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C Bossaller

Publications and source records attributed to C Bossaller.

47 records · Page 3Linked to original sources

Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta.

The dependence of vascular relaxation on an intact endothelium and the relationship between relaxation and cyclic GMP accumulation were determined in coronary arteries isolated from cardiac transplantation patients with or without coronary atherosclerosis. In nonatherosclerotic arteries, the endothelium-dependent agent acetylcholine produced concentration-related relaxations. In atherosclerotic arteries, endothelium-dependent relaxations were abolished with acetylcholine, partly suppressed with substance P and histamine, and completely preserved with the ionophore A23187. In these arteries, the endothelium-independent agent nitroglycerin remained fully active. Accumulation of cyclic GMP in atherosclerotic strips was suppressed with acetylcholine but unattenuated with A23187 and nitroglycerin. In aortas from rabbits with diet-induced atherosclerosis, there was likewise an impaired cholinergic relaxation and cyclic GMP accumulation in the presence of preserved responses to A23187 and nitroglycerin. The results demonstrate that impaired cholinergic responses in atherosclerotic arteries reflect a muscarinic defect and not an inability of endothelium to release endothelial factor or smooth muscle to respond to it.

Acetylcholine↗

Preservation of endothelium-dependent vascular relaxation in cholesterol-fed rabbit by treatment with the calcium blocker PN 200110.

We tested the effects of low doses of a dihydropyridine calcium antagonist, PN 200110, on endothelium-dependent vascular relaxation in rabbits fed a 1% cholesterol diet. The drug was given orally, 1 mg/day, and control rabbits received placebo. Plasma total cholesterol after 10 weeks, was similar in the placebo- and PN 200110-treated groups. The respective values averaged 2140 +/- 116 (n = 14; mean +/- SEM) and 2012 +/- 115 mg/dl (n = 13). In placebo-treated rabbits, sudanophilic aortic lesions covered 52 +/- 5% of the intimal surface, and the aortic cholesterol concentration was 72 +/- 6 mg/g protein. Corresponding values in aortas from PN 200110-treated rabbits were significantly lower [36 +/- 5% (P less than 0.03) and 52 +/- 3 mg/g protein (P less than 0.03)]. Maximal endothelium-dependent cholinergic relaxation of aortic strips in untreated (n = 14) and treated cholesterol-fed rabbits (n = 13) differed significantly (P less than 0.01) and averaged 31 +/- 4% and 61 +/- 7% of the value in normocholesterolemic controls (n = 13). We conclude that cholesterol feeding suppresses endothelium-dependent relaxation evoked by acetylcholine, and that PN 200110 reduces the severity of atherosclerosis and impairment of endothelium-dependent relaxation.

Animals↗

Quantitative determination of regional extravascular lung water and regional blood volume in congestive heart failure.

Regional extravascular lung water (rELW) and blood volume (rBV) in five controls and 14 patients with congestive heart failure (CHF) were measured by constant infusion of H215O and inhalation of 11CO using positron emission tomography (PET). The analysis of 18 regions per patient revealed a relatively homogeneous level of rELW in the controls (mean = 0.11 +/- 0.02 g/cc; range, 0.08-0.21), whereas this increase in patients with CHF (0.17 +/- 0.02 g/cc; range, 0.10-0.51). The rBV was 0.21 +/- 0.02 g/cc in the controls and 0.17 +/- 0.02 g/cc in patients with CHF. A good correlation was found between the severity of chronic heart failure (according to the grading of the New York Heart Association) and mean extravascular lung water (ELW) (r = 0.69), as well as between CHF and the ratio rELW/rBV (r = 0.87); however, the correlation to hemodynamic data was less satisfactory (cardiac index, r = 0.45; pulmonary capillary wedge pressure, r = 0.47; ejection fraction, r = 0.60). In supine controls, a progressive decrease in regional blood volume from the basal to the apical regions was observed, whereas the differences in ELW were only small. In patients with chronic heart failure, ELW in the basal parts was markedly increased, whereas in the apical regions, only minor deviations from the controls were observed. In the basal regions of these patients, the blood volume was reduced by about 30%. Instead of the normal basoapical gradient of blood volume, these patients showed a rather flat distribution. Radiographic findings of pulmonary edema generally appeared together with an ELW level of greater than 0.14 g/cc.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Positron emission tomography of regional extravascular lung water and regional pulmonary blood volume in chronic heart failure].

