Marked systemic hypotension depresses coronary thrombolysis induced by intracoronary administration of recombinant tissue-type plasminogen activator

Abstract

Objectives: This study was designed to test the hypothesis that the level of aortic blood pressure affects the rate and extent of coronary thrombolysis induced by intracoronary administration of recombinant tissue-type plasminogen activator (rt-PA).

Background: Although many studies have confirmed the efficacy of thrombolytic therapy in the treatment of acute myocardial infarction, the effects of altered blood pressure on coronary thrombolysis have not been studied. Because the aortic pressure represents the coronary artery inflow pressure, first principles predict that changes in blood pressure will affect the delivery of the thrombolytic agent and thus affect thrombolysis.

Methods: The effects of large changes in blood pressure on coronary thrombolysis were studied in a canine model. Coronary thrombosis was induced by injection of radioactive blood clot through a catheter placed in the left anterior descending coronary artery. Subsequently, 24 dogs were classified into three groups of 8 dogs each: Group 1 dogs underwent phlebotomy to adjust systolic blood pressure to 130 mm Hg; Group 2 dogs underwent phlebotomy to decrease systolic blood pressure to 75 mm Hg. Dogs in Group 3 also underwent phlebotomy to achieve a systolic blood pressure of 75 mm Hg and then received norepinephrine to increase this pressure to 130 mm Hg. After adjustment in blood pressure, all dogs received an infusion of rt-PA (0.25 mg/kg body weight) over 30 min through the left anterior descending artery catheter. In a fourth group of six dogs, the effect of altered blood pressure on the rate of coronary thrombolysis was assessed.

Results: In dogs in Groups 1 and 3, the rate and extent of coronary thrombolysis were significantly increased compared with values in Group 2. In each of the six Group 4 dogs the rate of coronary thrombolysis increased when norepinephrine increased systolic blood pressure from 75 to 130 mm Hg.

Conclusions: These results indicate that a moderate increase in coronary inflow pressure increases the rate and extent of coronary thrombolysis compared with values during marked systemic hypotension.