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 μg.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.