Coronary thrombolysis with intravenous streptokinase in the anesthetized dog: a dose-response study

GA Kopia, LJ Kopaciewicz and RR Ruffolo

Department of Pharmacology, Smith Kline & French Laboratories, Swedeland, Pennsylvania.

In order to study the in vivo coronary thrombolytic dose-response effectiveness of i.v. streptokinase, pentobarbital-anesthetized, open chest dogs were instrumented for the measurement of lead II ECG, systemic arterial blood pressure, left ventricular developed pressure, left ventricular end-diastolic pressure, left ventricular dP/dt and left anterior descending (LAD) coronary artery blood flow. In some animals, two pairs of ultrasonic dimension gauges were positioned in 1) an area of the left ventricle which would become ischemic after thrombotic occlusion of the LAD and 2) a reference area which would remain unaffected by LAD occlusion. After making an occlusive thrombus by injecting thrombin (50-200 U) and calcium chloride (50-100 mumols) into a cannulated and mechanically occluded side-branch of an isolated segment of the mid- to distal LAD, animals were given either streptokinase (5,000, 10,000, 20,000 or 40,000 U of bolus, followed by 500, 1000, 2000 or 4000 U/min of infusion, respectively) or saline, i.v. At the termination of the experiment, thrombus wet weight and, in some animals, infarct size (measured by tetrazolium staining) were determined. In control animals, thrombus wet weight was 26.7 +/- 5.4 mg (n = 8) and infarct size, as a percentage of the total left ventricle, was 30.1 +/- 4.7% (n = 6). Spontaneous reperfusion (return of LAD blood flow) was not observed in control animals that received saline. Intravenous administration of streptokinase produced a dose-dependent increase in the percentage of animals reperfusing, and a dose-dependent decrease in both thrombus wet weight and the time to reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 244, Issue 3, pp. 956-962, 03/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics