We examined the effects of a cardioselective beta-blocking drug on exercise-induced regional myocardial ischemia in 10 conscious dogs with chronic coronary artery stenosis. An ameroid constrictor, Doppler flowprobe, and hydraulic cuff were placed around the left circumflex coronary artery, and left ventricular pressure (LVP), systolic wall thickening (% delta WT; by sonomicrometry), and myocardial blood flow (MBF; microspheres) were measured during control standing, control treadmill exercise, and identical exercise after atenolol (1 mg/kg po). Prior to study, in every dog % delta WT and MBF in the ischemic area were normal at rest, indicating collateral development. During control exercise, % delta WT in the ischemic region markedly decreased from 27 to 4%, and transmural ischemia was evident in that region. Heart rate, systolic LVP, and LV (+)dP/dt were significantly lower during exercise after atenolol than during control exercise. % delta WT in the normal area was only 81% of that during control exercise, but dysfunction in the ischemic area was improved (77% increase compared with control exercise). Accompanying the improved function was a significant increase of MBF/beat and relative MBF in the ischemic zone; the endocardial-to-epicardial ratio increased from 0.27 to 0.47. Thus atenolol improved regional MBF distribution, thereby diminishing exercise-induced regional myocardial dysfunction and accelerating its recovery.

No. 4, 801-814, 1984. THE CALCIUM-ENTRY BLOCKER diltiazem was developed as a drug that inhibits the influx of calcium ions during cell depolarization in vascular smooth muscle, thereby producing coronary vasodilation.1A Several studies have documented the beneficial effect of diltiazem in controlling symptoms of coronary artery spasm5-' and effort angina pectoris. '2 Diltiazem is also effective in increasing the total duration of exercise and the time to the first onset of angina, and the pressure-rate product is significantly reduced at sub-

Preload reserve and mechanisms of afterload mismatch were examined in 10 normal conscious dogs. The left ventricular (LV) pressure, wall thickness, and external major and minor axis diameters (sonomicrometry) were measured during sinus rhythm, and beat-averaged pressure-volume loops were generated. With maximum angiotensin II infusion, LV end-diastolic volume (EDV) increased by 13 +/- 2% (SEM), LV peak pressure (LVSP) increased by 44 +/- 6%, and stroke volume decreased by 12 +/- 3% (P less than 0.01), demonstrating an apparent descending limb of LV performance. With volume load alone, EDV increased by 9 +/- 2% from control (P less than 0.01), and stroke volume increased by 13 +/- 2%; mean wall stress during ejection was not increased, and heart rate and end-systolic pressure-volume relations showed no changes. To test whether the descending limb of function was due to maximum use of preload reserve or to inadequate venous return, angiotensin infusion was repeated during volume load. The descending limb relating LVEDV to stroke volume was always shifted upward and to the right after volume load, and the stroke volume at a comparable wall stress was 12 +/- 3% higher than during control angiotensin infusion (P less than 0.01). During pressure loading plus volume loading, the maximum EDV increase was 16 +/- 2%, and assuming unchanged afterload and end-systolic volume, an average maximum stroke volume reserve of 31 +/- 4% is calculated. 1) We conclude that sizable preload and stroke volume reserves exist in the normal resting dog; and 2) we describe a mechanism for the descending limb of LV performance curves produced by pressure loading in the intact circulation, which is related to inadequate venous return.