Increased release of brain serotonin reduces vulnerability to ventricular fibrillation in the cat.
Brain serotoninergic neurons are known to participate in cardiovascular regulation. Administration of the serotonin precursor 5-l-hydroxytryptophan in conjunction with the monamine oxidase inhibitor phenelzine and the selective peripheral l-amino acid decarboxylase inhibitor carbidopa has been shown to raise the repetitive extrasystole threshold in the canine heart. The present investigation demonstrates that this drug regimen increases the cerebrospinal fluid concentration of serotonin and its major metabolite, 5-hydroxyindoleacetic acid, by 330 and 830%, respectively. By contrast, cerebrospinal fluid concentrations of norepinephrine and its major brain metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate, and of dopamine's metabolite, 3, 4-dihydroxyphenylacetic acid, were not significantly altered. Concomitantly, the ventricular fibrillation threshold was elevated by 42% and the effective refractory period prolonged by 7%. Efferent sympathetic neural activity was suppressed in the normal heart (from 7.9 +/- 1.3 to 3.9 +/- 1.1 impulses/s). The surge in sympathetic activity associated with acute myocardial ischemia was markedly attenuated. These results indicate that enhancement of central serotoninergic neurotransmission can reduce the susceptibility to ventricular fibrillation mediated through a decline in sympathetic neural traffic to the heart.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000134:cerebrospinal fluid; D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002230:Carbidopa / Q000494:pharmacology*; D002415:Cats; D003327:Coronary Disease / Q000503:physiopathology; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid / Q000378:metabolism; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid; D009638:Norepinephrine / Q000134:cerebrospinal fluid; D010624:Phenelzine / Q000494:pharmacology*; D012701:Serotonin / Q000134:cerebrospinal fluid* / Q000378:metabolism; D014693:Ventricular Fibrillation / Q000503:physiopathology*
D015102:3,4-Dihydroxyphenylacetic Acid; C030284:3-methoxy-4-hydroxyphenylglycol sulfate; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan; D002230:Carbidopa; D010624:Phenelzine; D009638:Norepinephrine