Effects of nicardipine and bupivacaine on early after depolarization in rabbit sinoatrial node cells: a possible mechanism of bupivacaine-induced arrhythmias.
The effects of nicardipine and bupivacaine on early afterdepolarizations (EADs) were investigated in rabbit sinoatrial (SA) nodes using the conventional microelectrode technique. In a nominally Ca2+ -free, Mg2+ -free solution, addition of 0.5 mM Sr2+ produced EADs following prolongation of action potential duration. Nicardipine (10 microM) as well as Mg2+ (1 mM), both of which block the L-type Ca2+ channel current (iCa,L), abolished Sr2+ -induced EADs. Bupivacaine (5 microM), blocking the delayed rectifier K+ current (iK), facilitated the generation of EADs in the Sr2+ solution containing 1 mM Mg2+. The EADs in Sr2+ solution and the effect of bupivacaine were well simulated by the mathematical model when enhancement of slowly inactivating iCa,L and suppression of iK were assumed. Bupivacaine may cause sinus arrhythmias by facilitating EAD generation in SA node cells.
Matsuda
T
T
Department of Anesthesiology, Kanazawa Medical University, Ishikawa, Japan. tom-m@kanazawa-med.ac.jp
Kurata
Y
Y
D000200:Action Potentials / Q000187:drug effects*; D000779:Anesthetics, Local / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001146:Arrhythmia, Sinus / Q000139:chemically induced; D002045:Bupivacaine / Q000009:adverse effects / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D008955:Models, Cardiovascular; D009529:Nicardipine / Q000494:pharmacology*; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects*
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D009529:Nicardipine; D002045:Bupivacaine