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

Cardiol Young. 2010 Apr;20(2):150-8. doi: 10.1017/S1047951109990643. Epub 2010 Mar 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Heart / innervation*
  • Heart / physiopathology*
  • Heart Rate / physiology
  • In Vitro Techniques
  • Norepinephrine / administration & dosage
  • Regional Blood Flow
  • Swine
  • Sympathomimetics / administration & dosage
  • Transposition of Great Vessels / physiopathology*
  • Transposition of Great Vessels / surgery*

Substances

  • Sympathomimetics
  • Norepinephrine