Pharmacological evidence that α1- and α2-adrenoceptors mediate vasoconstriction of carotid arteriovenous anastomoses in anaesthetized pigs

1. Vasoconstriction of carotid arteriovenous anastomoses may be involved in the therapeutic action of acutely acting antimigraine agents, including the triptans and ergot alkaloids. While 5-HT(1B/1D) receptors mediate the effect of triptans, ergotamine and dihydroergotamine also interact with α-adrenoceptors. In the present study, we investigated the potential role of α1- and α2-adrenoceptors in mediating vasoconstriction of carotid arteriovenous anastomoses in anaesthetized pigs. 2. Ten minute intracarotid infusions of phenylephrine (1, 3 and 10 μg kg-1 min-1) or BHT 933 (3, 10 and 30 μg kg-1 min-1) produced dose-dependent decreases in total carotid and arteriovenous anastomotic conductances; no changes were observed in the capillary fraction. 3. The carotid vascular effects of phenylephrine and BHT 933 were selectively abolished by prazosin (100 μg kg-1, i.v.) and rauwolscine (300 μg kg-1, i.v.), respectively. The responses to phenylephrine and BHT 933 were not affected by the selective 5-HT(1B/1D) receptor antagonist GR127935 (500 μg kg-1, i.v.). 4. These results show that both α1- and α2-adrenoceptors can mediate vasoconstriction of carotid arteriovenous anastomoses in anaesthetized pigs. Since vasoconstrictor activity in this in vivo model is predictive of anti-migraine activity, an agonist activity at particularly the α2-adrenoceptor subtypes, in view of their less ubiquitous nature, could provide migraine abortive potential. Thus, the present results may aid further understanding of the mode of action of some current antimigraine agents and may eventually be helpful in the development of future treatment in migraine

Treatment decisions in stable coronary artery disease: Insights from the Euro Heart Survey on Coronary Revascularization

Objective: We sought to assess determinants of clinical decision making in patients with stable coronary artery disease. Methods: The 2936 patients with stable angina pectoris who enrolled in the Euro Heart Survey on Coronary Revascularization were the subject of this analysis. After the diagnosis has been confirmed, physicians decided on treatment: medical management or revascularization therapy by means of percutaneous coronary intervention or coronary bypass surgery. We applied logistic regression analyses to evaluate the relation between baseline characteristics and treatment decision: medical treatment versus percutaneous coronary intervention, medical treatment versus coronary bypass surgery, and percutaneous coronary intervention versus coronary bypass surgery. Results: The median age was 64 years, 77% were men, and 20% had diabetes. Medical therapy was intended in 690 (24%) patients, percutaneous coronary intervention in 1503 (51%) patients, and coronary bypass surgery in the remaining 743 (25%) patients, respectively. Revascularization was generally preferred in patients with more severe anginal complaints, an intermediate-to-large area of myocardium at risk, and preserved left ventricular function who had not undergone prior coronary revascularization, provided lesions were suitable for treatment. Coronary bypass surgery was preferred over percutaneous coronary intervention in multivessel or left main disease, as well as in those with concomitant valvular heart disease, provided a sufficient number of lesions were suitable for coronary bypass surgery. In those with previous coronary bypass surgeries, more often percutaneous coronary intervention was preferred than redo coronary bypass surgery. Diabetes was not associated with more frequent preference for coronary bypass surgery. Conclusions: In the hospitals that participated in the Euro Heart Survey on Coronary Revascularization, treatment decisions in stable coronary artery disease were largely in agreement with professional guidelines and determined by multiple factors. Most important deviations between guideline recommendations and clinical practice were seen in patients with extensive coronary disease, impaired left ventricular function, and diabetes