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Published in: Heart Failure Reviews 2/2011

01-03-2011

Vagus nerve stimulation in experimental heart failure

Authors: Hani N. Sabbah, Itamar Ilsar, Asaph Zaretsky, Sharad Rastogi, Mengjun Wang, Ramesh C. Gupta

Published in: Heart Failure Reviews | Issue 2/2011

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Abstract

Chronic heart failure (HF) is associated with autonomic dysregulation characterized by a sustained increase in sympathetic drive and by withdrawal of parasympathetic activity. Sympathetic overdrive and increased heart rate are predictors of poor long-term outcome in patients with HF. Considerable evidence exists that supports the use of pharmacologic agents that partially inhibit sympathetic activity as effective long-term therapy for patients with HF; the classic example is the wide use of selective and non-selective beta-adrenergic receptor blockers. In contrast, modulation of parasympathetic activation as potential therapy for HF has received only limited attention over the years given its complex cardiovascular effects. In this article, we review the results of recent experimental animal studies that provide support for the possible use of electrical Vagus nerve stimulation (VNS) as a long-term therapy for the treatment of chronic HF. In addition to exploring the effects of chronic VNS on left ventricular (LV) function, the review will also address the effects of VNS on potential modifiers of the HF state that include cytokine production and nitric oxide elaboration. Finally, we will briefly review other nerve stimulation approaches which is also currently under investigation as potential therapeutic modalities for treating chronic HF.
Literature
1.
go back to reference Schwatrz PJ, Vanoli E, Stramba-Badiale M, De Ferrari GM, Billman GE, Foreman RD (1988) Autonomic mechanisms and sudden death. New insights from the analysis of baroreceptor reflexes in conscious dogs with and without myocardial infarction. Circulation 78:969–973 Schwatrz PJ, Vanoli E, Stramba-Badiale M, De Ferrari GM, Billman GE, Foreman RD (1988) Autonomic mechanisms and sudden death. New insights from the analysis of baroreceptor reflexes in conscious dogs with and without myocardial infarction. Circulation 78:969–973
2.
go back to reference Mortara A, La Rovere MT, Pinna GD, Prpa A, Maestri R, Febo O, Pozzoli M, Opasich C, Tavazzi L (1997) Arterial baroreflex modulation of heart rate in chronic heart failure: clinical and hemodynamic correlates and prognostic implications. Circulation 96:3450–3458PubMed Mortara A, La Rovere MT, Pinna GD, Prpa A, Maestri R, Febo O, Pozzoli M, Opasich C, Tavazzi L (1997) Arterial baroreflex modulation of heart rate in chronic heart failure: clinical and hemodynamic correlates and prognostic implications. Circulation 96:3450–3458PubMed
3.
go back to reference La Rovere MT, Bigger JT, Marcus FI, Mortara A, Schwartz PJ (1998) Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. Lancet 351:478–484CrossRefPubMed La Rovere MT, Bigger JT, Marcus FI, Mortara A, Schwartz PJ (1998) Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. Lancet 351:478–484CrossRefPubMed
4.
go back to reference Lechat P, Hulot JS, Escolano S, Mallet A, Leizorovicz A, Werhlen-Grandjean M, Pochmalicki G, Dargie H, on behalf of the CIBIS II Investigators (2001) Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II trial. Circulation 103:1428–1433PubMed Lechat P, Hulot JS, Escolano S, Mallet A, Leizorovicz A, Werhlen-Grandjean M, Pochmalicki G, Dargie H, on behalf of the CIBIS II Investigators (2001) Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II trial. Circulation 103:1428–1433PubMed
5.
go back to reference Sabbah HN, Shimoyama H, Kono T, Gupta RS, Sharov VG, Scicli G, Levine TB, Goldstein S (1994) Effects of long-term monotherapy with enalapril, metoprolol and digoxin on the progression of left ventricular dysfunction and dilation in dogs with reduced ejection fraction. Circulation 89:2852–2859PubMed Sabbah HN, Shimoyama H, Kono T, Gupta RS, Sharov VG, Scicli G, Levine TB, Goldstein S (1994) Effects of long-term monotherapy with enalapril, metoprolol and digoxin on the progression of left ventricular dysfunction and dilation in dogs with reduced ejection fraction. Circulation 89:2852–2859PubMed
6.
