THE ELECTROPHYSIOLOGIC EFFECTS OF SOTALOL IN THE IMMATURE MAMMALIAN HEART

Abstract

Sotalol (So), a new antiarrhythmic agent, is a beta-blocker that also has been shown to have some class III electrophysiologic (EP) effects. To evaluate the EP effects of So on the immature heart and to assess the relative importance of its class III actions, two groups of neonatal canines, ages 4-15 days, were studied and compared. Group I consisted of 6 puppies in whom EP studies were performed in the control state (C) and following 1.5, 2.5 and 4.0 mg/kg I.V. So. Group II consisted of 6 puppies in whom EP studies were performed prior to and following beta-blockade with 0.6 mg/kg I.V. propranolol (P). So caused a dose dependent decrease in heart rate (181 ± 27 to 125 ± 21 bpm, p< 0.001) while P caused no significant change (169 ± 9 to 159 ± 14, ns). So significantly prolonged atrial refractoriness (AERP: 67 ± 14 C, 117 ± 28 So; AFRP: 102 ± 9 C, 152 ± 31 So, p < 0.001) while P only slightly increased the AFRP (114 ± 12 C, 120 ± 10 P, p < 0.03). While the AV node FRP was prolonged by P (183 ± 9 C, 193 ± 19 P, p< 0.05) So caused a greater increase (171 ± 29 C, 244 ± 57 So, p< 0.01). Similarly, while P slightly increased the VERP (158 ± 12 C to 168 ± 13, p <0.05) So caused a far greater increase in ventricular refractoriness (VERP: 152 ± 26 C, 227 ± 41 So; VFRP: 173 ± 23 C, 253 ± 34 So, p < 0.001). Because the EP changes with beta-blockade in the immature heart are modest, the large changes in myocardial refractoriness induced by So must be largely due to a significant class III antiarrhythmic effect.