title: Transmyocardial laser revascularization remodels the intrinsic cardiac nervous system in a chronic setting.
abstract: BACKGROUND
  Prospective trials have demonstrated that transmyocardial laser revascularization (TMLR) imparts symptomatic relief to patients with refractory angina. Because peak clinical effectiveness of TMLR is usually delayed by several months, it has been proposed that ventricular denervation is one mechanism whereby TMLR imparts symptomatic relief. We have demonstrated that TMLR does not denervate the heart in the acute setting, nor does it modify the intrinsic cardiac nervous system (ICNS) in the acute setting. However, the long-term effects of TMLR on the ICNS remain unknown.
  
  
  RESULTS
  A holmium:yttrium-aluminum-garnet laser created 20 channels through the anterolateral left ventricular free wall of 10 dogs. Four weeks later, the function of cardiac sensory inputs to the ICNS was studied by applying veratridine (7.5 micromol/L) to ventricular sensory fields. Chronotropic and inotropic responses elicited by cardiac sympathetic or parasympathetic efferent neurons stimulated electrically (10 Hz, 4 V, 4 ms) or chemically (nicotine 5 to 20 microgram/kg IV) were also assessed. Chemical activation of epicardial sensory neurites with veratridine elicited expected ICNS excitatory responses. Electrical stimulation of sympathetic and parasympathetic efferent neurons induced expected altered cardiac responses. In contrast, the responsiveness of the ICNS to systemically administered nicotine was obtunded.
  
  
  CONCLUSIONS
  Although chronic TMLR does not affect cardiac afferent or extracardiac efferent neuronal function, it does "remodel" the ICNS so that its responsiveness to a known potent chemical agonist (ie, nicotine) becomes obtunded. Remodeling of the ICNS may account in part for the delayed symptomatic relief that TMLR imparts to patients with refractory angina.
authors.affiliation: Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada. rca72@hotmail.com
authors.forename: R C
authors.initials: RC
authors.lastname: Arora
authors.forename: G M
authors.initials: GM
authors.lastname: Hirsch
authors.forename: K
authors.initials: K
authors.lastname: Hirsch
authors.forename: J A
authors.initials: JA
authors.lastname: Armour
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D004558:Electric Stimulation; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000294:innervation* / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects / Q000294:innervation; D008297:Male; D008839:Microelectrodes; D009204:Myocardial Revascularization / Q000295:instrumentation / Q000379:methods*; D009476:Neurons, Efferent / Q000187:drug effects / Q000502:physiology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D019800:Phenol / Q000494:pharmacology; D013268:Stimulation, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013995:Time; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D016276:Ventricular Function; D014701:Veratridine / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D018722:Nicotinic Agonists; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019800:Phenol; D014701:Veratridine