title: Energy metabolism and contractile function after 15 beats of moderate myocardial ischemia.
abstract: Difficulties in studying myocardial metabolism with adequate time resolution have led to contradictory conclusions regarding the mechanisms causing contractile abnormalities during the early stages of ischemia. In acutely instrumented swine, we investigated whether abnormalities in subendocardial ATP, phosphocreatine, or lactate content develop rapidly enough during the first few heart beats after onset of partial myocardial ischemia to contribute to contractile failure. Within the first 15 beats of a 40-50% reduction in left anterior descending coronary artery blood flow, regional myocardial function was significantly reduced but continuing to deteriorate. Rapidly frozen transmural left ventricular biopsies obtained on the 15th heart beat (+/- 1.5 beats) after the onset of ischemia revealed significant decrements in subendocardial phosphocreatine and ATP levels to 77% (p less than 0.05) and 84% (p less than 0.005) of control values, respectively, but minimal change in lactate content. Metabolic effects as assessed by transmural averages took longer to become detectable; thus, there was a tendency to underestimate the importance of subendocardial metabolic effects on myocardial function. When left ventricular preload was assessed during this early time period, left ventricular end-diastolic wall thickness only decreased by 3%, and left ventricular end-diastolic pressure did not change significantly despite a large fall in coronary perfusion pressure. Thus, in an in vivo pig model with techniques optimized to detect subendocardial metabolic changes within the period of very early moderate myocardial ischemia, abnormalities in high energy phosphate compounds occurred rapidly enough to contribute to developing myocardial dysfunction, whereas preload-mediated mechanisms related to vascular distending pressure could not explain the functional deterioration under these conditions.
authors.affiliation: Department of Medicine, Oregon Health Sciences University, Portland.
authors.forename: A E
authors.initials: AE
authors.lastname: Arai
authors.forename: G A
authors.initials: GA
authors.lastname: Pantely
authors.forename: W J
authors.initials: WJ
authors.lastname: Thoma
authors.forename: C G
authors.initials: CG
authors.lastname: Anselone
authors.forename: J D
authors.initials: JD
authors.lastname: Bristow
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D004562:Electrocardiography; D004734:Energy Metabolism; D005260:Female; D006439:Hemodynamics; D007773:Lactates / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D013552:Swine; D013997:Time Factors
chemical_list: D007773:Lactates; D010725:Phosphocreatine; D000255:Adenosine Triphosphate