Skip to main content
Top
Published in: Annals of Nuclear Medicine 6/2013

01-07-2013 | Original Article

Myocardial sympathetic innervation, function, and oxidative metabolism in non-infarcted myocardium in patients with prior myocardial infarction

Authors: Hirofumi Aoki, Ichiro Matsunari, Yusuke Nomura, Wataru Fujita, Ryoko Komatsu, Yoshiharu Miyazaki, Stephan G. Nekolla, Kouji Kajinami

Published in: Annals of Nuclear Medicine | Issue 6/2013

Login to get access

Abstract

Objective

The purpose of this study was to investigate the relationship between sympathetic innervation, contractile function, and the oxidative metabolism of the non-infarcted myocardium in patients with prior myocardial infarction.

Methods

In 19 patients (14 men, 5 women, 65 ± 9 years) after prior myocardial infarction, sympathetic innervation was assessed by 11C-hydroxyephedrine (HED) positron emission tomography (PET). Oxidative metabolism was quantified using 11C-acetate PET. Left ventricular systolic function was measured by echocardiography with speckle tracking technique.

Results

The 11C-HED retention was positively correlated with left ventricular ejection fraction (LVEF) (r = 0.566, P < 0.05), and negatively with peak longitudinal strain in systole in the non-infarcted myocardium (r = −0.561, P < 0.05). Kmono, as an index of oxidative metabolism, was significantly correlated with rate pressure product (r = 0.649, P < 0.01), but not with 11C-HED retention (r = 0.188, P = 0.442). Furthermore, there was no significant correlation between Kmono and LVEF (r = 0.106, P = 0.666) or peak longitudinal strain in systole (r = −0.256, P = 0.291) in the non-infarcted myocardium. When the patients were divided into two groups based on the median value of left ventricular end-systolic volume index (LVESVI) (41 mL), there were no significant differences in age, sex, and rate pressure product between the groups. However, the large LVESVI group (>41 mL) was associated with reduced 11C-HED retention and peak longitudinal strain in systole, whereas Kmono was similar between the groups.

Conclusions

This study indicates that remodeled LV after myocardial infarction is associated with impaired sympathetic innervation and function even in the non-infarcted myocardial tissue. Furthermore, oxidative metabolism in the non-infarcted myocardium seems to be operated by normal regulatory mechanisms rather than pre-synaptic sympathetic neuronal function.
Literature
1.
go back to reference Beadle RM, Williams LK, Abozguia K, Patel K, Leon FL, Yousef Z, et al. Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial. Trials. 2011;12:140.PubMedCrossRef Beadle RM, Williams LK, Abozguia K, Patel K, Leon FL, Yousef Z, et al. Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial. Trials. 2011;12:140.PubMedCrossRef
2.
go back to reference Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation. 1990;81:1161–72.PubMedCrossRef Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation. 1990;81:1161–72.PubMedCrossRef
3.
go back to reference Pfeffer MA, Braunwald E. Ventricular enlargement following infarction is a modifiable process. Am J Cardiol. 1991;68:127D–31D.PubMedCrossRef Pfeffer MA, Braunwald E. Ventricular enlargement following infarction is a modifiable process. Am J Cardiol. 1991;68:127D–31D.PubMedCrossRef
4.
go back to reference Ohte N, Narita H, Iida A, Fukuta H, Iizuka N, Hayano J, et al. Cardiac beta-adrenergic receptor density and myocardial systolic function in the remote noninfarcted region after prior myocardial infarction with left ventricular remodelling. Eur J Nucl Med Mol Imaging. 2012. Ohte N, Narita H, Iida A, Fukuta H, Iizuka N, Hayano J, et al. Cardiac beta-adrenergic receptor density and myocardial systolic function in the remote noninfarcted region after prior myocardial infarction with left ventricular remodelling. Eur J Nucl Med Mol Imaging. 2012.
5.
go back to reference Ohte N, Narita H, Iida A, Wakami K, Asada K, Fukuta H, et al. Impaired myocardial oxidative metabolism in the remote normal region in patients in the chronic phase of myocardial infarction and left ventricular remodeling. J Nucl Cardiol. 2009;16:73–81.PubMedCrossRef Ohte N, Narita H, Iida A, Wakami K, Asada K, Fukuta H, et al. Impaired myocardial oxidative metabolism in the remote normal region in patients in the chronic phase of myocardial infarction and left ventricular remodeling. J Nucl Cardiol. 2009;16:73–81.PubMedCrossRef
6.
go back to reference Bengel FM, Permanetter B, Ungerer M, Nekolla SG, Schwaiger M. Relationship between altered sympathetic innervation, oxidative metabolism and contractile function in the cardiomyopathic human heart; a non-invasive study using positron emission tomography. Eur Heart J. 2001;22:1594–600.PubMedCrossRef Bengel FM, Permanetter B, Ungerer M, Nekolla SG, Schwaiger M. Relationship between altered sympathetic innervation, oxidative metabolism and contractile function in the cardiomyopathic human heart; a non-invasive study using positron emission tomography. Eur Heart J. 2001;22:1594–600.PubMedCrossRef
7.
go back to reference Leitman M, Lysyansky P, Sidenko S, Shir V, Peleg E, Binenbaum M, et al. Two-dimensional strain-a novel software for real-time quantitative echocardiographic assessment of myocardial function. J Am Soc Echocardiogr. 2004;17:1021–9.PubMedCrossRef Leitman M, Lysyansky P, Sidenko S, Shir V, Peleg E, Binenbaum M, et al. Two-dimensional strain-a novel software for real-time quantitative echocardiographic assessment of myocardial function. J Am Soc Echocardiogr. 2004;17:1021–9.PubMedCrossRef
8.
go back to reference Reisner SA, Lysyansky P, Agmon Y, Mutlak D, Lessick J, Friedman Z. Global longitudinal strain: a novel index of left ventricular systolic function. J Am Soc Echocardiogr. 2004;17:630–3.PubMedCrossRef Reisner SA, Lysyansky P, Agmon Y, Mutlak D, Lessick J, Friedman Z. Global longitudinal strain: a novel index of left ventricular systolic function. J Am Soc Echocardiogr. 2004;17:630–3.PubMedCrossRef