go back to reference Sabbah HN, Stanley WC, Sharov VG, Mishima T, Tanimura M, Benedict CR, Hegde S, Goldstein S (2000) Effects of dopamine β-hydroxylase inhibition with nepicastat on the progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure. Circulation 102:1990–1995PubMed Sabbah HN, Stanley WC, Sharov VG, Mishima T, Tanimura M, Benedict CR, Hegde S, Goldstein S (2000) Effects of dopamine β-hydroxylase inhibition with nepicastat on the progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure. Circulation 102:1990–1995PubMed
7.
go back to reference Morita H, Suzuki G, Chaudhry PA, Anagnostopoulos PV, Tanhehco EJ, Sharov VG, Goldstein S, Sabbah HN (2002) Effects of long-term monotherapy with metoprolol CR/XL on the progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure. Cardiovasc Drugs Ther 16:433–449CrossRef Morita H, Suzuki G, Chaudhry PA, Anagnostopoulos PV, Tanhehco EJ, Sharov VG, Goldstein S, Sabbah HN (2002) Effects of long-term monotherapy with metoprolol CR/XL on the progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure. Cardiovasc Drugs Ther 16:433–449CrossRef
8.
go back to reference Sabbah HN, Wang M, Jiang A, Ilsar I, Gupta RC, Rastogi S (2009) Long-term monotherapy with ivabradine improves left ventricular function and prevents progressive chamber remodeling in dogs with moderate heart failure (abstract). Circulation 120:S867CrossRef Sabbah HN, Wang M, Jiang A, Ilsar I, Gupta RC, Rastogi S (2009) Long-term monotherapy with ivabradine improves left ventricular function and prevents progressive chamber remodeling in dogs with moderate heart failure (abstract). Circulation 120:S867CrossRef
9.
go back to reference Kunze DL (1972) Reflex discharge patterns of cardiac vagal efferent fibers. J Physiol (Lond) 222:1–8 Kunze DL (1972) Reflex discharge patterns of cardiac vagal efferent fibers. J Physiol (Lond) 222:1–8
10.
go back to reference Harman MA, Reeves TJ (1968) Effects of efferent nerve stimulation on atrial and ventricular function. Am J Physiol 215:1210–1217PubMed Harman MA, Reeves TJ (1968) Effects of efferent nerve stimulation on atrial and ventricular function. Am J Physiol 215:1210–1217PubMed
11.
go back to reference Wiggers CJ (1916) Physiology of the mammalian auricles: II. Influence of the vagus nerves on the fractionate contraction of the right auricle. Am J Physiol 133–140 Wiggers CJ (1916) Physiology of the mammalian auricles: II. Influence of the vagus nerves on the fractionate contraction of the right auricle. Am J Physiol 133–140
12.
go back to reference DeGeest H, Levy M, Zieske H, Lipman RI (1965) Depression on ventricular contractility by stimulation of the vagus nerves. Circ Res 17:222–235PubMed DeGeest H, Levy M, Zieske H, Lipman RI (1965) Depression on ventricular contractility by stimulation of the vagus nerves. Circ Res 17:222–235PubMed
13.
go back to reference Henry JP, Meehan JP (1971) Circulation: integrative physiology study. Year Book Medical Publishers, Chicago, p 57 Henry JP, Meehan JP (1971) Circulation: integrative physiology study. Year Book Medical Publishers, Chicago, p 57
14.
go back to reference Vanoli E, De Ferrari GM, Stramba-Badiale M, Hull SS Jr, Foreman RD, Schwartz PJ (1991) Vagal stimulation and prevention of sudden death in conscious dogs with healed myocardial infarction. Circ Res 68:1471–1481PubMed Vanoli E, De Ferrari GM, Stramba-Badiale M, Hull SS Jr, Foreman RD, Schwartz PJ (1991) Vagal stimulation and prevention of sudden death in conscious dogs with healed myocardial infarction. Circ Res 68:1471–1481PubMed
15.
go back to reference Li M, Zheng C, Sato T, Kawada T, Sugimachi N, Sunagawa K (2004) Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats. Circulation 109:120–124CrossRefPubMed Li M, Zheng C, Sato T, Kawada T, Sugimachi N, Sunagawa K (2004) Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats. Circulation 109:120–124CrossRefPubMed
16.
