Hibernating Myocardium

Abstract

Abstract-The inability to reproduce spontaneous ventricular fibrillation in an animal model of chronic coronary artery disease has limited advances in understanding mechanisms of sudden cardiac death (SCD). Swine with hibernating myocardium arising from a chronic left anterior descending coronary artery (LAD) occlusion have a high rate of SCD that parallels the poor clinical survival of medically treated patients with hibernating myocardium. Kaplan-Meier analysis (nϭ426) demonstrated a cumulative mortality of 49% after 5 months that was almost entirely attributable to spontaneous SCD. Using implantable loop recorders, ventricular fibrillation was documented as the arrhythmic mechanism of death in all animals (nϭ10) and was usually preceded by ventricular tachycardia (nϭ8). Physiological studies before SCD (nϭ7) demonstrated total LAD occlusion and collateral-dependent myocardium (nϭ5), excluding acute occlusion as a major trigger of arrhythmia. The physiological substrate of hibernating myocardium was present before SCD, with reductions in LAD perfusion (SCD 0.79Ϯ0.13 versus 0.80Ϯ0.08 mL/min per g) and wall thickening (SCD 28Ϯ3% versus 22Ϯ3%) that were similar to survivors (nϭ14). Triphenyltetrazolium chloride infarcts among animals with SCD were infrequent (4 of 32) and small, averaging 4.6% of LV mass. Histology (nϭ4) showed postmortem changes but no acute inflammation nor contraction band necrosis. These data support the notion that hibernating myocardium is a pathophysiological substrate at high risk of SCD. This is independent of changes in functional stenosis severity, acute myocardial necrosis, or fibrotic scar. Thus, regional adaptations that promote myocyte survival in the setting of chronic repetitive ischemia result in a substrate with enhanced vulnerability to lethal arrhythmias and SCD.

Reductions in mitochondrial O2consumption and preservation of high-energy phosphate levels after simulated ischemia in chronic hibernating myocardium

“…A left thoracotomy was performed in the fourth intercostal space. The proximal LAD was dissected free and instrumented with a fixed-diameter Delrin stenosis (1.5 mm ID) (6,11,12). The chest incision was closed in layers, the intercostal nerves were infiltrated with 2% lidocaine for analgesia, and the pneumothorax was evacuated.…”

“…For ATP depletion studies and isolation of mitochondrion, a large wedge of LAD-perfused tissue was sampled from the most apical ring (ring 1), and the posterobasal ring (ring 3) was used for remote normally perfused tissue. The midventricular ring (ring 2) and remaining samples from rings 1 and 3 were used for quantification of myocardial perfusion (6,52). LAD and remote region perfusion measurements reflected the weighted average of all samples within a perfusion territory after review of the vasodilated perfusion map and exclusion of border zone samples ( Fig.…”

Noninvasive assessment myocardial viability: Current status and future directions

“…This model continues to add to our understanding of myocardial viability in humans. [16][17][18][19][20] It has also led to an ongoing human study for prediction of events (PAREPET). 21 A preliminary report from this study shows that extent of denervated myocardium on C-11 hydroxyephedrine PET in patients with heart failure predicts subsequent ventricular tachycardia/fibrillation.…”

Mechanisms of Postinfarction Electrophysiological Abnormality: Sympathetic Neural Remodeling, Electrical Remodeling and Gap Junction Remodeling

“…Thus, both exogenous and endogenous nerve growth factor can induce cardiac nerve sprouting, but they also can increase the incidence of ventricular arrhythmias and sudden death in canine models (Cao et al, 2000a). Increased neurotrophic factor expression and heterogeneous innervation also could induce side effects that contribute to the increased risk for sudden death after myocardial infarction (Luisi et al, 2002;Canty et al, 2004).…”