SYSTEMIC AND PULMONARY-HYPERTENSION AFTER RESUSCITATION WITH CELL-FREE HEMOGLOBIN

Human hemoglobin (Hb) and Hb cross-linked between the alpha subunits with bis(3,5-dibromosalicyl)fumarate (alphaalphaHb) were used to treat hemorrhagic shock in water-deprived swine. Water was withheld for 48 h to induce a 10% loss of body mass, and 25 ml/kg of blood were removed in 1 h to produce circulatory shock. Swine were resuscitated with 1) Hb, 2) alphaalphaHb, 3) human serum albumin, or 4) Ringer lactate. Mild high-output renal failure was observed in the non-cross-linked Hb-treated animals but not in other groups of animals. Swine treated with Hb and alphaalphaHb had increases in plasma creatine kinase and lactate dehydrogenase activity that were resolved within 7 days. Both Hb- and alphaalphaHb-treated swine displayed marked elevations of mean blood pressure in the systemic (39 +/- 6 Torr) and pulmonary (20 +/- 6 Torr) circulations that continued for 3 h and were associated with reduced cardiac output and a doubling of the systemic and pulmonary vascular resistances. Oxygen delivery was equivalent, and the rate of correction of the lactic acidosis was equal in all groups.