Effects of pH on nifekalant-induced electrophysiological change assessed in the Langendorff heart model of guinea pigs.
Since information regarding the effects of pH on the extent of nifekalant-induced repolarization delay and torsades de pointes remains limited, we assessed it with a Langendorff heart model of guinea pigs. First, we investigated the effects of pH change from 7.4 to 6.4 on the bipolar electrogram simulating surface lead II ECG, monophasic action potential (MAP), effective refractory period (ERP), and terminal repolarization period (TRP) and found that acidic condition transiently enhanced the ventricular repolarization. Next, we investigated the effects of pH change from 6.4 to 7.4 in the presence of nifekalant (10 μM) on the ECG, MAP, ERP, TRP, and short-term variability (STV) of MAP90 and found that the normalization of pH prolonged the MAP90 and ERP while the TRP remained unchanged, suggesting the increase in electrical vulnerability of the ventricle. Meanwhile, the STV of MAP90 was the largest at pH 6.4 in the presence of nifekalant, indicating the increase in temporal dispersion of repolarization, which gradually decreased with the return of pH to 7.4.Thus, a recovery period from acidosis might be more dangerous than during the acidosis, because electrical vulnerability may significantly increase for this period while temporal dispersion of repolarization remained increased.
Department of Pharmacology, Faculty of Medicine, Toho University, Japan.
Katsuyuki
K
Kazusa
Yuji
Y
Nakamura
Yudai
Y
Watanabe
Kentaro
K
Ando
Atsushi
A
Sugiyama
D000138:Acidosis / Q000503:physiopathology; D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000187:drug effects*; D006168:Guinea Pigs; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D010477:Perfusion; D011744:Pyrimidinones / Q000009:adverse effects*; D013997:Time Factors; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000503:physiopathology*
D000889:Anti-Arrhythmia Agents; D011744:Pyrimidinones; C076259:nifekalant