Document Detail

Effects of a pharmacologically-induced shift of hemoglobin-oxygen dissociation on myocardial energetics during ischemia in patients with coronary artery disease.
MedLine Citation:
PMID:  16136855     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Conventional strategies to treat myocardial ischemia include interventions that reduce oxygen demand and/or increase myocardial blood flow. Animal experiments suggest that right-shifting the hemoglobin-oxygen dissociation curve may also attenuate the metabolic consequences of myocardial ischemia. We evaluated whether exercise-induced myocardial ischemia can be alleviated in subjects with coronary artery disease (CAD) by enhancing oxygen release with an allosteric modifier of hemoglobin's affinity for oxygen (RSR13). METHODS AND RESULTS: Seven subjects with CAD underwent a randomized, double-blind, cross-over study of the metabolic consequences of RSR13 administration on myocardial ischemia. Myocardial high-energy phosphates were quantified with 31P nuclear magnetic resonance (NMR) spectroscopy before, during, and after isometric handgrip-exercise. Subjects underwent NMR studies at baseline and on two separate occasions following the infusion of RSR13 (100 mg/kg) or placebo. RSR13 infusion significantly increased mean p50 by 8.1 +/- 2.7 mmHg at the end of the infusion, and it was still elevated by 4.9 +/- 3.3 mmHg after the completion of the treadmill tests while placebo had no effect. The myocardial creatine-phosphate (PCr) to adenosine-triphosphate (ATP) ratio decreased during handgrip-exercise in the baseline studies (from 1.39 +/- 0.23 before exercise to 0.95 +/- 0.21 during handgrip-exercise, p = 0.0001) and in the placebo studies (from 1.29 +/- 0.16 to 0.98 +/- 0.37, p = 0.06) but not during administration of RSR13 (from 1.28 +/- 0.18 to 1.02 +/- 0.24, p = 0.12). However, the mean values of cardiac PCr/ATP during handgrip-exercise did not differ significantly among the three measurements (baseline, placebo, RSR13). CONCLUSIONS: A single infusion of RSR13 to subjects with CAD increased mean p50 by 4.9-8.1 mmHg but did not significantly alter myocardial PCr/ATP during exercise. This is the largest right-shift in hemoglobin-oxygen binding affinity achieved in CAD subjects, and it did not provide clear evidence of protection from cardiac ischemia.
Samer S Najjar; Paul A Bottomley; Steven P Schulman; Michele M Waldron; Robert P Steffen; Gary Gerstenblith; Robert G Weiss
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance     Volume:  7     ISSN:  1097-6647     ISO Abbreviation:  J Cardiovasc Magn Reson     Publication Date:  2005  
Date Detail:
Created Date:  2005-09-02     Completed Date:  2006-09-26     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9815616     Medline TA:  J Cardiovasc Magn Reson     Country:  United States    
Other Details:
Languages:  eng     Pagination:  657-66     Citation Subset:  IM    
Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
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MeSH Terms
Adenosine Triphosphate / blood
Analysis of Variance
Aniline Compounds / adverse effects,  blood,  pharmacology*,  therapeutic use
Antisickling Agents / adverse effects,  blood,  pharmacology*,  therapeutic use
Biological Markers / blood
Blood Flow Velocity / drug effects
Coronary Artery Disease / diagnosis,  drug therapy,  metabolism,  physiopathology
Coronary Circulation / drug effects
Cross-Over Studies
Double-Blind Method
Exercise Test
Magnetic Resonance Spectroscopy / methods
Middle Aged
Myocardial Ischemia / diagnosis,  drug therapy*,  metabolism*,  physiopathology
Oxygen Consumption / drug effects
Oxyhemoglobins / drug effects*,  metabolism*
Phosphocreatine / blood,  drug effects
Phosphorus Isotopes / diagnostic use
Propionic Acids / adverse effects,  blood,  pharmacology*,  therapeutic use
Treatment Outcome
Reg. No./Substance:
0/Aniline Compounds; 0/Antisickling Agents; 0/Biological Markers; 0/Oxyhemoglobins; 0/Phosphorus Isotopes; 0/Propionic Acids; 131179-95-8/efaproxiral; 56-65-5/Adenosine Triphosphate; 67-07-2/Phosphocreatine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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