9.
go back to reference Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Int J Cardiovasc Imaging. 2002;18:539–42.PubMed Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Int J Cardiovasc Imaging. 2002;18:539–42.PubMed
10.
go back to reference Kusunose K, Yamada H, Nishio S, Mizuguchi Y, Choraku M, Maeda Y, et al. Validation of longitudinal peak systolic strain by speckle tracking echocardiography with visual assessment and myocardial perfusion SPECT in patients with regional asynergy. Circ J. 2010;75:141–7.PubMedCrossRef Kusunose K, Yamada H, Nishio S, Mizuguchi Y, Choraku M, Maeda Y, et al. Validation of longitudinal peak systolic strain by speckle tracking echocardiography with visual assessment and myocardial perfusion SPECT in patients with regional asynergy. Circ J. 2010;75:141–7.PubMedCrossRef
11.
go back to reference Schwaiger M, Kalff V, Rosenspire K, Haka MS, Molina E, Hutchins GD, et al. Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography. Circulation. 1990;82:457–64.PubMedCrossRef Schwaiger M, Kalff V, Rosenspire K, Haka MS, Molina E, Hutchins GD, et al. Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography. Circulation. 1990;82:457–64.PubMedCrossRef
12.
go back to reference Matsunari I, Aoki H, Nomura Y, Takeda N, Chen WP, Taki J, et al. Iodine-123 metaiodobenzylguanidine imaging and carbon-11 hydroxyephedrine positron emission tomography compared in patients with left ventricular dysfunction. Circ Cardiovasc Imaging. 2010;3:595–603.PubMedCrossRef Matsunari I, Aoki H, Nomura Y, Takeda N, Chen WP, Taki J, et al. Iodine-123 metaiodobenzylguanidine imaging and carbon-11 hydroxyephedrine positron emission tomography compared in patients with left ventricular dysfunction. Circ Cardiovasc Imaging. 2010;3:595–603.PubMedCrossRef
13.
go back to reference Uren NG, Crake T, Lefroy DC, de Silva R, Davies GJ, Maseri A. Reduced coronary vasodilator function in infarcted and normal myocardium after myocardial infarction. N Engl J Med. 1994;331:222–7.PubMedCrossRef Uren NG, Crake T, Lefroy DC, de Silva R, Davies GJ, Maseri A. Reduced coronary vasodilator function in infarcted and normal myocardium after myocardial infarction. N Engl J Med. 1994;331:222–7.PubMedCrossRef
14.
go back to reference Wolpers HG, Nguyen N, Rosenspire K, Haka M, Wieland DM, Schwaiger M. 11C-hydroxyephedrine as marker for neuronal catecholamine retention in reperfused canine myocardium. Coron Artery Dis. 1991;2:923–9. Wolpers HG, Nguyen N, Rosenspire K, Haka M, Wieland DM, Schwaiger M. 11C-hydroxyephedrine as marker for neuronal catecholamine retention in reperfused canine myocardium. Coron Artery Dis. 1991;2:923–9.
15.
go back to reference Allman KC, Wieland DM, Muzik O, Degrado TR, Wolfe ER Jr, Schwaiger M. Carbon-11 hydroxyephedrine with positron emission tomography for serial assessment of cardiac adrenergic neuronal function after acute myocardial infarction in humans. J Am Coll Cardiol. 1993;22:368–75.PubMedCrossRef Allman KC, Wieland DM, Muzik O, Degrado TR, Wolfe ER Jr, Schwaiger M. Carbon-11 hydroxyephedrine with positron emission tomography for serial assessment of cardiac adrenergic neuronal function after acute myocardial infarction in humans. J Am Coll Cardiol. 1993;22:368–75.PubMedCrossRef
16.
go back to reference Di Carli MF, Tobes MC, Mangner T, Levine AB, Muzik O, Chakroborty P, et al. Effects of cardiac sympathetic innervation on coronary blood flow. N Engl J Med. 1997;336:1208–15.PubMedCrossRef Di Carli MF, Tobes MC, Mangner T, Levine AB, Muzik O, Chakroborty P, et al. Effects of cardiac sympathetic innervation on coronary blood flow. N Engl J Med. 1997;336:1208–15.PubMedCrossRef
17.
go back to reference Ungerer M, Hartmann F, Karoglan M, Chlistalla A, Ziegler S, Richardt G, et al. Regional in vivo and in vitro characterization of autonomic innervation in cardiomyopathic human heart. Circulation. 1998;97:174–80.PubMedCrossRef Ungerer M, Hartmann F, Karoglan M, Chlistalla A, Ziegler S, Richardt G, et al. Regional in vivo and in vitro characterization of autonomic innervation in cardiomyopathic human heart. Circulation. 1998;97:174–80.PubMedCrossRef
18.
go back to reference Bengel FM, Ueberfuhr P, Schiepel N, Nekolla SG, Reichart B, Schwaiger M. Effect of sympathetic reinnervation on cardiac performance after heart transplantation. N Engl J Med. 2001;345:731–8.PubMedCrossRef Bengel FM, Ueberfuhr P, Schiepel N, Nekolla SG, Reichart B, Schwaiger M. Effect of sympathetic reinnervation on cardiac performance after heart transplantation. N Engl J Med. 2001;345:731–8.PubMedCrossRef
19.
go back to reference Brown MA, Myears DW, Bergmann SR. Noninvasive assessment of canine myocardial oxidative metabolism with carbon-11 acetate and positron emission tomography. J Am Coll Cardiol. 1988;12:1054–63.PubMedCrossRef Brown MA, Myears DW, Bergmann SR. Noninvasive assessment of canine myocardial oxidative metabolism with carbon-11 acetate and positron emission tomography. J Am Coll Cardiol. 1988;12:1054–63.PubMedCrossRef
20.
go back to reference Gropler RJ, Geltman EM, Sampathkumaran K, Perez JE, Schechtman KB, Conversano A, et al. Comparison of carbon-11-acetate with fluorine-18-fluorodeoxyglucose for delineating viable myocardium by positron emission tomography. J Am Coll Cardiol. 1993;22:1587–97.PubMedCrossRef Gropler RJ, Geltman EM, Sampathkumaran K, Perez JE, Schechtman KB, Conversano A, et al. Comparison of carbon-11-acetate with fluorine-18-fluorodeoxyglucose for delineating viable myocardium by positron emission tomography. J Am Coll Cardiol. 1993;22:1587–97.PubMedCrossRef
21.
go back to reference Marwick TH, Schwaiger M. The future of cardiovascular imaging in the diagnosis and management of heart failure, part 1: tasks and tools. Circ Cardiovasc Imaging. 2008;1:58–69.PubMedCrossRef Marwick TH, Schwaiger M. The future of cardiovascular imaging in the diagnosis and management of heart failure, part 1: tasks and tools. Circ Cardiovasc Imaging. 2008;1:58–69.PubMedCrossRef
22.
go back to reference Matsunari I, Yoneyama T, Kanayama S, Matsudaira M, Nakajima K, Taki J, et al. Phantom studies for estimation of defect size on cardiac 18F SPECT and PET: implications for myocardial viability assessment. J Nucl Med. 2001;42:1579–85.PubMed Matsunari I, Yoneyama T, Kanayama S, Matsudaira M, Nakajima K, Taki J, et al. Phantom studies for estimation of defect size on cardiac 18F SPECT and PET: implications for myocardial viability assessment. J Nucl Med. 2001;42:1579–85.PubMed
23.
go back to reference Urheim S, Edvardsen T, Torp H, Angelsen B, Smiseth OA. Myocardial strain by Doppler echocardiography. Validation of a new method to quantify regional myocardial function. Circulation. 2000;102:1158–64.PubMedCrossRef Urheim S, Edvardsen T, Torp H, Angelsen B, Smiseth OA. Myocardial strain by Doppler echocardiography. Validation of a new method to quantify regional myocardial function. Circulation. 2000;102:1158–64.PubMedCrossRef
24.
go back to reference Marwick TH. Measurement of strain and strain rate by echocardiography: ready for prime time? J Am Coll Cardiol. 2006;47:1313–27.PubMedCrossRef Marwick TH. Measurement of strain and strain rate by echocardiography: ready for prime time? J Am Coll Cardiol. 2006;47:1313–27.PubMedCrossRef
25.
go back to reference Geyer H, Caracciolo G, Abe H, Wilansky S, Carerj S, Gentile F, et al. Assessment of myocardial mechanics using speckle tracking echocardiography: fundamentals and clinical applications. J Am Soc Echocardiogr. 2010;23:351–69. quiz 453-355.PubMedCrossRef Geyer H, Caracciolo G, Abe H, Wilansky S, Carerj S, Gentile F, et al. Assessment of myocardial mechanics using speckle tracking echocardiography: fundamentals and clinical applications. J Am Soc Echocardiogr. 2010;23:351–69. quiz 453-355.PubMedCrossRef
26.
go back to reference Nahum J, Bensaid A, Dussault C, Macron L, Clemence D, Bouhemad B, et al. Impact of longitudinal myocardial deformation on the prognosis of chronic heart failure patients. Circ Cardiovasc Imaging. 2010;3:249–56.PubMedCrossRef Nahum J, Bensaid A, Dussault C, Macron L, Clemence D, Bouhemad B, et al. Impact of longitudinal myocardial deformation on the prognosis of chronic heart failure patients. Circ Cardiovasc Imaging. 2010;3:249–56.PubMedCrossRef
27.
go back to reference Cohn JN. Abnormalities of peripheral sympathetic nervous system control in congestive heart failure. Circulation. 1990;82:I59–67.PubMed Cohn JN. Abnormalities of peripheral sympathetic nervous system control in congestive heart failure. Circulation. 1990;82:I59–67.PubMed
28.
go back to reference Kramer CM, Nicol PD, Rogers WJ, Suzuki MM, Shaffer A, Theobald TM, et al. Reduced sympathetic innervation underlies adjacent noninfarcted region dysfunction during left ventricular remodeling. J Am Coll Cardiol. 1997;30:1079–85.PubMedCrossRef Kramer CM, Nicol PD, Rogers WJ, Suzuki MM, Shaffer A, Theobald TM, et al. Reduced sympathetic innervation underlies adjacent noninfarcted region dysfunction during left ventricular remodeling. J Am Coll Cardiol. 1997;30:1079–85.PubMedCrossRef
29.
go back to reference Sakata K, Mochizuki M, Yoshida H, Nawada R, Ohbayashi K, Ishikawa J, et al. Cardiac sympathetic dysfunction contributes to left ventricular remodeling after acute myocardial infarction. Eur J Nucl Med. 2000;27:1641–9.PubMedCrossRef Sakata K, Mochizuki M, Yoshida H, Nawada R, Ohbayashi K, Ishikawa J, et al. Cardiac sympathetic dysfunction contributes to left ventricular remodeling after acute myocardial infarction. Eur J Nucl Med. 2000;27:1641–9.PubMedCrossRef
30.
go back to reference Bengel FM, Barthel P, Matsunari I, Schmidt G, Schwaiger M. Kinetics of 123I-MIBG after acute myocardial infarction and reperfusion therapy. J Nucl Med. 1999;40:904–10.PubMed Bengel FM, Barthel P, Matsunari I, Schmidt G, Schwaiger M. Kinetics of 123I-MIBG after acute myocardial infarction and reperfusion therapy. J Nucl Med. 1999;40:904–10.PubMed
31.
go back to reference Prichard BN, Owens CW, Smith CC, Walden RJ. Heart and catecholamines. Acta Cardiol. 1991;46:309–22.PubMed Prichard BN, Owens CW, Smith CC, Walden RJ. Heart and catecholamines. Acta Cardiol. 1991;46:309–22.PubMed
32.
go back to reference Bacaner M, Brietenbucher J, LaBree J. Prevention of ventricular fibrillation, acute myocardial infarction (myocardial necrosis), heart failure, and mortality by bretylium: is ischemic heart disease primarily adrenergic cardiovascular disease? Am J Ther. 2004;11:366–411.PubMedCrossRef Bacaner M, Brietenbucher J, LaBree J. Prevention of ventricular fibrillation, acute myocardial infarction (myocardial necrosis), heart failure, and mortality by bretylium: is ischemic heart disease primarily adrenergic cardiovascular disease? Am J Ther. 2004;11:366–411.PubMedCrossRef
33.
go back to reference Opie LH, Thandroyen FT, Muller C, Bricknell OL. Adrenaline-induced “oxygen-wastage” and enzyme release from working rat heart. Effects of calcium antagonism, beta-blockade, nicotinic acid and coronary artery ligation. J Mol Cell Cardiol. 1979;11:1073–94.PubMedCrossRef Opie LH, Thandroyen FT, Muller C, Bricknell OL. Adrenaline-induced “oxygen-wastage” and enzyme release from working rat heart. Effects of calcium antagonism, beta-blockade, nicotinic acid and coronary artery ligation. J Mol Cell Cardiol. 1979;11:1073–94.PubMedCrossRef
