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Biomedical subjects

H Kuhn

Publications and source records attributed to H Kuhn.

At least 19 recordsLinked to original sources
PubMed1992

Left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy: increase in gradient after exercise.

To define alterations in the magnitude of the left ventricular outflow tract gradient during supine exercise, 10 patients with hypertrophic obstructive cardiomyopathy were studied under basal conditions and during exercise and recovery with simultaneous invasive hemodynamic measurements, particularly of the peak to peak systolic pressure gradient across the left ventricular outflow tract. Basal outflow pressure gradient ranged from 0 to 89 mm Hg (average 37.4 +/- 9.6). No increase was observed during 5 min of exercise (average 29.6 +/- 10 mm Hg, range 0 to 91; p = NS), even though arterial blood pressure, heart rate and cardiac index increased significantly in association with a decrease in peripheral vascular resistance. However, a rapid and highly significant increase in left ventricular outflow gradient occurred after exercise was completed (average 83.5 +/- 11.4 mm Hg, range 10 to 130; p less than 0.001), while arterial blood pressure, heart rate and cardiac index closely approached basal levels and total peripheral vascular resistance increased. In contrast to previous assumptions regarding the behavior of the outflow gradient in hypertrophic cardiomyopathy, obstruction to left ventricular outflow increases after rather than during supine exercise. Rapid changes in preload during recovery represent the most likely explanation for the postexercise development of outflow obstruction. New considerations regarding the mechanisms of sudden cardiac death and the therapeutic approach in patients with hypertrophic cardiomyopathy may result from this pathophysiologic observation.

Adult↗
PubMed1992

Specific inflammatory cytokines regulate the expression of human monocyte 15-lipoxygenase.

Arachidonate 15-lipoxygenase (arachidonate:oxygen 15-oxidoreductase, EC 1.13.11.33) is a lipid-peroxidating enzyme that is implicated in oxidizing low density lipoprotein to its atherogenic form. Monocyte/macrophage 15-lipoxygenase is present in human atherosclerotic lesions. To pursue a basis for induction of the enzyme, which is not present in blood monocytes, the ability of relevant cytokines to regulate its expression was investigated. Interleukin 4 (IL-4), among 16 factors tested, specifically induced 15-lipoxygenase mRNA and protein in cultured human monocytes. Interferon gamma and hydrocortisone inhibited this induction. High-performance liquid chromatography analysis of lipid extracts from IL-4-treated monocytes detected 15-lipoxygenase products esterified to the cellular membrane lipids, indicating enzymatic action on endogenous substrates. Stimulation of IL-4-treated monocytes with calcium ionophore or opsonized zymosan A enhanced the formation of 15-lipoxygenase products. These data identify IL-4 and interferon gamma as physiological regulators of lipoxygenase expression and suggest an important link between 15-lipoxygenase function and the immune/inflammatory response in atherosclerosis as well as other diseases.

Arachidonate 15-Lipoxygenase↗
PubMed1992

Effects of chronic aortic coarctation on atherosclerosis and arterial lipid accumulation in the Watanabe hereditary hyperlipidemic (WHHL) rabbit.

The effects of high blood pressure on atherosclerosis were examined in the Watanabe heritable hyperlipidemic (WHHL) rabbit. For this purpose, the subdiaphragmatic aorta of rabbits was partially ligated (coarctation) to increase blood pressure. Atherosclerosis was assessed 4 months later by morphometric analyses and quantitation of arterial lipids. Results were compared to control WHHL rabbits with matched plasma triglycerides and cholesterol levels. A marked increase in atherosclerotic lesions was observed in the thoracic aorta of the hypertensive rabbits without qualitative changes in its morphometric features. The cross sectional area of the atherosclerotic plaques of the ascending and descending aorta in the hypertensive rabbits was two- and six-times larger than in normotensive rabbits, respectively. Lesions represented 12.0% +/- 3.5% of the total medial cross sectional area of the descending aorta of normotensive rabbits, versus 45.0% +/- 5.7% in hypertensive rabbits. No lesions were observed downstream of the coarctation in hypertensive rabbits, nor in the normotensive rabbits. Accumulation of cholesterol and choline-containing phospholipids in the descending aorta of hypertensive rabbits was increased 3.2- and 1.5-fold, respectively, when compared to normotensive rabbits. Hypertension did not change the unesterified cholesterol/total cholesterol and sphingomyelin/lecithin + lysolecithin molar ratios. In conclusion, chronic coarctation enhances the atherosclerotic response in WHHL rabbits in the high blood pressure compartment, and reduces the variability of this response.

