Right-shifting the oxyhemoglobin dissociation curve with RSR13: effects on high-energy phosphates and myocardial recovery after low-flow ischemia.
RSR13[2-(4[[(3,5-Dimethylanilino)carbonyl] methyl] phenoxy)-2-methyl propionic acid], a synthetic allosteric modifier of hemoglobin, increases O2 release from hemoglobin at low oxygen tension. The isolated blood-perfused rat heart was examined during potassium-arrest to determine the effects of RSR13 on the concentration of phosphocreatine (PCr) and adenosine triphosphate (ATP) by using 31P nuclear magnetic resonance (NMR) spectroscopy throughout an episode of low-flow ischemia. All hearts were perfused at constant flow during control (2.0 ml/min) and low-flow (0.2 ml/min) conditions. In normoxic hearts, RSR13 had no effect on either the 31P NMR spectrum or the rate-pressure product. In hearts subjected to 30 min of reduced flow, treatment with RSR13 improved mechanical function on reperfusion (p = 0.026 after 20 min; p = 0.032 after 25 min; and p = 0.045 after 30 min) at 2.0 ml/min with normokalemic blood perfusate. In potassium-arrested hearts, the rate of decrease of [ATP] was reduced in hearts exposed to RSR13 (p < or = 0.05 between 10 and 35.8 min of ischemia except at 28.4 min) during low flow. These results indicate a protective effect of RSR13 on high-energy phosphates during low-flow ischemia and mechanical recovery after reperfusion.
Woods
J A
JA
Mary Nell and Ralph B. Rogers Magnetic Resonance Center, Department of Radiology, University of Texas Southwestern Medical Center, Dallas 75235-9085, USA.
Storey
C J
CJ
Babcock
E E
EE
Malloy
C R
CR
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D010108:Oxyhemoglobins / Q000187:drug effects* / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000814:Aniline Compounds; D010108:Oxyhemoglobins; D010710:Phosphates; D011422:Propionates; C067396:efaproxiral