cinnarizine and Arteriosclerosis

Topics: Animals; Aorta; Arteries; Arteriosclerosis; Calcinosis; Calcium; Calcium Channel Blockers; Cell Survival; Cholesterol, Dietary; Cinnarizine; Diltiazem; Flunarizine; Humans; Membrane Lipids; Muscle, Smooth, Vascular; Nicardipine; Nifedipine; Propranolol; Rabbits; Verapamil

In order to understand blood circulation, knowledge of the rheological properties of blood is required. However, the characteristic parameters which must be considered differ according to the circulatory region investigated. A distinction must therefore be made between the macrorheological parameters (viscosity, viscoelasticity) and the microrheological parameters (aggregation, cell deformability). As far as the microrheological parameters are concerned, red blood cell deformability is quite definitely the most important parameter in any physiopathological study of capillary circulation and the resulting exchanges. The main intrinsic parameters of red blood cell deformability are: inner viscosity of the cell, surface/volume ratio and membrane properties related to the lipid bilayer or to the cytoskeleton. Abnormal erythrocyte microrheology may result form alterations any one of these three parameters and would affect the ability of the cell to transit in the capillaries. Disturbances of red blood cell deformability are encountered in many clinical cases, mainly during anomalies relating to hemoglobin structure or its oxygen affinity, in constitutional deficiency of the membrane and during degenerative cardiovascular diseases or diseases which are considered to be atherosclerosis risk factors.

Topics: Animals; Arteriosclerosis; Blood Viscosity; Calcium; Cardiovascular Diseases; Cinnarizine; Elasticity; Erythrocyte Indices; Erythrocyte Membrane; Erythrocytes; Hematologic Diseases; Humans; Membrane Fluidity; Microcirculation; Models, Biological; Pentoxifylline; Rheology; Risk

Thirty-one patients, mean age 60 years (range 45-80 years), with a typical history and objective symptoms of intermittent claudication with a reported maximal walking distance less than 500 m, were included in a cross-over study. After a one month's run-in period on placebo, the patients were randomized into two groups: one group started with flunarizine (5 mg t.i.d.) and the other with pentoxifylline (400 mg t.i.d.). The treatment lasted 3 months, whereafter the medications were changed. The trial followed a double-blind design. The median of the maximal walking distance was 255 m after the placebo period, increasing significantly (p less than 0.01) during both medication periods: by 43% and 18% during flunarizine and pentoxifylline, respectively. No changes were recorded in the ankle systolic blood pressure ratio ( ASBP -ratio) after placebo or either medication period. Red cell rigidity (Pmax), which was initially elevated, decreased significantly (p less than 0.05) during both medication periods, but there were no significant differences between the two drugs. No changes were found in whole blood or plasma viscosity. We conclude that the decrease in red cell rigidity may have contributed to the increased walking distance.

Topics: Aged; Arteriosclerosis; Blood Pressure; Blood Viscosity; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Erythrocytes; Exercise Test; Flunarizine; Humans; Intermittent Claudication; Leg; Middle Aged; Osmotic Fragility; Pentoxifylline; Physical Exertion; Piperazines; Regional Blood Flow; Rheology; Smoking; Theobromine; Vasodilator Agents

Topics: Arteriosclerosis; Calcium; Cerebrovascular Disorders; Cinnarizine; Clinical Trials as Topic; Double-Blind Method; Humans; Intermittent Claudication; Leg Ulcer; Paresthesia; Piperazines; Vascular Diseases; Vasodilator Agents; Venous Insufficiency

Topics: Arm; Arteriosclerosis; Blood Viscosity; Cinnarizine; Clinical Trials as Topic; Diabetes Mellitus; Double-Blind Method; Erythrocyte Membrane; Humans; Ischemia; Myocardial Infarction; Osmolar Concentration; Piperazines; Rheology; Vasodilator Agents

Flunarizine is a calcium entry blocker active in the treatment of peripheral vascular disease. The present study was performed to evaluate the effect of flunarizine on cerebral blood flow (CBF) and lipidic patterns in rabbits with dietary experimental atherosclerosis. Since it is well known that there is only a slight correlation between the severity of atheromatous lesions ascertained at necroscopy and the severity of clinical symptoms of cerebral vascular disease, the effect of the drug was assessed by measuring the CBF and compartmental distribution of blood flow in unanaesthetized rabbits by the intracarotid Xe-133 clearance method; blood pressure, plasma lipids and tissue fat infiltration were also checked. An atherogenic diet brings about significant impairment of CBF. Flunarizine is inactive in normal rabbits if chronically administered at the daily dose of 10 mg/kg p.o. In atherosclerotic rabbits chronic treatment with flunarizine induced a pronounced increase in cerebral haemodynamic parameters. Arterial pressure and blood pCO2 were not significantly modified. Lipidic patterns were not markedly improved by flunarizine treatment in comparison with values for atherosclerotic animals. These data demonstrate that flunarizine treatment counteracts the haemodynamic effects of cerebral atherosclerosis. The pronounced activity on the cerebral vessels is accompanied by a weak antilipaemic effect.

