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Biomedical subjects

C Bossaller

Publications and source records attributed to C Bossaller.

At least 37 records · Page 2Linked to original sources
PubMed1992

Effects of converting enzyme inhibition on endothelial bradykinin metabolism and endothelium-dependent vascular relaxation.

The effects of ACE-inhibitors on bradykinin metabolism and bradykinin-induced endothelium-dependent relaxation were studied in isolated coronary arteries and endothelial cells in culture. The results suggest that ACE-inhibitors affect coronary vascular tone by at least two endothelium-dependent and bradykinin-mediated mechanisms: First, ACE-inhibitors decrease endothelial bradykinin degredation which is accompanied by an augmented bradykinin mediated endothelium-dependent relaxation. Second, ACE-inhibitors evoke endothelium-dependent relaxations in coronary arteries stimulated with threshold concentrations of bradykinin, which cannot be attributed to an inhibition of bradykinin degradation. The effect appears to represent a new mechanism which may be based on an interaction of the bradykinin receptor and the angiotensin converting enzyme on the cellular level.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Myocardial catecholamine concentrations in dilated cardiomyopathy and heart failure of different origins.

Myocardial catecholamine concentrations were determined in endomyocardial biopsies from patients with heart failure to assess if tissue catecholamine levels relate to the severity of myocardial damage or the aetiology of the underlying disease. Methodological studies revealed a good reproducibility of catecholamine determinations in biopsies; the variance between paired biopsies was below 17% when myocardial catecholamines were related to non-collagen protein (NCP). Myocardial norepinephrine (in pg micrograms-1 NCP) levels were comparable in patients with dilated cardiomyopathy (DCM, 5.3 +/- 3.4, n = 22) and in patients with coronary or valvular heart disease (5.6 +/- 4.7, n = 14). In both groups, a significant reduction of myocardial norepinephrine was found (controls 12.0 +/- 3.4, P less than 0.0006). In a subgroup of patients with heart failure and a LVEF less than 30% (3.9 +/- 3.5, n = 17) myocardial norepinephrine content was lower than in patients with heart failure and LVEF of 31-55% (6.6 +/- 3.4, n = 19) (both P less than 0.05 against controls: 12.0 +/- 3.4, n = 16). A correlation between myocardial norepinephrine and LVEF was found in DCM (P less than 0.001, r = 0.70). The loss of myocardial norepinephrine is a characteristic feature of heart failure. It is independent of the origin of failure, but correlates with the impairment of LV function.

Cardiomyopathy, Dilated↗
PubMed1991

[Endothelial protection].

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Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Alterations in proteolytic enzymes of the proximal tubule in a rat model of cyclosporine nephrotoxicity.

The presence of autophagolysosomes in proximal tubule cells and the increased urine excretion of the lysosomal enzyme N-acetyl-glucosaminidase following administration of cyclosporine suggests involvement of the lysosomes in tubular toxicity of CsA. To evaluate the effect of CsA on lysosomal function, the activity of the lysosomal proteinases cathepsin B and L was measured in microdissected segments of the proximal tubule by means of a fluorometric microassay. Rats received oral doses of 30 mg/kg CsA for eight weeks. Controls received olive oil. CsA reduced renal blood flow, glomerular filtration rate, and kidney weight. Hence, a second control group was included where the left renal artery was clipped to reduce RBF and GFR. CsA administration was accompanied by a 130% increase in cathepsin activities in the S1 segments of the proximal convoluted tubule. The activity remained unchanged in the pars recta. Enzyme activities in convoluted proximal tubules and pars recta from the control groups were not increased irrespective of reduced RBF, decreased GFR, and decreased KW. Hence, cathepsin B and L stimulation was induced by CsA per se. Since lysosomes are involved in cellular protein catabolism, the increased cathepsin activities may reflect an increased rate of protein breakdown. The tubular atrophy induced by CsA may be related to increased intracellular protein degradation.

Animals↗
PubMed1990

Myocardial catecholamine content after heart transplantation.