go back to reference Zheng C, Li M, Inagaki M, Kawada T, Sunagawa K, Sugimachi M (2005) Vagal stimulation markedly suppresses arrhythmias in conscious rats with chronic heart failure after myocardial infarction. Conf Proc IEEE Eng Med Biol Soc 7:7072–7075PubMed Zheng C, Li M, Inagaki M, Kawada T, Sunagawa K, Sugimachi M (2005) Vagal stimulation markedly suppresses arrhythmias in conscious rats with chronic heart failure after myocardial infarction. Conf Proc IEEE Eng Med Biol Soc 7:7072–7075PubMed
17.
go back to reference Sabbah HN, Stein PD, Kono T, Gheorghiade M, Levine TB, Jafri S, Hawkins ET, Goldstein S (1991) A canine model of chronic heart failure produced by multiple sequential coronary microembolizations. Am J Physiol 260:H1379–H1384PubMed Sabbah HN, Stein PD, Kono T, Gheorghiade M, Levine TB, Jafri S, Hawkins ET, Goldstein S (1991) A canine model of chronic heart failure produced by multiple sequential coronary microembolizations. Am J Physiol 260:H1379–H1384PubMed
18.
go back to reference Zhang Y, Popovic ZB, Bibevski S, Fakhry I, Sica DA, Van Wagoner DR, Mazgalev TN (2009) Chronic Vagus nerve stimulation improves autonomic control and attenuates systemic inflammation and heart failure progression in a canine high-rate pacing model. Circulation 2:692–699PubMed Zhang Y, Popovic ZB, Bibevski S, Fakhry I, Sica DA, Van Wagoner DR, Mazgalev TN (2009) Chronic Vagus nerve stimulation improves autonomic control and attenuates systemic inflammation and heart failure progression in a canine high-rate pacing model. Circulation 2:692–699PubMed
19.
go back to reference Jones JFX, Wang Y, Jordan D (1998) Activity of C fibre cardiac vagal efferents in anaesthetized cats and rats. J Physiol 507:869–880CrossRefPubMed Jones JFX, Wang Y, Jordan D (1998) Activity of C fibre cardiac vagal efferents in anaesthetized cats and rats. J Physiol 507:869–880CrossRefPubMed
20.
go back to reference Tosato M, Yoshida K, Toft E, Nekrasas V, Struijk (2006) Closed-loop control of the heart rate by electrical stimulation of the vagus nerve. Med Biol Eng Comput 44:161–169CrossRefPubMed Tosato M, Yoshida K, Toft E, Nekrasas V, Struijk (2006) Closed-loop control of the heart rate by electrical stimulation of the vagus nerve. Med Biol Eng Comput 44:161–169CrossRefPubMed
21.
go back to reference Ben-Menachem E, Mañon-Espaillat R, Ristanovic R, Wilder BJ, Stefan H, Mirza W, Tarver WB, Wernicke JF (1994) Vagus nerve stimulation or treatment of partial seizures: 1. A controlled study of effect on seizures. First International Vagus Nerve Stimulation Study Group. Epilepsia 35:616–626CrossRefPubMed Ben-Menachem E, Mañon-Espaillat R, Ristanovic R, Wilder BJ, Stefan H, Mirza W, Tarver WB, Wernicke JF (1994) Vagus nerve stimulation or treatment of partial seizures: 1. A controlled study of effect on seizures. First International Vagus Nerve Stimulation Study Group. Epilepsia 35:616–626CrossRefPubMed
22.
go back to reference DeGiorgio C, Heck C, Bunch S, Britton J, Green P, Lancman M, Murphy J, Olejniczak P, Shih J, Arrambide S, Soss J (2005) Vagus nerve stimulation for epilepsy: randomized comparison of three stimulation paradigms. Neurology 65:317–319CrossRefPubMed DeGiorgio C, Heck C, Bunch S, Britton J, Green P, Lancman M, Murphy J, Olejniczak P, Shih J, Arrambide S, Soss J (2005) Vagus nerve stimulation for epilepsy: randomized comparison of three stimulation paradigms. Neurology 65:317–319CrossRefPubMed
23.
