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Biomedical subjects

A Lenaers

Publications and source records attributed to A Lenaers.

At least 19 recordsLinked to original sources

In vitro and ex vivo inhibition of the modification of low-density lipoprotein by indapamide.

The effect of an antihypertensive drug, indapamide, on copper- and endothelial cell-induced peroxidation of human low-density lipoprotein (LDL) was studied and compared with that of drugs previously shown to protect LDL against peroxidation: probucol and vitamin E and other thiazidic and nonthiazidic diuretics (clopamide, hydrochlorothiazide, and furosemide). Incubation with indapamide inhibited in a dose-dependent manner LDL peroxidation induced either by copper ions or by cultured endothelial cells. Both electrophoretic mobility and thiobarbituric acid-reactive substances (TBARS) content of LDL returned to almost normal values in the presence of 1 microM indapamide. This drug was at least 10 times more potent than probucol and vitamin E in inhibiting LDL peroxidation. No inhibitory effect has been observed with clopamide, hydrochlorothiazide, and furosemide in the same experimental conditions. Homozygote Watanabe rabbits were treated orally with indapamide (10 mg/kg/d for 3 days) to evaluate the potential protective effect of the compound on LDL peroxidation in vivo. Purified LDL from placebo and treated rabbits were submitted to peroxidation induced by copper ions, and indapamide was effectively able to protect LDL in these experimental conditions. This effect was especially obvious 6 and 8 h after the start of the incubation when LDL of the placebo-treated animals were modified. The mechanism of action of these drugs was examined in vitro using the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) test and in kinetic studies of arachidonic acid photoperoxidation. Indapamide as well as vitamin E and probucol were effective free radical scavengers, but the other diuretic molecules were not.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Decrease in enkephalinase A number in kidney membranes from hypercholesterolemic and hypertensive rats.

The variation of enkephalinase A number on the hypertensive and hypercholesterolemia rats kidney membranes is studied using the [3H]-acetorphan, a potent inhibitor of enkephalinase A to label the protease in rat kidney. The binding of [3H]-acetorphan to kidney membrane determined in vitro with both equilibrium and kinetic methods is saturable and reversible involving a single class of sites with a dissociation constant of 4-5.3 nM. The [3H]-acetorphan binding capacity is identical, Bmax approximately 51 pmoles per mg of proteins, for kidney membranes from Sprague Dawley and Wistar Kyoto rats. In contrast, the enkephalinase A number is decreased in the pathological states studied: 20% for hypertensive rats and 50% for hypercholesterolemic rats. Such pharmacological results provide a great deal of information about the modification appeared in the metabolism of peptidic substrates of enkephalinase A in hypercholesterolemia and hypertension.

Animals

Calcium antagonists prevent monocyte and endothelial cell-induced modification of low density lipoproteins.

Low density lipoprotein (LDL) incubated in the presence of the calcium antagonists verapamil, nifedipine and flunarizine were more resistant than control LDL to human monocyte- or endothelial cell-induced modification, as assessed by electrophoretic mobility in agarose gel, thiobarbituric acid reactive substance content, and degradation by J774 macrophages. The efficiency of the drugs was: flunarizine greater than nifedipine greater than verapamil. Moreover, a 24 h preculture with calcium antagonists significantly impaired the ability of cells to modify LDL in the absence of the drugs. All the studied drugs also inhibited copper-induced autooxidation of LDL. None of the studied calcium antagonists, at concentrations up to 10(-4) M, significantly reacted with free radicals as assessed by the 1,1-diphenyl-2-picrylhydrazyl test. It is suggested that such a protective effect of calcium antagonists against LDL peroxidation could play a role in the previously reported antiatherogenic effect of these drugs.

Animals

Phenothiazines inhibit copper and endothelial cell-induced peroxidation of low density lipoprotein. A comparative study with probucol, butylated hydroxytoluene and vitamin E.

The effect of two phenothiazines, chlorpromazine (CPZ) and trifluoperazine (TFP) on the copper and endothelial cell-induced peroxidation of low density lipoprotein (LDL) has been studied and compared to that of drugs previously shown to protect LDL against peroxidation: probucol (PBC) and butylated hydroxytoluene (BHT). Incubation with CPZ or TFP inhibited in a dose-dependent manner LDL peroxidation induced either by copper ions or by cultured endothelial cells. Both the electrophoretic mobility and the thiobarbituric reactive substance content of LDL returned to almost normal values in the presence of 50 microM CPZ or TFP. The two studied phenothiazines also strongly inhibited the hydrolysis of LDL phosphatidylcholine which accompanies copper or endothelial cell-induced peroxidation of the particle. CPZ and TFP were as effective as PBC and BHT in inhibiting the LDL peroxidation. Whereas copper or endothelial cell-oxidized LDL were recognized and rapidly catabolized by mouse peritoneal macrophages, CPZ- or TFP-, as well as PBC- or BHT-treated LDL were not. Moreover, it was found that, in contrast to vitamin E, neither CPZ nor PBC reacted with model peroxy radicals formed by gamma irradiation of aerated ethanol. The possible mechanisms underlying this protective effect of phenothiazines against LDL oxidative modification are discussed.

Animals

Mass concentration of creatine kinase MB isoenzyme and lactate dehydrogenase isoenzyme 1 in diagnosis of perioperative myocardial infarction after coronary bypass surgery.

Recent advances in methodology allow the mass concentration of creatine kinase MB isoenzyme (CK-MB), and of lactate dehydrogenase isoenzyme 1 (LD1) to be determined quickly and easily as routine, emergency tests. We evaluated these tests as diagnostic criteria of perioperative myocardial infarction (PMI) after coronary bypass surgery. These tests were compared with the usual measurements of CK-MB activity by immunoinhibition and LD1 by electrophoresis and with other biological markers of myocardial infarction such as total CK, total LD, and aspartate aminotransferase. Sixty-one patients who underwent coronary bypass grafting were followed pre- and postoperatively by enzyme determinations and electrocardiography; a subgroup was monitored by myocardial scintigraphy. CK-MB mass appeared to be the best marker of PMI during the first 48 h, although LD1 was the marker of choice from days 2 to 4.

Adult

[MRI of acute myocardial infarction with injection of Gd-DOTA (15 patients)].

We studied 15 patients 4 to 8 days after myocardial infarction by using ECG gated MR before and after administration of 0.2 mmol/kg Gd-DOTA. The diagnosis in each patient was confirmed by electrocardiographic criteria, elevated levels of fractionated creatine kinase (CK) isoenzyme, thallium scintigraphy, ventriculography and coronarography. T1-weighted, spin-echo images, were obtained before and immediately after injection of Gd-DOTA and were repeated 15 min later. The site of infarction was visualised in 10 patients as an area of high signal intensity after the injection of Gd-DOTA. Contrast between normal and infarcted myocardium was greatest 15 min after injection. Three patients were excluded because of failure to acquire adequate MR studies. In 2 other patients, the infarct were not detected. Before injection of Gd-DOTA, only 2 infarcts were detected. These results suggest that Gd-DOTA can improve MR visualisation and detection of acute myocardial infarction.

Adult

[Short- and long-term prognosis of myocardial infarct. Contributions and limitations of the clinical aspects and non-invasive technics].

Clinical variables and those obtained by non-invasive techniques were recorded in a series of 306 patients discharged from hospital after an acute myocardial infarction. We studied the prognostic value at 2 and 12 months of these variables (alive/dead). The results of simple clinical data were as discriminant as those from more elaborated techniques. When the prognostic value of the same data at 12 months was studied in those surviving for two months, most of the predictive variables lost their discriminant power. The study shows that the predictive value of many of the predischarge variables usually taken into account in the assessment of long term risk, does not extend beyond the first two months.

Echocardiography

Arterial reactivity, blood pressure, and plasma levels of atrial natriuretic peptides in normotensive and hypertensive rats: effects of acute and chronic administration of atriopeptin III.

We compared acute and chronic effects of atriopeptin III in normotensive and spontaneously hypertensive rats. Atriopeptin III relaxed isolated aortae and intrarenal microarteries but not coronary and mesenteric microarteries of normotensive rats. Effects on arterial smooth muscle were comparable in hypertensive and normotensive rats and were not affected by long-term treatment of the animals with the peptide. Acute administration of atriopeptin III (4-400 nmol/kg, intravenously) reduced systolic blood pressure in conscious spontaneously hypertensive and renal hypertensive rats but not in normotensive rats. In spontaneously hypertensive rats, nephrectomy increased the sensitivity to and the duration of the acute antihypertensive effect. Renal subcellular fractions rapidly inactivated atriopeptin III in vitro. This atriopeptinase activity was comparable for normotensive and spontaneously hypertensive rats and was not affected by long-term treatment of the rats with the peptide. Continuous administration of low doses of atriopeptin III (0.4 and 4.0 nmol/kg/h, intravenously (i.v.) during 7 days) caused a progressive reduction in systolic blood pressure in spontaneously hypertensive but not in normotensive rats. It did not affect plasma levels of aldosterone or renin and resulted in less than a doubling of the plasma levels of atrial natriuretic peptides. These findings confirm that atrial natriuretic peptides preferentially relax the renal microvasculature. They demonstrate that although atriopeptin III comparably relaxes arterial smooth muscle of normotensive and spontaneously hypertensive rats, both acute and chronic administration of the peptide preferentially lower blood pressure in hypertensive rats. Rather than contributing to the effects on blood pressure, the kidneys modulate the duration of action of atrial natriuretic peptides.

Animals

Postinfarction exercise capacity after lidoflazine treatment or physical training.