Animals↗
PubMed1992

Isoproterenol impairs the rat coronary vasculature: effects of angiotensin-converting enzyme inhibition.

The purpose of the present study was to evaluate whether in addition to its myocardial effects, chronic beta-adrenergic stimulation with isoproterenol could modify the coronary vasculature. For this purpose, rats were treated for 2 weeks with isoproterenol, and the hearts were isolated for determination of the minimal coronary vascular resistance under maximal vasodilation and then perfused-fixed for morphometry of the coronary arteries. In addition, because isoproterenol stimulates the renin-angiotensin system (RAS), the effects of angiotensin-converting enzyme (ACE) inhibition on the coronary vasculature were assessed. Isoproterenol increased heart weight by 65% and minimal coronary resistance by 55%. This effect was associated with medial thickening in intermediate (32%) and large coronary arterioles (26%). Cilazapril, a long-acting ACE inhibitor, completely prevented the medial thickening induced by isoproterenol and normalized the minimal coronary resistance. We conclude that impairment of the rat coronary vasculature induced by chronic beta-adrenergic stimulation might be in part mediated by activation of the RAS.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Protective effect of cilazapril on the cerebral circulation.

The goal of an antihypertensive treatment is to prevent "end-organ" damage. Cerebral vascular complications are among the most important because they are life threatening and can occur even at an early stage of the disease. Recently, it has been shown that cilazapril can decrease the mortality of stroke-prone rats, suggesting a decrease in the incidence of strokes, which occur spontaneously in these animals. The present article reviews the different functional and morphological changes that may explain the cerebral protective effects of cilazapril, such as the normalization of cerebral vascular reserve, decrease in the media, increase in the external diameter, and normalization of the mechanics and endothelial function of cerebral arterioles. In addition, the inhibition by cilazapril of injury-induced proliferation of smooth muscle cells and the infiltration of the endothelium by macrophages could prevent the development of atherosclerosis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Vascular protection with cilazapril in hypertension.

Anatomical changes of arteries and arterioles secondary to hypertension explain most of the late complications of this disease. Therefore, a series of experiments was performed to characterize the vascular protective effects of cilazapril in experimental hypertension. These experiments aimed to answer three types of questions: (a) In which vascular bed is cilazapril effective? (b) Are the vascular changes induced by cilazapril associated with functional effects? (c) Is the effect of cilazapril only preventive or can cilazapril also be effective when hypertension is already present? Our results show that cilazapril is acting on nearly every vascular bed. Its vascular morphological effects (decrease of vascular hypertrophy) are associated with functional changes such as improvements of coronary or cerebral vascular reserves. Cilazapril is active either as a preventive treatment or given when hypertension is already present.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

[Image quality parameters characterizing radiologic imaging systems].

The image quality of imaging systems can be characterized by a number of parameters, such as the easy to appreciate concepts of resolution or contrast or such precisely defined and measurable characteristics as the modulation transfer function or the noise spectrum. The meaning of these qualities and their interrelation are discussed. From these parameters, we can derive one of the most important characteristics for the description of the physical image quality = the signal-to-noise ratio.

Quality Assurance, Health Care↗
PubMed1991

Endothelial dysfunction and subendothelial monocyte macrophages in hypertension. Effect of angiotensin converting enzyme inhibition.