In 6 controls (group A), 4 patients with moderate congestive heart failure (NYHA II, II-III: group B) and 6 patients with severe heart failure (NYHA III, III-IV, IV: group C) regional lung water (rLW, constant infusion of H2 15O), regional pulmonary blood volume (rPBV, inhaled 11CO) and regional extravascular lung water (rELW = rLW -rPBV) were measured by positron emission tomography. The mean rELW was 0.12 +/- 0.02 g/cm3 in group A, 0.15 +/- 0.03 g/cm3 in group B and 0.19 +/- 0.06 g/cm3 in group C. In group C a significant increase in rELW was found from cranial to caudal regions (p less than 0.005), whereas in controls the distribution of rELW was almost homogeneous. The mean rPBV was 0.21 +/- 0.04 g/cm3 in group A, 0.22 +/- 0.04 g/cm3 in group B, and 0.17 +/- 0.03 g/cm3 in group C. There was a progressive increase in rPBV from cranial to caudal in group A. In group C the distribution of rPBV was almost uniform showing, compared to group A, significant lower values in the caudal regions (p less than 0.01). The study suggests that the amount and distribution of fluid in pulmonary congestion can be assessed noninvasively by positron emission tomography and that substantial differences in regional distribution exist between controls and patients with congestive heart failure.

Aged↗

Quantification of regional extravascular lung water in dogs with positron emission tomography, using constant infusion of 15O-labeled water.

Continuous infusion of 15O-labeled water allows a quantitative measurement of the total water pool in the chest region by positron emission tomography (PET). By subsequent inhalation of 11CO the intravascular space (blood pool) can be quantitated as well. After a suitable normalization of the intravascular activities the extravascular water can be determined by subtraction of the blood pool from the water pool. The regional extravascular lung water distribution can be visualized in tomographic slices. The method was validated in an animal experiment using five dogs. They were measured before and after induction of a lung edema by IV injection of oleic acid. The increase of extravascular lung water was monitored by the thermo-dye-dilution method (TDD). The correlation of extravascular lung water as measured by TDD with PET measurements is good (r = 0.94). The PET values agree also with gravimetric lung water determinations. An absolute quantitation of regional extravascular lung water is possible after absorption correction of the PET data via transmission measurements and calibration of the camera system. The uncertainty in the absolute quantification is +/- 20%. In the experiments described here the mean extravascular lung water was 0.13 g/cm3 before and 0.25 g/cm3 after induction of lung edema.

Animals↗

[Determination of regional extravascular lung water in heart failure].

The measurement of regional extravascular lung water (rELW) was evaluated by two double-indicator dilution methods both in normals and in patients with congestive heart failure. 1. Time-activity curves in various regions of the lungs were recorded with a positron camera (Cycl. Corp., model 4200) following a bolus application (H2O-15 as a diffusible and CO-15-Carboxyhemoglobin as an intravascular tracer). The mean transit times were computed and the extravascular lung water per unit of plasma volume (ELW/Vp was calculated. Investigations in 4 normals (ELW/Vp = 0.10-0.37, means = 0.22) and 7 patients (ELW/Vp = 0.08-0.57, means = 0.33) showed that due to constraints in the method a clinically useful index of rELW is not yielded with this particularly technique. 2. Total lung water (constant infusion of H2O-15), blood volume (single breath inhaled C-11-O), and extravascular lung water (ELW = total lung water - blood volume) were measured with a positron camera system under steady state conditions. This study showed a relatively homogenous distribution of rELW in 2 normals (0.10-0.14 g/cm3), whereas in 2 patients with congestive heart failure (NYHA III-IV) rELW was about twice as high as in normals and showed significant regional differences (0.17-0.34 g/cm3).

Adult↗

Altered potassium homeostasis in Crohn's disease.

The total body potassium (TBK), serum potassium, and the number of red blood cell ouabain-binding sites was studied in 94 patients with Crohn's disease. TBK was measured by counting the endogenous 40K in a whole body counter. TBK was 87% +/- 13% in 94 patients with Crohn's disease, while in control subjects, it was 97% +/- 12% (n = 24). This significant reduction in TBK was accompanied by normal serum potassium levels (4.4 +/- 0.5 mM). TBK was significantly correlated with the Crohn's disease activity index (r = 0.79, n = 113, P less than 0.01). The number of red cell ouabain binding sites measured by equilibrium binding of 3H-ouabain showed a significant increase in the number of Na-K pumps in Crohn's disease (396 +/- 65, n = 27) compared with the control group (290 +/- 45; n = 24). These results support the suggestion that changes in TBK may regulate the synthesis of Na-K pump molecules. The total body potassium depletion and the need for a preoperative nutritional support in Crohn's disease are discussed.

Adolescent↗

[Quantitative measurements of regional extra-vascular lung water in dogs using positron emission tomography].

