Pulmonary arterial pressure and working capacity as parameters for checking the development of tolerance under...

Testing of the chronic therapeutic effects of antianginal drugs is commonly performed by stress electrocardiography. It is well known that this type of testing is easy to be disturbed by the influence of circadian rhythmus and placebo. However, by hemodynamic measurements such as the determination of pulmonary arterial pressure each patient can serve as his own control in therapeutic studies if the reproducibility of these parameters is acceptable. In 29 patients with coronary heart disease the reproducibility of the following parameters was tested at rest and during exercise and found to be acceptable: heart rate, mean arterial pressure, mean pulmonary arterial pressure, and working capacity. In additional studies the application of these parameters on the control of chronic therapy with antianginal drugs was performed. The results were: 1. A 1-week placebo treatment does not influence the parameters. 2. Long-term therapy with 3 x 20 mg of ISDN or IS-5-N daily over 4 weeks does not induce tolerance, whereas the dosage of 3 x 60 mg ISDN resp. 3 x 50 mg IS-5-N induces a remarkable degree of tolerance. 3. A 4-week therapy with 3 x 4 mg or 3 x 8 mg molsidomine daily resp. 4 mg or 8 mg molsidomine retard does not induce significant attenuation of the hemodynamic effects. 4. On a single-dose therapy with 50 mg IS-5-N retard ("interval-therapy") the therapeutic effects are maintained over at least 1 week.