BACKGROUND: Regional cardiac sympathetic nerve dysfunction develops in hibernating myocardium and may play a role in its association with sudden cardiac death. Interventions to improve cardiac function (i.e., revascularization) improve survival, but the potential reversibility of sympathetic nerve dysfunction remains unclear. METHODS AND RESULTS: Pigs (n = 11) were chronically instrumented with a proximal left anterior descending coronary artery (LAD) stenosis to produce hibernating myocardium. Prior to therapeutic interventions, there was LAD occlusion with collateral-dependent myocardium, reduced regional function (echocardiographic LAD wall-thickening 23% +/- 4% vs 83% +/- 6% in Remote, P < .001), and large defects in (11)C-meta-hydroxyephedrine (HED) PET (48% +/- 4% of LV area, 26% +/- 2% integrated reduction). Successful PCI or pravastatin therapy improved regional (LAD wall-thickening 23% +/- 4% to 42% +/- 6%, P < .05) and global LV function (fractional shortening 24% +/- 2% to 31% +/- 2%, P < .01), but did not alter regional HED uptake, retention, defect size, or defect severity. CONCLUSIONS: Despite significant functional improvement of hibernating myocardium as a result of PCI or pravastatin therapy, there were no changes in HED defect size or severity. Thus, inhomogeneity in myocardial sympathetic innervation persisted, and the lack of plasticity suggests that even in the absence of significant infarction, structural rather than functional defects are responsible for reduced myocardial norepinephrine uptake in chronic ischemic heart disease.
BACKGROUND: Regional cardiac sympathetic nerve dysfunction develops in hibernating myocardium and may play a role in its association with sudden cardiac death. Interventions to improve cardiac function (i.e., revascularization) improve survival, but the potential reversibility of sympathetic nerve dysfunction remains unclear. METHODS AND RESULTS:Pigs (n = 11) were chronically instrumented with a proximal left anterior descending coronary artery (LAD) stenosis to produce hibernating myocardium. Prior to therapeutic interventions, there was LAD occlusion with collateral-dependent myocardium, reduced regional function (echocardiographic LAD wall-thickening 23% +/- 4% vs 83% +/- 6% in Remote, P < .001), and large defects in (11)C-meta-hydroxyephedrine (HED) PET (48% +/- 4% of LV area, 26% +/- 2% integrated reduction). Successful PCI or pravastatin therapy improved regional (LAD wall-thickening 23% +/- 4% to 42% +/- 6%, P < .05) and global LV function (fractional shortening 24% +/- 2% to 31% +/- 2%, P < .01), but did not alter regional HED uptake, retention, defect size, or defect severity. CONCLUSIONS: Despite significant functional improvement of hibernating myocardium as a result of PCI or pravastatin therapy, there were no changes in HED defect size or severity. Thus, inhomogeneity in myocardial sympathetic innervation persisted, and the lack of plasticity suggests that even in the absence of significant infarction, structural rather than functional defects are responsible for reduced myocardial norepinephrine uptake in chronic ischemic heart disease.
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