Angiology

A brief review of the pharmacology, pharmacokinetics, and metabolism of buf lomedil-HCl is presented providing a phar macologic basis for buflomedil therapy of ischemia associated with peripheral vascu lar disease. Buflomedil is readily absorbed in the gastrointestinal tract and has a plasma half-life of approximately 2-3 hours. The para-desmethyl derivative of buflo medil has been identified as a urinary me tabolite. Pharmacologically, buflomedil in creases perfusion to impaired vascular beds of the microcirculation, increases arterial perfusion with minimal effects on central hemodynamics, exhibits apparent oxygen "sparing" effects in animal experiments, demonstrates inhibitory effects on platelet aggregation, and, in preliminary experi ments, appears to improve deformability of erythrocytes with abnormal fluidity. A non specific α-receptor blocking activity ap pears to be involved, at least in part, in these pharmacologic effects. The relative importance of these mechanisms/effects in the treatment of symptoms of vascular dis ease is unknown.

Tissue pO₂ measurements on skeletal muscle surface both in patients and in ani mals in a model of occlusive disease re vealed local tissue hypoxia that, until now, had not been detected with any other method. This kind of local tissue hypoxia is interpreted as a disturbance of local micro- flow distribution in the presence of un changed regional blood flow rate.

In response to buflomedil infusion, tissue p02 histograms improved without any change in regional blood flow or distal blood pressure.

In comparison to healthy volunteers, transcutaneous pO₂ measurements in pa tients allowed establishment of tcpO2 pro files along the lower extremity which were in agreement with angiographic localization of vessel occlusion. In a preliminary study, buflomedil infusion (3 mg/kg) over 30 min utes caused a significant increase in tcpO2 in 5 patients in the absence of any signifi cant change of segmental blood pressure.

It is concluded that both tissue p02 and tcpO2 measurements are able to provide unique information about local changes of the microcirculation in occlusive vessel dis ease.

This brief communication outlines re cent experiments on the effects of buflo medil, a new vasoactive agent, on red cell deformability in patients with leg ischemia. In this randomized, double-blind cross-over study, 10 patients received 200 mg buflomedil and matching placebo intravenously. Red cell filterability in these patients was significantly improved after buflomedil administration versus baseline values with no significant change in filterability versus baseline after placebo administration.