Abnormal Sympathetic Innervation of Viable Myocardium and the Substrate of Ventricular Tachycardia After Myocardial Infarction

Tetsuo Sasano, M. Roselle Abraham, Kuan Cheng Chang, Hiroshi Ashikaga, Kevin J. Mills, Daniel Holt, John Hilton, Stephan G. Nekolla, Jun Dong, Albert C. Lardo, Henry R Halperin, Robert F Dannals, Eduardo Marbán, Frank M. Bengel

Research output: Contribution to journalArticle

Abstract

Objectives: The aim of this study was to characterize the relationship between impaired sympathetic innervation and arrhythmia with noninvasive biologic imaging in an animal model of post-infarct ventricular tachycardia (VT). Background: Innervation might be abnormal in the normally perfused borderzone of myocardial infarction, contributing to myocardial catecholamine overexposure and arrhythmogenic risk. Methods: Myocardial infarction was induced by mid-left anterior descending coronary artery balloon occlusion in 11 pigs. Positron emission tomography (PET) of tissue perfusion and catecholamine uptake and storage was performed with [13N]-ammonia and [11C]-epinephrine 4 to 12 weeks later. Magnetic resonance imaging and invasive electrophysiology (electroanatomic mapping, basket catheter, VT inducibility) were performed within 1 week of PET. Results: When compared with a normal database of 9 healthy animals, reduced perfusion was observed in 37 ± 7% of the left ventricle (LV). Epinephrine retention was reduced in 44 ± 7% of LV, resulting in a perfusion/innervation mismatch of 7 ± 4% LV. Sustained monomorphic VT was inducible in 7 of 11 animals. These animals showed a larger perfusion/innervation mismatch (10 ± 4% vs. 4 ± 2% LV for animals without VT; p = 0.02). Regionally, the degree of perfusion/innervation mismatch did not correlate with wall thickness or thickening but showed a significant correlation with reduced myocardial voltage (r = 0.93; p = 0.001) and with the site of earliest VT activation (chi-square 13.1; p <0.001). Conclusions: Noninvasive mapping of cardiac sympathetic nerve terminals reveals regionally impaired catecholamine uptake and storage in the normally perfused borderzone after experimental myocardial infarction. These areas might be useful to characterize the individual risk for ventricular arrhythmia.

Original languageEnglish (US)
Pages (from-to)2266-2275
Number of pages10
JournalJournal of the American College of Cardiology
Volume51
Issue number23
DOIs
StatePublished - Jun 10 2008

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Ventricular Tachycardia
Myocardium
Perfusion
Myocardial Infarction
Heart Ventricles
Catecholamines
Positron-Emission Tomography
Epinephrine
Cardiac Arrhythmias
Balloon Occlusion
Electrophysiology
Ammonia
Coronary Vessels
Swine
Catheters
Animal Models
Magnetic Resonance Imaging
Databases

ASJC Scopus subject areas

  • Nursing(all)

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Abnormal Sympathetic Innervation of Viable Myocardium and the Substrate of Ventricular Tachycardia After Myocardial Infarction. / Sasano, Tetsuo; Abraham, M. Roselle; Chang, Kuan Cheng; Ashikaga, Hiroshi; Mills, Kevin J.; Holt, Daniel; Hilton, John; Nekolla, Stephan G.; Dong, Jun; Lardo, Albert C.; Halperin, Henry R; Dannals, Robert F; Marbán, Eduardo; Bengel, Frank M.

In: Journal of the American College of Cardiology, Vol. 51, No. 23, 10.06.2008, p. 2266-2275.

Research output: Contribution to journalArticle

Sasano, Tetsuo ; Abraham, M. Roselle ; Chang, Kuan Cheng ; Ashikaga, Hiroshi ; Mills, Kevin J. ; Holt, Daniel ; Hilton, John ; Nekolla, Stephan G. ; Dong, Jun ; Lardo, Albert C. ; Halperin, Henry R ; Dannals, Robert F ; Marbán, Eduardo ; Bengel, Frank M. / Abnormal Sympathetic Innervation of Viable Myocardium and the Substrate of Ventricular Tachycardia After Myocardial Infarction. In: Journal of the American College of Cardiology. 2008 ; Vol. 51, No. 23. pp. 2266-2275.
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abstract = "Objectives: The aim of this study was to characterize the relationship between impaired sympathetic innervation and arrhythmia with noninvasive biologic imaging in an animal model of post-infarct ventricular tachycardia (VT). Background: Innervation might be abnormal in the normally perfused borderzone of myocardial infarction, contributing to myocardial catecholamine overexposure and arrhythmogenic risk. Methods: Myocardial infarction was induced by mid-left anterior descending coronary artery balloon occlusion in 11 pigs. Positron emission tomography (PET) of tissue perfusion and catecholamine uptake and storage was performed with [13N]-ammonia and [11C]-epinephrine 4 to 12 weeks later. Magnetic resonance imaging and invasive electrophysiology (electroanatomic mapping, basket catheter, VT inducibility) were performed within 1 week of PET. Results: When compared with a normal database of 9 healthy animals, reduced perfusion was observed in 37 ± 7{\%} of the left ventricle (LV). Epinephrine retention was reduced in 44 ± 7{\%} of LV, resulting in a perfusion/innervation mismatch of 7 ± 4{\%} LV. Sustained monomorphic VT was inducible in 7 of 11 animals. These animals showed a larger perfusion/innervation mismatch (10 ± 4{\%} vs. 4 ± 2{\%} LV for animals without VT; p = 0.02). Regionally, the degree of perfusion/innervation mismatch did not correlate with wall thickness or thickening but showed a significant correlation with reduced myocardial voltage (r = 0.93; p = 0.001) and with the site of earliest VT activation (chi-square 13.1; p <0.001). Conclusions: Noninvasive mapping of cardiac sympathetic nerve terminals reveals regionally impaired catecholamine uptake and storage in the normally perfused borderzone after experimental myocardial infarction. These areas might be useful to characterize the individual risk for ventricular arrhythmia.",
author = "Tetsuo Sasano and Abraham, {M. Roselle} and Chang, {Kuan Cheng} and Hiroshi Ashikaga and Mills, {Kevin J.} and Daniel Holt and John Hilton and Nekolla, {Stephan G.} and Jun Dong and Lardo, {Albert C.} and Halperin, {Henry R} and Dannals, {Robert F} and Eduardo Marb{\'a}n and Bengel, {Frank M.}",
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T1 - Abnormal Sympathetic Innervation of Viable Myocardium and the Substrate of Ventricular Tachycardia After Myocardial Infarction

