RETROGRADE CORONARY VENOUS ADMINISTRATION OF RECOMBINANT TISSUE-TYPE PLASMINOGEN-ACTIVATOR - A UNIQUE AND EFFECTIVE APPROACH TO CORONARY-ARTERY THROMBOLYSIS

Recent studies of interventional therapy by way of the coronary venous system have demonstrated that it can protect acutely ischemic myocardium. To evaluate the efficacy of coronary venous retroinfusion compared with systemic intravenous administration of recombinant tissue-type plasminogen activator (rt-PA), 14 dogs were studied with a copper coil-induced thrombus in the left anterior descending coronary artery. The rt-PA (24,000 fluorescence units/kg) was administered continuously, either intravenously (n = 8) or retrogradely (n = 6), for 30 min beginning 60 min after coronary occlusion. Thrombolysis was determined by repetitive coronary angiography. All dogs were killed 3 h after termination of rt-PA infusion and infarct size was measured by the triphenyltetrazolium chloride staining technique. Complete thrombolysis occurred in five of the six dogs in the retroinfusion group and four of the eight dogs in the systemic intravenous infusion group. Partial lysis was achieved in two dogs treated by intravenous infusion. Lysis did not occur in one dog treated with retroinfusion and in two dogs treated with intravenous infusion. Time to thrombolysis was 13.4 +/- 2.3 min in the retroinfusion group versus 27.8 +/- 4.8 min in the intravenous group (p < 0.001). Myocardial functional recovery in the ischemic zone measured by two-dimensional echocardiography 60 min after reperfusion was significant only in the retroinfusion group (p < 0.05). Infarct size expressed as a percent of the risk area (autoradiography) was significantly smaller in the retroinfusion group (34.9 +/- 11.9%) than in the intravenous group (54.5 +/- 19.1%; p < 0.05) despite <15 min difference in average ischemic time between the groups (73.4 vs. 87.8 min). It is speculated that retroinfusion of rt-PA may prevent downstream embolization of microthrombi. No myocardial hemorrhages or damage to the coronary venous system were observed. It is concluded that coronary venous retroinfusion of rt-PA provides more rapid clot lysis and better functional recovery and infarct size reduction compared with systemic intravenous administration.