Arterial compliance in hypertension and heart failure.

The purpose of this paper is to investigate the relation between the presence and degree of arterial compliance impairment and, respectively, the clinical conditions of systemic hypertension and/or heart failure. We investigated 19 patients with hypertension, without heart failure (group A), 13 patients with hypertension and heart failure class NYHA II (group B), 10 patients with coronary heart disease and heart failure class NYHA II (group C) and 7 control patients without clinically relevant cardio-vascular diseases (group D). Compliance was evaluated with a Complior device, by measuring carotid femoral and carotid-radial pulse-wave velocities (PWV). Carotid-radial PWV did not differ significantly between the various groups (10.8 +/- 2, 10.6 +/- 0.9, 9.5 +/- 1.5 and 9.9 +/- 1.6 m/s, for groups A, B, C and D, respectively). Carotid-femoral PWV, in group A hypertensive p without heart failure, was 13.1 +/- 2.9 m/s, significantly higher as compared to group C p with coronary heart disease and heart failure (10.5 +/- 2.4 m/s, p = 0.02), as well as compared to group D controls (9.8 +/- 2.6, p = 0.02). Group B p, with heart failure associated to hypertension, had a carotid-femoral PWV of 13.5 +/- 3.9 m/s, similar to the one found in group A hypertensive p without heart failure. When comparing groups B and C p with heart failure, we noted that the carotid-femoral PWV was significantly (p = 0.04) increased in hypertensive p, as compared to those with coronary heart disease. In conclusion, the results of our study confirm the impairment of arterial compliance, in hypertensive patients. The carotid-femoral, but not the carotid-radial PWV, were useful for identifying impaired compliance in these patients. Heart failure, associated to hypertension, was not accompanied by a supplemental deterioration of arterial compliance. In fact, our study could not confirm the decrease of arterial compliance, in heart failure patients, as compared to controls. This study suggests the importance of hypertension, with its structural arterial wall changes, in the genesis of arterial compliance impairment.

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.

Antineutrophil cytoplasmic autoantibodies (ANCA)--markers in diagnosis and monitoring systemic vasculitides.

We present a new class of autoantibodies--ANCA (antineutrophil cytoplasmic autoantibodies) which recognize as target antigen different enzyme constituents of primary granules of neutrophil granulocytes. These autoantibodies are present in a large number of diseases, such as: systemic vasculitides, idiopathic crescentic glomerulonephritis, inflammatory bowel diseases and in some other conditions, including rheumatoid arthritis, SLE, Felty syndrome, acute and chronic infections. ANCA not only facilitate the diagnosis but also have a pathophysiological role for some of the idiopathic vasculitides. In our study, including 110 patients referred to the laboratory for ANCA testing by indirect immunofluorescence technique, only 25 patients were positive with a diffuse cytoplasmic (c ANCA) or perinuclear (p-ANCA) pattern on alcohol fixed slides. Some relevant cases are presented in order to emphasize that ANCA antibodies are a useful marker in the early diagnosis of systemic vasculitides, allowing effective therapeutic handling.

Clinical evaluation of antineutrophil cytoplasmic autoantibodies in ANCA-associated diseases.

Antineutrophil cytoplasmic autoantibodies have been performed in 110 patients referred to the laboratory as a presumptive systemic vasculitis, idiopathic crescentic glomerulonephritis, inflammatory bowel disease or SLE with vascular manifestation. 25 patients were found to be positive with c-, or p-ANCA patterns in indirect immunofluorescent test. We describe several cases in which histological confirmation is not available, an early consideration of a positive ANCA test may offer a reliable diagnosis and effective therapeutic handling, while the cases when the test was not considered, the occurence of relapse was inevitable.

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.

Homozygous or compound heterozygous qualitative antithrombin III deficiency.

A male patient of 24 years who had experienced thrombotic episodes since the age of 15 displayed an unusually low antithrombin III (AT III) activity measured as heparin cofactor (13% of the normal), while a similarly decreased value (16% of normal) was found in a 26 year old brother who had suffered from thrombotic events since the age of 12 years. AT III heparin cofactor activities were close to 50% of normal in the father, mother, another brother and a sister, none of whom had experienced thrombotic episodes. Since all available members of the family, including the patient, displayed near normal AT III antigen levels (73-85%) normal total progressive antithrombin activities (92-110%) as assessed by the thrombin agarose diffusion technique and normal total progressive anti-Xa activities, the propositus and his brother could be considered to be homozygotes or compound heterozygotes for a qualitative familial AT III deficiency probably caused by an abnormality of the heparin binding site. Molecular techniques would be required to elucidate the precise mutation giving rise to the deficiency.

Antithrombin III deficiency.

Data on clinical features and laboratory diagnosis of familial antithrombin deficiency, a rather heterogeneous group of disorders, are illustrated by observations on two Romanian kindreds afflicted by recurrent thrombotic episodes. In a first family, both plasma antithrombin III antigen and activity were reduced to 50% of normal, a condition characteristic for a heterozygous type I (quantitative) familial antithrombin III deficiency. In a second kindred, the two brothers who had experienced thrombotic events since they were teenagers, displayed exceedingly low AT III heparin cofactor activity (13% and 16% of the normal, respectively) while values around 50% of the normal were recorded in their parents who had not experienced thrombotic episodes. Since plasma antithrombin III antigen and total progressive antithrombin III activity were within normal limits in all the investigated members of this family it was considered that the two brothers were homozygotes or compound heterozygotes and the parents were heterozygotes for a qualitative-antithrombin III deficiency caused by an abnormality of the heparin binding site.

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.

His-Purkinje waveforms on externally recorded averaged unfiltered electrocardiograms.

Electrocardiographic signal recorded in right unipolar leads (2V1, 3V1, V1) was amplified (up to 500,000 times) averaged (256 or 512 cardiac cycles) and finally digitally filtered, in order to record His-Purkinje (HP) activity. A group of 41 patients with sinus rhythm and PR intervals ranging between 100 and 250 ms was repeatedly investigated. Distinct and highly reproducible waveforms located in the PR segment, attributable to HP activity, were recorded on the averaged unfiltered traces in 14 patients (34%). Waveforms, with an amplitude ranging between 4 and 80 microV, were positive in 13 patients and negative in one. In one patient, with atrial tachycardia with 2:1 atrioventricular block, two positive successive deflections suggested the possibility of recording the proximal and distal His activity. Externally recorded averaged unfiltered traces could be useful for the investigation of HP activity in a relatively large proportion of patients.

Observations on the diagnostic criteria of the "nontransmural" acute myocardial infarction.

In 15 patients with acute myocardial infarction (AMI) lacking Q waves ("nontransmural"), selected from 317 patients with AMI, successively observed, diagnostic criteria and evolution were analysed. Clinical and enzymatic diagnostic criteria of the "nontransmural" AMI indicated a significant myocardial necrosis. Anginal pain was particularly recurrent. Various and variable electrocardiographic signs (ST--T changes, arrhythmias, etc.) suggested a significant, extensive, myocardial damage. Complications (heart pump failure, arrhythmias, peripheral and cerebral ischemic attacks), frequently severe, occurred in the majority of the patients. "Nontransmural" AMI occurred mainly in patients older than 60, with systemic arterial involvement. Four of the patients died (two during the acute phase); in one of them, transmural AMI, suggested by a complicating pericarditis, was confirmed by necropsy. The so-called "nontransmural" AMI proved to be an actual or potentially severe condition. Its differentiation from the "transmural" AMI on the basis of electrocardiographic criteria is artificial and unjustified.