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.


METHODS
Prospective, randomized trial.


METHODS
Animal laboratory, Jefferson Medical College.


METHODS
Eighty-four male Sprague-Dawley rats.


METHODS
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.


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 B2 concentrations (14.6 +/- 6 pg/100 microL, 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.
Rabinovici
R
R
Department of Surgery, Jefferson Medical College, Philadelphia, PA 19107-5083.
Rudolph
A S
AS
Vernick
J
J
Feuerstein
G
G
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D004337:Drug Carriers; D005612:Freeze Drying; D006439:Hemodynamics / Q000187:drug effects*; D006454:Hemoglobins / Q000494:pharmacology*; D008081:Liposomes; D008297:Male; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004337:Drug Carriers; D006454:Hemoglobins; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha