Effects of sympathetic stimulation on use dependence of lidocaine, mexiletine, and quinidine in an intact canine model.
The use- or rate-dependent effects of a continuous infusion of lidocaine (n = 6, serum level 3.1 +/- 0.34 micrograms/mL), mexiletine (n = 8, serum level 7.08 +/- 0.90 micrograms/mL), and quinidine (n = 6, serum level 6.8 +/- 1.22 micrograms/mL) were studied in an open chest canine preparation. A use-dependent effect on conduction was assessed by measuring the change in the His to surface ventricular activation (HV) time at differing atrial paced rates during drug infusion. Global sympathetic activation was achieved by nondecentralized left stellate ganglion stimulation (4-10 Hz, 6-12 V, 2 ms) and use dependence at the same cycle lengths was compared. Repolarization times were measured from epicardial monophasic action potentials recorded from the anterior left ventricle throughout the study. There was no significant change in the HV time during control studies with or without left stellate stimulation. Use-dependent slowing of conduction was seen in all studies during drug infusion. This was evident at cycle lengths of 300-190 ms for quinidine and at cycle lengths less than 250 ms for lidocaine and mexiletine. Stellate stimulation attenuated use dependence in all studies. This effect was significant from cycle lengths of 300-190 ms for lidocaine and quinidine and at cycle lengths shorter than 230 ms for mexiletine (p less than 0.05). Stellate stimulation significantly reduced use-dependent prolongation of the HV interval by an average of 60%. During stellate stimulation there was a nonsignificant trend towards cycle length independent shortening of action potential duration both at baseline and in the presence of drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Newman
D
D
Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco.
Herre
J M
JM
Chin
M
M
Scheinman
M M
MM
Franz
M
M
Katzung
B
B
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D008801:Mexiletine / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D013233:Stellate Ganglion / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*
D015222:Sodium Channels; D008801:Mexiletine; D008012:Lidocaine; D011802:Quinidine