PT  - JOURNAL ARTICLE
AU  - P J Simpson
AU  - J A Schelm
AU  - G F Smith
TI  - Therapeutic defibrination with ancrod does not protect canine myocardium from reperfusion injury.
DP  - 1991 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 780--786
VI  - 256
IP  - 2
4099  - http://jpet.aspetjournals.org/content/256/2/780.short
4100  - http://jpet.aspetjournals.org/content/256/2/780.full
SO  - J Pharmacol Exp Ther1991 Feb 01; 256
AB  - 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)