Abstract 5696: Dynamic Alterations in Ventricular Repolarization in Pigs with Hibernatimg Myocardium and a Chronic LAD Stenosis
Altered ventricular repolarization manifested as QT-RR hysteresis occurs in Long QT Syndrome and with acute ischemia. We hypothesized that this might identify risk of sudden cardiac death (SCD) associated with chronic coronary disease. Pigs were chronically instrumented with a left anterior descending (LAD) coronary stenosis to produce hibernating myocardium (n=11). This model develops frequent, spontaneous SCD due to ventricular tachycardia degenerating into ventricular fibrillation, in the absence of infarction. As compared to 13 Controls there was reduced LAD wall-thickening (25±2 vs 54±9%, p<0.001) and flow reserve (1.4±0.3 vs 2.7±0.5, p<0.05), with preserved ejection fraction (63±3 vs 71±4%, p=0.09), and minimal necrosis (0.4±0.2% of LV). Regional electrograms were obtained from subendocardial piezoelectric crystals. Baseline QT intervals from the LAD region were similar in both groups (Hibernating – 354±13 vs. 356±15 ms in Controls, p=0.93). The QT intervals shortened to a similar extent during atrial pacing (Hibernating – 247±8 vs. 249±10 ms, p=0.92), stellate ganglion stimulation (Hibernating – 259±16 vs. 242±11 ms, p=0.37), and intravenous epinephrine infusion (Hibernating – 255±16 vs. 237±9 ms, p=0.31), with no differences between groups. In contrast, the LAD region QT-RR relationships during epinephrine stimulation were altered in pigs with hibernating myocardium, resulting in greater hysteresis loop areas as compared to Controls (7247±2334 vs 1927±943 ms2, p<0.05). Interestingly, this did not reflect stress-induced ischemia since pigs with hibernating myocardium also had greater hysteresis loop areas in the remote normally-perfused regions (9295±1319 ms2, p=0.40 vs LAD). There were no significant regional differences in either group. Hibernating myocardium in pigs is associated with altered ventricular repolarization hysteresis. This abnormality is global, and thus dissociated from regional dysfunction, reduced flow reserve and the propensity to develop acute ischemia. Thus, dynamic alterations in ventricular repolarization may be a substrate for SCD in patients with ischemic heart disease and chronic remodeling from hibernating myocardium.