Effect of liposome-encapsulated hemoglobin on the development of endotoxin-induced shock in the rat.
Liposome-encapsulated hemoglobin (LEH) is an experimental oxygen-carrying resuscitation fluid. Because LEH is cleared from the circulation primarily by the reticuloendothelial system, its effect on the development of sepsis remains a major concern. Thus, the present study aimed to evaluate whether LEH modifies consequences of endotoxemia in the conscious normovolemic rat. LEH infusion at 10% of estimated blood volume (n = 10) did not affect mortality (30%, p < .05) and serum tumor necrosis factor-alpha levels (6204 +/- 414, p < .05) induced by 3.6 mg/kg Escherichia coli endotoxin administered (intravenous bolus) 22 h later. In contrast, when a shorter LEH-endotoxin time interval (<12 h, n = 10) or a higher dose of endotoxin (14.4 mg/kg, n = 20) was tested, LEH enhanced endotoxin-induced mortality (90% and 100%, respectively, p < .05) and broadened serum tumor necrosis factor-alpha response without modifying its peak levels. LEH (n = 20) did not exacerbate the endotoxin-induced tachycardia, leukopenia, and thrombocytopenia. Therefore, in this model, the effect of LEH on endotoxin-induced responses was dependent on the time interval between LEH and endotoxin administration as well as the endotoxin dose. The clinical relevance of these results should be further investigated.
Whiteford
M
M
Department of Surgery, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
Spirig
A
A
Rudolph
A
A
Neville
L
L
Abdullah
F
F
Feuerstein
G
G
Rabinovici
R
R
D000818:Animals; D001802:Blood Substitutes / Q000008:administration & dosage* / Q000627:therapeutic use*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D006339:Heart Rate; D006454:Hemoglobins / Q000008:administration & dosage* / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008081:Liposomes; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy*; D013929:Thromboxane B2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001802:Blood Substitutes; D006454:Hemoglobins; D008070:Lipopolysaccharides; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D013929:Thromboxane B2