go back to reference De Herdt V, Boon P, Ceulemans B, Hauman H, Lagae L, Legros B, Sadzot B, Van Bogaert P, van Rijckevorsel K, Verhelst H, Vonck K (2007) Vagus nerve stimulation for refractory epilepsy: a Belgian multicenter study. Eur J Paediatr Neurol 11:261–269CrossRefPubMed De Herdt V, Boon P, Ceulemans B, Hauman H, Lagae L, Legros B, Sadzot B, Van Bogaert P, van Rijckevorsel K, Verhelst H, Vonck K (2007) Vagus nerve stimulation for refractory epilepsy: a Belgian multicenter study. Eur J Paediatr Neurol 11:261–269CrossRefPubMed
24.
go back to reference Labiner DM, Ahern GL (2007) Vagus nerve stimulation therapy in depression and epilepsy: therapeutic parameter settings. Acta Neurol Scand 115:23–33CrossRefPubMed Labiner DM, Ahern GL (2007) Vagus nerve stimulation therapy in depression and epilepsy: therapeutic parameter settings. Acta Neurol Scand 115:23–33CrossRefPubMed
25.
go back to reference Sabbah HN, Rastogi S, Mishra S, Gupta RC, Ilsar I, Imai M, Cohen U, Ben-David T, Ben-Ezra O (2005) Long-term therapy with neuroselective electric Vagus nerve stimulation improves LV function and attenuates global LV remodelling in dogs with chronic heart failure (abstract). Eur J Heart Fail Suppl 4:166 Sabbah HN, Rastogi S, Mishra S, Gupta RC, Ilsar I, Imai M, Cohen U, Ben-David T, Ben-Ezra O (2005) Long-term therapy with neuroselective electric Vagus nerve stimulation improves LV function and attenuates global LV remodelling in dogs with chronic heart failure (abstract). Eur J Heart Fail Suppl 4:166
26.
go back to reference Sabbah HN, Imai M, Zaretsky A, Rastogi S, Wang M, Jiang A, Zaca V (2007) Therapy with Vagus nerve electrical stimulation combined with beta-blockade improves left ventricular function in dogs with heart failure beyond that seen with beta-blockade alone (abstract). Eur J Heart Fail 6:114 Sabbah HN, Imai M, Zaretsky A, Rastogi S, Wang M, Jiang A, Zaca V (2007) Therapy with Vagus nerve electrical stimulation combined with beta-blockade improves left ventricular function in dogs with heart failure beyond that seen with beta-blockade alone (abstract). Eur J Heart Fail 6:114
27.
go back to reference Liu YH, Yang XP, Sharov VG, Nass O, Sabbah HN, Peterson E, Carretero OA (1997) Effects of angiotensin-converting enzyme inhibitors and angiotensin ii type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors. J Clin Invest 99:1926–1935CrossRefPubMed Liu YH, Yang XP, Sharov VG, Nass O, Sabbah HN, Peterson E, Carretero OA (1997) Effects of angiotensin-converting enzyme inhibitors and angiotensin ii type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors. J Clin Invest 99:1926–1935CrossRefPubMed
29.
go back to reference Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa L, Czura CJ, Tracey KJ (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421:384–388CrossRefPubMed Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa L, Czura CJ, Tracey KJ (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421:384–388CrossRefPubMed
30.
go back to reference Gupta RC, Imai M, Jiang AJ, Wang M, Sabbah HN (2006) Chronic therapy with selective electric Vagus nerve stimulation normalizes plasma concentration of tissue necrosis factor-α, interleukin-6 and B-type natriuretic peptide in dogs with heart failure (abstract). J Am Coll Cardiol 47:77ACrossRef Gupta RC, Imai M, Jiang AJ, Wang M, Sabbah HN (2006) Chronic therapy with selective electric Vagus nerve stimulation normalizes plasma concentration of tissue necrosis factor-α, interleukin-6 and B-type natriuretic peptide in dogs with heart failure (abstract). J Am Coll Cardiol 47:77ACrossRef
31.
go back to reference Feng Q, Song W, Lu X, Hamilton JA, Lei M, Peng T, Yee S-P (2002) Development of Heart Failure and congenital septal defects in mice lacking endothelial nitric oxide synthase. Circulation 106:873–879CrossRefPubMed Feng Q, Song W, Lu X, Hamilton JA, Lei M, Peng T, Yee S-P (2002) Development of Heart Failure and congenital septal defects in mice lacking endothelial nitric oxide synthase. Circulation 106:873–879CrossRefPubMed
32.
go back to reference Kelly RA, Balligand JL, Smith TW (1996) Nitric oxide and cardiac function. Circ Res 79:363–380PubMed Kelly RA, Balligand JL, Smith TW (1996) Nitric oxide and cardiac function. Circ Res 79:363–380PubMed
33.
