Key result
In a halothane-anesthetized guinea-pig model, chromanol 293B prolonged the QT interval by 35 ms, and the addition of d-sotalol further prolonged it by 48 ms.
Why the study?
Does the halothane-anesthetized guinea-pig model sensitively detect QT-interval prolongation induced by IKr and IKs blockers?
Does the halothane-anesthetized guinea-pig model sensitively detect QT-interval prolongation induced by IKr and IKs blockers?
The halothane-anesthetized guinea-pig model is highly sensitive for predicting QT-interval prolonging effects of new drugs, particularly those affecting IKs and IKr channels.
Answers are grounded in this paper and cite their sources.
Supports utility of halothane-anesthetized guinea-pig model for IKs/IKr studies; leaves open clinical predictive value for new drugs.
Our previous study using the urethane-anesthetized guinea-pig model has shown that an I(Ks) blocker chromanol 293B hardly affects the QT interval itself nor potentiates the I(Kr) blocker-induced QT-interval prolongation. The former is in good accordance with the previous results in the human isolated intact ventricular tissue, but the latter is in sharp contrast with them. In this study, we characterized the ventricular repolarization ability of a newly developed halothane-anesthetized guinea-pig model by using I(Kr) and I(Ks) blockers. Intravenous administration of a selective I(Kr) blocker d-sotalol (3 mg/kg) prolonged the QT interval by +27 ms. On the other hand, intravenous administration of chromanol 293B (1 mg/kg) prolonged the QT interval by +35 ms, and additional administration of the same dose of d-sotalol further prolonged the QT interval by +48 ms. These results suggest that the abundance of the repolarization reserve among the current and previous models may be in the order of the urethane-anesthetized guinea-pig heart>human intact ventricular tissue>halothane-anesthetized guinea-pig heart. Thus, the halothane-anesthetized guinea-pig model may be considered to be more sensitive than the previous models in predicting the QT-interval prolonging effects of new drugs in patients with high risks for the acquired long QT syndrome.
No takes yet. Share an insight, caveat, or question.
Takahara et al. (2006) studied QT-interval prolongation (n=8). Chromanol 293B and d-sotalol vs. Baseline was evaluated on Change in QT interval (p=<0.01). In a halothane-anesthetized guinea-pig model, chromanol 293B prolonged the QT interval by 35 ms, and the addition of d-sotalol further prolonged it by 48 ms.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: