Increased plasma levels of interleukin-8 in patients with unstable angina pectoris.

Interleukin-8 is a proinflammatory cytokine with chemo-attractive and major activator properties on neutrophils. The very few studies in literature on the IL-8 behaviour in myocardial ischaemia refer only to acute myocardial infarction. This study investigates the IL-8 behaviour in stable angina pectoris after myocardial ischaemia induced by dipyridamole (14 patients) and in unstable angina pectoris, Braunwald's class III (35 patients). In stable exercise angina following dipyridamole-induced myocardial ischaemia, the plasma IL-8 levels did not increase. In unstable angina pectoris increased plasma IL-8 levels were evidenced in 25 of the 35 patients, after an average interval of 20 +/- 1.2 hours from the last spontaneous episode of angina pectoris. The IL-8 behaviour was different in class III B patients as compared to class III A: only 30% of the patients in class III A presented transient increase of IL-8, while 70% of the class III B presented increased IL-8 with a median value of 900 pg/ml within the first 24 hours from the last spontaneous episode of angina pectoris. The increased plasma IL-8 levels within the first 24 hours from the spontaneous episode could represent a marker of primary angina pectoris, Braunwald's class III B.

Clinical and etiopathogenetic profile of heart failure in the First Medical Clinic of Cluj-Napoca. A study of 5 years.

The authors analysed the main etiopathogenetic conditions and the clinical and evolutional profile of 1586 patients with heart failure (HF), admitted to the First Medical Clinic of Cluj-Napoca between 1990 and 1994. Ischemic heart disease was found in 1,236 patients (78%), followed by chronic cor pulmonale, valvulopathies and congenital heart diseases. Among the precipitating and/or aggravating factors of HF, the most important were infections in 434 patients (33.10%), and arrhythmias, especially atrial fibrillation, in 332 patients (25.39%). In decreased order of frequency there were also failure to observe prescribed therapy, uncontrolled arterial hypertension, anemias, dyselectrolytemias, dysproteinemias. HF had a chronic evolution in 1,450 patients (91.40%), and an acute one in 136 (8.6%). In conditions of complex therapy including cardiotonics, diuretics, plus, more recently, conversion enzyme inhibitors, the clinical evolution was favourable in 1,432 patients (90.20%), which had a lower functional class on discharge from hospital.

The effect of slow-release nifedipine on ST-segment depression induced by effort test. Correlations with serum levels.

To study the anti-ischemic effect of slow-release nifedipine ten patients with stable angina pectoris and a positive effort test were selected. Nifedipinemia was measured by a gas chromatographic method. At the peak level of effort intensity slow-release nifedipine significantly decreased the mean ST-segment depression (p < 0.05) and the ischemic score (p < 0.01) when compared to the control effort test, without decreasing the double product. Nifedipine induced no more tachycardia additional to that produced by effort. At the beginning of the effort test the level of nifedipine (15.9 +/- 2.51 ng/ml) was superior to the value considered as minimal effective and was positively correlated with the ischemic score (r = 0.67; p < 0.05). A worsening of ischemia was noted in 2 patients probably due to a steal phenomenon.

Correlation between fibronectin and cardiothoracic ratio in heart failure treated with angiotensin converting enzyme inhibitors.

A group of 17 patients with ischemic heart disease, significant left ventricular dilatation and congestive heart failure, class III NYHA (9 patients) and class IV NYHA (8 patients) was studied. The patients received angiotensin converting enzyme inhibitor--captopril 75 mg/day or perindopril 4 mg/day--added to diuretics, digitalis and nitrates. The plasmatic level of fibronectin was investigated, by radial immunodiffusion, before and one month after the beginning of the treatment with angiotensin converting enzyme (ACE) inhibitor. The plasmatic level of fibronectin is increased significantly (p < 0.001) while the cardiothoracic ratio is decreased significantly (p < 0.02) after one month of ACE inhibitors treatment. A positive correlation between the increase of the plasmatic level of fibronectin and the decrease of cardiothoracic ratio is found (r = 0.62; p < 0.01). The increased fibronectin plasmatic level can be a marker of the favorable effect of ACE inhibitor on the myocardium interstitium.

Microalbuminuria in hypertensive patients.

