Therapeutic defibrination with ancrod does not protect canine myocardium from reperfusion injury.
The purpose of this study was to determine whether normal fibrinogen contributes to the development of myocardial reperfusion injury by acting as a substrate in vivo for neutrophil adhesion. This was tested in a dog model of acute myocardial infarction that used pentobarbital anesthetized dogs subjected to 90 min regional myocardial ischemia and 5 h reperfusion. Dogs were treated with 1 unit/kg Ancrod (venom from the Malayan pit viper, Agkistrodon rhodostoma) or vehicle i.v. 60 min after left circumflex coronary artery occlusion. Therapeutic defibrination was verified in Ancrod-treated dogs by measurements of clottable fibrinogen, alpha-2 antiplasmin and plasminogen, by the activated partial thromboplastin time and by immunoelectrophoresis. Fibrinogen was depleted to below detectable limits of the assay (less than 0.05 mg/ml) after treatment with Ancrod. The defibrination effect was accomplished by the expected activation of the fibrinolytic system: alpha-2 antiplasmin was decreased by 10% and plasminogen activity was decreased by 30% with Ancrod treatment. There were no measureable differences between the two treatment groups in heart rate, mean arterial blood pressure, rate pressure product or circumflex coronary blood flow throughout the 90 min of regional ischemia or during the 5 h of reperfusion. The relative severity of ischemia between the two treatment groups was similar when assessed with radiolabeled microsphere measurement of myocardial blood flow. The accumulation of neutrophils (measured by myeloperoxidase activity) within the myocardium after reperfusion was not reduced by prior depletion of fibrinogen.(ABSTRACT TRUNCATED AT 250 WORDS)
Simpson
P J
PJ
Department of Cardiovascular Research, Eli Lilly and Company Lilly Corporate Center, Indianapolis, Indiana.
Schelm
J A
JA
Smith
G F
GF
D000721:Ancrod / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005340:Fibrinogen / Q000032:analysis*; D005341:Fibrinolysin / Q000032:analysis; D006339:Heart Rate / Q000187:drug effects; D007958:Leukocyte Count; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009195:Peroxidase / Q000032:analysis; D010959:Tissue Plasminogen Activator / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000209:etiology; D000511:alpha-Macroglobulins / Q000032:analysis
D000511:alpha-Macroglobulins; C024668:plasmin-alpha(2)-macroglobulin complex; D005340:Fibrinogen; D009195:Peroxidase; D000721:Ancrod; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin