CYCLIC NUCLEOTIDES CONCENTRATIONS IN THE CANINE HEART WITH REGIONAL ISCHEMIA : The Role of Cyclic AMP in Ventricular Fibrillation and the Effect of Dibutyryl Cyclic AMP

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The effect of the left anterior descending (LAD) coronary artery ligation on myocardial cyclic nucleotides and the role of these nucleotides in the development of ventricular fibrillation (VF) were studied in 135 mongrel dogs by means of sequential punching biopsies from the left ventricle. VF occurred in 50% of the non-premedicated groups. Significant increases of cyclic AMP (c-AMP) concentrations in the ischemic zone were observed after the ligation in VF group. C-AMP concentrations in the ischemic zone were significantly higher after the ligation compared with the border and non-ischemic zone as well as with the non-VF group. They also increased significantly from 30 sec before the onset of VF compared with 2 to 25 min before. No significant change was observed in the control group. In 41 dibutyryl cyclic AMP (DBc-AMP) premedicated dogs, the incidence of VF significantly increased, and c-AMP concentrations were significantly higher than in the non-premedicated group before and after the ligation. They were significantly higher in the ischemic zone 10, 15 and 20 min after the ligation than in the non-ischemic zone. There was a discrepancy of c-AMP concentration between the ischemic zone and the non-ischemic zone in VF induced group, whether DBc-AMP was premedicated or not. Significantly decreased cyclic GMP (c-GMP) levels in the ischemic and the non-ischemic zone were observed after the ligation. C-GMP concentrations with the DBc-AMP premedicated were significantly lower after the ligation compared with the non-premedicated group. Thus, it was concluded that increased c-AMP concentrations in the ischemic zone compared with in the non-ischemic zone had a dangerous tendency to induce VF.