Topics: Animals; Arteriosclerosis; Cerebrovascular Circulation; Cinnarizine; Diet, Atherogenic; Flunarizine; Hypolipidemic Agents; Lipids; Male; Rabbits

Repeated weak electrical stimulations of rabbit carotid artery walls with implanted electrodes cause intimal proliferations of smooth muscle cells (SMC) and lead to fibromuscular plaques beneath the anode. If the animals receive a cholesterol-enriched diet the plaques become typical atheromas. The endothelial lining is maintained. The procedure for the production of an atheroma with 11 +/- 4 layers of SMC lasts 4 weeks. Addition of the calcium antagonist Flunarizine to the food during the stimulation periods inhibits the growth of the plaque. The inhibition is dose-dependent. Whether the drug inhibits atherogenesis by direct action on SMC or via an effect on permeation of macromolecules through the endothelium has been studied by measurement of (1) peroxidase (MW 40,000 dalton) permeability through the stimulated endothelium of the artery and (2) the inhibitory effects of Flunarizine on cultures of arterial SMC. Endothelial permeability increases for some hours after stimulation mainly beneath the anode. Flunarizine inhibits the permeation of peroxidase through the endothelial lining for the most part by its action on intercellular transport. The drug also inhibits the growth of SMC in mass cultures and clone cultures. The inhibition of proliferation is not specific for SMC. Skin fibroblasts obtained from the same animals as the artery smooth muscle cells are also inhibited in mass cultures and clone cultures. From the results it can be concluded that Flunarizine exerts its inhibitory action not only by its effect on the permeation through the endothelial lining but by a combined action on permeability and proliferation of cells in the artery wall.

Topics: Animals; Arteriosclerosis; Carotid Arteries; Cell Division; Cells, Cultured; Cinnarizine; Disease Models, Animal; Electric Stimulation; Endothelium; Fibroblasts; Flunarizine; Horseradish Peroxidase; Male; Muscle, Smooth, Vascular; Rabbits; Vasodilator Agents

Topics: Aged; Arteriosclerosis; Cinnarizine; Female; Flunarizine; Humans; Intracranial Arteriosclerosis; Male; Middle Aged; Ultrasonography

We tested the effects of the calcium antagonists lanthanum, diltiazem, and flunarizine on the development of atherosclerosis in rabbits fed a 2% cholesterol diet. The drugs were given orally and were well tolerated. In the cholesterol control animals, 52.2% of the thoracic aortic intimal surface was Sudan IV positive. This was reduced by 37% (p less than 0.05) with lanthanum, 37% (p less than 0.05) with diltiazem, and 34% (p less than or equal to 0.06) with flunarizine. In all cholesterol-fed animals, the intramural, but not subepicardial, coronary arteries were severely diseased. The extent and distribution of this disease were not altered by the various drug interventions. Thus, the calcium antagonists lanthanum, diltiazem, and flunarizine suppress atherogenesis of the rabbit aorta but have no effect on the extent or distribution of atherosclerosis in the intramural coronary arteries.

Topics: Animals; Aortic Diseases; Arteriosclerosis; Calcium Channel Blockers; Cholesterol, Dietary; Cinnarizine; Coronary Disease; Diltiazem; Female; Flunarizine; Lanthanum; Organ Size; Rabbits

Topics: Arteriosclerosis; Cinnarizine; Complement Activation; Humans; Piperazines

Topics: Aged; Arteriosclerosis; Cinnarizine; Female; Humans; Male; Middle Aged; Piperazines; Radioisotope Renography

Topics: Arterial Occlusive Diseases; Arteriosclerosis; Biological Transport; Blood Viscosity; Calcium; Cell Membrane Permeability; Cinnarizine; Humans; Intermittent Claudication; Muscle, Smooth; Papaverine; Vascular Diseases

Topics: Adult; Aged; Arteriosclerosis; Cinnarizine; Extremities; Humans; Intracranial Arteriosclerosis; Male; Middle Aged; Phosphatidylcholines; Piperazines