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SUMMARY The effects of equipotent fl3-receptor-blocking doses of propranolol, metoprolol and sotalol on distal coronary pressure, stenosis resistance and regional myocardial blood flow (endo/epi) were studied in anesthetized dogs with a severe noncircumferential stenosis of the left circumflex coronary artery. No significant differences between the three blockers were observed for overall hemodynamics and regional myocardial blood flow. After drug treatment, subendocardial blood flow (0.47 ± 0.05 to 0.78 ± 0.05 ml/min/g) and endo/epi (0.67 ± 0.04 to 1.18 ± 0.04) increased significantly (p < 0.05) in the ischemic region. These changes were associated with a marked increase in distal coronary perfusion pressure and a decrease in heart rate. Resistance across the stenosis decreased significantly (p < 0.05) after,-receptor blockade (3.2 ± 0.3 to 1.4 ± 0.2 units). Atrial pacing to control heart rate only partially attenuated these changes. These results suggest that a favorable redistribution of ischemic blood flow after blockade is the result of an increase in distal diastolic pressure-time index and an autoregulation-induced increase in distal bed vascular resistance due to a decrease in myocardial oxygen demand associated with blockade. The latter effect also resulted in a decrease in the dynamic severity of a proximal coronary stenosis.BETA-ADRENERGIC-RECEPTOR antagonists effectively alleviate the symptoms of angina pectoris."' 2 How these agents reduce myocardial ischemia, however, is controversial. Most investigators favor the concept that d-receptor antagonists reduce ischemia by decreasing myocardial oxygen demands through negative inotropic and chronotropic actions,8 but an increase in oxygen supply caused by enhanced blood flow to ischemic areas may also be an important factor.' Beta antagonists produce a redistribution of blood flow from subepicardium to subendocardium in nonischemic and acutely ischemic dog hearts.5 e The non-/3-blocking properties of these drugs, such as intrinsic sympathomimetic or membrane-stabilizing activity, do not appear to influence their ability to redistribute tissue blood flow. ported by previous in vitro investigations." Since then, Santamore and Walinsky'2 found that interventions that lower coronary arterial pressure distal to a stenosis increase stenotic resistance and, paradoxically, may decrease total coronary blood flow, whereas interventions that increase distal pressure may act to decrease stenotic resistance to flow. An interaction between stenosis and distal bed coronary resistances ultimately determined whether a vasoactive agent increased or decreased coronary blood flow. According to Santamore and Walinsky,12 a reduction in coronary perfusion pressure would lead to a maldistribution of myocardial blood flow and an increase in subendocardial ischemia or, conversely, an elevation of perfusion pressure would lead to a decrease in subendocardial ischemia. The effect of d blockade on distal coronary pressure and transmural blood flow has not been studied experimentally...

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The role of coronary muscarinic receptors in the distribution of transmural blood flow across the left ventricular wall of the working heart was studied in anesthetized open-chest dogs. Tissue blood flow in subepicardium, midmyocardium, and subendocardium was determined with radioactive microspheres before and during activation of muscarinic vasodilator receptors by intracoronary infusions of acetylcholine. Myocardial and coronary vascular beta-receptors were blocked by sotalol (2.0 mg/kg iv). Equivalent submaximal coronary vasodilator doses of acetylcholine and adenosine were compared for effects on transmural blood flow. Intracoronary infusions of acetylcholine (5.0 and 10.7 micrograms/min) produced a dose-related increase in the subendocardial-subepicardial blood flow ratio (endo/epi) from 1.07 to 1.32 and 1.57, respectively. A progressively larger decrease in coronary vascular resistance occurred in the subendocardium than midmyocardium or subepicardium following acetylcholine administration. In contrast, intracoronary administration of adenosine (54.4 micrograms/min) produced no change in endo/epi. Atropine effectively blocked acetylcholine-induced coronary vasodilation but not vasodilation produced by adenosine. Neither agent affected heart rate, left ventricular pressure, coronary perfusion pressure, or myocardial contractility. These results suggest that activation of muscarinic coronary vasodilator receptors redistributes blood flow preferentially to the subendocardium independent of cardiac mechanical influences.

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