Effects of Ar-l115-bs and Dobutamine On Myocardial-metabolism and High-energy Phosphate Stores
(1982)
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- (en) Eflects of AR-L115 BS anrl dohutarnine on myocardial metabolism and high energy phosphate stores (l figure). AR-LI 15 BS [2-((2-methoxy-4-methysylfinyl)phenyl)-lH-imidazo (4,5-b) pyridine] is a non sympathomimetic, non-glycoside positive inotrope. Various mechanisms such as changes in calcium sensitivity of the contractile proteins, caf-feineJike effects on the sarcoplasmic reticulum or a phosphodiesterase inhibition have been advocated to explain the positive inotropic effects of this agent. The aim of this study was to determine the effects of AR-L115 BS on the high energy phosphate stores of the normal as well as of the hypertrophied myocardium. Six normal anaesthetized open-chest dogs and seven dogs with left ventricular (LV) hypertrophy were studied. LV hypertrophy resulted from a 6-10 weeks volume overload (aortocaval flstula) which increased LV mass from 4.8 + 1.2 g/kg (SD) in normal dogs to 6.5 l:0.7 glkg e < 0.01). LV and aortic pressures were recorded by means of micromanometers; coronary blood flow and oxygen content of arterial and coronary sinus blood were also determined. Epicardial biopsies, sampled by means of a bone-forceps precooled with liquid nitrogen, were obtained under basal conditions, during a dobutamine infusion (0.1-0.8 mg/min) and during AR-LI15 BS infusion (2-6 mg/min). Dobutamine, a full B, adrenoreceptor agonist with limited B, activity, was used to produce a reference positive inotropic stimulation; the doses were adapted to increase peak (*) dP/dr or dP/dr/DP4O to the same extent with both drugs. Thus, in normal dogs, positive inotropic stimulation with either dobutamine or AR-L115 BS resulted in significant decreases in ADP without significant changes in ATF. Accordingly, the ATP/ADP ratio increased significantly witl, both drugs (Fig. 1) and the adenylate charge rose slightly from 0.861 + 0.025 in control to 0.887 + 0.036 (NS) with dobutamine and to0.912 + 0.009 (P < 0.05) with AR-LI15 B...
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Rasheed, B., Pouleur, H., Maréchal, G., Lefevre, J., Van Mechelen, H., & Charlier, AA. (1982). Effects of Ar-l115-bs and Dobutamine On Myocardial-metabolism and High-energy Phosphate Stores. Archives Internationales de Physiologie et de Biochimie, 90(5), P49-P50. (Original work published 1982)