PMID: 9535987May 16, 1998Paper

RSR13, a synthetic modifier of hemoglobin-oxygen affinity, enhances the recovery of stunned myocardium in anesthetized dogs

The Journal of Pharmacology and Experimental Therapeutics
P S PagelD C Warltier

Abstract

RSR13 (2-[4-[[(3, 5-dimethylanilino)carbonyl]methyl]phenoxyl]-2-methylpropr ionic acid) is a synthetic allosteric modifier of oxygen (O2)-hemoglobin affinity that increases O2 release to tissue by allosterically stabilizing deoxyhemoglobin. We tested the hypothesis that RSR13 enhances the functional recovery of stunned myocardium in barbiturate-anesthetized dogs instrumented for measurement of left ventricular (LV) and aortic blood pressure, LV +dP/dtmax and subendocardial segment shortening (%SS) in ischemic [left anterior descending (LAD) coronary artery] and normal (left circumflex coronary artery) zones. The partial pressure of oxygen and the Hill coefficient at 50% saturation (P50 and n50, respectively) were determined in arterial blood samples by multiple point tonometry and nonlinear regression analysis. Coronary collateral blood flow in the LAD zone was quantified with radioactive microspheres. Dogs received intravenous vehicle (0.45% saline) or one of two doses of RSR13 (100 or 150 mg.kg-1 bolus followed by a 0.50 or 0.75 mg.kg-1.min-1 infusion, respectively) in a random manner. All dogs were subjected to five 5-min periods of LAD occlusion separated by 5-min periods of reperfusion and followed by 180 min of final repe...Continue Reading

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