Maintenance of atrial fibrillation in anesthetized and unanesthetized sheep 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 stimulation of the right atrium with a catheter electrode and the duration of AF was determined. Intravenous neostigmine (10 micrograms/kg IV) was administered and the duration of AF was again measured. Then cholinergic drive was increased by bilateral electrical vagal stimulation; AF was induced and the duration of AF was measured. In the anesthetized animals with no neostigmine or vagal stimulation, 34% of the episodes of AF lasted 10 seconds, 11% lasted 20 seconds, and only 1% lasted 200 seconds. However, in one anesthetized animal AF was sustained for 4,800 seconds with no drug or vagal support. The administration of neostigmine alone in 3 anesthetized animals more than doubled the average duration of AF. In the animals with vagal stimulation (after neostigmine), AF persisted throughout stimulation, but ceased shortly after vagal stimulation was terminated at 2,220, 4,500, and 3,840 seconds. The AF frequency ranged from 325-750/min. The unanesthetized sheep were lightly sedated with a small dose (200 micrograms/kg IM) of xylazine to make them less sensitive to environmental noise; then AF was induced and its duration was timed. After these measurements, neostigmine was administered (30 micrograms/kg IM) and cholinergic drive was produced reflexly by intravenous injection of 60-2,000 micrograms of phenylephrine. AF was electrically induced at the time of maximum reflex slowing in heart rate. For the control (no drug) studies, 64% of the AF episodes lasted 10 seconds, 20% lasted 20 seconds, and only 2% of the episodes lasted as long as 140 seconds. When phenylephrine was injected after neostigmine to provide increased 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 micrograms to 700 seconds with an intravenous dose of 2,000 micrograms. However, there was a considerable range in responsiveness to the reflex cholinergic drive provided by the intravenous phenylephrine; for example a single intravenous 500-micrograms dose produced AF ranging from 190-540 seconds among the sheep. The duration of AF was most controllable in the anesthetized sheep, following neostigmine administration and with bilateral vagal stimulation. In the unanesthetized sheep, AF could generally be sustained for more than the duration of the half-life (about 4 minutes) of phenylephrine following neostigmine. However, there was a large variation in the duration of AF among the animals for the same dose of phenylephrine. This study 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.