Metabolic adaptation to a gradual reduction in myocardial blood flow

Background: Studies during 20% to 50% reductions in regional coronary blood flow have revealed a number of metabolic and functional adaptations that suggest the heart downregulates energy requirements and contractility in response to ischemia. In contrast to prior studies of sudden changes in coronary blood flow, we tested whether the heart could reduce ATP consumption commensurate with a gradual decrease in coronary brood flow or whether transient metabolic abnormalities are a necessary trigger in this process. Methods and Results: From 0 to 35 minutes, mean left anterior descending coronary artery blood flow was reduced by ≃1% per minute in 10 acutely anesthetized and instrumented swine. Coronary blood flow then was held constant between 35 and 60 minutes at the resulting 35% net blood flow reduction. Although systemic hemodynamics remained stable, a significant decrease in regional left ventricular systolic wall thickening developed (from control value of 45±11% to 18±11% at 60 minutes, P<.001) without a sustained decrease in the phosphorylation potential (as assessed by a <2% decrease in either the transmural or subendocardial phosphocreatine-to-ATP ratio) and with minimal myocardial lactate production (4±44 μmol · min^{- 1} · 100 g^-1). Conclusions: Metabolic markers of ischemia such as ratio of phosphocreatine to ATP, ATP content, lactate content, and lactate production were blunted during this protocol of gradually worsening ischemia. Thus, contractile abnormalities of mild ischemia can develop with minimal metabolic evidence of ischemia. The downregulation of myocardial energy requirements can almost keep pace with the gradual decline in coronary blood flow.