dihydroergotoxine and Carotid-Artery-Diseases

Effects of co-dergocrine mesylate (Hydergine), a drug widely used for the therapy of cerebral vascular disease on local platelet accumulation in the carotid artery region was studied by means of the platelet uptake ratio (PUR) and on the systemic platelet-vascular wall interaction as calculated from platelet half-life were investigated. A placebo controlled, double blind, randomised protocol was used, 18 patients were treated with co-dergocrine and compared to placebo (n = 18). Co-dergocrine treatment resulted in a significant decrease in platelet deposition, PUR decreased from 1.28 +/- 0.05 before treatment to 1.25 +/- 0.06 on day 5 of therapy with a statistically significant (p less than 0.001) in the paired comparison. In the control group the corresponding changes from 1.29 +/- 0.04 before to 1.28 +/- 0.04 did not show a p-value of less than 0.05 in paired comparison. Platelet half-life (72 +/- 11 before vs. 76 +/- 11 hours after 5 days of co-dergocrine treatment) showed a statistically significant (p less than 0.001) prolongation, whereas in the placebo group no relevant change of T/2 was observed (71 +/- 10 before vs. 72 +/- 10 hours on day 5, p greater than 0.10). No relevant effects on ADP-induced platelet aggregation, platelet-release reaction, platelet aggregate ratio, TXB2 plasma levels and thrombin-induced MDA-formation could be detected. These results indicate that co-dergocrine decreased in-vivo platelet residence time to atherosclerotic lesions of the carotid artery. Co-dergocrine may thereby be of benefit in prevention of mural thrombus formation and prevention of transient ischemic attacks, but also of atherosclerosis in man.

Topics: Aged; Arteriosclerosis; Blood Platelets; Carotid Arteries; Carotid Artery Diseases; Carotid Artery Thrombosis; Dihydroergotoxine; Double-Blind Method; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Platelet Adhesiveness; Platelet Function Tests; Random Allocation

The alpha-adrenergic blocking drugs, phentolamine and Hydergine, both act centrally at different sites to depress and enhance the pressor and sympathetic nerve response to decreased baroreceptor afferent input in anesthetized cats. Depression of the rise in blood pressure and sympathetic nerve discharge during bilateral carotid occlusion (BCO) followed injection of the agents into the 4th cerebral ventricle when the brain was intact but not when connections were interrupted at the midcollicular level by transection or lesion. Enhancement of responses occurred when drug distribution was confined to the brain rostral to the midcollicular level via injection into the 3rd cerebral ventricle with the cerebral aqueduct cannulated. Both agents decreased resting blood pressure and Hydergine decreased heart rate in intact and decerebrate preparations but not in 3rd ventricle-cerebral aqueduct experiments. We found that pretreatment with the noradrenergic precursor. L-dopa consistently prevented depression by phentolamine but was less effective against Hydergine. The results indicate that mechanisms which enhance and suppress the baroreceptor pressor response are normally operative in anesthetized cats and, furthermore, that neural pathways mediating the effects are ones connecting the caudal brainstem with supracollicular levels of the brain. It is further suggested that the pathways may be noradrenergic.

Topics: Animals; Arterial Occlusive Diseases; Bradycardia; Carotid Artery Diseases; Cats; Decerebrate State; Depression, Chemical; Dihydroergotoxine; Dose-Response Relationship, Drug; Hemodynamics; Injections, Intraventricular; Levodopa; Norepinephrine; Phentolamine; Phenylephrine; Pressoreceptors; Stimulation, Chemical; Superior Colliculi; Sympathetic Nervous System