title: Neurochemical approaches to the prevention of ventricular fibrillation.
abstract: Current evidence indicates that susceptibility to ventricular fibrillation (VF) can be reduced by decreasing cardiac sympathetic activity and by increasing vagal tone. Pharmacological agents that favor such a pattern of autonomic outflow protect the heart against fibrillation. These include morphine sulfate, clonidine, digitalis drugs, and bromocriptine. An intriguing new approach involves changing the serum concentration of amino acid precursors of the central neurotransmitters that modulate autonomic traffic. Considerable evidence indicates that accumulation of serotonin in the brain reduces sympathetic neural activity. When L-tryptophan or 5-hydroxytryptophan is administered with phenelzine (a monoamine oxidase inhibitor) and carbidopa (a selective peripheral L-amino acid decarboxylase inhibitor) to raise brain serotonin, a significant increase in myocardial electrical stability is observed. This effect results from a decrease in cardiac sympathetic tone as indicated by selective denervation and nerve recording studies. Enhancing serotoninergic neurotransmission can also significantly reduce vulnerability to VF during acute coronary artery occlusion. The effect of augmenting serotoninergic activity without the use of enzyme inhibitors has been investigated by administering agents such as melatonin, 5-methoxytryptophol, and 6-chloro-2-(1-piperazinyl) pyrazine (MK-212). Each of these substances increases cardiac electrical stability. The protective influence is unaffected by bilateral vagotomy but is blocked by the specific serotonin antagonist methergoline. Diminution of cardiac sympathetic drive appears to be the main mechanism of action. Thus, neurochemical interventions can exert a profound effect on cardiac electrical stability. Recent advances in neurochemistry and psychopharmacology promise new insights into the problem of sudden death and suggest a fresh approach for the management of life-threatening arrhythmias.
authors.forename: R L
authors.initials: RL
authors.lastname: Verrier
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001923:Brain Chemistry; D002301:Cardiac Glycosides / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology*; D004198:Disease Susceptibility; D004285:Dogs; D006801:Humans; D009020:Morphine / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013315:Stress, Psychological / Q000503:physiopathology; D014628:Vagotomy; D014693:Ventricular Fibrillation / Q000517:prevention & control*
chemical_list: D002301:Cardiac Glycosides; D018377:Neurotransmitter Agents; D012701:Serotonin; D009020:Morphine; D001285:Atropine; D003000:Clonidine