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

Abstract

Epicardial phenol application or transmural myocardial infarction in dogs produces sympathetic denervation of myocardium apical to the site of the intervention. Because efferent denervation is probably postganglionic, reinnervation most likely occurs but has not been shown. We investigated whether 123I-labeled metaiodobenzylguanidine (MIBG), a norepinephrine analogue taken up by sympathetic nerve terminals, could provide a scintigraphic image that would detect apical sympathetic denervation and possible reinnervation. Dogs underwent MIBG scintigraphic imaging at various times after phenol application or transmural myocardial infarction. The results of MIBG scintigraphy were correlated with electrophysiological responses obtained during ansae subclaviae and norepinephrine stimulation to establish the presence of neural denervation and reinnervation. Apical defects in the MIBG scan, which were associated with either normal perfusion by thallium or a smaller-sized defect, were found consistently in dogs that had apical sympathetic innervation. MIBG scintigraphic images returned to normal after 14 weeks (mean) at a time when reinnervation was shown to have occurred. Thus, the results of MIBG scintigraphy correlated accurately with the presence of denervation and reinnervation established by neuroelectrophysiological testing. Supersensitive refractory period shortening in response to norepinephrine infusion was present after denervation and persisted for more than 3 weeks after scintigraphic and electrophysiological evidence ofmore » reinnervation. Conclusions are that 1) MIBG can be used noninvasively to determine the presence of regional myocardial efferent sympathetic denervation and subsequent reinnervation, 2) reinnervation occurs after phenol application or transmural myocardial infarction, and 3) denervation supersensitivity persists even after reinnervation occurs.« less

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Indiana Univ. School of Medicine, Indianapolis (USA)
OSTI Identifier:
6558295
Resource Type:
Journal Article
Resource Relation:
Journal Name: Circulation; (United States); Journal Volume: 78:4
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; HEART; SCINTISCANNING; NERVES; BIOLOGICAL REGENERATION; PHENOLS; BIOLOGICAL EFFECTS; DOGS; ELECTROPHYSIOLOGY; IMAGE PROCESSING; IODINE 123; MYOCARDIAL INFARCTION; PERFUSED ORGANS; RADIOPHARMACEUTICALS; ANIMALS; AROMATICS; BETA DECAY RADIOISOTOPES; BIOLOGICAL RECOVERY; BODY; CARDIOVASCULAR DISEASES; CARDIOVASCULAR SYSTEM; COUNTING TECHNIQUES; DIAGNOSTIC TECHNIQUES; DISEASES; DRUGS; ELECTRON CAPTURE RADIOISOTOPES; HOURS LIVING RADIOISOTOPES; HYDROXY COMPOUNDS; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOTOPES; LABELLED COMPOUNDS; MAMMALS; NERVOUS SYSTEM; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANS; PHYSIOLOGY; PROCESSING; RADIOISOTOPE SCANNING; RADIOISOTOPES; RECOVERY; VERTEBRATES; 550601* - Medicine- Unsealed Radionuclides in Diagnostics; 560300 - Chemicals Metabolism & Toxicology