Myocardial catecholamine levels have not yet been determined in the transplanted human heart. We measured norepinephrine, epinephrine, and dopamine in endomyocardial biopsies from 19 short-term (organ age, 6.6 +/- 6 months) and five long-term (organ age, 62 +/- 2 months) heart transplant patients. Results were compared with those from 10 normal control subjects. In 17 of 19 short-term heart transplant patients, myocardial catecholamines were undetectable, indicating values below 0.1 pg/micrograms noncollagen protein, which was the detection threshold of our assay. In the remaining two patients, myocardial catecholamines (pg/microgram noncollagen protein) were norepinephrine (1.4 and 3.2), epinephrine (0.8 and 1.9), and dopamine (0.9 and 2.3), respectively. In the five long-term heart transplant patients, myocardial catecholamines were not detected. Catecholamine concentrations in 10 healthy control subjects were norepinephrine (10.3 +/- 2.9), epinephrine (0.36 +/- 0.51), and dopamine (0.52 +/- 0.40). Low myocardial norepinephrine levels (less than 20% of control values) with unexplained high levels of epinephrine and dopamine were found in single transplant patients. In most heart transplant patients, however, myocardial catecholamines were undetectable up to five years after transplantation, indicating that the adrenergic response of these hearts probably depends on variations in plasma catecholamines or cardiac beta-receptor density.

Biopsy↗
PubMed1990

Metabolic alterations in end-stage and less severe heart failure--myocardial carnitine decrease.

Severe tissue carnitine deficiency impairs fatty acid oxidation. In explanted hearts from patients with end stage heart failure a 57% carnitine decrease was found in comparison with healthy donor hearts (p less than 0.05). The reduction of myocardial carnitine levels affected all areas of the explanted hearts to a comparable extent. Carnitine decreases in patients with dilated cardiomyopathy or coronary artery disease were similar. Endomyocardial biopsies from patients with less severe heart failure due to cardiomyopathy (n = 28) or other myocardial diseases (n = 8) showed a 42% decrease of total myocardial carnitine (in nmol/mg non-collagen protein) in comparison with biopsies from patients with normal cardiac function (controls) (heart failure: 5.7, confidence interval 4.2-7.0; controls 9.3, confidence interval 7.6-12.0, p less than 0.005). Free myocardial carnitine in heart failure was also different from controls (heart failure: 4.2, confidence interval 3.7-5.3; controls 10.3, confidence interval 7.5-12.2, p less than 0.001). The decrease of free and total myocardial carnitine was comparable in dilated cardiomyopathy and heart failure due to other diseases. Alterations in myocardial carnitine content represent therefore non-specific biochemical markers in heart failure with yet unknown consequences for myocardial function.

Adult↗
PubMed1990

[Directional atherectomy--current status].

To deal with the problem of restenosis after PTCA, several new methods and devices for treating atheromatous lesions have been developed. Among the promising techniques, is the opportunity to remove atheromatous material with the directional coronary atherectomy catheter designed by J.B. Simpson. The atherectomy catheter consists of a housing at the catheter tip with a concave cutting device which is rotated at a speed of 2000 r.p.m. The housing is positioned at the stenosis by means of a central guidewire; the material to be removed protrudes into the housing. With an inflatable balloon on the opposite side, the position of the housing is fixed in the coronary artery, the plaque is pressed further into the orifice and severed by the rotating blade. The material removed remains in the tip of the housing and can be used for morphologic examination as well as for functional studies with individual cell cultures. Experience published to date encompasses the results of 1032 treated stenoses. The majority of the treated lesions, 53%, were localized in the left anterior descending coronary artery; in 22% the lesion were located in the right coronary artery, in 17% in an aorto-coronary venous bypass graft. Due to the difficulty in positioning the relatively rigid atherectomy catheter, the method has only been employed in the circumflex artery in 6%. In a substantial number of patients, the stenoses had already been subjected to PTCA; in 57% of 963 patients treated with atherectomy, angioplasty had been performed previously, in 25% bypass grafting had been carried out. The primary success rate was 93%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Ciclosporin A inhibits endothelium-dependent vasodilatation and vascular prostacyclin production.

Aortic rings dissected from rats treated with ciclosporin A (30 mg/kg per day for five days) showed reduced relaxation induced by the endothelium-dependent vasodilator acetylcholine, but unchanged responses induced by glyceryl trinitrate. After eight weeks of ciclosporin A treatment, the relaxation induced by both acetylcholine and glyceryl trinitrate was inhibited. In addition, phenylephrine-induced contractions were slightly enhanced and vascular prostacyclin production was reduced by more than 80%. These effects may participate in the hypertensive and thrombo-embolic complications associated with the clinical use of ciclosporin A.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Coronary vasodilation with dihydropyridines--a pharmacokinetic study.

In 26 patients with coronary artery disease, the mean diameters of angiographically 'normal' epicardial coronary arteries were assessed with the aid of a computer-assisted contour detection system (CAAS) before and up to 15 min after onset of a 4-min intravenous-infusion of 2 mg nifedipine (13 patients, group I) or 1 mg nisoldipine (13 patients, group II). Maximal coronary dilation amounted to 20 +/- 9% (4th min) in group I and to 18 +/- 9% (15th min) in group II. In addition, in group II changes of the minimal diameters of 9 coronary obstructions were measured; the maximum increase averaged 28 +/- 15% (7th min). In order to compare the pharmacokinetic properties of these compounds the dilation of the 'normal' coronary segments was correlated with the respective drug plasma levels; maximal plasma concentrations averaged 62 +/- 21 ng ml-1 (7th min) in group I and 17 +/- 7 ng ml-1 (4th min) in group II respectively. A positive, linear correlation between coronary dilation and plasma levels was only found with nifedipine (P less than 0.05); with nisoldipine, however, coronary dilation developed in form of a hysteresis curve, when plotted against plasma levels, probably due to the high receptor affinity of this substance. The prolonged efficacy of nisoldipine could be favourable in oral long-term treatment of patients with coronary artery disease.

Adult↗
PubMed1989

Angiographic assessment of human coronary artery endothelial function by measurement of endothelium-dependent vasodilation.

In isolated atherosclerotic human coronary arteries endothelium-dependent vascular relaxation is abolished with acetylcholine whereas another EDRF-dependent vasodilator, substance P, still produces significant relaxation. To study further these in vitro findings, graded doses of acetylcholine and substance P, which produced no systemic effects, were infused into the left anterior descending artery of patients with angiographically moderate coronary artery disease. The effects of acetylcholine and substance P on LAD diameter were analysed by quantitative angiography. Generally, acetylcholine caused no relaxation but concentration-dependent contraction from 1.67 +/- 0.06 mm to 1.45 +/- 0.09 mm (P less than 0.01), whereas substance P dilated the arteries to 1.89 +/- 0.10 mm (P less than 0.01). In contrast, both drugs caused a marked increase in great cardiac vein oxygen saturation, indicating an increase of coronary flow. The results suggest that the failure of the atherosclerotic epicardial human coronary artery to vasodilate in response to acetylcholine represents a muscarinic endothelial defect. The preserved vasodilation with substance P in the presence of a refractoriness to acetylcholine suggests that atherosclerotic human coronary endothelial cells exposed to appropriate non-muscarinic stimuli are still capable to release EDRF and that atherosclerotic smooth muscle retains a responsive receptor mechanism for EDRF.

Acetylcholine↗
PubMed1989

Correlation between isosorbide dinitrate plasma levels and coronary vasodilation after chewing capsules.

