Beneficial effects of tissue-type plasminogen activator in acute myocardial ischemia in cats

Tissue-type plasminogen activator is a new thrombolytic agent that dissolves intravascular thrombi in coronary and peripheral vessels with less pronounced systemic lysis than that produced by streptokinase. Plasminogen activator was shown to induce reperfusion, and to salvage ischemic myocardium, by lysing experimentally induced coronary artery thrombi. The effect of a melanoma cell-derived tissue-type plasminogen activator was studied in cat myocardium rendered ischemic by coronary artery ligation for 2 hours and reperfused for another 4 hours. Plasminogen activator was infused at a rate of 500 IU·kg⁻¹·min⁻¹ for the first 30 minutes of reperfusion. The marked increase in plasma creatine kinase activity during reperfusion was significantly lower in plasminogen activator-treated cats at 4,5 and 6 hours, with 7.7 ± 1.5 × 10⁻³ IU·mg protein⁻¹ (n = 8) in the plasminogen activator group versus 17.8 ± 3.5 × 10⁻³ IU·mg protein⁻¹ (n = 7) in the vehicle group at 6 hours (mean ± SEM). The area at risk in the two ischemic groups was not different, being 14.6 ± 1.5 and 16.6 ± 1.4% of total left ventricular mass for the treated and untreated groups, respectively. However, the mass of necrotic tissue determined histochemically was significantly lower in the plasminogen activator-treated group, accounting for 29.5 ± 3.9% of the area at risk compared with 46.8 ± 4.2% of area at risk in cats receiving only the vehicle (p < 0.02). The possible mechanisms of these cardioprotective effects, independent of the lysis of large coronary artery thrombi, are probably related to cyto-protective effects of the plasminogen activator and are probably unrelated to hemodynamic effects.