Hostname: page-component-78c5997874-t5tsf Total loading time: 0 Render date: 2024-11-10T05:46:38.324Z Has data issue: false hasContentIssue false
  • English
  • Français

A study of the physiological consequences of sympathetic denervation of the heart caused by the arterial switch procedure

Published online by Cambridge University Press:  11 March 2010

Cecilia Falkenberg ,
Stefan Hallhagen ,
Krister Nilsson ,
Boris Nilsson  and
Ingegerd Östman-Smith
Cecilia Falkenberg
Affiliation:
Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, Queen Silvia Children’s Hospital, Gothenburg, Sweden
Stefan Hallhagen
Affiliation:
Department of Cardiothoracic Surgery, Sahlgrenska University Hospital/Queen Silvia Children’s Hospital, Gothenburg, Sweden
Krister Nilsson
Affiliation:
Department of Anaesthetics, Institute of Clinical Sciences, The Sahlgrenska Academy, Queen Silvia Children’s Hospital, Gothenburg, Sweden
Boris Nilsson
Affiliation:
Department of Cardiothoracic Surgery, Sahlgrenska University Hospital/Queen Silvia Children’s Hospital, Gothenburg, Sweden
Ingegerd Östman-Smith*
Affiliation:
Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, Queen Silvia Children’s Hospital, Gothenburg, Sweden
*
Correspondence to: Professor Ingegerd Östman-Smith, Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, Queen Silvia Children’s Hospital, Gothenburg University, SE-416 85, Gothenburg, Sweden. Tel: +46 31 3434512; Fax: +46 31 3435947; E-mail: ingegerd.ostman-smith@pediat.gu.se
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

The arterial switch operation is the corrective operation for transposition of the great arteries, defined as the combination of concordant atrioventricular and discordant ventriculo–arterial connections, but there have been concerns about silent subendocardial ischaemia on exercise and coronary artery growth. The arterial switch divides the majority of the sympathetic nerves entering the heart; we have studied the effects of coronary flow and sensitivity to catecholamine stimulation in an animal model.

Methods

A total of 10 piglets were operated on cardiopulmonary bypass with section and resuturing of aortic trunk, pulmonary artery and both coronary arteries, with 13 sham-operated controls. After 5–7 weeks of recovery, seven simulated switch survivors and 13 controls were studied.

Results

Basal heart rate was significantly higher in switch piglets: in vivo mean (standard deviation) 112 (12) versus sham 100 (10) beats per minute, (p = 0.042); in vitro (Langendorff preparation): 89 (9) versus sham 73 (8) beats per minute (p = 0.0056). In vivo maximal heart rate in response to epinephrine was increased in switch piglets, 209 (13) versus 190 (17) beats per minute (p = 0.044). In vitro dose–response curves to norepinephrine were shifted leftward and upwards (p = 0.0014), with an 80% increase in heart rate induced by 0.095 (0.053) norepinephrine micromole per litre perfusate in switch hearts versus 0.180 (0.035) norepinephrine micromole per litre (p = 0.023). Increase in coronary flow on norepinephrine stimulation and maximal coronary flow were significantly reduced in switch hearts: 0.3 (0.2) versus 0.8 (0.4) millilitre per gram heart weight (p = 0.045) and 2.5 (0.4) versus 3.1 (0.4) millilitre per gram heart (p = 0.030), respectively.

Conclusions

A combination of increased intrinsic heart rate, increased sensitivity to chronotropic actions of norepinephrine, and a decreased maximal coronary flow creates potential for a mismatch between perfusion and energy demands.

