title: Myocardial metabolism during increased work states in the porcine left ventricle in vivo.
abstract: It is not known whether myocardial energy requirements can be increased to the degree that they exceed myocardial O2 availability in the absence of abnormalities of coronary blood flow or coronary reserve. To determine whether this form of "demand ischemia" occurs, 10 swine were subjected to pressure overload induced by aortic constriction, inotropic and chronotropic stimulation by dobutamine, and the combination of these interventions. In an additional 9 animals, intravenous adenosine was administered during the combination of constriction and dobutamine to determine whether further increases in coronary flow could be achieved and if they would attenuate the metabolic changes. Left ventricular anterior wall transmural blood flow was measured by radioactive microspheres. Energy phosphates were assessed by 31P magnetic resonance spectroscopy using the Fourier series window technique to increase the proportion of signal derived from the subendocardium. Myocardial lactate release was quantified independent of net lactate uptake using an isotopic tracer technique. The three interventions produced 39% to 195% increases in myocardial O2 uptake from control measurements. The phosphocreatine to ATP ratio (PCr/ATP), uncorrected for partial saturation, fell significantly, from 1.39 +/- 0.10 at control conditions to 1.25 +/- 0.10 with dobutamine alone and 1.15 +/- 0.08 with dobutamine plus constriction (P < .05 for both). Myocardial lactate release rose from 0.21 +/- 0.03 mumol.g-1.min-1 at control conditions to 0.45 +/- 0.05 and 0.59 +/- 0.10 mumol.g-1.min-1, respectively (P < .05 for both), with these two interventions. Although transmurally averaged left ventricular blood flow rose from 0.97 +/- 0.09 mL.g-1.min-1 at control conditions to 3.25 +/- 0.47 mL.g-1.min-1 (P < .001) and subendocardial blood flow increased from 1.02 +/- 0.09 to 2.92 +/- 0.45 mL.g-1.min-1 (P < .001) at the highest of the three increased work states, the subendocardial to subepicardial flow ratio declined progressively from 1.13 +/- 0.08 to 0.87 +/- 0.04 (P < .05). With a further increase in aortic constriction, myocardial O2 uptake and subepicardial blood flow rose, whereas subendocardial blood flow did not change, and there was a further decline in PCr/ATP and a rise in lactate release. Although adenosine increased the average myocardial blood flow during high work state from 3.79 +/- 0.91 to 6.29 +/- 1.08 mL.g-1.min-1 (P < .001), the further rise in subendocardial flow from 3.08 +/- 0.62 to 3.78 +/- 0.68 mL.g-1.min-1 was not significant, nor were the accompanying changes in PCr/ATP or lactate metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Cardiology Section, San Francisco Department of Veterans Affairs Medical Center, CA 94121.
authors.forename: B M
authors.initials: BM
authors.lastname: Massie
authors.forename: G G
authors.initials: GG
authors.lastname: Schwartz
authors.forename: J
authors.initials: J
authors.lastname: Garcia
authors.forename: J A
authors.initials: JA
authors.lastname: Wisneski
authors.forename: M W
authors.initials: MW
authors.lastname: Weiner
authors.forename: T
authors.initials: T
authors.lastname: Owens
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D005260:Female; D006439:Hemodynamics; D009682:Magnetic Resonance Spectroscopy; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D013552:Swine; D016277:Ventricular Function, Left
chemical_list: D000241:Adenosine