of central hemodynamics, although it causes an elevation of the arterial blood pressure; the latter is accompanied by vasoconstriction in the skeletal muscle vascular bed and in the renal cortex; (b) there is no significant improvement of diffusive oxygen supply to the tissue at rest; and (c) that glutaraldehyde cross-linked SFHS administered to hypotensive dogs causes a brief further aggravation of hypotension as well as renal vasoconstriction accompanied by renal functional impairment. The findings suggest that coronary autoregulatory mechanisms in vivo can override the vasoconstrictor potency demonstrated in viero, but the renal effects of SFHS containing unmodified hemoglobin can give rise to significant concern.

Perfluoro-octyl-bromide (recently renamed perflubron) preparations were tested in isolated perfused rat and pig hearts. Aqueous perfusate supplemented with an earlier preparation of PFOB increased contractile performance of rat hearts. Later preparations of PFOB used to supplement perfusate of low hematocrit (< 10%) red cell suspension, while having no deleterious effects, did not augment contractile performance of isolated, perfused pig hearts. There was, however, a significant augmentation of contractile performance when PFOB was used as a supplement to an aqueous buffer perfusate in isolated pig hearts.