Carlo Patrono

Failure of thromboxane A2 blockade to prevent attacks of vasospastic angina.

Thromboxane A2 (TxA2), released by aggregating platelets, has been proposed as a potential mediator of coronary vasospasm. We studied six patients with variant angina, a clinical syndrome due to coronary vasospasm, and one patient with frequent recurrent episodes of transient ST-segment depression at rest in whom the spasm was demonstrated angiographically. All patients underwent continuous ECG monitoring for 2 days before and 2 days after a single, low, i.v. dose of aspirin (2 mg/kg), which reduced TxB2 (the stable metabolite of TxA2) to less than 3% of the control values. There were 129 transient ischemic episodes during control and 146 after aspirin, when platelet TxB2 was reduced to negligible levels. The duration, severity and incidence of symptomatic episodes were not significantly affected by TxA2 blockade. We conclude that platelet TxA2 is probably not responsible for the initiation of coronary vasospasm.

Effects of intravenous prostacyclin in variant angina.

A lack in prostacyclin (PGI2) production due to atherosclerosis may play a role in the pathophysiology of some of the clinical manifestations of ischemic heart disease and, in particular, of coronary vasospasm. We therefore evaluated the effects of i.v. PGI, in nine patients with variant angina and six normal volunteers. In normal subjects, PGI2 (2.5, 5, 10 and 20 jg/kg/min) had significant antiplatelet effects, caused a dosedependent decrease in both systolic and diastolic arterial pressure and a decrease in pulmonary resistance. Heart rate increased in a dose-dependent manner, but no consistent effects on myocardial contractility (evaluated by ultrasound) were observed. Side effects were negligible and readily reversible. Although producing obvious antiplatelet and vasodilatory effects, PGI2 did not affect the number, severity and duration of spontaneous ischemic episodes due to coronary vasospasm in five patients and ergonovineinduced spasm in three. However, the number of ischemic episodes was consistently reduced in one patient during four consecutive periods of PGI2 infusion alternated with placebo. A severe, prolonged ischemic episode with ST elevation and pain was consistently observed in this patient every time PGI2 was discontinued. In the appropriate environment, PGI2 can be administered safely to patients with ischemic heart disease. Occasionally, PGI2 may result in a complete disappearance of ischemic episodes due to coronary vasospasm, but usually it is ineffective. These conflicting results could be related to different etiologies of coronary spasm.

Documento de Consenso de Expertos sobre el uso de agentes antiplaquetarios

Carlo Patrono (Chairperson)* (Italy), Fedor Bachmann (Switzerland), Colin Baigent (UK), Christopher Bode (Germany), Raffaele De Caterina (Italy), Bernard Charbonnier (France), Desmond Fitzgerald (Ireland), Jack Hirsh (Canada), Steen Husted (Denmark), Jan Kvasnicka (Czech Republic), Gilles Montalescot (France), Luis Alberto Garcia Rodriguez (Spain), Freek Verheugt (The Netherlands), Jozef Vermylen (Belgium), Lars Wallentin (Sweden)

Release of Contracting Autacoids by Aortae of Normal and Atherosclerotic Rabbits

Summary: The aim of our study was to examine the release of various lipid and peptide contracting autacoids by aortae of normal and atherosclerotic rabbits. Leukotriene (LT) E4, an enzymatic derivative of LTC4, thromboxane (Tx) B2, and endothelin‐1 (ET‐1) were measured by radioimmunoassay techniques in aortic preparations of normal and cholesterol‐fed rabbits. Intact aortae of normal rabbits incubated with the calcium ionophore A23187 for 1 h at 37°C released LTE4 and TxB2 (22 ± 3.5 and 14.8 ± 2 pg/mg of tissue, respectively, mean ± SEM, n = 33). Removal of aortic endothelium was associated with a significant reduction in LTE4 (44%) and TxB2 (58%) release. In aortic preparations from cholesterol‐fed rabbits, the release of LTE4 was significantly enhanced (41 ± 8 pg/mg of tissue, mean ± SEM, n = 27) whereas TxB2 was not significantly altered. No detectable amounts of ET‐1 were measured after 1 h of incubation. However, at 4 h, an endothelium‐dependent release of ET‐1 from normal aortae was demonstrated. In atherosclerotic aortae, ET‐1 release was significantly higher than in controls (10 ± 1.3 vs. 5 ± 0.5 pg/cm2, mean ± SEM, n = 16). We conclude that enhanced formation of vasoconstrictor autacoids may contribute to altered vasomotion of atherosclerotic blood vessels.