Alleviation of myocardial ischaemia after administration of the cardioselective beta adrenoceptor antagonist bevantolol.
A 15 min reduction in blood flow in the left anterior descending coronary artery to 35% of baseline in open chest anaesthetised pigs produced a 25% decrease in cardiac output and a similar fall in maximum left ventricular dP/dt, whereas left ventricular filling pressure increased from 10(1) to 14(1) mmHg. The decrease in perfusion of the myocardial area nourished by the left anterior descending coronary artery was not evenly distributed since the endocardial to epicardial flow ratio decreased from 0.93(0.07) to 0.48(0.06). Regional myocardial wall thickening of the ischaemic segment decreased from 0.36(0.03) to 0.14(0.03), whereas the arterial-coronary venous differences in pH and PCO2 tripled. Subsequently, eight animals received 1.5 mg X kg-1 of the cardioselective beta adrenoceptor antagonist bevantolol, whereas seven other animals were treated with the solvent. In the following 15 min the cardiovascular performance of the solvent treated animals did not change appreciably, although there was a tendency to further deterioration. Bevantolol did not improve transmural myocardial blood flow to the ischaemic zone but caused a redistribution in favour of the endocardial layers since the endocardial to epicardial flow ratio almost returned to baseline. These changes in flow were accompanied by a narrowing of the arterial-coronary venous differences in pH and PCO2, but regional myocardial function did not improve. In another series of experiments, however, bevantolol (1.5 mg X kg-1) decreased the velocity of regional wall thickening of normal myocardium by 22(2)% as a result of its negative inotropic properties. Thus bevantolol appears to alleviate ischaemia, and the increase in diastolic perfusion time (17%) may be one of the major mechanisms.
Hartog
J M
JM
Verdouw
P D
PD
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy*; D004195:Disease Models, Animal; D004341:Drug Evaluation; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D011412:Propanolamines / Q000627:therapeutic use*; D013552:Swine
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C021148:bevantolol