Effects of retrovenous myocardial drug delivery after coronary artery occlusion in sheep. Retrovenous (RV) myocardial delivery of blood and drugs into the coronary sinus (CS) through a 3 lumen balloon catheter was evaluated in sheep (no coronary collaterals) for protection from ventricular fibrillation (VF) during coronary artery occlusion. The balloon was asynchronously inflated (CS occlusion) for 5 sec and then deflated for 5 sec with 1 cc/sec of flow. The left anterior descending coronary artery was occluded with inflation of a percutaneous transluminal coronary angiography balloon and therapy started immediately. In a control group (no therapy, n = 4) all developed VF by 30 min after coronary artery occlusion. The drugs lidocaine (L), esmolol (E), adenosine (A), and deferoxamine (D) were evaluated for effects on eliminating developing VF with intravenous (i.v.) administration compared with RV administration with venous blood (VB) or arterial blood (AB). The percent survival after CA occlusion (no VF) was: L i.v., 0%; L RV with VB, 43%; L RV with AB, 17%; E i.v., 50%; E RV with VB, 70%; A. i.v., 29%; A RV with VB, 88%; D i.v., 17%; and D RV with AB, 80%. There was a trend toward lower myocardial necrosis (seen by tetrazolium stain and/or light microscopy) in the RV survivors (especially with VB) compared with the group i.v. survivors. These data suggest that RV antiarrhythmic drug delivery is a feasible alternative to i.v. administration during CA occlusion. 