Elimination of exercise-induced regional myocardial dysfunction by a bradycardiac agent in dogs with chronic coronary stenosis.
We have previously demonstrated that the beneficial effect of cardioselective beta-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 X 10(-3) to 2.5 X 10(-3) ml/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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001552:Benzazepines / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy*; D003864:Depression, Chemical; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D005082:Physical Exertion
D001552:Benzazepines; D002317:Cardiovascular Agents; C043636:zatebradine