Preservation of canine myocardial high-energy phosphates during low-flow ischemia with modification of hemoglobin–oxygen affinity

摘要: Conventional approaches for the treatment of myocardial ischemia increase coronary blood flow or reduce demand. To determine whether a rightward shift in hemoglobin-oxygen saturation curve would metabolic and contractile effects oxygen-supply imbalance, we studied impact potent synthetic allosteric modifier affinity, 2-[4-[[(3,5-disubstituted anilino)carbonyl]methyl] phenoxy] -2-methylproprionic acid derivative (RSR13), during low-flow ischemia. Changes high-energy phosphate levels pH were by 31P nuclear magnetic resonance (NMR) spectroscopy 12 open-chest dogs randomized to receive RSR13 vehicle control reversible reduction left anterior descending (LAD) artery flow. cardiac metabolites regional ventricular function pressure segment-length relations also investigated additional animals before after administration LAD The intravenous resulted substantial mean hemoglobin p50 attenuated decline creatine phosphate/adenosine triphosphate (PCr/ATP), percent PCr, without change flow, heart rate, systolic pressure. given onset improved PCr/ATP ratios as measured fractional shortening work. Thus, affinity may be new important therapeutic strategy ameliorate functional consequences