Cardiac sympathetic nerve function assessed by [131I]metaiodobenzylguanidine after ischemia and reperfusion in anesthetized dogs.
BACKGROUND
Accumulation of 131I-labeled metaiodobenzylguanidine ([131I]MIBG), a radiolabeled norepinephrine analog, is reduced in infarcted myocardium, suggesting loss of cardiac sympathetic nerve viability. Histopathologic studies, however, indicate that the nerve endings ae morphologically intact. Experiments were therefore designed to determine the mechanism of reduced MIBG accumulation.


RESULTS
Desipramine, a specific blocker or neuronal norepinephrine reuptake, was used to separate the portions of total myocardial [131I]MIBG accumulation attributable to neuronal and nonneuronal uptake mechanisms. Sixteen dogs underwent circumflex coronary artery occlusion for 60 minutes followed by a 5-hour reperfusion. [131I]MIBG was injected intravenously 1 hour after reperfusion. The left ventricle was removed and incubated in triphenyltetrazolium chloride to identify infarcted and viable myocardium within the zone at risk. Preliminary studies in sham-operated dogs showed that pretreatment with desipramine (5 mg/kg) reduced [131I]MIBG accumulation 4 hours after injection to 38.9% of untreated controls. Chemical sympathectomy by topical phenol resulted in a similar decrease in [131I]MIBG accumulation (to 45.7% of normal), and desipramine did not produce further inhibition of [131I]MIBG accumulation over that produced by phenol alone, indicating that the inhibitory effect of desipramine on neuronal accumulation of [131I]MIBG was essentially complete. In dogs undergoing ischemia-reperfusion, myocardial samples from infarcted and viable postischemic areas showed 64.5% +/- 11.85 and 84.7% +/- 9.1% of normal [131I]MIBG activity, respectively (both, p < 0.01 vs normal area, n = 9). With desipramine pretreatment (n = 7), accumulation of [131I]MIBG decreased in all areas. Neuronal accumulation was reduced uniformly in infarcted, viable postischemic, and normal areas by 30% to 35% compared with sham-operated controls. In contrast, nonneuronal accumulation was only 39.3% in infarcted areas and 84.6% in viable postischemic areas compared with normal areas, and these decreases accounted entirely for the reduced total [131I]MIBG accumulation.


CONCLUSIONS
Reduced [131I]MIBG accumulation in infarcted myocardium after 60 minutes of ischemia and 5 hours of reperfusion is attributable to a deficit in nonneuronal accumulation and not to decreased accumulation by sympathetic nerves.
Takatsu
H
H
Department of Medicine, Johns Hopkins University School of Medicine, Baltimoe, Md, USA.
Duncker
C M
CM
Arai
M
M
Becker
L C
LC
D019797:3-Iodobenzylguanidine; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D004396:Coloring Agents; D003891:Desipramine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007462:Iodobenzenes / Q000493:pharmacokinetics; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D009411:Nerve Endings / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D019800:Phenol; D010636:Phenols; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013565:Sympatholytics / Q000493:pharmacokinetics; D013778:Tetrazolium Salts
D018759:Adrenergic Uptake Inhibitors; D004396:Coloring Agents; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D010636:Phenols; D019275:Radiopharmaceuticals; D013565:Sympatholytics; D013778:Tetrazolium Salts; D019800:Phenol; D019797:3-Iodobenzylguanidine; C009591:triphenyltetrazolium; D003891:Desipramine