INFLUENCE OF PENTOBARBITAL AND CHLORALOSE ANESTHESIA ON QUINIDINE-INDUCED EFFECTS ON ATRIAL REFRACTORINESS AND HEART-RATE IN THE DOG

The effects of pentobarbital and chloralose on the atrial effective refractory period (AERP), atrial and venticular rates, and mean blood pressure and also on the effects of quinidine on the same parameters were investigated in dogs with chronic atrioventricular block and implanted atrial pacing electrodes. Pentobarbital (30 mg/kg) increased the AERP by up to 12%, atrial and ventricular rates by 39 and 40%, respectively, and after initial lowering (48%) it increased the mean blood pressure (46%). Chloralose (100 mg/kg) increased the AERP (< 30 min) by up to 7%, the atrial rate by 49%, the ventricular rate (< 5 min) by 18%, and the mean blood pressure by 47%. In conscious dogs, quinidine at cumulative doses of 2, 4, and 8 mg/kg, i.e., at plasma levels between 2.7 +/- 0.6 and 6.3 +/- 1.3-mu-g/ml, increased the AERP by up to 21, 28, and 46%, the atrial rate by 49, 65, and 72%, and the ventricular rate (less-than-or-equal-to 5 min) by 17, 14, and 14%, and lowered the mean blood pressure by 19, 33, and 43%, respectively. Pentobarbital increased the quinidine-induced lengthening of the AERP by up to 10, 21, and 25 ms, respectively, and reduced the corresponding atrial (38, 53, and 67 beats/min) and ventricular (4, 4, and 5 beats/min) chronotropic effects. In contrast, chloralose reduced the quinidine-induced lengthening of the AERP (5, 12, and 22 ms, respectively), but did not modify the corresponding atrial and ventricular chronotropic effects. Neither pentobarbital nor chloralose altered quinidine plasma levels or the hypotensive effects of this drug. Thus, the interactions observed here between these two anesthetics and quinidine, the mechanisms of which may involve the complex interrelations existing between cardiac sympathetic and parasympathetic systems, stress the difficulties involved in comparing experimental results from different studies and even more so in transposing experimental results to human beings, particularly as regards antiarrhythmics, which very often interact with the autonomic nervous system. They also strongly suggest the use, whenever possible, of conscious animals so as to give the experimental results more predictive value for therapeutic practice.