A new method for quantifying regional variations in extravascular lung water (rELW) has been developed. The positron source 15O (T1/2 = 2.0 min.) was provided as H215O 'on line' by constant intravenous injection. Tomographic images (PET) of the water distribution were obtained during equilibrium. The distribution of blood volume was obtained by marking erythrocytes (carboxyhaemoglobin) using a bolus inhalation [C-11)-CO; T1/2 = 20.4 min). Absorption is calculated from transmission tomography. The rELW is defined as: total lung water minus intravascular space. The method was carried out in five intubated and anaesthetised dogs before and after induction of pulmonary oedema with oleic acid (0.06 ml./kg.). Mean ELW (PET) rose from 0.13 +/- 0.02 g./cm.3 to 0.24 +/- 0.04 g./cm.3. There was good correlation with a simultaneously performed thermo-dye method (7.1 +/- 1.3 ml./kg. KG to 13.3 +/- 1.9 ml./kg. KG; r = 0.94). Gravimetric estimations resulted in 13.7 +/- 2.6 ml./kg. KG. The development and distribution of the pulmonary oedema was non-homogeneous and varied regionally.

Animals↗

The effect of digitalis glycosides-specific antisera on the binding of the glycosides to (Na+ + K+)-ATPase.

The capability of digitalis glycoside-specific antisera to reverse the glycoside-induced inhibition of (Na+ + K+)-ATPase activity was examined. The antisera-induced reversal of the ATPase inhibition caused by digoxin was considerably slower (k-1 = 0.1177 . 10-3 .S-1) than the reversal caused by dihydrodigoxin and dihydrodigitoxin (k-1 = 4.462 . 10-3 . S-1 and K-1 = 3.609 .10-3 . S-1, respectively). In addition, the dissociation rate constants of the ouabain-induced dissociation of the various glycosides from the glycoside-ATPase complex were determined: The dissociation rate constants of the antisera-induced restoration of enzyme activity and that of the ouabain-induced dissociation of glycosides from the glycoside-enzyme complex were not significantly different.

Animals↗

Dehydro-digitoxosides of digitoxigenin and digoxigenin: binding to beef heart (Na+ + K+)-ATPase in relation to unchanged digitoxosides.

Dehydro-digitoxosides are metabolites of digitalis glycosides. In order to study their possible biological activity their affinity to (Na+ + K+)-activated ATPase was determined and compared with unchanged glycosides. Based on the dissociation constants of glycoside-enzyme-complexes, the affinity of the dehydro-digitoxosides ranged in the same order of magnitude as that of the native glycosides. Comparing mono-, bis-, and tris-digitoxosides of digitoxigenin (dt-1, dt-2, dt-3) and of digoxin (dg-1, dg-2, dg-3) with the corresponding dehydrodigitoxosides (3'-dehydro-dt-1, 9'-dehydro-dt-2, 15'-dehydro-dt3, 3'-dehydro-dg-1 and 9'-dehydro-dg-2, respectively) the dehydro-digitoxosides had lower affinities to the enzyme. The highest dissociation constants (KD) were found for 3'-dehydro-dt-1 and 3'-dehydro-dg-1. The half maximal inhibition of (Na+ + K+)-ATPase activity (I50) coresponded to affinity measurements in all but two cases: dehydro-dt-3 and dehydro-dt-2 showed very low I50 values.

Animals↗

Impaired cholinergic vasodilation in the cholesterol-fed rabbit in vivo.

Endothelium-dependent cholinergic relaxation in vitro is impaired in large arteries of animals and man with atherosclerosis. To assess the physiological importance of this impairment, we compared vasodilator effects of acetylcholine and nitroprusside, an endothelium-independent agent, in control rabbits (n = 12) and rabbits fed a 1% cholesterol diet for 10 weeks (n = 8). The hindlimb of the rabbits was perfused via an extracorporal loop at a constant flow, and perfusion pressure was used as an index of total vascular resistance. The hindlimb vascular resistance was monitored during intraarterial bolus injections with graded concentrations of acetylcholine (0.01-1.000 ng) and nitroprusside (0.1-1.000 ng) which produced no change in systemic hemodynamics. Between 0.1 and 1.000 ng nitroprusside, resistance changes in control and cholesterol-fed rabbits were virtually identical. In contrast, the resistance change induced by acetylcholine was significantly suppressed in cholesterol-fed rabbits over a wide range of concentrations (1.0-1.000 ng; p less than 0.05). The results indicate that in a model of atherosclerosis there is a reduced vasodilatory responsiveness to the endothelium-dependent acetylcholine, whereas the effect of the endothelium-independent nitroprusside is fully preserved.

Acetylcholine↗