ergoline and Arterial-Occlusive-Diseases

Topics: Aged; Arterial Occlusive Diseases; Blood Pressure; Clinical Trials as Topic; Electroencephalography; Ergolines; Female; Humans; Male; Memory; Nicergoline; Placebos; Psychology

Topics: Arterial Occlusive Diseases; Clinical Trials as Topic; Drug Evaluation; Ergolines; Humans; Injections, Intra-Arterial; Leg; Nicergoline; Raynaud Disease; Vasodilator Agents

The present study was designed to evaluate the effectiveness of the ergoline 5HT2 receptor antagonist, LY53857 in a rabbit model of vascular arterial occlusion. LY53857 (1 and 10 microM) inhibited serotonin amplified platelet aggregation responses to threshold concentrations of ADP in rabbit platelets in vitro. LY53857 (1 microM) not only inhibited the serotonin component of rabbit platelet aggregation, but also inhibited in vitro aggregation induced by ADP (48.7 +/- 16.7% inhibition), collagen (76.1 +/- 15.9% inhibition) and U46619 (65.2 +/- 12.3% inhibition). The effectiveness of this ergoline 5HT2 receptor antagonist in blocking aggregation to ADP, collagen and U46619 may be related to its ability to inhibit a serotonin component of platelet aggregation since rabbit platelets possess high concentrations of serotonin that may be released during aggregation produced by other agents. Based on the effectiveness of LY53857 to inhibit rabbit platelet aggregation, we explored the ability of LY53857 to extend the time to carotid artery occlusion in rabbits following electrical stimulation of the artery. Reproducible carotid artery occlusion was induced in rabbits by moderate stenosis coupled to arterial cross clamping, followed by electrical stimulation. With this procedure, occlusion occurred at 47.0 +/- 7 min (n = 30) after initiation of the electrical stimulation. Animals pretreated with LY53857 (50 to 500 micrograms/kg i.v.) showed a delay in the time to carotid artery occlusion (at 100 micrograms/kg i.v. occlusion time extended to 164 +/- 16 min). Furthermore, ex vivo platelet aggregation from animals treated with LY53857 (300 micrograms/kg i.v.) resulted in 40.5% inhibition of platelet aggregation in response to the combination of ADP (1 microM) and serotonin (1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arterial Occlusive Diseases; Carotid Artery Diseases; Disease Models, Animal; Ergolines; In Vitro Techniques; Male; Platelet Aggregation Inhibitors; Rabbits; Serotonin Antagonists; Time Factors

Recent experimental and clinical data have stimulated interest in the use of alpha-adrenergic antagonists in acute myocardial infarction. We evaluated nicergoline, a new relatively selective alpha 1-antagonist which uniquely lowers heart rate. Open-chest dogs, randomized to control (n = 25) or intravenously treated group (n = 20; 0.5 mg/kg bolus, then 0.10 to 0.15 mg/kg/min), underwent coronary artery occlusion (CAO) followed after 25 minutes by coronary artery reperfusion (CAR). Nicergoline decreased heart rate by 47 +/- 5 bpm and mean aortic pressure by 39 +/- 4 mm Hg. Following CAO, nicergoline reduced total coronary collateral resistance (radiolabeled microspheres; 698 +/- 75 vs 2167 +/- 530 mm Hg/ml/min/gm, p less than 0.05), increased the ischemic zone/nonischemic zone flow ratio (0.14 +/- 0.04 vs 0.06 +/- 0.02, p less than 0.05), and reduced the rise in intramyocardial CO2 tension in the ischemic zone (mass spectrometry, p less than 0.001). Furthermore, the drug decreased the rate of ventricular tachycardia (VT; 191 +/- 13 vs 243 +/- 3 bpm, p less than 0.001) and the incidence of ventricular fibrillation (VF; 1 of 20 [5%] vs 7 of 25 [28%], p less than 0.05). Following CAR, nicergoline did not significantly reduce the incidence of VF but did lower rate (154 +/- 8 vs 212 +/- 10 bpm, p less than 0.001) and incidence (p less than 0.05) of VT. Thus nicergoline reduced severity of ischemia and afforded protection against arrhythmias induced by myocardial ischemia and reperfusion. The observed reduction in heart rate may have contributed importantly to these beneficial effects. Clinical investigation of this potentially useful vasodilator seems warranted.

Topics: Animals; Arrhythmias, Cardiac; Arterial Occlusive Diseases; Carbon Dioxide; Coronary Circulation; Dogs; Dose-Response Relationship, Drug; Ergolines; Female; Heart Rate; Male; Myocardial Infarction; Nicergoline; Partial Pressure; Perfusion; Phenylephrine; Pressure; Vascular Resistance

Topics: Adrenergic alpha-Antagonists; Adult; Aged; Ambulatory Care; Arterial Occlusive Diseases; Arteriosclerosis Obliterans; Arteriovenous Shunt, Surgical; Diabetic Angiopathies; Ergolines; Female; Ganglia, Sympathetic; Humans; Leg; Lumbosacral Region; Male; Middle Aged; Nicergoline

Topics: Aged; Arterial Occlusive Diseases; Cerebrovascular Disorders; Ergolines; Female; Humans; Intracranial Arteriosclerosis; Ischemic Attack, Transient; Leg; Male; Middle Aged; Vasodilator Agents