Hypertension is associated with an impairment of endothelium-dependent relaxation. The angiotensin converting enzyme inhibitors captopril and cilazapril can prevent this endothelial dysfunction. We recently observed that long-term treatment with cilazapril could also prevent subendothelial infiltration by mononuclear cells in spontaneously hypertensive rats. This prompted us to examine whether, in spontaneously hypertensive rats, endothelial dysfunction and subendothelial infiltration by mononuclear cells are associated. These cells were characterized as monocyte macrophages. Infiltration by monocyte macrophages was quantified by morphometry. Endothelial function was estimated by calculating serotonin ratio (maximal contraction to serotonin on isolated arterial rings with endothelium over maximal contraction on paired rings without endothelium). The regional distribution of endothelial dysfunction and subendothelial monocyte macrophages was similar. Both were maximal in the carotid artery, less in the aorta, and nonexistent in the renal artery. A 2-week treatment with cilazapril decreased both endothelial dysfunction (serotonin ratio decreased by 32%) and the number of subendothelial monocyte macrophages in the aorta, which decreased by 38%. We conclude that in spontaneously hypertensive rats, endothelial dysfunction and subendothelial monocyte macrophage infiltration are associated and that cilazapril can decrease both. The observation that angiotensin converting enzyme inhibitors affect subendothelial accumulation of monocyte macrophage may lead to a better understanding of the mechanism of action of this class of drugs.

Acetylcholine↗
PubMed1991

Cilazapril inhibits wall thickening of vein bypass graft in the rat.

Venous grafts implanted in the systemic circulation progressively undergo wall thickening, a phenomenon thought to be responsible for late saphenous graft disease after bypass surgery. Angiotensin converting enzyme (ACE) inhibitors recently have been shown to prevent myointimal thickening after arterial injury. Thus, the goal of the present study was to test the effects of ACE inhibition in a rat model of venous graft. For this purpose, a segment of jugular vein was interposed in the right carotid artery of normotensive rats that received either placebo or 10 mg/kg/day cilazapril, a long-acting ACE inhibitor. Three weeks later, the venous grafts and the implanted carotid arteries were fixed under perfusion and embedded for morphometric analysis. In the control group, the wall of the venous graft thickened dramatically compared with the nonimplanted contralateral jugular vein (up to 20 times increase in total cross-sectional area). On the arterial side, thickening of the wall and a neointima also were observed, most likely because of the surgical arterial injury. Cilazapril decreased by 33% (p less than 0.05) and 26% (p less than 0.01) the total cross-sectional area of the wall of the venous grafts and of the carotid arteries, respectively. Thus, these results suggest a role of the renin-angiotensin system in the early process of venous graft thickening. This study also suggests that ACE inhibitors could be a new therapeutic means to prevent late saphenous graft disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Vascular protection with cilazapril.

The hypertrophy of the media of coronary arteries associated with hypertension reduces cross-sectional area and limits vascular reserve. Cilazapril 10 mg/kg daily decreased cardiac hypertrophy, and decreased minimal coronary vascular resistance by 40% when administered to spontaneously hypertensive rats (SHR) at the onset of hypertension. After hypertension had developed, cilazapril restored arterial pressure to normal and increased the maximal coronary blood flow in isolated perfused hearts by 96%, which was probably a result of a marked decrease in medial hypertrophy of the coronary arteries. Similarly, cilazapril improved cerebral vascular reserve in the mesenteric and renal arteries of SHR. In the rat model of vascular injury produced by ballooning, cilazapril 10 mg/kg daily demonstrated a marked preventive effect on the myointimal proliferation that resulted in untreated controls, a phenomenon responsible for restenosis in humans after arterial angioplasty. Although this effect occurred with usual antihypertensive dosages in rats, it appeared to be independent of the decrease in arterial pressure since effective antihypertensive dosages of verapamil did not prevent neointima formation. In view of the clinical potential for preventing restenosis after coronary angioplasty, 2 multicentre trials of cilazapril are ongoing to test this hypothesis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Serotonin organelles of rabbit platelets contain synaptophysin.

Synaptophysin, an integral membrane protein of synaptic vesicles in nerve terminals and a class of small translucent vesicles in neuroendocrine cells, was detected in intact rabbit platelets by immunoblotting, immunofluorescence staining and immuno-electron microscopy. In a highly purified preparation of serotonin organelles isolated from rabbit platelets, synaptophysin was enriched approximately 10-15-fold over platelet homogenate. About 80% of total platelet synaptophysin was present in this purified fraction. The apparent molecular mass (approximately 38 kDa) and the extent of glycosylation of platelet-derived synaptophysin was more similar to the neuronal than to the neuroendocrine form of the protein. Immunofluorescence microscopy revealed that synaptophysin was compartmentalized in intact rabbit platelets and immuno-electron microscopy of subcellular fractions showed that it was localized exclusively to the membrane surface of serotonin organelles. No synaptophysin-like immunoreactivity was detected in platelets from other species such as human, guinea pig and rat. Another integral membrane protein of synaptic vesicles, p65, and a family of synaptic vesicle-associated phosphoproteins, the synapsins, were not detected in platelets of any species tested. These results provide evidence that serotonin organelles from rabbit platelets share a subset of protein components with synaptic vesicles from neurons. Synaptophysin in serotonin organelles from rabbit platelets, as suggested for small synaptic vesicles in neurons, might play a role in the formation of protein channels for the exocytotic release of serotonin.

Animals↗
PubMed1990

Oxygenation of biological membranes by the pure reticulocyte lipoxygenase.

We find that the reticulocyte lipoxygenase can oxygenate rat liver mitochondrial membranes, beef heart submitochondrial particles, rat liver endoplasmic membranes, and erythrocyte plasma membranes (inside-out and right side-out ghosts) without prior action of a phospholipase. After alkaline hydrolysis of the ester lipids, the main products were identified as 15S-hydro(pero)xy-5Z,8Z,11Z,13E-eicosatetr aenoic acid, 17S-hydro(pero)xy-4Z,7Z,10Z,13Z,15E, 19Z,-docosahexaenoic acid, 13S-hydro(pero)xy-9Z,11E-octadecadienoic acid, 9(S/R)-hydro(pero)xy-10E,12Z-octadecadienoic acid as well as the two all-E hydro(pero)xy octadecadienoic acid isomers. At low membrane concentrations (1 mg of protein/ml), the enzyme maintains a high stereospecificity for the S-configuration, but at higher concentrations (20 mg/ml), the products were virtually racemic. Addition of the antioxidant 2,6-ditert-butyl-p-cresol counteracted this tendency to lose stereospecificity. During these enzyme-catalyzed reactions, substantially more oxygen is consumed than can be accounted for as the hydro(pero)xy products. This discrepancy is due to secondary reactions which lead to the decomposition of the primary oxygenation products, the hydroperoxy lipids, and to oxidative modifications of membrane proteins. These data indicate that the reticulocyte lipoxygenase can oxygenate polyenoic fatty acids in various types of biological membrane and that the oxidative modifications are not restricted to the membrane lipids. The results are discussed in terms of the proposed role of the enzyme in the breakdown of mitochondria and other intracellular organelles during the maturation of red blood cells.

Animals↗
PubMed1990

The proliferative response to vascular injury is suppressed by angiotensin-converting enzyme inhibition.

Smooth muscle cell (SMC) proliferation and formation of extracellular matrix in the intima of muscular arteries are major processes that can lead to vascular stenosis in arteriosclerosis or after coronary angioplasty. These processes are also seen in the proliferative response to balloon catheter-induced vascular injury of the rat carotid artery, and result in marked neointima formation by 14 days after catheterization. We have shown recently that the angiotensin-converting enzyme (ACE) inhibitor cilazapril strongly suppressed this development of neointima. In this report, we show that the beneficial effects on neointima formation persist for at least 8 weeks after stopping treatment with cilazapril, and that continuous treatment may have additional inhibitory effects during the late phases of vascular remodeling after injury. To investigate further the possible mechanisms, we examined several vasoactive compounds in this model. Another ACE inhibitor of a different chemical class, captopril, reduced neointima formation as strongly as cilazapril (67 and 78%, respectively), but the calcium antagonist verapamil was not active as an inhibitor of neointima formation, despite similar lowering of blood pressure. Hydralazine and a new calcium antagonist, Ro 40-5967, partially suppressed neointima formation (36%, p less than 0.005 and 33%, p less than 0.05, respectively). In vitro, neither cilazapril nor its active metabolite, cilazaprilate, had any effect on SMC proliferation in response to serum or PDGF. To characterize further the role of angiotensin II (Ang II), we tested in cell culture the effects of Ang II and cilazaprilate on mRNA levels of several proteins potentially involved in regulating the SMC response.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1990

Effects of angiotensin converting enzyme inhibitors and of hydralazine on endothelial function in hypertensive rats.

The function of the endothelium is impaired in hypertension. In spontaneously hypertensive rats (SHR), acetylcholine-induced relaxation is decreased and serotonin-induced constriction is increased. The goal of our study was to evaluate the effect of a long-term treatment with cilazapril, a new angiotensin converting enzyme inhibitor, or hydralazine, a vasodilator, on the endothelium-dependent responses in aorta of SHR. Wistar-Kyoto rats were used as normotensive reference. Isolated aortic rings with or without endothelium were suspended in organ chambers. The rings with intact endothelium were contracted with norepinephrine. Acetylcholine-induced relaxation was markedly enhanced by cilazapril treatment. The tension achieved at maximal relaxation was 8 +/- 4% of norepinephrine contraction in the cilazapril-treated SHR versus 55 +/- 5% in the untreated SHR (p less than 0.001). Hydralazine had no significant effect. The effect of serotonin was also markedly modified by cilazapril. In untreated SHR, serotonin induced the release of a vasoconstrictor substance by the endothelium as assessed by the ratio of maximal tension induced by serotonin in rings with endothelium over maximal tension in rings without endothelium, which was greater than 1. This ratio was reversed in cilazapril-treated SHR but not in hydralazine-treated SHR. Captopril had effects similar to cilazapril. Finally, evaluation of carotid arteries showed that cilazapril also prevented morphological changes of the intima in SHR (i.e., infiltration by mononuclear cells). We conclude that angiotensin converting enzyme inhibitors prevent the functional and morphological alterations in endothelium that are found in hypertension and speculate that this action might participate in their antihypertensive effect.

Acetylcholine↗
PubMed1990

Investigation of blood-biomaterial interaction by means of a new quantitative dynamic measuring principle.

In this study a new dynamic measuring chamber for flat biomaterials allowing the estimation of cell adhesion on test surfaces by measuring the cell lost from surface contacting test blood under defined rheological conditions is introduced. This was achieved by constructing a test chamber permitting the contact of small amount of blood with a large geometrical test surface. The construction consists of a spiral-shaped flow channel of 0.3 cm width, 0.02 cm height and 78 cm length. The applicability of the new method was demonstrated by evaluation of platelet adhesion on siliconized glass, fibrinogen coated glass, cuprophane and polyacrylnitrile.

Biocompatible Materials↗
PubMed1989

Decreases of vascular hypertrophy in four different types of arteries in spontaneously hypertensive rats.

The goal of the present study was to describe the relative extent of vascular hypertrophy in four different types of arteries (coronary, renal, carotid, and mesenteric) of spontaneously hypertensive rats (SHR) and to evaluate the effects of long-term treatment with cilazapril, a new long-acting angiotensin-converting enzyme inhibitor on this vascular hypertrophy. For this purpose, a group of spontaneously hypertensive rats treated for four months with cilazapril (10 mg/kg orally) was compared with a group of spontaneously hypertensive rats treated with placebo. Another group of Wistar Kyoto (WKY) rats treated with placebo was used as a reference. At the end of the treatment period, the rats were perfused-fixed and morphometry of the carotid, renal, mesenteric and coronary arteries was performed. Vascular hypertrophy (increase of the thickness of the medial layer) was present in the four different types of arteries in a similar extent. Cilazapril normalized completely the arterial wall thickness:diameter ratio in the four different types of arteries. Further studies are required to determine whether this effect of cilazapril was due to the decrease of arterial blood pressure or to an effect of cilazapril on growth factors such as angiotensin II.

Angiotensin-Converting Enzyme Inhibitors↗