Treatment of peripheral vascular disease with misoprostol (Cytotec): a pilot study.

Misoprostol, the oral analogue of alprostadil, was used to treat 20 patients (aged 40-60 years) with peripheral arterial disease (PAD) according to Fontaine's classification at stages IIa and IIb. All patients received 200 micrograms of misoprostol 3 times a day during a month. The therapy with misoprostol resulted in clinical improvement in all patients. Elongation of pain-free (before treatment: 129 m +/- 78 m; after treatment: 214 m +/- 109 m) and maximum walking distance (before treatment: 304 m +/- 169 m; after treatment: 471 m +/- 264 m) was observed. At the same time, a shortening of the duration of pain was noted (before treatment: 100 sec +/- 37 sec; after treatment: 71 sec +/- 23 sec). The ankle/arm pressure ratio (AAPR) and arterial blood flow increased in both limbs after 4 weeks of treatment. Activation of the fibrinolytic system was seen in the course of therapy (shortening of euglobulin clot lysis time (ECLT) and increase in t-PA activity). The platelets became less sensitive to ADP and collagen after intake of misoprostol. The results justify administration of misoprostol as a new therapeutic agent for the treatment of patients with PAD.

Influence of cadmium intoxication on thromboresistance of vascular endothelium in rabbits.

Here, using our original technique for measuring of thrombogenesis on the surface of rabbit aorta endothelium superfused with whole blood, we demonstrate that the thrombogenic property of endothelium is potentiated in the course of 3 months cadmium intoxication. The loss of endothelial thromboresistance is accompanied by suppressed generation of endogenous prostacyclin, leukopenia, increased platelet aggregability and by the presence of quasi-atherosclerotic, focal proliferative, glassy-protein lesions formed in aortic endothelium. We hypothesize that the final loss of vessel thromboresistance with all sequence of events that accompany cadmium intoxication, may result from the cadmium-induced inhibition of the generation of endothelial prostacyclin. However, the exact mechanism by which cadmium intoxication may affect the generation of prostacyclin and, then, functioning of blood platelets and vascular endothelium requires further investigations.

Influence of bezafibrate on total antioxidant activity of serum and deformability of blood cells in hypercholesterolaemic patients.

Fourteen patients with hypercholesterolaemia were treated with bezafibrate (600 mg/day) for a month. Before and after the treatment some biochemical and physical parameters were investigated. Plasma cholesterol levels, elevated before treatment, significantly decreased after one month (p<0.001). Deformability of red blood cells increased significantly in this time (p<0.05). Total antioxidant status of serum decreased statistically significantly (p<0.01). It is concluded that the mechanism of action of bezafibrate is not connected with resistance to oxygen free radicals since the drug has no antioxidant activity. A main mechanism of action of bezafibrate seems to be lowering the cholesterol level. An increase in deformability of red blood cells may make some contribution to this mechanism.

[The effect of treatment with sulphur water from the spring in Wieslaw in Busko-Solec on levels of lipids,the fibrinolytic system and thrombogenic platelet function in patients with arteriosclerosis]. / Wplyw kuracji pitnej woda siarczkowa ze zródla Wieslaw z uzdrowiska Busko-Solec na gospodarke lipidowa, uklad fibrynolityczny i trombogeneze plytkowa u pacjentów z miazdzyca.

29 patients with arteriosclerosis obliterans and elevated level of cholesterol and/or triglycerides in blood received undiluted sulphur water from the spring Wieslaw in Busko-Solec at the dose of 50 ml 3 times a day for 4 weeks. Such a treatment resulted in statistically significant decrease of blood levels of cholesterol, triglycerides and LDL cholesterol. The concentration of HDL cholesterol did not change significantly. Moreover, therapy with sulphur water resulted in decreasing of platelet aggregability evoked by ADP and collagen, spontaneous platelet aggregability and increasing fibrinolytic activity of the blood (elongation of euglobulin clot lysis time). We concluded that orally administered sulphur water from the spring Wieslaw in Busko-Solec may be an additional means of treatment of patients with arteriosclerosis obliterans and high levels of cholesterol and/or triglycerides.

[Misoprostol--oral prostanoid--the first clinical trial for use in patients with peripheral vascular disease]. / Mizoprostol--doustny prostanoid--pierwsza próba klinicznego zastosowania w chorobie niedokrwiennej konczyn dolnych.

