摘要
Slowing conduction and prolonged repolarization have been implicated in cocaine-induced cardiac arrhythmia.However,the importance of these properties at any given cocaine concentration[C]remains unknown. Using standard microelectrode techniques, we studied the effect of different [C] (ranging from 9.spmol/L to 300 μmol/L) on action potential duration(APD)and dv/dtmax of phase 0 in 16 canine papillary muscle preparations Paced at 1 000 msec cycle. In contrast to dy/dtmax which showed progressive decrease from(201±19)v/s during control to (33±7)v/s at [C] of 300μmol/L, APD90showed an initial increase from(193±15) msec to a peak of(232±17)msec at 113μmol/ L and a gradual decrease back to control at 188 μmol/L and further decrease to below baseline to a nadir of (168±14) msec at 263 μmol/L. The resting membrane potentials did not change significantly during the progressive increase of [C]. The bimodal response of APD may be explained by blockade of the delayed rectifier potassium current as well as blockade of window sodium current by cocaine. The findings imply that up to [C] of 188μmol/L may cause arrhythmia by slowing of conduction and prolongation of repolarization. At [C] above 188μmol/L the prolongation of repolarization is unlikely to be the mechanism.
Slowing conduction and prolonged repolarization have been implicated in cocaine-induced cardiac arrhythmia.However,the importance of these properties at any given cocaine concentration[C]remains unknown. Using standard microelectrode techniques, we studied the effect of different [C] (ranging from 9.spmol/L to 300 μmol/L) on action potential duration(APD)and dv/dtmax of phase 0 in 16 canine papillary muscle preparations Paced at 1 000 msec cycle. In contrast to dy/dtmax which showed progressive decrease from(201±19)v/s during control to (33±7)v/s at [C] of 300μmol/L, APD90showed an initial increase from(193±15) msec to a peak of(232±17)msec at 113μmol/ L and a gradual decrease back to control at 188 μmol/L and further decrease to below baseline to a nadir of (168±14) msec at 263 μmol/L. The resting membrane potentials did not change significantly during the progressive increase of [C]. The bimodal response of APD may be explained by blockade of the delayed rectifier potassium current as well as blockade of window sodium current by cocaine. The findings imply that up to [C] of 188μmol/L may cause arrhythmia by slowing of conduction and prolongation of repolarization. At [C] above 188μmol/L the prolongation of repolarization is unlikely to be the mechanism.