34.
go back to reference Gupta RC, Mishra S, Rastogi S, Imai M, Zaca V, Sabbah HN (2006) Chronic therapy with electric Vagus nerve stimulation normalizes mRNA and protein expression of nitric oxide synthase in myocardium of dogs with heart failure (abstract). Eur Heart J 27:477CrossRef Gupta RC, Mishra S, Rastogi S, Imai M, Zaca V, Sabbah HN (2006) Chronic therapy with electric Vagus nerve stimulation normalizes mRNA and protein expression of nitric oxide synthase in myocardium of dogs with heart failure (abstract). Eur Heart J 27:477CrossRef
35.
go back to reference Pattern RD, DeNofrio D, El-Zaru M, Kakkar R, Saunders J, Celestin F, Warner K, Rastegar H, Khabbaz KR, Udelson JE, Konstam MA, Karas RH (2005) Ventricular assist device therapy normalizes inducible nitric oxide synthase expression and reduces cardiomyocyte apoptosis in the failing human heart. J Am Coll Cardiol 45:1419–1424CrossRef Pattern RD, DeNofrio D, El-Zaru M, Kakkar R, Saunders J, Celestin F, Warner K, Rastegar H, Khabbaz KR, Udelson JE, Konstam MA, Karas RH (2005) Ventricular assist device therapy normalizes inducible nitric oxide synthase expression and reduces cardiomyocyte apoptosis in the failing human heart. J Am Coll Cardiol 45:1419–1424CrossRef
36.
go back to reference Mungrue IN, Gros R, You X, Pirani A, Azad A, Csont T, Schulz R, Butany J, Stewart DJ, Husain M (2002) Cardiomyocyte overexpression of iNOS in mice results in peroxynitrite generation, heart block and sudden death. J Clin Invest 109:735–743PubMed Mungrue IN, Gros R, You X, Pirani A, Azad A, Csont T, Schulz R, Butany J, Stewart DJ, Husain M (2002) Cardiomyocyte overexpression of iNOS in mice results in peroxynitrite generation, heart block and sudden death. J Clin Invest 109:735–743PubMed
37.
go back to reference Xu KY, Huso DL, Dawson TM, Bredt DS, Becker LC (1999) Nitric oxide synthase in cardiac sarcoplasmic reticulum. Proc Natl Acad Sci USA 96:657–662CrossRefPubMed Xu KY, Huso DL, Dawson TM, Bredt DS, Becker LC (1999) Nitric oxide synthase in cardiac sarcoplasmic reticulum. Proc Natl Acad Sci USA 96:657–662CrossRefPubMed
38.
go back to reference Barouch LA, Harrison RW, Skaf MW, Rosas GO, Cappola TP, Kobeissi ZA, Hobai IA, Lemmon CA, Burnett AL, O’Rourke B, Rodriguez ER, Huang PL, Lima JA, Berkowitz DE, Hare JM (2002) Nitric oxide regulates the heart by special confinement of nitric oxide synthase isoforms. Nature 416:337–339PubMed Barouch LA, Harrison RW, Skaf MW, Rosas GO, Cappola TP, Kobeissi ZA, Hobai IA, Lemmon CA, Burnett AL, O’Rourke B, Rodriguez ER, Huang PL, Lima JA, Berkowitz DE, Hare JM (2002) Nitric oxide regulates the heart by special confinement of nitric oxide synthase isoforms. Nature 416:337–339PubMed
39.
go back to reference Damy T, Ratajczak P, Shah AM, Camors E, Marty I, Hasenfuss G, Marotte F, Samuel JL, Heymes C (2004) Increased neuronal nitric oxide synthase-derived NO production in the failing human heart. Lancet 363:1365–1367CrossRefPubMed Damy T, Ratajczak P, Shah AM, Camors E, Marty I, Hasenfuss G, Marotte F, Samuel JL, Heymes C (2004) Increased neuronal nitric oxide synthase-derived NO production in the failing human heart. Lancet 363:1365–1367CrossRefPubMed
40.