Misoprostol, the oral analogue of alprostadil was used for the treatment of 20 patients (aged 40-60) with peripheral arterial disease according to Fontaine's classification at stages IIa and IIb (PAD). All patients received 200 micrograms of misoprostol 3 times a day during a month. The therapy with misoprostol resulted in a clinical improvement in all patients. Elongation of pain free (before treatment 129 m +/- 78 m, after treatment 214 m +/- 109 m) and maximum walking distance (before treatment 304 m +/- 169 m, after treatment 471 m +/- 264 m) was observed. At the same time a shortening of the pain duration was noted (before treatment 100 sec +/- 37 sec, after treatment 71 sec +/- 23 sec). The ankle/arm pressure ratio (AAPR) and arterial blood flow increased in both limbs after 4 weeks of the treatment. Activation of the fibrinolytic system was seen in the course of the therapy (shortening of euglobulin clot lysis time-ECLT and increase in t-PA activity). The platelets became less sensitive to ADP and collagen after intake of misoprostol. The results justify administration of misoprostol as a new therapeutic agent for the treatment of patients with PAD.

Treatment with L-arginine is likely to stimulate generation of nitric oxide in patients with peripheral arterial obstructive disease.

The impairment of endothelial function in hypercholesterolaemic animals and humans is known to be reversed by intravenous infusions of L-arginine (L-ARG), the precursor of NO. 22 patients with peripheral arterial obstructive disease (PAOD) received L-ARG (60 mmol) as intravenous infusions, each lasting three hours, daily for seven consecutive days. This treatment resulted in elongation of the painfree and maximum walking distances, as well as shortening of the period of time required for pain relief after walking the maximum distance. A rise in the ankle/arm pressure ratio (AAPR) was associated with an increase of arterial blood flow in both calves. The transcutaneous oxygen tension (tcpO2) in the ischaemic foot was also increased. After the 1st and the 7th infusion of L-ARG the spontaneous (PAR) as well as the ADP- and collagen-induced platelet aggregation were suppressed, the euglobulin clot lysis time (ECLT) shortened, plasma levels of platelet activator inhibitor (PAI) decreased, and cGMP levels increased. These data indicate beneficial effects of L-ARG as a therapeutic agent in patients with PAOD. We presume that in these patients high doses of exogenous L-ARG can be partially converted to NO.

Misoprostol (cytotec) in the treatment of peripheral ischaemic disease.

The stable prostacyclin analogue-iloprost and prostaglandin E1 (Alprostadil) showed a beneficial effect on activated platelets and leukocytes, and thrombocyte and leukocyte vessel interaction and damaged endothelium, improving microvascular perfusion and were useful in treatment of patients with peripheral arterial disease. The 4 weeks therapy with misoprostol caused a clinical improvement in all 14 patients and resulted in vasorelaxation and showed antiplatelet and fibrinolytic effects.

L-arginine--substrate for no synthesis--its beneficial effects in therapy of patients with peripheral arterial disease: comparison with placebo-preliminary results.

Intravenous infusions of L-arginine (L-ARG) and placebo (saline) resulted in improvement of clinical assessments, statistically significant after L-ARG but not after saline. Results of laboratory estimations for platelet and fibrynolysis changed significantly following L-ARG infusions but not after infusions of placebo. These data indicate beneficial effects of L-ARG as a therapeutic agent in patients with peripheral arterial obliterative disease (PAOD). In these patients exogenous L-ARG can be converted to NO.

[Kallikrein in the treatment of patients with obliterative atherosclerosis of the lower limbs and its mechanism of action]. / Kalikreina w leczeniu chorych na zarostowa miazdzyce tetnic konczyn dolnych oraz próba wyjasnienia mechanizmu jej dzialania.

Kallikrein (Padutin-Depot) was administered to 20 patients with obliterative atherosclerosis of the lower limbs of the II degree (19 patients) and IV degree (1 patient). The drug was given in the daily dose of 40 U i.m. for 28 days. An effect of kallikrein on the distance in intermittent claudication, rate of pain relieve after walking the maximal distance, blood flow in the lower limbs, and on the index of circulating aggregates have been determined. Clinical improvement has been noted after a 4-week therapy with kallikrein. The drug in a single dose of 40 U activates plasma fibrinolytic system for 5 hours and decreases the number of circulating aggregates (2-5 h). The authors explain kallikrein action as the release of endogenous bradykinin, which subsequently releases two epithelial mediators, i.e. PFG1 and EDRF.

[Use of nitrendipine in treating patients with obliterative atherosclerosis of arteries in the lower extremities]. / Zastosowanie nitrendypiny w leczeniu chorych z miazdzyca tetnic konczyn dolnych.

Twenty patients with obliterative atherosclerosis in the lower extremities arteries (Fontaine's stage II) were treated with nitrendipine (Bayotensin) given in the dose of 20 mg daily for 6 weeks. This therapy with nitrendipine produced improvement manifested by the prolongation of the distance of intermittent claudication, shortening of pain duration, increase in blood flow in the ischemic extremity, and increase in pressure index. At the same time, nitrendipine decreased ADP-produced platelet aggregation and activated fibrinolytic system. Clinical trials have shown that nitrendipine is effective in the obliterative atherosclerosis in the lower extremities.

Kallikrein-thrombolytic and hypotensive action in cats--preliminary results.

An intravenous injection of kallikrein produced hypotensive and thrombolytic effects in anesthetized cats, using the blood superfused tendon technique. The thrombolytic action of kallikrein was mediated by an unstable substance. The generation of this substance was abolished by either acetylsalicylic acid (ASA) or aprotonin and enhanced by captopril. The hypotensive action of kallikrein was only partially inhibited by ASA. It is proposed that both these pharmacological effects of kallikrein are mediated by bradykinin which in turn releases prostacyclin from the endothelium. However, in contrast to the thrombolytic effect of kallikrein which is totally mediated by prostacyclin the hypotensive action of kallikrein depends not only on prostacyclin but also on another endothelium-derived vasorelaxant, e.g. EDRF.

[Administration of prostacyclin in sudden deafness. Evaluation with the double blind method]. / Zastosowanie prostacykliny w naglej gluchocie. Ocena metoda "podwójnie slepej próby".

Prostacyclin (PGI2) connects all the pharmacologic properties of drugs being used till now in sudden deafness. 30 patients with sensori-neural sudden deafness were treated by prostacyclin and placebo in the double-blind test situation. In therapeutic group of 15 patients were 87% of complete recovery, but in placebo only 6%.

[Effectiveness of etofibrate in arteriosclerosis obliterans. Pilot study in hyperlipidemic patients with arteriosclerosis obliterans]. / Wirksamkeit von Etofibrat bei Arteriosclerosis obliterans. Pilotstudie bei hyperlipidämischen Patienten mit Arteriosclerosis obliterans.

In a pilot study the therapeutic effect of 2 x 500 mg etofibrate (Lipo Merz retard) on lipids and lipoproteins, fibrinolytic activity and clinical parameters was studied for four weeks in hyperlipidemic patients suffering from arteriosclerosis obliterans (Fontaine stage II/III). The study parameters were evaluated prior to and after the four weeks of treatment. Administration of etofibrate resulted in a significant decrease in serum cholesterol and triglyceride levels, the decrease in LDL-/HDL-cholesterol-ratio due mainly to an elevation of the HDL-cholesterol fraction, an increase in plasma fibrinolytic activity, an increased peripheral blood flow in the ischemic leg, and an increase in the pain-free walking distance. Thus, etofibrate applied twice daily might be recommended for the treatment of hyperlipidemic patients with signs of arteriosclerosis obliterans, Fontaine stage II/III.

Nitrendipine-stimulated release of prostacyclin-like substance in normal and atherosclerotic animals.

Nitrendipine (Bayotensin) is a dihydropyridine derivative that appears to preferentially dilate peripheral vessels by a cellular mechanism similar to those found with other calcium blocking agents. In this study nitrendipine when infused (0.2-0.3 mg/kg i.v.) into anaesthetized cats caused a release of a substance disaggregating platelet clumps which had adhered to blood superfused collagen strip. The appearance of this unstable disaggregating substance was prevented by the pretreatment of cats with acetylsalicylic acid (50 mg/kg i.v.). In atherosclerotic rabbits nitrendipine stimulated release of prostacyclin-like substance without effect on proaggregatory concentrations of arachidonic acid and adenosine diphosphate. In rats nitrendipine inhibited the development of atherosclerotic changes in the aorta evoked by the atherogenic diet with ergocalciferol (vitamin D2). It is suggested that nitrendipine may promote formation of prostacyclin in arteries and inhibit the development of atherosclerosis.