Effects of the bradycardic agent UL-FS 49 on exercise-induced regional contractile dysfunction in dogs

The effects of the bradycardic agent UL-FS 49 on hemodynamic and segmental parameters were studied in a canine model of exercise-induced myocardial dysfunction which mimics exercise-induced angina pectoris. Ten dogs, trained to subunit to five treadmill exercise cycles consisting of 4 min of running and 11 min of recovery, were chronically instrumented with a microtip manometer in the left ventricle, two pairs of crystals for sonomicrometry, a hydraulic occluder around the circumflex branch of the left coronary artery and arterial and venous catheters. Control experiments with coronary stenosis clarified the reproducibility of exercise-induced regional contractile dysfunction and recovery of function in the intervening resting periods. In each individual dog, a similar degree of stenosis was used in the subsequent experiments with UL-FS 49. After two control runs, which exhibited regional contractile dysfunction of comparable magnitude, UL-FS 49 was administered intravenously at a dosage of 0.5 mg/kg/5 min (6 dogs) or 0.25 mg/kg/5 min (4 dogs). Both doses of UL-FS 49 markedly reduced heart rate without alteration of left ventricular positive dp/dtmax at rest and during exercise. A marked improvement of regional function in the area perfused by the stenosed coronary artery was also observed during exercise. This beneficial effect of selective bradycardia, here observed with UL-FS 49, remains to be confirmed in clinical trials.