Transmural Gradients in Ventricular Tissue Metabolites Produced by Stopping Coronary Blood Flow in the Dog

• Published in: Circulation research Vol. 37; no. 4; pp. 438 - 445
• Main Authors: Dunn, Robert B, Griggs, Douglas M
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.10.1975
• Subjects: Adenosine Triphosphate - metabolism; Animals; Cardiac Volume; Coronary Circulation; Coronary Disease - metabolism; Dogs; Endocardium - metabolism; Energy Metabolism; Heart - drug effects; Heart Ventricles; Lactates - metabolism; Male; Myocardial Contraction; Myocardium - metabolism; Phosphocreatine - metabolism; Propranolol - pharmacology; Ventricular Fibrillation - metabolism
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.37.4.438

To determine whether transmural metabolite gradients develop in the contracting, ischemic left ventricle due to factors other than a nonuniform distribution of myocardial blood flow, right and left coronary artery inflow was completely stopped with vessel occluders in open-chest dogs for 15 or 30 seconds before a transmural myocardial tissue sample was obtained for regional analysis of creatine phosphate, adenosine triphosphate (ATP), and lactate. Heart rate was controlled, and the decline in left ventricular systolic pressure during the period in which coronary blood flow was stopped was attenuated by aortic constriction. Studies were also performed in dogs that were (1) pretreated with propranolol, (2) subjected to ventricular fibrillation, and (3) volume loaded. Control studies revealed no transmural metabolite gradients in the normally perfused ventricle, but creatine phosphate was slightly lower in the inner region than it was in the outer and middle ventricular wall regions. With coronary blood flow stopped for 30 seconds, a significant lactate gradient, increasing from the outer to the inner region, was present. Propranolol-treated dogs with their coronary blood flow stopped for 30 seconds also exhibited a lactate gradient, but dogs with ventricular fibrillation and their coronary blood flow stopped for 30 seconds did not. Volume-loaded dogs with their coronary blood flow stopped for only 15 seconds had a significant lactate gradient. Reciprocal gradients occurred in creatine phosphate but not in ATP. The findings suggest that the contracting ventricle uses energy unevenly and that in myocardial ischemia one of the factors causing greater subendocardial vulnerability is a greater energy need in this region.