An examination was made of the coronary thrombolytic effects of
nasaruplase in a canine model of acute
myocardial infarction. The model was produced by selective injection of an artificial
thrombus into the coronary artery stenosed by
laser ablation. Intravenous
nasaruplase (8 U/kg/min) showed an equivalent thrombolytic effect to a recombinant
tissue-type plasminogen activator (rt-PA, 10,000 IU/kg/min) as assessed by reperfusion rate (78.6 versus 79.2%) and reperfusion time (37.4 +/- 5.2 versus 37.0 +/- 2.5 min).
Nasaruplase decreased the plasma
alpha 2-plasmin inhibitor (alpha 2-PI) level by 28% immediately after reperfusion, but hardly altered
fibrinogen or
plasmin-
alpha 2-plasmin inhibitor complex (PIC) levels. By contrast, rt-PA significantly decreased plasma alpha 2-PI and
fibrinogen levels, by 84% and 92% respectively, and, increased PIC level more than 70-fold. Hemorrhagic
infarction occurred in 2 of 14 animals in the
nasaruplase group and in 9 of 19 animals in the rt-PA group. In these animals, significant correlations were found between the ratio of the hemorrhagic
infarction area to total
infarct area and the plasma alpha 2-PI (r = -0.740, p < 0.05) or
fibrinogen (r = -0.798, p < 0.05) concentrations, as well as between the recovery rate of left ventricular regional wall motion and the plasma alpha 2-PI (r = 0.924, p < 0.01) or
fibrinogen (r = 0.864, p < 0.01) concentrations. It is concluded that
nasaruplase is a potent
thrombolytic agent which preserves left ventricular function with a lesser rate of hemorrhagic
infarction than rt-PA. Further,
nasaruplase administration results in recovery of left ventricular regional wall motion and systolic function, such as Vmax.