Right-shifting the oxyhemoglobin dissociation curve with RSR13

Effects on high-energy phosphates and myocardial recovery after low-flow ischemia

Jason A. Woods, Charles J. Storey, Evelyn E. Babcock, Craig R. Malloy

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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 ≤ 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.

Original languageEnglish (US)
Pages (from-to)359-363
Number of pages5
JournalJournal of Cardiovascular Pharmacology
Volume31
Issue number3
DOIs
StatePublished - Mar 1998

Fingerprint

Oxyhemoglobins
Ischemia
Phosphates
Reperfusion
Potassium
Hemoglobins
Magnetic Resonance Spectroscopy
Adenosine Triphosphate
Phosphocreatine
efaproxiral
Heart Rate
Oxygen
Pressure

Keywords

  • P NMR
  • Heart
  • Hemoglobin
  • Rat
  • RSR13

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Right-shifting the oxyhemoglobin dissociation curve with RSR13: Effects on high-energy phosphates and myocardial recovery after low-flow ischemia",
abstract = "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 ≤ 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.",
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T1 - Right-shifting the oxyhemoglobin dissociation curve with RSR13

T2 - Effects on high-energy phosphates and myocardial recovery after low-flow ischemia

AU - Woods, Jason A.

AU - Storey, Charles J.

AU - Babcock, Evelyn E.

AU - Malloy, Craig R.

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N2 - 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 ≤ 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.

AB - 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 ≤ 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.

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