Akira Nakagomi

Reduction of ST elevation in repeated coronary occlusion model depends on both altered metabolic response and conduction property

The aim of this study was to elucidate the mechanisms of altered electrical response to ischemia in repeated coronary occlusion model. To test its dependence on metabolic response, extracellular K+ concentration (eKC), myocardial pH and PCO2 were simultaneously measured with epicardial ECG during three consecutive 4 min of left anterior descending coronary artery (LAD) occlusion separated by 15 min of reperfusion in canine hearts. ECG changes induced by infusion of high K+-buffer (10 mM) into the coronary arterial bed via carotid artery-LAD bypass (referred to as high K+-challenges: HKC) were also tested prior to (the first HKC), and during each reperfusion period (the second to the fourth HKC). ST elevation was significantly reduced in subsequent occlusions (3.14 +/- 0.48 and 2.98 +/- 0.47 mV in the second and third occlusion, both P<0.05, compared to 4.91 +/- 0.78 mV in the first). This was accompanied by significant attenuation of the changes in eKC, tissue pH and PCO2. ST elevation induced by HKC also significantly reduced after repeated occlusion (4.09 +/- 0.79 mV in the fourth HKC vs. 5.64 +/- 0.68 mV in the first, P<0.05) in spite of the identical changes in eKC during HKC. This progressive decrease in ST changes by HKC was rather consistent with augmented conduction delay (86.4 +/- 7.1% increase in activation time in the fourth vs. 54.3 +/- 3.4% in the first, P<0.01). These findings indicate that repeated ischemia induces altered electrical response to subsequent ischemia based on both attenuated metabolic response and altered conduction property.

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

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.