title: Myocardial bioenergetic abnormalities in a canine model of left ventricular dysfunction.
abstract: OBJECTIVE
  The purpose of this study was to assess high energy phosphate compound metabolism in remodeled left ventricular myocardium.
  
  
  BACKGROUND
  The development of heart failure several years after myocardial infarction is often unexplained. Certain abnormalities of remodeled myocardium suggest that structural changes occurring in viable myocardium after discrete myocardial damage may contribute to the later appearance of heart failure. Whether these abnormalities alter metabolism in the surviving muscle and thereby possibly contribute to ventricular dysfunction is unknown.
  
  
  METHODS
  High energy phosphate compound metabolism was assessed using spatially localized phosphorus-31 nuclear magnetic resonance spectroscopy. Eleven dogs with documented left ventricular dysfunction, resulting from infarction produced by transmyocardial direct current shock, were compared with eight normal dogs. Analyses were performed at baseline and during coronary hyperperfusion induced by intravenous adenosine. Myocardial blood flow was measured with radioactive microspheres.
  
  
  RESULTS
  The creatine phosphate/adenosine triphosphate (CP/ATP) ratio was significantly reduced in the left ventricular dysfunction group in both the subepicardium ([mean +/- SE] 1.94 +/- 0.08 vs. 2.32 +/- 0.13, p = 0.019) and the subendocardium (1.71 +/- 0.07 vs. 2.05 +/- 0.07, p = 0.004). Intravenous adenosine produced significant coronary hyperemia in both groups but was less marked in dogs with left ventricular dysfunction. The improvement in myocardial perfusion was accompanied by a significant increase in the subendocardial CP/ATP ratio (from 1.71 +/- 0.07 to 1.92 +/- 0.08, p = 0.01) in dogs with left ventricular dysfunction.
  
  
  CONCLUSIONS
  An abnormal transmural distribution of high energy phosphate compounds is evident in remodeled myocardium. This abnormality may be related in part to mismatch of oxygen delivery and demand.
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis.
authors.forename: K M
authors.initials: KM
authors.lastname: McDonald
authors.forename: M
authors.initials: M
authors.lastname: Yoshiyama
authors.forename: G S
authors.initials: GS
authors.lastname: Francis
authors.forename: K
authors.initials: K
authors.lastname: Ugurbil
authors.forename: J N
authors.initials: JN
authors.lastname: Cohn
authors.forename: J
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D006333:Heart Failure / Q000209:etiology*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009203:Myocardial Infarction / Q000150:complications*; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism*; D013997:Time Factors; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D000241:Adenosine