A novel hemoglobin-based blood substitute protects against myocardial reperfusion injury.
HBOC-201 (Biopure; Cambridge, MA) is a glutaraldehyde-polymerized bovine hemoglobin (Hb) solution that is stroma free, has lower viscosity than blood, and promotes O(2) unloading. We investigated the effects of HBOC-201 in a canine model of myocardial ischemia-reperfusion injury. Dogs were anesthetized and subjected to 90 min of regional myocardial ischemia and 270 min of reperfusion. HBOC-201 or 0.9% saline vehicle equivalent to 10% total blood volume was infused 30 min before myocardial ischemia. Hemodynamic data and peripheral blood samples were taken at baseline, 1 h of myocardial ischemia, and 1, 2, and 4 h of reperfusion. At 270 min of reperfusion, the area at risk (AAR) per left ventricle and the area of infarction (Inf) per AAR were determined. The myocardial AARs in the two study groups were similar. In addition, myocardial blood flow (as measured by radioactive microspheres) in the ischemic zone was similar between the vehicle and HBOC-201 groups. HBOC-201-infused dogs demonstrated a significant (P < 0.01) 56% reduction in Inf/AAR. Analysis of blood samples taken at 4 h of reperfusion showed a significant (P < 0.05) reduction in creatine kinase MB isoform for the HBOC-201 group. Histological analysis of the myocardium demonstrated significant (P < 0.01) reductions in neutrophil infiltration in the HBOC-201 group. These data indicate that treatment with HBOC-201 before myocardial ischemia-reperfusion reduces the extent of myocardial inflammation and ischemia-reperfusion injury in the canine myocardium.
Caswell
John E
JE
Dept. of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
Strange
Micah B
MB
Rimmer
David M
DM
Gibson
Michael F
MF
Cole
Phillip
P
Lefer
David J
DJ
D000818:Animals; D001794:Blood Pressure; D001802:Blood Substitutes / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D052279:Creatine Kinase, MB Form; D004285:Dogs; D005260:Female; D006339:Heart Rate; D006454:Hemoglobins / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D009504:Neutrophils / Q000166:cytology; D010976:Platelet Count; D017725:Ventricular Pressure
D001802:Blood Substitutes; D006454:Hemoglobins; D007527:Isoenzymes; C096798:HBOC 201; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form