Spatial inhomogeneity of sympathetic nerve function in hibernating myocardium.
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.


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) x 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 x g(-1) x min(-1) in normal, P<0.05; LAD subepicardium 0.31+/-0.03 versus 0.38+/-0.04 mL x g(-1) x 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.
Luisi
Andrew J
AJ
Veterans Administration Western New York Health Care System and the Department of Medicine, University at Buffalo, New York 14214, USA.
Fallavollita
James A
JA
Suzuki
Gen
G
Canty
John M
JM
D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics; D000818:Animals; D002908:Chronic Disease; D003326:Coronary Circulation; D023921:Coronary Stenosis / Q000150:complications / Q000503:physiopathology; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004195:Disease Models, Animal; D006321:Heart / Q000294:innervation* / Q000503:physiopathology*; D007457:Iodine Radioisotopes; D017682:Myocardial Stunning / Q000209:etiology / Q000503:physiopathology*; D009638:Norepinephrine / Q000378:metabolism; D013552:Swine; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D019797:3-Iodobenzylguanidine; D009638:Norepinephrine