34.
go back to reference Goodwin GW, Ahmad F, Doenst T, Taegtmeyer H. Energy provision from glycogen, glucose, and fatty acids on adrenergic stimulation of isolated working rat hearts. Am J Physiol. 1998;274:H1239–47.PubMed Goodwin GW, Ahmad F, Doenst T, Taegtmeyer H. Energy provision from glycogen, glucose, and fatty acids on adrenergic stimulation of isolated working rat hearts. Am J Physiol. 1998;274:H1239–47.PubMed
35.
go back to reference Bengel FM, Ueberfuhr P, Ziegler SI, Nekolla SG, Odaka K, Reichart B, et al. Non-invasive assessment of the effect of cardiac sympathetic innervation on metabolism of the human heart. Eur J Nucl Med. 2000;27:1650–7.PubMedCrossRef Bengel FM, Ueberfuhr P, Ziegler SI, Nekolla SG, Odaka K, Reichart B, et al. Non-invasive assessment of the effect of cardiac sympathetic innervation on metabolism of the human heart. Eur J Nucl Med. 2000;27:1650–7.PubMedCrossRef
36.
go back to reference Schafers M, Lerch H, Wichter T, Rhodes CG, Lammertsma AA, Borggrefe M, et al. Cardiac sympathetic innervation in patients with idiopathic right ventricular outflow tract tachycardia. J Am Coll Cardiol. 1998;32:181–6.PubMedCrossRef Schafers M, Lerch H, Wichter T, Rhodes CG, Lammertsma AA, Borggrefe M, et al. Cardiac sympathetic innervation in patients with idiopathic right ventricular outflow tract tachycardia. J Am Coll Cardiol. 1998;32:181–6.PubMedCrossRef
37.
go back to reference Wichter T, Schafers M, Rhodes CG, Borggrefe M, Lerch H, Lammertsma AA, et al. Abnormalities of cardiac sympathetic innervation in arrhythmogenic right ventricular cardiomyopathy: quantitative assessment of presynaptic norepinephrine reuptake and postsynaptic beta-adrenergic receptor density with positron emission tomography. Circulation. 2000;101:1552–8.PubMedCrossRef Wichter T, Schafers M, Rhodes CG, Borggrefe M, Lerch H, Lammertsma AA, et al. Abnormalities of cardiac sympathetic innervation in arrhythmogenic right ventricular cardiomyopathy: quantitative assessment of presynaptic norepinephrine reuptake and postsynaptic beta-adrenergic receptor density with positron emission tomography. Circulation. 2000;101:1552–8.PubMedCrossRef
38.
go back to reference Caldwell JH, Link JM, Levy WC, Poole JE, Stratton JR. Evidence for pre- to postsynaptic mismatch of the cardiac sympathetic nervous system in ischemic congestive heart failure. J Nucl Med. 2008;49:234–41.PubMedCrossRef Caldwell JH, Link JM, Levy WC, Poole JE, Stratton JR. Evidence for pre- to postsynaptic mismatch of the cardiac sympathetic nervous system in ischemic congestive heart failure. J Nucl Med. 2008;49:234–41.PubMedCrossRef
39.
go back to reference Kakuchi H, Sasaki T, Ishida Y, Komamura K, Miyatake K. Clinical usefulness of 123I meta-iodobenzylguanidine imaging in predicting the effectiveness of beta blockers for patients with idiopathic dilated cardiomyopathy before and soon after treatment. Heart. 1999;81:148–52.PubMed Kakuchi H, Sasaki T, Ishida Y, Komamura K, Miyatake K. Clinical usefulness of 123I meta-iodobenzylguanidine imaging in predicting the effectiveness of beta blockers for patients with idiopathic dilated cardiomyopathy before and soon after treatment. Heart. 1999;81:148–52.PubMed
Metadata
Title
Myocardial sympathetic innervation, function, and oxidative metabolism in non-infarcted myocardium in patients with prior myocardial infarction
Authors
Hirofumi Aoki
Ichiro Matsunari
Yusuke Nomura
Wataru Fujita
Ryoko Komatsu
Yoshiharu Miyazaki
Stephan G. Nekolla
Kouji Kajinami
Publication date
01-07-2013
Publisher
Springer Japan
Published in
Annals of Nuclear Medicine / Issue 6/2013
Print ISSN: 0914-7187
Electronic ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-013-0716-6

Other articles of this Issue 6/2013

Annals of Nuclear Medicine 6/2013 Go to the issue