In 10 patients with coronary artery disease coronary angiograms were performed in identical projections before and 5, 10 and 15 min after sublingual administration of two chewing capsules with 5 mg of isosorbide dinitrate (ISDN) each. Simultaneously, blood samples were taken for gas-chromatographical determination of nitrate plasma levels. The average ISDN plasma levels amounted to 138 +/- 73 ng/ml, 102 +/- 76 ng/ml and 62 +/- 34 ng/ml in the fifth, tenth and fifteenth min, resp. In the fifteenth min significant isosorbide mononitrate plasma levels (greater than 70 ng/ml) were found only in three patients. Mean diameters of angiographically normal coronary segments were measured with the automatic edge detection system CAAS; they increased by an average of 20 +/- 10%, 26 +/- 11%, and 27 +/- 13% (p less than 0.001) in the fifth, tenth and fifteenth min, resp. Due to hysteresis of the coronary dilation in relation to ISDN plasma levels no significant correlation was found between these parameters. The minimal diameters of seven of 10 coronary stenoses analyzed in seven patients reacted with a maximal increase of 23%-98%. Thus, ISDN chewing capsules may be preferable for rapid and prolonged relief of anginal attacks as well as for potent dilation of epicardial coronary arteries as desired during angiography.

Administration, Sublingual↗
PubMed1989

Effects of chronic cyclosporine. A treatment on the skin microcirculation of conscious rats.

We investigated capillary diameter and red blood cell velocity ("flying spot technique") in the skin of conscious rats treated for eight weeks with oral doses of Cyclosporine A (CyA, 30 mg/day) or placebo. For the intravital microscopic analysis (transmitted light), the depilated auricle was used as a model. The capillary diameter did not differ between CyA and controls (6.95 +/- 0.08 microns vs 6.95 +/- 0.09 microns, p greater than 0.05). However, the red blood cell velocity was significantly different (304 +/- 5 microns/s in CyA and 140 +/- 4 microns/s in controls, p less than 0.001). Additional experiments of our group phi, with isolated arteries revealed an impaired response to endothelium-dependent and -independent vasodilators in the presence of an enhanced response to alpha adrenergic vasoconstriction in the CyA-treated rats. Thus, the increase of capillary red blood cell velocity in chronically CyA-treated rats may reflect an enhanced vascular tone of the precapillary circulation.

Animals↗
PubMed1989

Drug plasma levels and coronary vasodilation after isosorbide dinitrate chewing capsules.

Five, ten and fifteen min after sublingual administration of 10mg isosorbide dinitrate (ISDN) in chewing capsules, in 10 patients with coronary artery disease, ISDN plasma levels were correlated with the dilation of epicardial coronary arteries as well as with changes in aortic blood pressure and heart rate. Due to the rapid and extensive drug absorption, maximal ISDN plasma levels averaged 138 +/- 73 ng ml-1 and were already obtained after 5 min; they declined to 102 +/- 76 and 62 +/- 34 ng ml-1 in the 10th and 15th min respectively. In 7 patients isosorbide mononitrate plasma levels were still negligibly low (less than 30 ng ml-1). Mean diameters of 'normal' coronary segments increased by an average of 20 +/- 10%, 26 +/- 11% and 27 +/- 13% (P less than 0.001) at 5, 10 and 15 min respectively compared to control. The maximal drop in systolic aortic pressure (147 +/- 19 to 115 +/- 15 mmHg; P less than 0.01) as well as the maximal increase in heart rate (66 +/- 4 to 80 +/- 11 beats min-1; P less than 0.01) were observed in the 15th min; diastolic aortic pressure and double product remained constant. Due to the long persistence of coronary dilation and haemodynamic changes, none of these drug effects correlated significantly with the ISDN plasma levels. In addition, the minimal diameters of 10 coronary stenoses were measured in 7 patients; with ISDN 7 stenoses showed dilation ranging from 23% to 98%.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Sublingual↗
PubMed1989

[Myocardial catecholamine content in heart failure--I: Regional distribution in explanted hearts. Comparison between dilated cardiomyopathy and coronary heart disease].

