LYOPHILIZED LIPOSOME-ENCAPSULATED HEMOGLOBIN - EVALUATION OF HEMODYNAMIC, BIOCHEMICAL, AND HEMATOLOGIC RESPONSES

Objective: To characterize the hemodynamic, biochemical, and hematologic responses to the administration of the oxygen-carrying fluid lyophilized Liposome-encapsulated hemoglobin in the conscious, normovolemic rat. Design: Prospective, randomized trial. Setting: Animal laboratory, Jefferson Medical College. Subjects: Eighty-four male Sprague-Dawley rats. Interventions: Catheters were introduced into the right atrium (through the jugular vein) and both femoral arteries of test animals, and a thermistor was placed in the ascending aorta through the left common carotid artery for infusion of lyophilized liposome-encapsulated hemoglobin, blood collection, and blood pressure (BP) and cardiac output determinations. Measurements and Main Results: Lyophilized liposome-encapsulated hemoglobin (n = 8) infusion (1 mL/min iv) at 1 or 6 mL/kg (10% of estimated blood volume) had no detectable effect on BP, cardiac output, total peripheral resistance, and heart rate during the 5-hr observation period, The infusion also had no effect on hematocrit, leukocyte count, and serum tumor necrosis factor-alpha concentrations. Survival at 7 days was 100% (n = 20). Lyophilized liposome-encapsulated hemoglobin caused transient (2-hr) thrombocytopenia (-24+/-9% vs. a Ringer's lactate control group, p < .01), and marginally increased serum thromboxane B-2 concentrations (14.6+/-6 pg/100 mu L, p < .01). Conclusions: These data suggest that lyophilized liposome-encapsulated hemoglobin can be safely administered to conscious rats, supporting the development of this substance as a potential blood substitute.