ABSTRACTWe have previously demonstrated that the beneficial effect of cardioselective 13-blockade on exercise-induced ischemia is due entirely to negative chronotropism. Therefore we studied the effect of a new bradycardiac agent (UL-FS 49) in 10 dogs with chronic coronary artery stenosis produced by an ameroid constrictor. Regional myocardial function (sonomicrometers, wall thickness) and blood flow (microspheres) were measured during a control treadmill exercise bout and an identical run 3 hr later after the administration of UL-FS 49 (1.0 mg/kg iv). In the control run, heart rate increased from 114 ± 20 to 230 ± 19 beats/min and systolic wall thickening (%WT) in the poststenotic myocardium decreased from 23.3 ± 5.2% at rest to 9.3 ± 5.0%, a 60% reduction. Subendocardial blood flow in the ischemic area decreased from 1.04 ± 0.30 to 0.55 0.40 ml/min/g, blood flow per beat decreased from 9.1 × 10-3to 2.5 × 10-3ml/g, and mean transmural flow failed to increase (1.06 + 0.30 vs 1.08 ± 0.39 ml/min/g). During exercise with UL-FS 49, heart rate increased from 89 10 to only 139 ± 10 beats/min. End-diastolic left ventricular pressure was increased compared with that during the control run (35.7 ± 3.0 vs 28.9 ± 5.5 mm Hg) but left ventricular peak systolic pressure and dP/dt were unchanged. %WT in the ischemic zone did not change significantly during exercise with UL-FS 49 (23.3 ± 7.9% at rest, 21.5 ± 8.4% during the run), and in the nonischemic zone it increased to the same extent as during the control run. Absolute subendocardial blood flow (0.75 ± 0.32 ml/min/g) and flow per beat (5.3 ± 2.0 × 10-3ml/g) were significantly increased compared with those during the control run (p > .05), and transmural blood flow per beat increased to 9.8 ± 1.7 × 10-3ml/g (p > .01). These data demonstrate that UL-FS 49 is an effective bradycardiac agent that can markedly attenuate exercise-induced ischemic dysfunction and improve regional perfusion without compromising contractile function of nonischemic areas or global left ventricular contractility.