Influence of aspirin on the hemodynamic effects of sublingual nitroglycerin.

We studied the possible interaction between aspirin and nitroglycerin (NTG) in seven healthy volunteers. Effects of NTG (0.8 mg sublingual spray) were assessed by the decrease in diastolic arterial pressure, increase in heart rate, and decrease in M-mode echocardiographic end-diastolic and end-systolic diameters of the left ventricle. Measurements were performed before and during 30 min after NTG. Plasma levels of NTG were monitored during the experimental procedure. Each of the following trials was repeated three times, in random order, in each volunteer: NTG without aspirin pretreatment, NTG 1 h after 1 g of oral aspirin, and NTG after 8 days of aspirin, 500 mg every 48 h. Aspirin at the 1-g dose level significantly increased the effects of NTG on diastolic blood pressure (p less than 0.05) and left ventricular end-diastolic (p less than 0.001) and end-systolic (p less than 0.001) diameters. Aspirin (1 g) significantly increased (p less than 0.01) mean NTG plasma levels from 0.24 +/- 0.13 ng . ml-1 (control) to 0.37 +/- 0.26 ng . ml-1. We conclude that pretreatment with 1 g of aspirin increases NTG plasma levels and therefore significantly enhances the pharmacodynamic effects of NTG.

[Cardiac disorders induced by mianserin in guinea pigs. Comparison with imipramine]. / Troubles cardiaques engendrés par la miansérine chez le cobaye. Comparaison avec l'imipramine.

Infusion of mianserin to anesthetized guinea-pigs induced electrocardiographic changes (auriculo-ventricular and intraventricular conduction lenghthening, bradycardia, QRS axis and T axis rotations) quite identical to those induced by imipramine. However they appeared later and mianserin produced cardiac arrest at higher dose (133 mg/kg) than did imipramine (73 mg/kg). In vitro, increasing concentrations of mianserin suppressed the electrical response of stimulated, isolated ventricular heart strips, but this suppression was obtained by a higher concentration (172 micrograms/ml) than with imipramine (80 micrograms/ml). Transmembrane potentials were not affected by a 5 or 10 micrograms/ml mianserin or a 5 micrograms/ml imipramine perfusion. With 20 micrograms/ml mianserin or 10 micrograms/ml imipramine, only a reduced duration of the action potential was obtained. With 50 micrograms/ml mianserin or 20 micrograms/ml imipramine, the resting potential was reduced. However, with imipramine only it was preceded by a decrease in the maximal velocity of depolarisation. These results show that mianserin induces transmembrane permeability changes which appear to differ from and to be less marked than those induced by imipramine. Molar sodium bicarbonate reversed in vivo and in vitro the electrophysiologic changes elicited either by mianserin or by imipramine, but with mianserin the transient improvement was followed by an aggravation of the cardiac troubles.