go back to reference Bendall JK, Damy T, Ratajczak P, Loyer X, Monceau V, Marty I, Milliez P, Robidel E, Marotte F, Samuel J-L, Heymes C (2004) Role of myocardial neuronal nitric oxide synthase-derived nitric oxide in β-adrenergic hyporesponsiveness after myocardial infarction-induced heart failure in rat. Circulation 110:2368–2375CrossRefPubMed Bendall JK, Damy T, Ratajczak P, Loyer X, Monceau V, Marty I, Milliez P, Robidel E, Marotte F, Samuel J-L, Heymes C (2004) Role of myocardial neuronal nitric oxide synthase-derived nitric oxide in β-adrenergic hyporesponsiveness after myocardial infarction-induced heart failure in rat. Circulation 110:2368–2375CrossRefPubMed
41.
go back to reference Jongsma HJ, Wilders R (2000) Gap junctions in cardiovascular disease. Circ Res 86:1193–1197PubMed Jongsma HJ, Wilders R (2000) Gap junctions in cardiovascular disease. Circ Res 86:1193–1197PubMed
42.
go back to reference Severs NJ, Bruce AF, Dupont E, Rothery S (2008) Remodelling of gap junctions and connexin expression in diseased myocardium. Cardiovasc Res 80:9–19CrossRefPubMed Severs NJ, Bruce AF, Dupont E, Rothery S (2008) Remodelling of gap junctions and connexin expression in diseased myocardium. Cardiovasc Res 80:9–19CrossRefPubMed
43.
go back to reference Van Kempen MJA, Ten Velde I, Wessels A, Oosthoek PW, Gros D, Jongsma HJ, Moorman AFM, Lamers WH (1995) Differential connexins distribution accommodates cardiac function in different species. Microsc Res Tech 31:420–436CrossRefPubMed Van Kempen MJA, Ten Velde I, Wessels A, Oosthoek PW, Gros D, Jongsma HJ, Moorman AFM, Lamers WH (1995) Differential connexins distribution accommodates cardiac function in different species. Microsc Res Tech 31:420–436CrossRefPubMed
44.
go back to reference Wang XJ, Gerdes AM (1999) Chronic pressure overload cardiac hypertrophy and failure in guinea pigs: III. Intercalated disc remodeling. J Mol Cell Cardiol 31:333–343CrossRefPubMed Wang XJ, Gerdes AM (1999) Chronic pressure overload cardiac hypertrophy and failure in guinea pigs: III. Intercalated disc remodeling. J Mol Cell Cardiol 31:333–343CrossRefPubMed
45.
go back to reference Ai X, Pogwizd M (2005) Connexin 43 downregulation and dephosphorylation in nonischemic heart failure is associated with enhanced colocalized protein phosphatase type 2A. Circ Res 96:54–63CrossRefPubMed Ai X, Pogwizd M (2005) Connexin 43 downregulation and dephosphorylation in nonischemic heart failure is associated with enhanced colocalized protein phosphatase type 2A. Circ Res 96:54–63CrossRefPubMed
46.
go back to reference Rastogi S, Mishra S, Ilsar I, Zaretsky A, Sabbah HN (2007) Chronic therapy with electric Vagus nerve stimulation normalizes mRNA and protein expression of connexin-40, -43 and -45 in left ventricular myocardium of dogs with heart failure (abstract). Circulation 116:II–218 Rastogi S, Mishra S, Ilsar I, Zaretsky A, Sabbah HN (2007) Chronic therapy with electric Vagus nerve stimulation normalizes mRNA and protein expression of connexin-40, -43 and -45 in left ventricular myocardium of dogs with heart failure (abstract). Circulation 116:II–218
Metadata
Title
Vagus nerve stimulation in experimental heart failure
Authors
Hani N. Sabbah
Itamar Ilsar
Asaph Zaretsky
Sharad Rastogi
Mengjun Wang
Ramesh C. Gupta
Publication date
01-03-2011
Publisher
Springer US
Published in
Heart Failure Reviews / Issue 2/2011
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI
https://doi.org/10.1007/s10741-010-9209-z

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