Low Incidence of Hemorrhagic Infarction Following Coronary Reperfusion with Nasaruplase in a Canine Model of Acute Myocardial Infarction. Comparison with Recombinant t-PA.

Abstract

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.