The present study was designed to evaluate the urinary albumin excretion in 62 patients with essential hypertension. None of them had prior proteinuria or history of nephropathy or uropathy. Patient data, blood pressure, proteinuria using Bradford's method, albuminuria by radial immunodiffusion, urinary SDS-PAA electrophoresis, plasma glucose, serum creatinine, serum cholesterol were determined. The urinary albumin excretion was significantly higher (p < 0.001) in the group of hypertensive patients (19.22 +/- 2.36 micrograms/min) compared to a group of 20 control subjects (4.17 +/- 0.67 microgram/min). Compared to a subgroup of hypertensive patients without ischemic heart disease (12.07 +/- 1.30 micrograms/min) microalbuminuria was higher (43.74 +/- +/- 5.74 micrograms/min; p < 0.001) in a subgroup of 14 patients with essential hypertension and ischemic heart disease with severe coronary events: unstable angina pectoris (9 patients), myocardial reinfarction (2 patients), ventricular arrhythmias (3 patients). A positive correlation between the microalbuminuria and the duration of hypertension was found (r = 0.64; p < 0.001). Therefore, microalbuminuria may represent a marker of the severity of vascular involvement in hypertensive patients.

[The bioavailability of nifedipine in different solid pharmaceutical preparations for oral use]. / Biodisponibilitatea nifedipinei din diferite preparate farmaceutice solide pentru uz oral.

The paper reports on the bioavailability of niphedipine in various pharmaceutic preparations administered in a single dose of 10 mg, per os, to volunteer subjects: Niphedipine dragees (Terapia, Cluj-Napoca), Adalat capsules (Bayer); Adalat coated tablets (Bayer and Birlasik Alman Ilac Fabricalari, Istanbul) and Corinfar dragées (VEB Arzneimittelwerk, Dresden). In the blood samples collected, niphedipine was determined by a gas-chromatographic procedure. Pharmacokinetic analysis of the experimental data was made by a digital computer. Bioavailability of niphedipine was the best with Adalat capsules. The relative bioavailability of the other products was: tablets (Adalat); 93%; dragées (Niphedipine): 92%; dragées (Corinfar 86%). Absorption speed of Niphedipine decreases in the order: capsules, tablets, indigenous and imported dragées. Statistical analysis (Student test) shows that the differences in bioavailability among the preparations are not important. Efficiently therapeutic plasmatic concentrations are maintained for about 6 hours after a single dose of 10 mg administered as tablets and dragées and for 8 hours in the case of capsules. Important differences exist between the maximum concentration of niphedipine in blood, following some differences in the absorption speed, achieved after administration of capsules, on the one hand, and of tablets and dragées on the other hand. Choosing the type of tablet depends, therefore, on the nature of the affection treated. Niphedipine (Terapia) has corresponding biopharmaceutic properties and is useful in treating hypertension and for preventing and treating anginal attacks.

Bioavailability of nifedipine from different oral dosage forms in healthy volunteers.

The absolute and relative bioavailability of nifedipine (1) from different formulations administered as single oral doses in healthy volunteers was determined. Serum concentrations of 1 were measured by GC. The absolute bioavailability of 1 was 53% because of presystemic metabolism. The bioavailability of Adalat (Bayer) tablets, Nifedipina (Terapia) and Corinfar (VEB Arzneimittelwerk Dresden) sugar-coated tablets was 93%, 92% and 86% (respectively) as compared with Adalat capsules. The AUC were not significantly different. The Cmax and tmax values were different, indicating that the absorption of 1 showed differences in first-order rate constants of dissolution in the above mentioned order. Despite the differences among the formulations studied, each preparation may have its merits. In a multiple dose regimen of 20 mg 1 (Nifedipina, Terapia) t.i.d., minimal therapeutic drug levels were achieved and maintained during steady state, from the 1st d of treatment.

Viral myocarditis. Clinical, electrocardiographic and evolutive diversity.

Five observations of severe viral myocarditis are presented. Diverse cardiac emergencies (pump failure, ventricular premature beats or tachycardia, left bundle branch block, trifascicular block, grade 2 or 3 a-v block, severe hypotension, etc.) as well as associated conditions (pericarditis, interstitial nephritis, pneumonia, pulmonary massive thromboembolism) could be found. The course of the disease was acute in three cases, subacute in one and chronic in another. Two patients died with severe pump failure (associated with pulmonary thromboembolism in one case), The clinical, evolutive and histologic aspects were in good correlation. These cases illustrate the clinical, electrocardiographic and evolutive diversity of viral myocarditis.