EXPERIMENTAL EFFECTS OF VASOACTIVE DRUGS FROM THE PHYSIOPATHOLOGICAL POINT-OF-VIEW

The therapeutical efficacy of the vasoactive drugs buflomedil, naftidr ofuryl, and pentoxifyllin in patients with intermittent claudication s eems to be pr-oven by appropriate clinical trials. However considerabl e uncertainty exists concerning their pharmacological modes of action that might be responsible for the increase in walking capacity. During the past three decades several mechanisms were studied mainly followi ng new results of basic microcirculatory research. This paper is based on about 2500 references retrieved from the MEDLINE literature data b ase for the key words ''buflomedil'', ''naftidrofuryl'', and ''pentoxi fyllin''. For review purposes papers were grouped according to reporte d effects on vascular smooth musculature, hemorheology, hemostasis, ti ssue metabolism, and reperfusion injury and results were checked for c linical relevance. This analysis reveals that almost all mechanisms us ed to explain the drug-related improvement of intermittent claudicatio n seem to be merely speculative with the exception of their vasodilato ry activity which can be demonstrated directly in patients. Furthermor e, drug concentrations far above the corresponding therapeutical plasm a levels were applied in a large. number of in-vitro studies and anima l experiments. Especially, the frequently assumed beneficial hemorheol ogical effects did not bear a critical analysis of underlying methodol ogy and clinical data. This also applies to experimental results regar ding protection against reperfusion injury which are contradictory and based on models not representing peripheral arterial occlusive diseas e. In conclusion it is suggested that according to their vasodilatory activity bulfomedil, naftidrofuryl, and pentoxifyllin might enhance co llateral growth stimulated during exercise hyperemia by an improved re cruitment of the collateral reserve.