The treatment of inoperable patients in terminal stages of chronic arterial occlusive disease is difficult and associated with high incidence of limb amputations and lethal outcomes . Prostacyclin (Pgl2) is a strong vasodilator and the most potent endogenous platelet aggregation inhibitor in men [1-6]. Application of Pgl2 in such conditions is justifiable since it represents the exogenous substitution therapy [7, 8].
An open blind study included 80 patients with inoperable peripheral arterial occlusion (Fontens stages III and IV) who were divided in two groups: Prostacyclin (PG) and Pentoxyfillyne (CG). Clinical characteristics of the groups were comparable (Table 1). Diagnosis of unreconstructable state was based on clinical and arteriographic results. Prostacyclin in the form of Epoprostenol sodium (Flolan) was used in doses of 5 ng/kg/h of continuous intravenous infusions during 24 h (9), 48 h (21) and 72 h (12). Pentoxyfillyne was also administered in continuous intravenous infusions during 24 h (2), 48 h (3) and 72 h (33) in daily dose of 300 mg. Duration of treatment was based on the subjective condition of the patients, i.e., when the patient reported the improvement the therapy was discontinued. Following the completion of infusion therapy, medicamentous therapy was initiated in all patients (Pentoxyfillyne 3 x 400 mg, Aspirin 100 mg). Routine laboratory tests (RBC, haemoglobin, haematocrit, platelet count, WBC, urea, glycaemia, Na, K, lipids, cholesterol, triglycerides), platelet aggregation (Collagen 60 mg/ml; ADP 1.5 mM/ml; RI-PA 1.5 mg/mL), BP, ABI (Doppler) indices and claudication distance were evaluated in all patients after day 1, 7 and 90 following the end of the therapy.
The infusion treatment led to subjective reduction or elimination of pain in 52 (32 PG, 20 CG) patients during the immediate course (up to 7 days). The therapy induced no significant changes in laboratory findings, platelet count and BP during the whole follow-up period. Significant decrease in platelet aggregation was recorded 24 hours and 7 days after the initiation of the study only in PG group, while after 3 months no significant decrease in aggregation was found (Table 2). Doppler index changes in both groups were not significant. Significant improvement in claudication distance was recorded 3 months after the infusion therapy: in PG for distance under 100 m (15 patients) and more than 100 m (17 patients), in CG for distance under 100 m (22 pts). In the course of infusion therapy the following complications were recorded: blushing (3 PG), tachycardia (2 PG, 1 CG) and nausea and vomiting (1 PG, 2 CG). Deceleration or temporary discontinuation of infusion led to the improvement of condition, and thus none of the patients was withdrawn from the study. Over a three-month follow-up period 4 lethal outcomes were recorded (2 PG, 2 CG). Causes of death (diabetic nephrosclerosis and renal insufficiency, septic endocarditis, heart insufficiency, CVI) could not have been related to infusion therapy. Due to the progression of gangrene, extremity amputation on different levels was performed in 27 patients (12 PG, 15 CG) of which 15 (7 PG and 8 CG) were performed during the immediate 7-day period while the other amputations were carried out 8-90 days after the treatment.
The use of prostacyclin leads to temporary and limited distant improvement in arterial flow in patients with occlusive diseases . During the immediate course these effects are manifested by complete absence of pain at rest and initial demarcation of the gangrenous process [1, 4]. Doppler index values established in our series suggest that prostacyclin does not reduce vascular resistance in the major blood vessels; however, it expresses potent vasodilation, antiaggregation and disaggregation effects at the level of microcirculation flow [6, 7]. (ABSTRACT TRUNCATED)