This study was designed to compare the effect of a mechanical vs a pharmacologic increase in BP on coronary artery blood flow and thrombolysis induced by IV administration of recombinant tissue plasminogen activator. We employed a canine model of coronary thrombosis induced by injection of radioactive blood clot in the left anterior descending coronary artery. Subsequently, all dogs underwent phlebotomy to decrease systolic BP to 75 mm Hg and this decreased coronary blood flow by 50%. BP was increased to 130 mm Hg by norepinephrine (NE) infusion or by inflation of a Fogarty catheter placed in the descending aorta. Interventions with NE or with a Fogarty balloon catheter increased coronary artery blood flow to similar values and rates of coronary thrombolysis were similar. However, cardiac output was significantly higher with NE. These results indicate coronary clot lysis is dependent on perfusion pressure and coronary blood flow, not cardiac output.