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P Jaillon

Publications and source records attributed to P Jaillon.

193 records · Page 11Linked to original sources
PubMedDate not supplied

[Quinidine plasma concentration-cardiac electrophysiologic effects relationships in anesthetized dogs (author's transl)].

1. The electrophysiologic effects of quinidine (Q)were studied in 15 pentobarbital-anesthetized dogs using intracardiac electrography and programmed stimulation. With four successive bolus i.v. injections of Q gluconate (1, 3, 9, 18 mg/kg cumulative doses) at 30 min intervals, Q plasma concentration (Cp) ranged from 1.02 +/- 0.1 micrograms/ml to 5.7 +/- 0.6 micrograms at the time of electrophysiologic measurements 20 min after each injection. 2. In six control dogs, heart rate (HR), sinus node recovery time (TRS), conduction times (StH, HV, QRS), ventricular repolarization time (QTc) Wenckebach cycle length (L.W), and atrial refractory periods (RP) did not change significantly while the functional nodal (PRFN) and the effective ventricular (PREV) RPs significantly increased with time. 3. Quinidine produced a significant log- Cp related decrease in HR and increase in TRS corresponding to a decreased sinus automaticity. 4. StH and HV conduction times increased proportionally to log CpQ while the increase in QRS was not Cp-dependent. QTc did not increase significantly. 5. Quinidine resulted in significant log Cp-related increases in atrial RP PRFN and LW while the Q-induced changes in PREV were not Cp-dependent.

Anesthesia↗
PubMedDate not supplied

[Pre-clinical and clinical electrophysiological studies for the prediction of iatrogenic proarrhythmic effect (torsade de pointes)].

The risk of drug-induced torsade de pointes, a potentially lethal ventricular arrhythmia, raises the problem of the early detection of the effects of any new chemical entity (NCE) on ventricular repolarization since prolongation of myocardial repolarization is a major trigger among others (hypokalaemia, bradycardia, congenital abnormalities in cellular ionic channels) for this arrhythmia. During pre-clinical studies, the effects of a range of concentrations (10(-9) M to 10(-4) M) of NCE on the duration of the action potential of Purkinje and left ventricular myocardial cells (guinea-pig and rabbit) have to be measured. If these effects are present, the duration of QT interval on ECG recorded in animal studies (dogs) has to be carefully measured and correlated with plasma concentrations of NCE and/or its metabolite(s). During clinical trials, additional studies have to be performed in order to document QT interval-plasma concentration relationships and the influence of heart rate on QT interval duration. Ambulatory ECG recordings will attest to the safety of the NCE and precautions for use of the drug will be established according to our knowledge of predisposing factors for a proarrhythmic effect. Should there be a notification of a case of torsade de points after a new drug has been launched, urgent consultations with the drug file will be necessary in order to assess which pre-clinical and clinical studies may be needed for a better evaluation of the benefit/risk ratio of the new drug.

Animals↗