44 male postinfarction volunteers were divided into 4 groups and submitted to performance tests. Groups I and II consisted of 24 patients, 12 of whom followed a 2-month physical training program, while the other 12 served as controls. Groups III and IV (10 patients each) were included in a 10-month double-blind crossover study with lidoflazine 240 mg/day vs. placebo. The cardiovascular adaptation of the patients treated for 5 months with lidoflazine had two features in common with that observed after 2 months of physical training, namely an increase in maximal exercise capacity and, during submaximal exercise tests, a decrease in heart rate compensated for by an increase in stroke volume. In contrast to physical training, treatment with lidoflazine did not improve the peripheral oxygen consumption by the muscles.

Blood Pressure

Radioactive isotopes in the diagnosis of heart disease.

Since the first application of radionuclides in cardiology, fifty years ago, a lot of invasive and noninvasive techniques have been developed. Invasive methods, performed in the catheterization room, have increased our comprehension of physiopathological mechanisms in congestive heart failure and coronary insuffiency. Noninvasive methods have allowed assessment of regional left ventricular wall motion and ejection fraction, of myocardial perfusion at rest and after exercise and of intracardiac shunts, in ambulatory patients. Most of these methods have been developed in the last two decades, and particularly in the last few years. Technical improvements, like scintillation cameras, computers and shortlived tracers, have considerably improved their possibilities. New techniques, like positron imaging with three-dimensional reconstruction, current use of ultra-short life indicators and further refinements in radio-immunoassays, will undoubtly increase our fundamental and clinical knowledge of congenital and acquired heart diseases.

Blood Volume

Cardiac output monitoring during the acute phase of myocardial infarction: accuracy and precision of the thermodilution method.

A triple human catheter was used for the determination of cardiac output during the acute phase of moycardial infarction in 23 patients. The correlation coefficient between thermodilution and the Fick method was 0.91. Precision of the method assessed by multiple repeated determinations was 4.8 or 5.6%. Quadruplicate determinations allowed to detect variations of cardiac output in the range of 0.465 1/min. Variation between two successive determinations of more than 9.4% can probably be attributed to a technical error.

Acute Disease

Influence of short-term physical training on exercise tolerance after myocardial infarction.

14 patients with stabilized myocardial infarction were submitted to a functional evaluation before and after 3 sessions of interval training on the bicycle ergometer. With submaximal exercise, myocardial load decreases after short-term training, the heart rate and the blood pressure--heart rate product being significantly lower for the same oxygen consumption. Maximal working capacity, expressed in watts or oxygen consumption, increases significantly after short-term training, the benefit being one-third of that obtained after 6 weeks' training. These early changes in functional capacity are positively correlated with those obtained by a more prolonged rehabilitation program. Leg muscular blood flow during submaximal and maximal exercise tends to increase after short-term training, although this change is not systematic and thus not significant.

Adult

Segmental analysis of Ti-201 stress myocardial scintigraphy.

Thallium-201 scintigraphy of the exercised myocardium was performed in 70 male patients admitted for coronary arteriography and left-ventricular angiography. Left ventricular scintigrams were collected in left lateral, left anterior oblique (65 degrees, 45 degrees, and 25 degrees), and anterior views, and the images were divided into eight segments: apical, anteroseptal, anterior, antero-lateral, posterolateral, posterior, inferior, and posteroseptal. A correlative study between segmental hypoperfusion on scintigram and coronary-artery stenosis visualized by contrast artriorgraphy allowed selection of specific segments for each main coronary artery. Hypoactivity in the apical and posterior segments did not appear reliable. Using selected segments, we were able to identify LAD disease in 84%, LCx disease in 49%, and RCA disease in 79% of documented significant stenosis, with specificity of 95%, 89%, and 88%, respectively. Coronary-artery disease could be detected in 95% of patients having more than 50% coronary-artery stenosis, with 93% specificity. In most cases, patients with two-vessels disease and three-vessel disease could not be distinguished from each other. Multiple-vessel disease suggested by segmental analysis of myocardial scinitgrams after exercise was confirmed artriographically in 88% of the patients, but 52% with scintigrams suggesting signle-vessel disease had, in fact, multiple-vessel disease.

Adult

Surface maps and myocardial scanning at rest and during exercise: comparison with coronary angiography.

The observations of surface electromaps recorded at rest and during exercise in two examplative cases are reported: the first one deals with a normal man while the second refers to a patient suffering from an old inferior myocardial infarction with bouts of angina pectoris; these surface maps are compared with myocardial scanning also performed at rest and during exercise. Special attention is devoted to the possible relation of the above described, non-invasive, techniques to the anatomical description of coronary lesions as demonstrated by coronary angiography. A close relationship is found between the surface potential distribution pattern and the area of hypofixation observed on the scan as far as the presumed location of ischemic myocardial tissue is concerned.

Adult