Citation Formats

Minardo, J.D., Tuli, M.M., Mock, B.H., Weiner, R.E., Pride, H.P., Wellman, H.N., and Zipes, D.P.. Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application. United States: N. p., 1988. Web. doi:10.1161/01.CIR.78.4.1008.
Minardo, J.D., Tuli, M.M., Mock, B.H., Weiner, R.E., Pride, H.P., Wellman, H.N., & Zipes, D.P.. Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application. United States. doi:10.1161/01.CIR.78.4.1008.
Minardo, J.D., Tuli, M.M., Mock, B.H., Weiner, R.E., Pride, H.P., Wellman, H.N., and Zipes, D.P.. 1988. "Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application". United States. doi:10.1161/01.CIR.78.4.1008.
@article{osti_6558295,
title = {Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application},
author = {Minardo, J.D. and Tuli, M.M. and Mock, B.H. and Weiner, R.E. and Pride, H.P. and Wellman, H.N. and Zipes, D.P.},
abstractNote = {Epicardial phenol application or transmural myocardial infarction in dogs produces sympathetic denervation of myocardium apical to the site of the intervention. Because efferent denervation is probably postganglionic, reinnervation most likely occurs but has not been shown. We investigated whether 123I-labeled metaiodobenzylguanidine (MIBG), a norepinephrine analogue taken up by sympathetic nerve terminals, could provide a scintigraphic image that would detect apical sympathetic denervation and possible reinnervation. Dogs underwent MIBG scintigraphic imaging at various times after phenol application or transmural myocardial infarction. The results of MIBG scintigraphy were correlated with electrophysiological responses obtained during ansae subclaviae and norepinephrine stimulation to establish the presence of neural denervation and reinnervation. Apical defects in the MIBG scan, which were associated with either normal perfusion by thallium or a smaller-sized defect, were found consistently in dogs that had apical sympathetic innervation. MIBG scintigraphic images returned to normal after 14 weeks (mean) at a time when reinnervation was shown to have occurred. Thus, the results of MIBG scintigraphy correlated accurately with the presence of denervation and reinnervation established by neuroelectrophysiological testing. Supersensitive refractory period shortening in response to norepinephrine infusion was present after denervation and persisted for more than 3 weeks after scintigraphic and electrophysiological evidence of reinnervation. Conclusions are that 1) MIBG can be used noninvasively to determine the presence of regional myocardial efferent sympathetic denervation and subsequent reinnervation, 2) reinnervation occurs after phenol application or transmural myocardial infarction, and 3) denervation supersensitivity persists even after reinnervation occurs.},
doi = {10.1161/01.CIR.78.4.1008},
journal = {Circulation; (United States)},
number = ,
volume = 78:4,
place = {United States},
year = 1988,
month =
}
  • Transmural myocardial infarction in dogs produces denervation of sympathetic nerves in viable myocardium apical to the infarct that may be arrhythmogenic. It is unknown whether sympathetic denervation occurs in humans. The purpose of this study was to use iodine-123-metaiodobenzylguanidine (MIBG), a radiolabeled guanethidine analog that is actively taken up by sympathetic nerve terminals, to image noninvasively the cardiac sympathetic nerves in patients with and without ventricular arrhythmias after myocardial infarction. Results showed that 10 of 12 patients with spontaneous ventricular tachyarrhythmias after myocardial infarction exhibited regions of thallium-201 uptake indicating viable perfused myocardium, with no MIBG uptake. Such a findingmore » is consistent with sympathetic denervation. One patient had frequent episodes of nonsustained ventricular tachycardia induced at exercise testing that was eliminated by beta-adrenoceptor blockade. Eleven of the 12 patients had ventricular tachycardia induced at electrophysiologic study and metoprolol never prevented induction. Sympathetic denervation was also detected in two of seven postinfarction patients without ventricular arrhythmias. Normal control subjects had no regions lacking MIBG uptake. This study provides evidence that regional sympathetic denervation occurs in humans after myocardial infarction and can be detected noninvasively by comparing MIBG and thallium-201 images. Although the presence of sympathetic denervation may be related to the onset of spontaneous ventricular tachyarrhythmias in some patients, it does not appear to be related to sustained ventricular tachycardia induced at electrophysiologic study.« less
  • To evaluate the feasibility of detecting denervated myocardium in the infarcted canine heart, the distribution of sympathetic nerve endings using I-123 metaiodobenzylguanidine (MIBG) was compared with the distribution of perfusion using thallium-201, with the aid of color-coded computer functional map in 16 dogs. Twelve dogs underwent myocardial infarction by injection of vinyl latex into the left anterior descending coronary artery (transmural myocardial infarction, n = 6), or ligation of the left anterior descending coronary artery (nontransmural myocardial infarction, n = 6). Four dogs served as sham-operated controls. Image patterns were compared with tissue norepinephrine content and with histofluorescence microscopic findingsmore » in biopsy specimens. Hearts with transmural infarction showed zones of absent MIBG and thallium, indicating scar. Adjacent and distal regions showed reduced MIBG but normal thallium uptake, indicating viable but denervated myocardium. Denervation distal to infarction was confirmed by reduced norepinephrine content and absence of nerve fluorescence. Nontransmural myocardial infarction showed zones of wall thinning with decreased thallium uptake and a greater reduction or absence of MIBG localized to the region of the infarct, with minimal extension of denervation beyond the infarct. Norepinephrine content was significantly reduced in the infarct zone, and nerve fluorescence was absent. These findings suggest that (1) MIBG imaging can detect viable and perfused but denervated myocardium after infarction; and (2) as opposed to the distal denervation produced by transmural infarction, nontransmural infarction may lead to regional ischemic damage of sympathetic nerves, but may spare subepicardial nerve trunks that course through the region of infarction to provide a source of innervation to distal areas of myocardium.« less
  • To investigate the myocardial perfusion correlates of precordial ST segment depression during acute inferior myocardial infarction, a rest thallium-201 scintigram and a closely timed 12 lead electrocardiogram were obtained within 6 hours of the onset of infarction in 44 patients admitted with their first acute inferior myocardial infarction. Thirty-six patients demonstrated precordial ST segment depression (group 1) and eight did not (group 2). A perfusion defect involving the inferior wall was present in all 44 patients. Additional perfusion defects of the adjacent posterolateral wall (n . 20), the ventricular septum (n . 9) or both (n . 6) were presentmore » in 35 of 36 patients from group 1 compared with only 1 of 8 patients from group 2 (p less than 0.001). There was no significant difference in the frequency of multivessel coronary artery disease or disease of the left anterior descending artery between group 1 and group 2 or between patients with and those without a thallium-201 perfusion defect involving the ventricular septum. Thus, precordial ST segment depression during an acute inferior myocardial infarction is associated with thallium-201 scintigraphic evidence of more extensive involvement of the adjacent posterolateral or inferoseptal myocardial segments, which probably reflects the extent and pattern of distribution of the artery of infarction, rather than the presence of coexistent multivessel coronary artery disease or disease of the left anterior descending artery.« less
  • Perfusion scintigraphy with thallium-201, infarct scintigraphy with technetium-99m pyrophosphate (TcPYP), and equilibrium blood pool scintigraphy were performed during the initial hospitalization for acute myocardial infarction (MI) in 25 patients without evidence of heart failure who presented with advanced electrocardiographic rhythm and conduction disturbances requiring treatment. Scintigraphic findings during short-term hospitalization were related to the late clinical follow-up performed an average of 14 months later, where patients were grouped as asymptomatic, 8 patients; symptomatic, 9 patients; and deceased, 8 patients. Quantitation of perfusion abnormalities, TcPYP image abnormalities, and left ventricular ejection fraction (EF) revealed that the deceased group had significantly largermore » TcPYP abnormalities (36 +/- 20 cm2), absolute perfusion abnormalities (32 +/- 16 cm2), and perfusion abnormalities expressed as a percentage of the projected left ventricular area (42 +/- 8%) than the asymptomatic group (13 +/- 8 cm2, 14 +/- 6 cm2, and 20 +/- 9%; p less than 0.05, p greater than 0.05, and p less than 0.01, respectively). The percent perfusion abnormality was significantly larger in the deceased group (42 +/- 8%, p less than 0.01) than in either the symptomatic group (35 +/- 13%, p less than 0.01) or the asymptomatic group (20 +/- 9%), and this parameter in the symptomatic group also differed from that in the asymptomatic group (p less than 0.01). The study indicates that patients with rhythm and conduction disturbances and without congestive heart failure during acute MI may follow an uncomplicated or a complicated late clinical course. Early scintigraphic measurements of MI and perfusion correlate well with this outcome; however, EF could not differentiate among prognostic subgroups.« less
  • To assess the incidence of perioperative myocardial infarction, 214 consecutive patients were evaluated 1 to 5 days after coronary bypass surgery, using Tc-99m pyrophosphate (TcPPi) myocardial imaging, serial electrocardiograms (ECG), and enzyme levels (SGOT, LDH, CPK). On the basis of the clinical course and scintigraphic, enzymatic, and ECG changes, the diagnosis of perioperative infarction was definite in 17 of 214 cases (7.9%) and probable in six of 214 (2.8%). In all of these 23 patients, TcPPi scans were abnormal; one additional patient had a false-positive scintigram. Only 13 of the 23 had ECG evidence of infarction, but there were nomore » false positives. We set the threshold for abnormality of enzyme changes quite high, owing to experience in more than 900 postoperative patients (SGOT > 200, LDH > 500, CPK > 500 on the same day). Using these criteria, 22 of the 23 infarct patients had abnormal enzymes, and six others were falsely positive. These results indicate a relatively low sensitivity for the ECG in diagnosing perioperative infarction, but the lack of false positives suggests high specificity. The sensitivity and specificity of the enzymes and the TcPPi image were both excellent and quite similar; the main difference was a reduction of certainty of infarction with the enzyme criteria, caused by the six patients whose enzyme values were falsely positive. Considering its sensitivity,specificity, and ability to locate and to a certain extent quantitate necrosis, TcPPi imaging is probably the most valuable means of diagnosing perioperative myocardial infarction.« less