PEG-Hemoglobin as a resuscitation solution in the treatment of hypovolemic shock in the anesthetized rat.
This study was designed to determine the advantages of using the hemoglobin-based oxygen carrier, polyethylene glycol conjugated bovine hemoglobin (PEG-Hb), as an additive to Ringer's lactate solution (RLS) for the treatment of acute hemorrhage in anesthetized female rats. Different compositions of PEG-Hb and RLS were administered intravenously in a paradigm that provided 30 ml/kg of resuscitation fluid following an episode of 15 min of hypotension. Hypotension was achieved by the removal of blood (1 ml/min) from the femoral vein until the mean arterial pressure was lowered to or below 50 mmHg and subsequently maintained until resuscitation. Short-term cardiovascular assessment showed that resuscitation fluids containing PEG-Hb resulted in higher mean arterial pressure, aortic blood flow, renal blood flow, and less dramatic shifts in arterial base excess and respiratory blood gases than plain RLS. The long-term survival experiment showed lower lactate dehydrogenase, alkaline phosphatase, and serum glutamic pyruvic transaminase levels in most groups resuscitated with solutions containing PEG-Hb, but no differences in survival (100%) were observed. The data suggest that the addition of PEG-Hb to RLS improves its resuscitative effects. Specifically, a solution of 50% RLS:50% PEG-Hb appeared to have the most favorable cardiovascular and metabolic effects in this anesthetized rat hypovolemic shock resuscitation model. Presumably, the improved effects seen with the addition of PEG-Hb were due to its innate plasma expansion and oxygen-delivery capabilities.
Conover
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Research and Development, Pharmacology and Toxicology Department, Enzon, Inc., Piscataway, NJ 08854
Linberg
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R
Lejeune
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L
Nagy
M
M
Shum
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KL
D000704:Analysis of Variance; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000008:administration & dosage*; D002245:Carbon Dioxide / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006454:Hemoglobins / Q000008:administration & dosage*; D006863:Hydrogen-Ion Concentration; D010100:Oxygen / Q000097:blood; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000503:physiopathology / Q000628:therapy*; D012996:Solutions; D014655:Vascular Resistance / Q000187:drug effects
D001802:Blood Substitutes; D006454:Hemoglobins; C109960:PEG-hemoglobin; D012996:Solutions; D002245:Carbon Dioxide; D011092:Polyethylene Glycols; D010100:Oxygen