To quantify the myocardial catecholamine content in heart failure patients and to assess the regional distribution of catecholamines, we investigated norepinephrine and dopamine concentrations in explanted hearts from 34 patients in end-stage heart failure. 28 patients with cardiomyopathy were compared with six patients with coronary artery disease. In comparison with the right atria of a control group without heart failure, reduced myocardial norepinephrine contents (in pg/micrograms non-collagen protein (NCP] were found in all areas of the explanted hearts: controls: right atrium 17.6 +/- 6.6; cardiomyopathy: right atrium 7.1 +/- 7.9, right ventricle 4.4 +/- 2.7, septum 3.8 +/- 1.5, left ventricle 3.5 +/- 1.4. Coronary artery disease: right atrium 7.0 +/- 6.9, right ventricle 4.2 +/- 2.6, septum 3.6 +/- 1.4, left ventricle 3.4 +/- 1.4. Highest norepinephrine levels were measured in the right atrium. Right ventricle, septum, base and midventricular portion of the left ventricle had lower concentrations and were not different from each other. In contrast to reduced norepinephrine (NE) levels in all patients, dopamine (Dop) was inhomogenously elevated (only in a subgroup of 44%). Catecholamine contents in any two arbitrarily selected areas correlated significantly (NA: r = 0.53-0.77; Dop: r = 0.81-0.93, p less than 0.05 in all cases). The patients with heart failure due to dilated cardiomyopathy and to coronary artery disease did not differ in myocardial catecholamine levels or distribution. In end-stage heart failure a significant loss of myocardial norepinephrine independent from the underlying disease is found. It affects all areas of the hearts but does not equalize catecholamine content in ventricles and atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Endothelium-derived relaxing factor in human coronary artery.

Over the last few years it has become apparent that endothelial cells release many vasoactive substances, including prostacyclin, endothelium-derived relaxing factor (EDRF), endothelium-derived contracting factor(s), and endothelium-derived hyperpolarizing factor. The picture that is rapidly emerging from research in this field is that abnormalities in the production and release of these substances may occur and contribute to many pathophysiologic states. For example, an impaired release of EDRF, the endogenous prototype of the nitrovasodilator drugs and a powerful vasodilator, appears to be involved in abnormal vasomotor function in diseases, such as atherosclerosis and hypertension. This view is supported by recent pharmacological experiments with isolated human coronary arteries freshly obtained from patients at heart transplantation, and clinical studies using quantitative coronary angiography. However, even in atherosclerotic arteries, EDRF-mediated vasodilation may contribute considerably to the actual vascular tone, since the release of EDRF upon appropriate stimulation in patients with moderate coronary artery disease appears to result in a vasodilation which is similar to that induced by an intracoronary infusion of nitroglycerin.

Coronary Artery Disease↗
PubMed1988

Videomicroscopic demonstration of defective cholinergic arteriolar vasodilation in atherosclerotic rabbit.

In atherosclerotic rabbits (SCLER), decreases in vascular resistance in response to acetylcholine (ACH), an endothelium-dependent agent, are suppressed, whereas those to nitroprusside (NP), an endothelium-independent vasodilator, are preserved. To determine whether defective vasodilation in SCLER is related to altered reactivity of resistance vessels, we visualized arterioles of rabbit cremaster muscle by videomicroscopy. Arteriolar diameter was monitored during topical (superfusional) delivery of ACh and NO, interventions that did not affect systemic hemodynamics. Diameter changes in response to NP (0.01-100.0 microM) did not differ between SCLER and controls; maximal dilations amounted to 110 +/- 10% (mean +/- SE). In contrast, responses to ACH (0.001-100 microM) differed; maximal dilations averaged 54 +/- 4% in SCLER and 124 +/- 9% in controls (P less than 0.001). These differences persisted after blockade with phentolamine, propranolol, and indomethacin. Phenidone and hydroquinone blockers of endothelium-dependent vasodilation, inhibited arteriolar dilation to ACH without affecting that to NP. Microvascular responses to intra-arterial drug were similar to those elicited by topical drug. Thus, hypercholesterolemia and atherosclerosis in the rabbit appear to produce a microvascular defect characterized by an impaired endothelium-dependent dilation and a preserved endothelium-independent dilation. This defect could play a role in limiting vasodilator reserve in atherosclerosis.

Acetylcholine↗