A comparative study on the effects of diethyl ether and thiopentone sodium on plasma catecholamine levels in the rat.

1. The primary aim of this investigation was to ascertain the effects of thiopentone sodium and diethyl ether as anaesthetics on plasma catecholamine levels of Sprague-Dawley and Long-Evans rats. A secondary aim was to investigate the effect of norepinephrine on susceptibility to electrically induced arrhythmia in the Langendorff perfused isolated rat heart. 2. Thiopentone sodium anaesthesia resulted in significantly lower plasma norepinephrine and epinephrine levels when compared with diethyl ether anaesthesia. 3. Long-Evans rats exhibited significantly higher epinephrine levels regarding both anaesthetics in comparison with their Sprague-Dawley counterparts. 4. If plasma catecholamines are an indicator of the level of induced stress then diethyl ether anaesthesia resulted in more stress both of a psychological and physiological origin when compared with thiopentone sodium anaesthesia. 5. Long-Evans rats seem to be more prone to the physiologically-induced component of stress than Sprague-Dawley rats. 6. In isolated hearts, norepinephrine increased susceptibility (P less than 0.002) to electrically induced arrhythmia. This occurred at a concentration corresponding to measured upper levels of total catecholamines in diethyl ether anaesthetised animals.

The effects of imipramine, mianserin and trazodone on the chronotropic, inotropic and coronary vascular responses in the isolated perfused rat heart.

1. The cardiovascular effects of the tricyclic antidepressant imipramine and two second generation antidepressants mianserin, a tetracyclic, and trazodone, a triazolopyridine derivative, were investigated in the isolated perfused rat heart. 2. Imipramine caused cardiac slowing and a negative inotropic effect at 2.5 microM after 30 min of perfusion. Conversely mianserin and trazodone had no effect on heart rate at 5 microM with inotropic state remaining above control values after 30 min of perfusion. 3. Varying effects on coronary flow, which appear to correlate well with the documented receptor actions of each drug, were demonstrated. Imipramine caused a decrease in coronary flow at 1.25 and 2.5 microM, followed by an increase at 10 microM. Mianserin decreased coronary flow at all concentrations between 1 and 20 microM. Trazodone elicited a marked elevation in coronary flow over the dose range of 2.5 to 250 microM. 4. The results in this model suggest that although the second generation agents appear to cause less cardiodepression all three agents elicit quantitatively different coronary vascular responses.

Antidepressant drugs: imipramine, mianserin and trazodone.

The advent of newer antidepressant drugs (second generation) during the past two decades has provided an alternative to the use of tricyclic antidepressants in the alleviation of depression. These antidepressants have not been proven to be superior in the therapy of depression to the tricyclic antidepressants but they have been reported to cause fewer cardiac effects. Most of the reported adverse cardiac reactions elicited by antidepressant drugs are based on observations from clinical studies. The possible underlying mechanisms by which these adverse reactions arise have for the large part been proposed on the basis of clinical findings which have been extrapolated back to the known pharmacological actions of such drugs. There is a paucity of hard experimental data in this respect.