AU - Sasano, Tetsuo

AU - Abraham, M. Roselle

AU - Chang, Kuan Cheng

AU - Ashikaga, Hiroshi

AU - Mills, Kevin J.

AU - Holt, Daniel

AU - Hilton, John

AU - Nekolla, Stephan G.

AU - Dong, Jun

AU - Lardo, Albert C.

AU - Halperin, Henry R

AU - Dannals, Robert F

AU - Marbán, Eduardo

AU - Bengel, Frank M.

PY - 2008/6/10

Y1 - 2008/6/10

N2 - Objectives: The aim of this study was to characterize the relationship between impaired sympathetic innervation and arrhythmia with noninvasive biologic imaging in an animal model of post-infarct ventricular tachycardia (VT). Background: Innervation might be abnormal in the normally perfused borderzone of myocardial infarction, contributing to myocardial catecholamine overexposure and arrhythmogenic risk. Methods: Myocardial infarction was induced by mid-left anterior descending coronary artery balloon occlusion in 11 pigs. Positron emission tomography (PET) of tissue perfusion and catecholamine uptake and storage was performed with [13N]-ammonia and [11C]-epinephrine 4 to 12 weeks later. Magnetic resonance imaging and invasive electrophysiology (electroanatomic mapping, basket catheter, VT inducibility) were performed within 1 week of PET. Results: When compared with a normal database of 9 healthy animals, reduced perfusion was observed in 37 ± 7% of the left ventricle (LV). Epinephrine retention was reduced in 44 ± 7% of LV, resulting in a perfusion/innervation mismatch of 7 ± 4% LV. Sustained monomorphic VT was inducible in 7 of 11 animals. These animals showed a larger perfusion/innervation mismatch (10 ± 4% vs. 4 ± 2% LV for animals without VT; p = 0.02). Regionally, the degree of perfusion/innervation mismatch did not correlate with wall thickness or thickening but showed a significant correlation with reduced myocardial voltage (r = 0.93; p = 0.001) and with the site of earliest VT activation (chi-square 13.1; p <0.001). Conclusions: Noninvasive mapping of cardiac sympathetic nerve terminals reveals regionally impaired catecholamine uptake and storage in the normally perfused borderzone after experimental myocardial infarction. These areas might be useful to characterize the individual risk for ventricular arrhythmia.

AB - Objectives: The aim of this study was to characterize the relationship between impaired sympathetic innervation and arrhythmia with noninvasive biologic imaging in an animal model of post-infarct ventricular tachycardia (VT). Background: Innervation might be abnormal in the normally perfused borderzone of myocardial infarction, contributing to myocardial catecholamine overexposure and arrhythmogenic risk. Methods: Myocardial infarction was induced by mid-left anterior descending coronary artery balloon occlusion in 11 pigs. Positron emission tomography (PET) of tissue perfusion and catecholamine uptake and storage was performed with [13N]-ammonia and [11C]-epinephrine 4 to 12 weeks later. Magnetic resonance imaging and invasive electrophysiology (electroanatomic mapping, basket catheter, VT inducibility) were performed within 1 week of PET. Results: When compared with a normal database of 9 healthy animals, reduced perfusion was observed in 37 ± 7% of the left ventricle (LV). Epinephrine retention was reduced in 44 ± 7% of LV, resulting in a perfusion/innervation mismatch of 7 ± 4% LV. Sustained monomorphic VT was inducible in 7 of 11 animals. These animals showed a larger perfusion/innervation mismatch (10 ± 4% vs. 4 ± 2% LV for animals without VT; p = 0.02). Regionally, the degree of perfusion/innervation mismatch did not correlate with wall thickness or thickening but showed a significant correlation with reduced myocardial voltage (r = 0.93; p = 0.001) and with the site of earliest VT activation (chi-square 13.1; p <0.001). Conclusions: Noninvasive mapping of cardiac sympathetic nerve terminals reveals regionally impaired catecholamine uptake and storage in the normally perfused borderzone after experimental myocardial infarction. These areas might be useful to characterize the individual risk for ventricular arrhythmia.

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