MAINTENANCE OF ATRIAL-FIBRILLATION IN ANESTHETIZED AND UNANESTHETIZEDSHEEP USING CHOLINERGIC DRIVE

Atrial fibrillation (AF) was induced electrically and the duration of AF was measured in six isoflurane-anesthetized sheep (weight range 54. 5-72.7 kg), and in five unanesthetized sheep (weight range 60-75 kg). In the anesthetized sheep, AF was induced by direct electrical stimula tion of the right atrium with a catheter electrode and the duration of AF was determined. Intravenous neostigmine (10 mu g/kg IV) was admini stered and the duration of AF was again measured. Then cholinergic dri ve was increased by bilateral electrical vagal stimulation; AF was ind uced and the duration of AF was measured. In the anesthetized animals with no neostigmine or vagal stimulation, 34% of the episodes of AF la sted 10 seconds, 11% lasted 20 seconds, and only 1% lasted 200 seconds . However, in one anesthetized animal AF was sustained for 4,800 secon ds with no drug or vagal support. The administration of neostigmine al one in 3 anesthetized animals more than doubled the average duration o f AF. In the animals with vagal stimulation (after neostigmine), AF pe rsisted throughout stimulation, but ceased shortly after vagal stimula tion was terminated at 2,220, 4,500, and 3,840 seconds. The AF frequen cy ranged from 325-750/min. The unanesthetized sheep were lightly seda ted with a small dose (200 mu g/kg IM) of xylazine to make them less s ensitive to environmental noise; then AF was induced and its duration was timed. After these measurements, neostigmine was administered (30 mu g/kg IM) and cholinergic drive was produced reflexly by intravenous injection of 60-2,000 mu g of phenylephrine. AF was electrically indu ced at the time of maximum reflex slowing in heart rate. For the contr ol (no drug) studies, 64% of the AF episodes lasted 10 seconds, 20% la sted 20 seconds, and only 2% of the episodes lasted as long as 140 sec onds. When phenylephrine was injected after neostigmine to provide inc reased cholinergic drive, the duration of fibrillation depended on the dose of phenylephrine. In a 60-kg sheep, the duration of AF increased from 1 second With an intravenous dose of 60 mu g to 700 seconds with an intravenous dose of 2,000 mu g. However, there was a considerable range in responsiveness to the reflex cholinergic drive provided by th e intravenous phenylephrine; for example a single intravenous 500-mu g dose produced AF ranging from 190-540 seconds among the sheep. The du ration of AF was most controllable in the anesthetized sheep, followin g neostigmine administration and with bilateral vagal stimulation. In the unanesthetized sheep, AF could generally be sustained for more tha n the duration of the half-life (about 4 minutes) of phenylephrine fol lowing neostigmine. However, there was a large variation in the durati on of AF among the animals for the same dose of phenylephrine. This st udy identifies two methods (direct vagal stimulation and reflex vagal stimulation) for providing the cholinergic drive needed to sustain AF in the adult sheep. The duration of AF is sufficiently long to enable the measurement of electrical atrial defibrillation threshold.