Selective thromboxane A2 receptor blockade in experimental exercise-induced myocardial ischaemia in dogs

Thromboxane A2 receptor stimulation induces blood platelet aggregation and vasoconstriction, both potential causes of impaired perfusion of ischaemic myocardium. To study the potential role of thromboxane A2 receptor blockade in exercise-induced myocardial ischaemia and post-exercise myocardial dysfunction, nine conscious chronically instrumented dogs with single-vessel coronary artery stenosis (ameroid constrictor) were studied before, during and after steady-state treadmill runs which induced regional myocardial ischaemia. Three hours after a control run, the dogs were exercised again after the infusion of a selective thromboxane A2 receptor blocker: BM 13.177 (10 mg kg-1 i.v.). In the control run, systolic wall thickening (WTh, sonomicrometer) in the post-stenotic myocardium decreased from 22.1 +/- 9.1% at rest to 8.8 +/- 5.2% (mean +/- SD). Subendocardial blood flow (microspheres) in the ischaemic area decreased from 0.75 +/- 0.25 to 0.45 +/- 0.27 (ml min-1 g). The WTh in the ischaemic region remained depressed at 20 min after the run. BM 13.177 reduced peak left ventricular (+) dP/dt (micromanometer) and WTh in both control and post-stenotic myocardium at rest, during and after the run. WTh in the ischaemic area was reduced to approximately the same levels during running with BM 13.177 (not significantly different from control exercise) and remained depressed for at least 30 min after the run. Regional myocardial blood flow was not affected by BM 13.177. Thus, selective thromboxane A2 receptor blockade with BM 13.177 had a modest negative inotropic effect and did not improve regional function or blood flow in post-stenotic ischaemic subendocardium.