title: Response of high-energy phosphates and lactate release during prolonged regional ischemia in vivo.
abstract: BACKGROUND
  The functional impairment of persistently ischemic, or "hibernating," myocardium may serve to maintain myocardial cell viability through a reduction of energy requirements. Although previous studies have, in a variety of experimental models, independently shown variable responses in lactate metabolism and intracellular phosphates during prolonged ischemia, the responses of these metabolites under identical flow conditions have not been adequately described.
  
  
  RESULTS
  To examine the responses of high-energy phosphates and lactate metabolism to prolonged ischemia induced by partial coronary artery stenosis, 12 open-chest pigs were studied using 31P nuclear magnetic resonance spectroscopy. Concurrent measurements of blood flow, segment shortening, high-energy phosphates, and lactate release (in nine animals) were made during 2 hours of regional ischemia. Subendocardial blood flow and segment shortening were persistently depressed during ischemia, with parallel reductions in ATP, phosphocreatine (PCr), and the ratio of phosphocreatine to inorganic phosphate (PCr/Pi). Pi was persistently elevated during the ischemic period. In contrast, lactate release increased significantly from 0.23 +/- 0.04 to 1.34 +/- 0.28 mumol/ml after 15 minutes of ischemia (p less than 0.05) but then decreased to 0.73 +/- 0.17 mumol/ml at 2 hours (p less than 0.05 versus 15 minutes, p = NS versus control). Similarly, pH increased significantly from a nadir of 6.82 +/- 0.07 at 30 minutes of ischemia to 6.98 +/- 0.05 at 2 hours.
  
  
  CONCLUSIONS
  Changes in high-energy phosphates parallel changes in blood flow and function during prolonged ischemia, whereas there is a partial amelioration in lactate production and acidosis. These data support the concept that reduction of myocardial energy requirements during prolonged flow reduction results in signs of reduced ischemia.
authors.affiliation: Department of Medicine, VA Medical Center, San Francisco, Calif.
authors.forename: S
authors.initials: S
authors.lastname: Schaefer
authors.forename: G G
authors.initials: GG
authors.lastname: Schwartz
authors.forename: J A
authors.initials: JA
authors.lastname: Wisneski
authors.forename: S D
authors.initials: SD
authors.lastname: Trocha
authors.forename: I
authors.initials: I
authors.lastname: Christoph
authors.forename: S K
authors.initials: SK
authors.lastname: Steinman
authors.forename: J
authors.initials: J
authors.lastname: Garcia
authors.forename: B M
authors.initials: BM
authors.lastname: Massie
authors.forename: M W
authors.initials: MW
authors.lastname: Weiner
mesh_terms: D000818:Animals; D003326:Coronary Circulation; D003327:Coronary Disease / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D004734:Energy Metabolism; D006321:Heart / Q000503:physiopathology; D007773:Lactates / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009206:Myocardium / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D010758:Phosphorus; D013552:Swine; D013997:Time Factors
chemical_list: D007773:Lactates; D010710:Phosphates; D010758:Phosphorus