Keywords

Congenital heart diseasecoronary artery flowsympathectomysupersensitivitynorepinephrineepinephrine
Type
Original Articles
Information
Cardiology in the Young , Volume 20 , Issue 2 , April 2010 , pp. 150 - 158
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Bonchek, LI, Starr, A. Total correction of transposition of the great arteries in infancy as initial surgical management. Ann Thorac Surg 1972; 14: 376–389.CrossRefGoogle ScholarPubMed
2.Zavanella, C, Subramanian, S. Review: surgery for transposition of the great arteries in the first year of life. Ann Surg 1978; 187: 143–150.CrossRefGoogle ScholarPubMed
3.Williams, WG, McCrindle, BW, Ashburn, DA, Jonas, RA, Mavroudis, C, Blackstone, EH. Outcomes of 829 neonates with complete transposition of the great arteries 12–17 years after repair. Eur J Cardiothorac Surg 2003; 24: 1–9; discussion 9–10.CrossRefGoogle ScholarPubMed
4.Warnes, CA. Transposition of the great arteries. Circulation 2006; 114: 2699–2709.CrossRefGoogle ScholarPubMed
5.Janes, RD, Brandys, JC, Hopkins, DA, Jonas, RA, Mavroudis, C, Blackstone, EH. Anatomy of human extrinsic cardiac nerves and ganglia. Am J Cardiol 1986; 57: 299–309.CrossRefGoogle ScholarPubMed
6.Trendelburg, U. Factors influencing the concentration of cathecholamines at the receptors. In: Blaschko H, Muscholl E (eds). Catecholamines, Handbook of Experimental Physiology, Vol. 33. Springer Verlag, Berlin, 1972, pp 726–761.Google Scholar
7.Tamisier, D, Ouaknine, R, Pouard, P, et al. Neonatal arterial switch operation: coronary artery patterns and coronary events. Eur J Cardiothorac Surg 1997; 11: 810–817.CrossRefGoogle ScholarPubMed
8.Rundqvist, B, Elam, M, Eisenhofer, G, Friberg, P. Normalization of total body and regional sympathetic hyperactivity in heart failure after heart transplantation. J Heart Lung Transplant 1996; 15: 516–526.Google ScholarPubMed
9.Regitz, V, Bossaller, C, Strasser, R, Schuler, S, Hetzer, R, Fleck, E. Myocardial catecholamine content after heart transplantation. Circulation 1990; 82: 620–623.CrossRefGoogle ScholarPubMed
10.Wilson, RF, Johnson, TH, Haidet, GC, Kubo, SH, Mianuelli, M. Sympathetic reinnervation of the sinus node and exercise hemodynamics after cardiac transplantation. Circulation 2000; 101: 2727–2733.CrossRefGoogle ScholarPubMed
11.Schwaiblmair, M, von Scheidt, W, Uberfuhr, P, et al. Functional significance of cardiac reinnervation in heart transplant recipients. J Heart Lung Transplant 1999; 18: 838–845.CrossRefGoogle ScholarPubMed
12.Kondo, C, Nakazawa, M, Momma, K, Kusakabe, K. Sympathetic denervation and reinnervation after arterial switch operation for complete transposition. Circulation 1998; 97: 2414–2419.CrossRefGoogle ScholarPubMed
13.Wells, H, Handelman, C, Milgram, E. Regulation by sympathetic nervous system of accelerated growth of salivary glands of rats. Am J Physiol 1961; 201: 707–710.CrossRefGoogle ScholarPubMed
14.Östman-Smith, I. Prevention of exercise-induced cardiac hypertrophy in rats by chemical sympathectomy (guanethidine treatment). Neuroscience 1976; 1: 497–507.CrossRefGoogle ScholarPubMed
15.Östman-Smith, I. Cardiac sympathetic nerves as the final common pathway in the induction of adaptive cardiac hypertrophy. Clin Sci (Lond) 1981; 61: 265–272.CrossRefGoogle ScholarPubMed
16.Östman-Smith, I. Reduction by oral propranolol treatment of left ventricular hypertrophy secondary to pressure-overload in the rat. Br J Pharmacol 1995; 116: 2703–2709.CrossRefGoogle ScholarPubMed
17.Östman-Smith, I. Reduction by beta-adrenoceptor blockade of hypoxia-induced right heart hypertrophy in the rat. Br J Pharmacol 1995; 116: 2698–2702.CrossRefGoogle ScholarPubMed
18.Zukowska-Grojec, Z, Karwatowska-Prokopczuk, E, Fisher, TA, Ji, H. Mechanisms of vascular growth-promoting effects of neuropeptide Y: role of its inducible receptors. Regul Pept 1998; 75–76: 231–238.CrossRefGoogle ScholarPubMed
19.Lazarovici, P, Marcinkiewicz, C, Lelkes, PI. Cross talk between the cardiovascular and nervous systems: neurotrophic effects of vascular endothelial growth factor (VEGF) and angiogenic effects of nerve growth factor (NGF)-implications in drug development. Curr Pharm Des 2006; 12: 2609–2622.CrossRefGoogle ScholarPubMed
20.Gagliardi, MG, Adorisio, R, Crea, F, Versacci, P, Di Donato, R, Sanders, SP. Abnormal vasomotor function of the epicardial coronary arteries in children five to eight years after arterial switch operation: an angiographic and intracoronary Doppler flow wire study. J Am Coll Cardiol 2005; 46: 1565–1572.CrossRefGoogle ScholarPubMed
21.Hauser, M, Bengel, FM, Kuhn, A, et al. Myocardial blood flow and flow reserve after coronary reimplantation in patients after arterial switch and Ross operation. Circulation 2001; 103: 1875–1880.CrossRefGoogle ScholarPubMed
22.Pretre, R, Tamisier, D, Bonhoeffer, P, et al. Results of the arterial switch operation in neonates with transposed great arteries. Lancet 2001; 357: 1826–1830.CrossRefGoogle ScholarPubMed
23.Brown, JW, Park, HJ, Turrentine, MW. Arterial switch operation: factors impacting survival in the current era. Ann Thorac Surg 2001; 71: 1978–1984.CrossRefGoogle ScholarPubMed
24.Hayashi, G, Kurosaki, K, Echigo, S, et al. Prevalence of arrhythmias and their risk factors mid- and long-term after the arterial switch operation. Pediatr Cardiol 2006; 27: 689–694.CrossRefGoogle ScholarPubMed
25.Uberfuhr, P, Frey, AW, Reichart, B. Vagal reinnervation in the long term after orthotopic heart transplantation. J Heart Lung Transplant 2000; 19: 946–950.CrossRefGoogle Scholar
26.Odaka, K, von Scheidt, W, Ziegler, SI, et al. Reappearance of cardiac presynaptic sympathetic nerve terminals in the transplanted heart: correlation between PET using (11)C-hydroxyephedrine and invasively measured norepinephrine release. J Nucl Med 2001; 42: 1011–1016.Google ScholarPubMed
27.Rodenbaugh, DW, Collins, HL, DiCarlo, SE. Increased susceptibility to ventricular arrhythmias in hypertensive paraplegic rats. Clin Exp Hypertens 2003; 25: 349–358.CrossRefGoogle ScholarPubMed
28.Olgin, JE, Takahashi, T, Wilson, E, Vereckei, A, Steinberg, H, Zipes, DP. Effects of thoracic spinal cord stimulation on cardiac autonomic regulation of the sinus and atrioventricular nodes. J Cardiovasc Electrophysiol 2002; 13: 475–481.CrossRefGoogle ScholarPubMed
29.Such, L, Rodriguez, A, Alberola, A, et al. Intrinsic changes on automatism, conduction, and refractoriness by exercise in isolated rabbit heart. J Appl Physiol 2002; 92: 225–229.CrossRefGoogle ScholarPubMed
30.Verkerk, AO, Wilders, R, Coronel, R, Ravesloot, JH, Verheijck, EE. Ionic remodeling of sinoatrial node cells by heart failure. Circulation 2003; 108: 760–766.CrossRefGoogle ScholarPubMed
31.Iversen, LL. The Uptake and Storage of Noradrenaline in Sympathetic Nerves. Cambridge University Press, Cambridge, 1967.Google Scholar
32.Yates, RW, Marsden, PK, Badawi, RD, et al. Evaluation of myocardial perfusion using positron emission tomography in infants following a neonatal arterial switch operation. Pediatr Cardiol 2000; 21: 111–118.CrossRefGoogle ScholarPubMed
33.Bengel, FM, Hauser, M, Duvernoy, CS, et al. Myocardial blood flow and coronary flow reserve late after anatomical correction of transposition of the great arteries. J Am Coll Cardiol 1998; 32: 1955–1961.CrossRefGoogle ScholarPubMed
34.Oskarsson, G, Pesonen, E, Munkhammar, P, Sandström, S, Jögi, P. Normal coronary flow reserve after arterial switch operation for transposition of the great arteries: an intracoronary Doppler guidewire study. Circulation 2002; 106: 1696–1702.CrossRefGoogle ScholarPubMed
35.Weindling, SN, Wernovsky, G, Colan, SD, et al. Myocardial perfusion, function and exercise tolerance after the arterial switch operation. J Am Coll Cardiol 1994; 23: 424–433.CrossRefGoogle ScholarPubMed
36.Massin, M, Hovels-Gurich, H, Dabritz, S, Messmer, B, von Bernuth, G. Results of the Bruce treadmill test in children after arterial switch operation for simple transposition of the great arteries. Am J Cardiol 1998; 81: 56–60.CrossRefGoogle ScholarPubMed
37.von Bernuth, G. 25 years after the first arterial switch procedure: mid-term results. Thorac Cardiovasc Surg 2000; 48: 228–232.CrossRefGoogle ScholarPubMed
38.Hui, L, Chau, AK, Leung, MP, Chiu, CS, Cheung, YF. Assessment of left ventricular function long term after arterial switch operation for transposition of the great arteries by dobutamine stress echocardiography. Heart 2005; 91: 68–72.CrossRefGoogle ScholarPubMed
39.Legendre, A, Losay, J, Touchot-Kone, A, et al. Coronary events after arterial switch operation for transposition of the great arteries. Circulation 2003; 108 (Suppl. 1): II186–II190.CrossRefGoogle ScholarPubMed
40.Yatsunami, K, Nakazawa, M, Kondo, C, et al. Small left coronary arteries after arterial switch operation for complete transposition. Ann Thorac Surg 1997; 64: 746–750; discussion 750–741.CrossRefGoogle ScholarPubMed
41.Gallego-Page, JC, Segovia, J, Alonso-Pulpon, L, Alonso-Rodriguez, M, Salas, C, Ortiz-Berrocal, J. Re-innervation after heart transplantation: a multidisciplinary study. J Heart Lung Transplant 2004; 23: 674–682.CrossRefGoogle ScholarPubMed