Optimization of the synthesis of a key intermediate for the preparation of glucocorticoids.

A short and efficient synthesis, based on a one-step double elimination, of a key intermediate in the synthesis of various glucocorticosteroids has been developed. This method can be carried out on large scale for further industrial applications. The synthesis allowed us to identify a novel prednisolone derivative 10 and its anti-inflammatory activity was determined in an in vivo model of inflammation.

[Platelet antiaggregants in other pathologies].

Platelet aggregation inhibitors are used in numerous clinical situations on the basis of claims that platelets are involved. As a result of controlled clinical trials, some of these situations have become formal indications for some of these drugs. The situations in which platelet aggregation inhibitors are used include: arteritis of the lower limb at the intermittent claudication stage, leg ulcers of arterial origin, emboligenic arteritis with focus of platelet hyperfixation, progression of atherosclerosis as assessed by angiography, implantation of vascular surfaces, diabetic retinopathy, retinal venous thrombosis, cycle cell anaemia and perhaps thrombocythaemia.

[Calcium channel blockers in ischemic cardiopathies].

Calcium-entry blockers are the drugs of choice in coronary spasm, unstable angina, and when patients do not have any effort limitation. However, beta-blockers, without sympathomimetic activity, remain the treatment of angina pectoris. When clinical situation is difficult to control, association calcium blockers and bêta-blockers are more efficient than monotherapy.

Evaluation of 10 QT prediction formulas in 881 middle-aged men from the seven countries study: emphasis on the cubic root Fridericia's equation.

In 881 middle-aged men from one Italian cohort of the Seven Countries Study, QT and RR intervals were measured in lead 2 from resting ECGs (25 mm/sec) and fitted separately with 10 mathematically different QT prediction formulas. The relative accuracy of fit to data was assessed from the minimum mean-squared residual and the minimum Akaike Information Criterion values. Using the Minnesota code, 588 men had normal (group 1) and 293 had abnormal (group 2) ECGs.

[Prevalence of arterial hypertension and its treatment in 2,595 adults].

The prevalence of arterial hypertension, as defined by the W.H.O.

Prevention of postischemic ventricular fibrillation late after right or left stellate ganglionectomy in dogs.

To gain insight into the differences in antiarrhythmic potential of right vs left stellate ganglionectomy, 72 dogs were randomized to either unilateral stellectomy or second intercostal space thoracotomy and left circumflex coronary arteriovenous pedicle occlusion was performed, without vagotomy, a mean of 8 weeks later under anesthesia. The type and timing of ventricular ectopic beats, including both nonsustained and sustained ventricular tachycardia and ventricular fibrillation, were investigated. Several covariates, including postischemic electrocardiographic changes, were considered.

Effects of cicletanine in the left circumflex coronary artery occlusion-reperfusion canine model of sudden death: analysis of 107 experiments using Cox's proportional hazards model.

Multivariate analysis of survival using Cox's proportional hazards model demonstrates that several clinically measurable covariates are determinants of life-threatening arrhythmias following left circumflex coronary artery occlusion-reperfusion in 107 dogs. These are heart rate, ST segment elevation and mean aortic pressure immediately (3 min) following occlusion, and the presence of early (0-10 min) post-occlusion sustained ventricular tachycardia. The risk of occlusion-reperfusion ventricular fibrillation was determined according to Cox's solution based on ST segment elevation, thus enabling quantification of the role of cicletanine.

Prevention of postischaemic ventricular fibrillation by long term beta adrenoceptor blockade with acebutolol in the anaesthetised dog.

Acute occlusions of the proximal left circumflex coronary arteriovenous pedicle were performed in open chest anaesthetised dogs. Twenty eight dogs were randomly allocated to receive acebutolol (3 mg X kg-1 twice daily) or placebo given blindly by mouth for five days; a control group of 14 dogs without any pretreatment underwent the same procedure. Coronary ligations in the randomised study were performed during seven consecutive days, and four dogs were operated on each day.

Molsidomine prevents post-ischaemic ventricular fibrillation in dogs.

Forty anaesthetized dogs were subjected to left circumflex coronary artery ligation followed by reperfusion. Molsidomine was randomly administered to 20 dogs (50 micrograms kg-1 as an i.v.

Experimental and clinical pharmacology of bretylium tosylate in acute myocardial infarction: a 15-year journey.

Experimental and clinical studies demonstrate the antifibrillatory effectiveness of bretylium tosylate: Experimental ventricular fibrillation induced either by electrical stimulation or by ischemia is prevented by bretylium. In 2,000 acute myocardial infarction patients who received bretylium prophylactically primary ventricular fibrillation occurred in less than 1% of cases. In a randomized hemodynamic study in acute myocardial infarction patients bretylium induced a significant decrease in heart rate, systolic and mean left ventricular pressures, and in systolic and mean aortic pressures.

The circumflex coronary artery occlusion canine model of sudden death: methodology and electrocardiographic observations.

This study deals with a left circumflex coronary artery occlusion-reperfusion canine model of sudden death using multiple electrocardiographic leads to define a subgroup of animals at high risk of ventricular fibrillation. Occlusion was followed by ventricular fibrillation in 15 of 30 animals (50%). In the 15 dogs surviving 60 min postocclusion, reperfusion gave rise to ten cases of ventricular fibrillation (66.

Cicletanide improves outcome after left circumflex coronary artery occlusion-reperfusion in the dog.

The possible antifibrillatory effect of cicletanide, a new diuretic antihypertensive drug, was investigated at random in 50 anesthetized dogs subjected to left circumflex coronary artery ligation for 60 min and later reperfused. In this model, standard electrocardiographic leads 2 and 3 were continuously registered to measure delta R wave percent changes, to count the number of ventricular premature beats, and to document the onset of ventricular fibrillation; aortic pressure was recorded; 6-keto PGF1 alpha and TXB2 plasma levels were determined. Cicletanide significantly reduced early (Phase 1a) postischemic ventricular fibrillation (5 of 25 vs.

[Eicosanoids, myocardial ischemia and sudden death].

An activation of the arachidonic acid cascade has long been reported in coronary artery diseases. However, no clear-cut connection has been demonstrated between this activation and the clinical manifestations of myocardial ischemia. Controlled trials with the available cyclooxygenase inhibitory drugs support the view that these agents might be useful in subgroups of patients.

[Eicosanoids, vascular function and atherosclerosis].

Icosanoides (prostaglandins, leukotrienes) seem to play an essential part in cardiovascular pathology. A range of experimental data obtained both in vitro and in vivo has resulted in a rapid progression of our understanding of their biochemical and functional properties and has opened up new fields of pharmacological research. However, a clear cut demonstration of their clinical relevance remains difficult.

Epoprostenol (PGI2) prevents postischemic ventricular fibrillation and improves outcome in a canine model of sudden death.

In a left circumflex coronary artery occlusion-reperfusion canine model of sudden death the hemodynamic, antiplatelet, antiischemic and antifibrillatory activities of 100 ng.kg-1.min-1 infusion of epoprostenol (Prostacyclin, Flolan, Wellcome Foundation, London, UK) were investigated at random in 40 animals.

[An anesthetic technic in dogs for studying the arrhythmogenic effects of acute coronary occlusion].

Intramuscular injection of levomepromazine (0.5 mg/kg) 30 min before intravenous injection of 10 mg/kg pentobarbital sodium induces a good surgical anaesthesia in dogs artificially ventilated with 50% N2O and 50% O2 and given 0.01 mg/kg atropine and 0.

[Evaluation of the effectiveness of medical treatment of intermittent claudication].

The effectiveness of drugs to improve the walking distance in intermittent claudication patients is looked into five points: pathophysiology, drugs, methodology of clinical trials, sample survey among the members of the hemodynamic section of the French College of Vascular Diseases and biometric aspects. Finally, some important points of a clinical trial in this field are presented.

Alteration in prostacyclin and prostaglandin E2 production. Correlation with changes in human aortic atherosclerotic disease.

Prostacyclin (PGI2) and prostaglandin E2 (PGE2) production was investigated in human aortas (five controls and 27 with atherosclerotic lesions). The specific activities of PGI2 and PGE2 synthetase were studied using radioimmunoassays of PGE2 and 6-keto-PGE1 alpha of aortic microsomes incubated in the presence of additional substrate and cofactors. The atherosclerotic lesions were examined under the light microscope and were classified as Stage 1 when the disease was restricted to the intima and as Stages 2 and 3 when there were moderate or advanced lesions.

Thromboxane B2, 6-keto-PGF1 alpha, PGE2, PGF2 alpha, and PGA1 plasma levels in arteriosclerosis obliterans: relationship to clinical manifestations, risk factors, and arterial pathoanatomy.

Current concepts of atherogenesis based on animal and human investigations indicate prostaglandins as a key factor in atherosclerotic lesions. The plasma profiles of thromboxane B2 (TXB2), 6-keto-PGF1 alpha, PGE2, PGF2 alpha, and PGA1 were investigated by means of a sensitive radioimmunoassay technique in 40 patients with arteriosclerosis obliterans and in 30 healthy control subjects. Abnormally high levels of TXB2 and PGE2 (222.