DELAYED DEVELOPMENT OF VENTRICULAR ARRHYTHMIAS FOLLOWING EXPERIMENTAL CORONARY OCCLUSION IN PIGS

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Abstract
Single and 2 step ligation experiments were carried out on domestic pigs in India and the effective site of ligation in relation to mortality and development of ventricular ectopic activity and ventricular tachycardia with respect to time were studied in order to develop a suitable model for studying antiarrhythmic drugs. Electrocardiograms of all the animals were recorded through bipolar leads at various intervals. Only 1 out of 16 animals died 10 hr after the 2-stage ligation. Three out of 4 pigs died within 1 h after the single step ligation, due to the onset of ventricular fibrillation, while none of the 3 died after the sham operation. The difference in the arrhythmia after 1 step and 2 step ligation is that after 1 step occlusion the first phase is missing. Two to 3 min after 1 step occlusion complexes of ectopic ventricular origin had begun though their rate was not yet rapid. After 5-7 min the ectopic discharges were multifocal and the rate was about 350/min. Twelve minutes after occlusion the rate was about 225-250/min. Normal beats were restored after 15-18 min. The early development of ventricular ectopic is only prevalent after the 1 step occlusion. Gross infarcts were seen in all hearts that had been ligated by either of the techniques. The survival of a large number of animals in the 2-stage ligation is probably not due to the development of collateral circulation during the 30 min period of occlusion. Due to an end-artery pattern of coronary circulation, a longer period is required for the development of collateral circulation in both pigs and humans. The arrhythmias that occur in distinct phase are well separated in time and involve different generating factors at different times, but this does not preclude the possibility that one or more common factors may become effective after varying degrees and kinds of cellular injury produced by specific duration of ischemia. Ischemia produces substantial changes in myocardial electrolytes. The basis of the injury potential is the K diffusion gradient. A K gradient across the boundary joining ischemic with the non-ischemic tissue is an important factor in producing rapid ventricular tachycardia and fibrillation at least in the first few minutes after abrupt occlusion. The ectopic activity in the 3rd phase may not be due to K, as after 10-20 h the myocardial electrolytes showed a tendency to return to normal. Degenerative changes which are in progress may also lead to a gradual beginning of the ectopic activity. Norepinephrine may be one of the important contributory factors in the delayed development of arrhythmias. Also dog and pig hearts are more sensitive to catecholamines after coronary occlusion and this hypersensitivity persists to some degree up to 5 days. The 2 step occlusion effectively eliminates the early phase of danger period and a high morality can be prevented. Due to the similarity between the cardiovascular system of humans and pigs, this preparation could serve as an excellant model for testing drugs which control arrhythmias.