Metaiodobenzylguanidine [131I] scintigraphy detects impaired myocardial sympathetic neuronal transport function of canine mechanical-overload heart failure.

Abstract

In heart failure secondary to chronic mechanical overload, cardiac sympathetic neurons demonstrate depressed catecholamine synthetic and transport function. To assess the potential of sympathetic neuronal imaging for detection of depressed transport function, serial scintigrams were acquired after the intravenous administration of metaiodobenzylguanidine [131I] to 13 normal dogs, 3 autotransplanted (denervated) dogs, 5 dogs with left ventricular failure, and 5 dogs with compensated left ventricular hypertrophy due to a surgical arteriovenous shunt. Nine dogs were killed at 14 hours postinjection for determination of metaiodobenzylguanidine [131I] and endogenous norepinephrine content in left atrium, left ventricle, liver, and spleen. By 4 hours postinjection, autotransplanted dogs had a 39% reduction in mean left ventricular tracer accumulation, reflecting an absent intraneuronal tracer pool. Failure dogs demonstrated an accelerated early mean left ventricular tracer efflux rate (26.0%/hour versus 13.7%/hour in normals), reflecting a disproportionately increased extraneuronal tracer pool. They also showed reduced late left ventricular and left atrial concentrations of tracer, consistent with a reduced intraneuronal tracer pool. By contrast, compensated hypertrophy dogs demonstrated a normal early mean left ventricular tracer efflux rate (16.4%/hour) and essentially normal late left ventricular and left atrial concentrations of tracer. Metaiodobenzylguanidine [131I] scintigraphic findings reflect the integrity of the cardiac sympathetic neuronal transport system in canine mechanical-overload heart failure. Metaiodobenzylguanidine [123I] scintigraphy should be explored as a means of early detection of mechanical-overload heart failure in patients.

The Role of the Autonomic Nervous System in Sudden Cardiac Death

“…MIBG studies had shown both sympathetic denervation and reinnervation in injured myocardium in both ischemic and nonischemic cardiomyopathy in humans. 37,38 A consequence of peripheral nerve injury resulting in Wallerian degeneration is regeneration via nerve sprouting. The axonal regeneration is slow but accelerates to reach a constant rate by third day after injury and is triggered by NGF produced by surrounding myocardium.…”

Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application.

“…The norepinephrine storage mechanism lags behind the specific membrane mechanism for uptake in the reinnervated heart after surgical denervation. [34][35][36] It is important to caution that such MIBG defects may have also arisen from some physiological change in the uptake pathway for MIBG such as might occur if there were competition for the uptake mechanism from a sympathetic agent such as norepinephrine. Nevertheless, it appears that a similar interplay between myocardial injury and autonomic nervous system innervation may exist in humans.…”

Effects of the Angiotensin-converting Enzyme Inhibitor Enalapril on Sympathetic Neuronal Function and .BETA.-adrenergic Desensitization in Heart Failure after Myocardial Infarction in Rats.

“…24,25) A decrease in myocardial MIBG accumulation and NE has been reported in heart failure 21,[26][27][28][29] and also in experimental models of MI. 19,30) In the present study, it is unlikely that reduced MIBG accumulation and NE content would be due to sympathetic denervation by the surgical procedure because MIBG accumulation and NE content did not decrease in the sham-operated rats.…”