Antiarrhythmic effect of reducing myocardial noradrenaline stores with alpha-methyl-meta-tyrosine.
In the adrenergic neurons the amino acid alpha-methyl-meta-tyrosine (alpha-MmT) is converted to metaraminol via the noradrenaline (NA) synthetic pathway. Metaraminol thereby displaces NA from its neuronal stores, and as a consequence NA levels can be drastically reduced, although normal sympathetic tone is essentially maintained by release of newly synthetized NA. In rats treated with alpha-MmT methylester (400 + 200 mg/kg) myocardial NA was reduced to less than 10% of control. Under barbiturate anesthesia, the left coronary artery was ligated, and the incidence of ventricular fibrillation and mortality during a 30-min period was recorded. Before ligation, mean arterial blood pressure was unchanged and heart rate slightly increased by alpha-MmT pretreatment. The energy state of the myocardium was also unchanged by the alpha-MmT pretreatment, as seen in a separate study where hearts from identically treated rats were taken for analysis of glycogen and adenine nucleotides. Thus, alpha-MmT pretreatment appeared not to have reduced the sympathetic tone of the heart. In spite of this, alpha-MmT pretreatment reduced the ventricular fibrillation from 65 to 33% (p less than 0.01; chi 2 test) and mortality from 37 to 15% (p less than 0.05). The results indicate an important role of myocardial NA stores in the development of early ischemic arrhythmias.
T
T
Abrahamsson
O
O
Almgren
L
L
Carlsson
L
L
Svensson
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D005665:Furosemide / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology*; D009206:Myocardium / Q000032:analysis*; D009638:Norepinephrine / Q000032:analysis*; D011188:Potassium / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D000889:Anti-Arrhythmia Agents; D008781:Methyltyrosines; D005665:Furosemide; C031476:alpha-methyl-m-tyrosine; D011188:Potassium; D009638:Norepinephrine