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Transmural gradients in ventricular tissue metabolites produced by stopping coronary blood flow in the dog
Insights
The contracting heart ventricle uses energy unevenly. During ischemia, this uneven energy use, not just blood flow, causes greater subendocardial vulnerability, leading to lactate buildup in the inner heart wall.
Area of Science:
- Cardiovascular Physiology
- Metabolic Biochemistry
Background:
- Myocardial ischemia can lead to transmural metabolite gradients.
- The role of uneven energy utilization versus non-uniform blood flow in gradient development is unclear.
Purpose of the Study:
- To investigate transmural metabolite gradients in the ischemic left ventricle.
- To differentiate the effects of uneven energy use from non-uniform blood flow.
Main Methods:
- Open-chest dogs underwent temporary coronary artery occlusion (15-30 seconds).
- Transmural myocardial samples were analyzed for creatine phosphate, ATP, and lactate.
- Studies included controls, propranolol treatment, ventricular fibrillation, and volume loading.
Main Results:
- No transmural gradients in normally perfused ventricles, but slight creatine phosphate gradient.
- 30 seconds of ischemia induced a significant lactate gradient (outer to inner).
- Lactate gradients persisted with propranolol but not ventricular fibrillation; volume loading induced gradients faster.
Conclusions:
- The contracting ventricle exhibits uneven energy utilization.
- Uneven energy demand contributes to subendocardial vulnerability during myocardial ischemia.
- Metabolite gradients during ischemia are influenced by both energy demand and blood flow dynamics.
Abstract:
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.