Comparison of Four Rate-Correction Algorisms for the Ventricular Repolarization Period in Assessing Net Effects of IKr Blockers in Dogs

Abstract

Abstract. The utility of corrected and uncorrected QT interval changes for assessing net repolarization delay by I Kr (a rapid component of delayed rectifier K + currents) blockers was assessed in halothane-anesthetized dogs using the electrocardiogram and monophasic action potential (MAP) recordings with electrical ventricular pacing. Intravenous administration of dlsotalol (0.2 -2 mg / kg) prolonged the MAP duration and RR interval, while terfenadine (3 mg / kg) increased the MAP duration but transiently shortened RR interval. The order of correlation coefficient between the MAP duration at a pacing cycle length of 400 ms and MAP duration itself or that with arithmetical correction was uncorrected > Van de Water = Matsunaga > Fridericia > Bazett. These results suggest that Matsunaga's and Van de Water's formulae would better predict the net repolarization delay in the in vivo canine model. Also, the risk of drug candidates that may prolong the QT interval should be judged by change in uncorrected QT interval as well as corrected QT interval.

Induction of mast cell accumulation, histamine release and skin edema by N49 phospholipase A2

“…To investigate potential mechanisms involved in TM-N49 induced inflammatory cell accumulation, several anti-inflammatory compounds including cyproheptadine (2 mg·kg -1 ) [ 17 ], terfenadine (3 mg·kg -1 ) [ 45 , 46 ], ginkgolide B (5 mg·kg -1 ) [ 39 ] and quinacrine (10 mg·kg -1 ) [ 40 ] were co-injected into the peritoneum of mice with TM-N49 (5 μg per mouse). Control animals received an injection of drug alone.…”

Induction of Mast-Cell Accumulation by Promutoxin, an Arg-49 PhospholipaseA2

“…To investigate potential mechanisms involved in promutoxin-induced mast-cell accumulation, several anti-inflammatory compounds including cyproheptadine (2 mg·kg −1 ) [17], terfenadine (3 mg·kg −1 ) [32, 33], ginkgolide B (5 mg·kg −1 ) [34], and quinacrine (10 mg·kg −1 ) [35] were coinjected into the peritoneum of mice with promutoxin (5  μ g per mouse). Control animals received an injection of drug alone.…”