SummaryThe effects of the imidazo-pyridine AR-L 115 BS on global and regional myocardial function were investigated in anesthetized pigs in the absence and in the presence of the bradycardiac action of alinidine. AR-L 115 BS (0.1-0.8 mg 9 kg -1 9 rain -1) increased myocardial contractility (up to 75 %) and reduced preload (50 %) and afterload (50 %) in a dose-dependent manner. These changes were accompanied by moderate increases in heart rate (up to 20 %). The increase in cardiac output was only moderate (20 %), due to the reduction in preload. Renal blood flow increased slightly, but coronary blood flow was not significantly affected, due to the marked decrease in coronary vascular resistance (up to 50 %). Regional perfusion was not impaired as the endo/epi flow ratio was not affected and the coronary venous 02-saturation increased slightly but significantly. Myocardial wall thickness tracings (ultrasound principle) showed some pronounced changes. The positive inotropic action of AR-L 115 BS were best reflected by the changes in the velocity of wall thickening (up to 90 %, P < 0.001), and the timing of the occurrence of maximal wall thickness (maxT) with respect to aortic valve closure, as maxT, which occurred 5-10 msee after aortic valve closure during base line, preceded aortic valve closure with 45 msee after AR-L 115 BS (P < 0.001).Since the adverse effects of positive chronotropy on isehemie myocardium are well documented, AR-L 115 BS was also investigated in combination with alinidine, an agent which has predominantly negative chronotropie properties. This study revealed that alinidine did not interfere with the positive inotropic action of AR-L115BS but mainly reduced heart rate. Consequently, combination of the two drugs, which resulted in an improved myocardial function at a lower O2-demand, may offer an attractive addition in the treatment of myocardial pump failure.
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