THE THROMBOXANE-A2 MIMETIC U46619 WORSENS CANINE MYOCARDIAL HYPOPERFUSION DURING EXERCISE IN THE PRESENCE OF A CORONARY-ARTERY STENOSIS

Objective: The aim was to test the hypothesis that thromboxane A2 can cause vasoconstriction of coronary resistance vessels during exercise in hypoperfused regions of myocardium distal to an arterial stenosis. Methods: Eight adult mongrel dogs were studied. Chronically instrumented animals with a left circumflex coronary artery Doppler flow meter, hydraulic occluder, and indwelling catheter underwent treadmill exercise at heart rates of 190-200 beats.min-1. Myocardial blood flow was measured with microspheres during unimpeded arterial inflow and in the presence of a coronary stenosis which decreased distal pressure to 42-45 mm Hg. Measurements were repeated during infusion of the thromboxane A2 analogue, U46619. Results: When the occluder was partially inflated to produce a stenosis, blood flow in the region perfused by the stenotic artery was 58(SEM 6)% of flow in the normally perfused region (p < 0.01). U46619 (0.01-mu-g.kg-1.min-1) caused a further 21(7%) decrease in blood flow in the region perfused by the stenotic artery (p < 0.05). The vasoconstriction produced by U46619 was uniform across the left ventricular wall from epicardium to endocardium. U46619 did not significantly decrease myocardial blood flow in the absence of a coronary stenosis. Conclusions: Even during hypoperfusion produced by a flow limiting arterial stenosis, the coronary resistance vessels remain responsive to the vasoconstrictor effect of thromboxane A2. Liberation of thromboxane A2 during platelet activation at the site of a proximal coronary stenosis may worsen myocardial hypoperfusion by causing vasoconstriction of the distal resistance vessels.