title: Controlled intermittent asystole: pharmacologic potentiation of vagal-induced asystole.
abstract: BACKGROUND
  Minimally invasive direct coronary artery bypass graft operations have, to date, displayed a higher rate of early graft failure than conventional coronary artery bypass procedures using extracorporeal technology. Construction of the coronary artery anastomosis on a beating heart versus a quiescent heart is likely an important factor in this difference between the two approaches. Controlled intermittent asystole induced by vagal stimulation to give transient nonchemically induced asystole for brief intervals sufficient for placement of coronary artery sutures might improve the precision of minimally invasive direct coronary artery bypass graft anastomoses and reduce graft failure while increasing the technical ease of operation.
  
  
  METHODS
  The feasibility of producing transient, reversible asystole with combined vagus nerve stimulation and treatment with a pharmacologic regimen of (1) an acetylcholinesterase inhibitor (pyridostigmine, 0.5 mg/kg), (2) a beta-adrenergic receptor blocker (propranolol, 80 microg/kg), and (3) a calcium-channel blocker (verapamil, 50 microg/kg) was studied in a sheep model. Seven animals underwent right vagus nerve stimulation in two modes: (1) a single continuous 60-second impulse and (2) multiple sequential 15-second impulses.
  
  
  RESULTS
  Vagal stimulation alone achieved bradycardia without consistent and reproducible cardiac arrest. After drug administration 6 animals displayed significant potentiation of vagal-induced asystole in the 60-second stimulation protocol (1.6+/-0.9 seconds non-drug-treated versus 52.0+/-5.6 seconds drug-treated; p < 0.05). In the sequential 15-second impulse protocol after drug treatment, 6 animals achieved consistent, escape-free asystole during five to six sequential 15-second stimulations versus a brief pause and bradycardia produced without drug treatment.
  
  
  CONCLUSIONS
  Increased acetylcholine activity by acetylcholinesterase inhibition and prevention of electromechanical escape activity by beta-adrenergic receptor and calcium-channel blockade during vagal stimulation produced a marked potentiation of vagal-induced asystole and a means of achieving controlled intermittent asystole. Controlled intermittent asystole achieved by pharmacologic potentiation of vagal-induced asystole may be a useful technique for enhancing technical ease in minimally invasive direct coronary artery bypass graft operations.
authors.affiliation: Department of Surgery, Emory University School of Medicine, Carlyle Fraser Heart Center, Crawford Long Hospital, Atlanta, Georgia 30365-2225, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Bufkin
authors.forename: J D
authors.initials: JD
authors.lastname: Puskas
authors.forename: J
authors.initials: J
authors.lastname: Vinten-Johansen
authors.forename: S T
authors.initials: ST
authors.lastname: Shearer
authors.forename: R A
authors.initials: RA
authors.lastname: Guyton
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D001026:Coronary Artery Bypass / Q000379:methods*; D004558:Electric Stimulation; D005240:Feasibility Studies; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D019060:Minimally Invasive Surgical Procedures / Q000379:methods; D011433:Propranolol / Q000494:pharmacology*; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D012756:Sheep; D013997:Time Factors; D014630:Vagus Nerve / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D002800:Cholinesterase Inhibitors; D011433:Propranolol; D014700:Verapamil; D011729:Pyridostigmine Bromide