The ability of PK 8165, a quinoline derivative, to reduce responses to a stressful situation in a double-blind study in man.

A double-blind and cross-over study was carried out in order to explore the effects of PK 8165 (a quinoline derivative) on the heart rate, respiratory rate and motor reflex responses produced by an experimental model of stress in 8 healthy volunteers. The stress was induced by repetitive sequences of anticipation of pain (stressful stimulus: S) spaced by resting periods (R). In a control session, the cumulative effects of S resulted, in all subjects, in a progressive increase in heart and respiratory rates; 5 subjects showed a cumulative facilitation in the H reflex (motor reflex response) while the 3 others exhibited a cumulative depression in this motor parameter as a function of repetition of S during the session. The three doses (50, 100, 150 mg) of PK 8165 produced a very significant dose-dependent reduction in these responses during both stressful periods and resting sequences. Furthermore, the baseline values of respiratory and especially heart rate were also significantly reduced in a dose-dependent fashion by PK 8165. In contrast, the treatment with placebo did not significantly modify these parameters, compared to control values. The functional implications of these data are discussed in terms of stress-induced activation of some CNS structures and of the possible mechanisms of the "anti-stress" effect of PK 8165.

[Ventricular arrhythmia in ischemic cardiopathy]. / Contribution à l'étude des arythmies ventriculaires dans la cardiopathie ischémique.

The authors undertook a retrospective study of 200 cases of documented ischaemic heart disease. Seven variables were considered in a statistical analysis: age, sex, localisation of myocardial lesions, left ventricular function, ventricular arrhythmias in density and grade, and death due to cardiac or other causes. The statistical analysis using the Chi squared test showed no correlation between death and the variables: age, sex and localisation of the infarct. However, statistically significant relationship was observed between death, in particular when due to cardiac causes, and: left ventricular function, especially when the ejection fraction was less than 0.40, ventricular arrhythmias, especially with a density of between 10 and 50% and when repetitive were observed. Analysis of correspondences confirmed these results. Log-linear analysis of the variables or combinations of variables which allows prediction of the prevalence of death showed ventricular arrhythmias to be more important than left ventricular function when these two variables were considered singly. When the association of two variables was considered, the best predictive association was ventricular arrhythmias with repetitive ectopic rhythms; the second best predictive association was ventricular arrhythmias with abnormal ventricular function. These results should be interpreted taking into consideration the patient group studied, the criteria of selection and the limitations of 24 h ECG monitoring; in addition, some arrhythmias may have added importance (e.g. ventricular parasystole).