title: The heart reinnervates after transplantation.
abstract: BACKGROUND
  Whether cardiac reinnervation occurs after transplantation remains controversial. If reinnervation does occur, how sympathetic and parasympathetic efferent neurons do this remains unknown.
  
  
  METHODS
  Power spectral analysis of heart rate variability was assessed for 1 year after cardiac autotransplantation in 9 dogs. After induction of anesthesia 13 months after transplantation, cardiac and intrinsic cardiac neuronal responses elicited by both electrical stimulation of parasympathetic or sympathetic efferent neurons and systemic or local coronary artery administration of nicotine (5 microg/kg), angiotensin II (0.75 microg/kg), and tyramine (1.2 microg/kg) were studied. The transmembrane electrical properties of intrinsic cardiac neurons were studied in vitro. Ventricular tissue catecholamine content, alpha-tubulin expression, and beta-adrenergic receptor density and affinity were studied. The presence of axons crossing suture lines was sought histologically.
  
  
  RESULTS
  Nerves were identified crossing suture lines. Electrical or chemical (ie, nicotine or angiotensin II) activation of sympathetic efferent neurons enhanced cardiodynamics, as did tyramine. Stimulating vagal efferent preganglionic axons induced bradycardia in half of the dogs. Functional reinnervation did not correlate with specific power spectra derived from rate variability in the conscious state. Responding to nicotine and angiotensin II in situ, transplanted intrinsic cardiac neurons generated spontaneous activity. These neurons displayed nicotine-dependent synaptic inputs in vitro. Ventricular tissue had normal beta-adrenergic receptor affinity and density but reduced catecholamine and alpha-tubulin contents.
  
  
  CONCLUSIONS
  The intrinsic cardiac nervous system receives reduced input from extracardiac sympathetic efferent neurons after transplantation and inconsistent input from parasympathetic efferent preganglionic neurons. These heterogeneous neuronal inputs are not reflected in heart rate variability or ventricular beta-adrenergic receptor function. Transplanted angiotensin II-sensitive intrinsic cardiac neurons exert greater cardiac control than do nicotine-sensitive ones. The intrinsic cardiac nervous system remodels itself after cardiac transplantation, and this indicates that direct assessment of extracardiac and intrinsic cardiac neuronal behavior is required to fully understand cardiac control after transplantation.
authors.affiliation: Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: D A
authors.initials: DA
authors.lastname: Murphy
authors.forename: G W
authors.initials: GW
authors.lastname: Thompson
authors.forename: J L
authors.initials: JL
authors.lastname: Ardell
authors.forename: R
authors.initials: R
authors.lastname: McCraty
authors.forename: R S
authors.initials: RS
authors.lastname: Stevenson
authors.forename: V E
authors.initials: VE
authors.lastname: Sangalang
authors.forename: R
authors.initials: R
authors.lastname: Cardinal
authors.forename: M
authors.initials: M
authors.lastname: Wilkinson
authors.forename: S
authors.initials: S
authors.lastname: Craig
authors.forename: F M
authors.initials: FM
authors.lastname: Smith
authors.forename: J G
authors.initials: JG
authors.lastname: Kingma
authors.forename: J A
authors.initials: JA
authors.lastname: Armour
mesh_terms: D000818:Animals; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D005583:Fourier Analysis; D006321:Heart / Q000294:innervation*; D006329:Heart Conduction System / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D016027:Heart Transplantation / Q000502:physiology*; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000473:pathology / Q000503:physiopathology*; D012815:Signal Processing, Computer-Assisted; D013564:Sympathetic Nervous System / Q000473:pathology / Q000503:physiopathology*