Altered Metabolic Response Accounts for Reduced ST-Elevation to Subsequent Coronary Occlusion in Ischemia-Sensitized Myocardium

Abstract

Schroeder et al. reported that a preceding 5-min coronary occlusion caused earlier deterioration of myocardial function (MF) in subsequent ischemia. This study was designed to reveal the mechanism responsible for this latent abnormality and associated ECG response. In 26 dogs, we measured MF by sonomicrometry, tissue PCO₂, pH, extracellular K⁺(KC), and epicardial surface electrocardiograms. The experimental protocol was as follows: the left anterior descending coronary artery (LAD) was occluded for 2 min, followed by 15-min reperfusion (Trial 1: Tr-1). In the control group (Gr-C), reperfusion was continued for another 95 min, while in the other groups LAD was occluded for 5 or 15 min, followed by 80- or 90-min reperfusion after Tr-1. The LAD was then occluded again, for 2 min (Tr-2), in all groups. In the Gr-C, there were no significant differences between the trials in any of the above variables, while in the 5-min group, MF (% systolic shortening) recovered to the control level prior to Tr-2, but showed earlier deterioration in Tr-2 than in Tr-1. Further, reduced ST-elevation was noted in Tr-2, associated with the decreases in KC, PCO₂, and pH. Similar reductions in metabolic and electrical parameters were also observed in the 15-min occlusion group. CO₂ and protons are the end-products of cardiac metabolism, so their reduced production rate reflects depressed metabolic viability in reperfused myocardium; this phenomenon indicates a sensitization-like effect produced by the preceding ischemia (“ischemia-sensitized myocardium”). This phenomenon may be related to limited substrate use in energy metabolism and may also play a crucial role in the preconditioning effect.