Regional sympathetic denervation after myocardial infarction in humans detected noninvasively using I-123-metaiodobenzylguanidine

Abstract

Transmural myocardial infarction in dogs produces denervation of sympathetic nerves in viable myocardium apical to the infarct that may be arrhythmogenic. It is unknown whether sympathetic denervation occurs in humans. The purpose of this study was to use iodine-123-metaiodobenzylguanidine (MIBG), a radiolabeled guanethidine analog that is actively taken up by sympathetic nerve terminals, to image noninvasively the cardiac sympathetic nerves in patients with and without ventricular arrhythmias after myocardial infarction. Results showed that 10 of 12 patients with spontaneous ventricular tachyarrhythmias after myocardial infarction exhibited regions of thallium-201 uptake indicating viable perfused myocardium, with no MIBG uptake. Such a finding is consistent with sympathetic denervation. One patient had frequent episodes of nonsustained ventricular tachycardia induced at exercise testing that was eliminated by beta-adrenoceptor blockade. Eleven of the 12 patients had ventricular tachycardia induced at electrophysiologic study and metoprolol never prevented induction. Sympathetic denervation was also detected in two of seven postinfarction patients without ventricular arrhythmias. Normal control subjects had no regions lacking MIBG uptake. This study provides evidence that regional sympathetic denervation occurs in humans after myocardial infarction and can be detected noninvasively by comparing MIBG and thallium-201 images. Although the presence of sympathetic denervation may be related to the onset of spontaneous ventricular tachyarrhythmias in some patients, it does not appear to be related to sustained ventricular tachycardia induced at electrophysiologic study.

Cardiac Sympathetic Denervation After Transmyocardial Laser Revascularization

“…Functional stress testing results are consistent with the concept that TMR causes sympathetic denervation, masking ischemic symptoms and reducing stress-induced angina without actually improving maximal exercise capacity. The sympathetic innervation defects were significantly larger than the perfusion defects before the intervention, which could be a result of chronic ischemia, 31 previous myocardial infarction, 32 and/or diabetic autonomic neuropathy. 17,33 Whether the extent of sympathetic denervation noted in our study after TMR can alone explain the improvement in angina is yet to be determined.…”

Atrial Fibrillation Produced by Prolonged Rapid Atrial Pacing Is Associated With Heterogeneous Changes in Atrial Sympathetic Innervation

“…Recent findings of reduced atrial myocardial blood flow 16 and histological similarities between chronically ischemic ventricular myocardium and atrial myocardium in sustained AF 31 suggest the possibility of ischemia as a trigger. Myocardial infarction causes sympathetic denervation in the ventricle 32 ; however, the effects of long-term ischemia on ventricular sympathetic innervation are unknown. In diabetic cardiac autonomic neuropathy, regional hyperinnervation (increased HED retention) can accompany sympathetic denervation.…”

Brief Episode of Myocardial Ischemia Before Prolonged Ischemia Attenuates Cardiac Sympathetic Nerve Injury

“…26 In addition, heterogeneity of ventricular repolarization because of heterogeneous sympathetic innervation after MI may have a potential arrhythmogenic effect. [27][28][29] A previous study demonstrated that ventricular arrhythmias occurring in patients who had suffered MI were associated with increased mortality during the follow-up period. 30 In a multicenter study, paired VPCs after MI were associated with a more than 3-fold increase in the odds ratio of mortality compared with those with no VPC, and ventricular tachycardia with a 5-to 6-fold increase in the odds ratio.…”