Regional 11C-hydroxyephedrine retention in hibernating myocardium: chronic inhomogeneity of sympathetic innervation in the absence of infarction.
We have previously shown that ex vivo counting of (131)I-metaiodobenzylguanidine can identify regional reductions in sympathetic norepinephrine uptake in pigs with hibernating myocardium. However, nonneuronal uptake limited relative differences between regions and would preclude accurate assessment with conventional imaging. We therefore hypothesized that the superior specificity of the positron-emitting isotope (11)C-hydroxyephedrine (HED) would facilitate the imaging of regional differences, and we designed this study to determine whether altered uptake of norepinephrine by sympathetic nerves in viable, dysfunctional myocardium can be imaged in vivo and to determine the temporal progression and stability of sympathetic dysinnervation in hibernating myocardium.


METHODS
Pigs (n = 15) were chronically instrumented with a 1.5-mm stenosis of the left anterior descending coronary artery, a procedure that we have previously shown to produce viable chronically dysfunctional myocardium with reduced resting flow, or hibernating myocardium, after 3 mo. Physiologic studies and HED PET were performed 1-5 mo later with the animals in the closed-chest sedated state. One animal with a myocardial infarct was analyzed separately.


RESULTS
After 3 mo, anterior hypokinesis developed (wall thickening, 32% +/- 4% vs. 60% +/- 4%, P < 0.001), with reductions in resting flow (subendocardial flow, 0.81 +/- 0.11 vs. 1.20 +/- 0.18 mL/min/g, P < 0.05) and a critical reduction in subendocardial flow reserve (subendocardial adenosine flow, 0.53 +/- 0.20 vs. 3.96 +/- 0.43 mL/min/g, P < 0.001). Extensive defects in HED uptake were found for hibernating myocardium, with regional retention approximately 50% lower than that in normally perfused remote myocardium (0.035 +/- 0.002 vs. 0.066 +/- 0.002 min(-1), P < 0.001). Relative HED uptake (left anterior descending coronary artery/remote) was lower in chronically instrumented animals than in control animals (n = 4, P < 0.001) and animals studied 1 mo after instrumentation (n = 2, P < 0.05). The regional reduction in sympathetic nerve function was persistent and unaltered for at least 2 mo after the development of hibernating myocardium.


CONCLUSIONS
Hibernating myocardium is associated with persistent reductions in regional uptake of norepinephrine by sympathetic nerves. The inhomogeneity in sympathetic innervation in viable dysfunctional myocardium is similar to that occurring after myocardial infarction and may contribute to arrhythmic death in patients with ischemic cardiomyopathy.
Luisi
Andrew J
AJ
Department of Medicine, SUNY at Buffalo, VA Western New York Health Care System, NY 14214, USA.
Suzuki
Gen
G
Dekemp
Robert
R
Haka
Michael S
MS
Toorongian
Steven A
SA
Canty
John M
JM
Fallavollita
James A
JA
D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000150:complications* / Q000000981:diagnostic imaging* / Q000378:metabolism; D002986:Clinical Trials as Topic; D004809:Ephedrine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006321:Heart / Q000000981:diagnostic imaging / Q000294:innervation; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism; D017682:Myocardial Stunning / Q000150:complications* / Q000000981:diagnostic imaging*; D009206:Myocardium / Q000378:metabolism; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013552:Swine; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging* / Q000378:metabolism; D014018:Tissue Distribution
D019275:Radiopharmaceuticals; C065363:3-hydroxyephedrine; D004809:Ephedrine