Published Online
on July 29, 2002

A more recent version of this article appeared on August 13, 2002

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Submitted on June 4, 2002
Revised on June 21, 2002
Accepted on June 21, 2002

Spatial Inhomogeneity of Sympathetic Nerve Function in Hibernating Myocardium

Andrew J. Luisi Jr MD, James A. Fallavollita MD, Gen Suzuki MD, PhD, and John M. Canty Jr MD^*

From the Veterans Administration Western New York Health Care System and the Departments of Medicine, Nuclear Medicine, and Physiology and Biophysics, University at Buffalo, New York.

^* To whom correspondence should be addressed. E-mail: canty{at}buffalo.edu.

Background—Although humans and swine with hibernating myocardium have an increased risk of sudden death, the contribution of chronic alterations in sympathetic nerve function is unknown. Acute transmural ischemia causes inhomogeneity in sympathetic innervation that may lead to lethal arrhythmias, but it is unclear whether similar abnormalities develop in response to chronic reversible ischemia.

Methods and Results—Swine were chronically instrumented with a left anterior descending coronary artery (LAD) stenosis that produced hibernating myocardium after 3 months. Resting subendocardial flow (LAD 0.75±0.14 versus 1.19±0.14 mL · min^-1 · g^-1, P<0.05) and wall thickening (LAD 15±3% versus 40±2%, P<0.05) were reduced compared with normal remote regions, without triphenyltetrazolium chloride evidence of necrosis. ¹³¹I-meta-iodobenzylguanidine (MIBG) was used to assess integrity of the norepinephrine uptake-1 mechanism, and the spatial and transmural distributions were quantified by ex vivo counting. In hibernating myocardium, MIBG deposition was decreased in each layer, with the greatest reduction in the subendocardium (LAD subendocardium 0.28±0.02 versus 0.42±0.04 mL · g^-1 · min^-1 in normal, P<0.05; LAD subepicardium 0.31±0.03 versus 0.38±0.04 mL · g^-1 · min^-1 in normal, P<0.05). In contrast, there were no spatial alterations of MIBG deposition in sham-instrumented animals.

Conclusions—The sympathetic norepinephrine uptake-1 mechanism is impaired in hibernating myocardium. These findings raise the possibility that chronic alterations in sympathetic innervation contribute to the excess mortality seen in the setting of hibernating myocardium.

Key words: hibernation • myocardial stunning • nervous system, sympathetic • death, sudden • ischemia

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