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.