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Biomedical subjects

C Hirth

Publications and source records attributed to C Hirth.

At least 73 records · Page 4Linked to original sources
PubMed1984

Influence of arrhythmogenic and antiarrhythmic agents on alternating current-induced arrhythmias in guinea-pig heart preparations.

The method for inducing arrhythmias or asystole by the application of a 50 Hz alternating current (ac) has been applied to isolated guinea-pig left atria and papillary muscles in order to characterize arrhythmogenic and antiarrhythmic substances. Aconitine, BaCl2 (less than 2 mmol/l) and hypoxia decrease threshold of ac-arrhythmia and ac-asystole, in both tissues to a similar extent, whereas carbachol and BaCl2 (greater than 2 mmol/l) increase threshold. The calcium antagonists nifedipine and diltiazem lower threshold of ac-asystole but differ with respect to threshold of ac-arrhythmia, which is increased by 10(-6) mol/l diltiazem in left atria and papillary muscles by about 30% and remains nearly unaffected with nifedipine. The Na+-inhibitory substance flecainide reverses the decrease in threshold of ac-arrhythmia and ac-asystole brought about by aconitine. Threshold of ac-arrhythmia lowered by hypoxia is increased by diltiazem in a concentration-dependent manner, whereas decrease of threshold of ac-asystole is even augmented. Therefore, the method offers an opportunity of quantifying the action of arrhythmogenic agents at concentrations which are too low to induce arrhythmia, as well as to characterize the activity of antiarrhythmic drugs in the presence of arrhythmogenic substances.

Aconitine↗
PubMed1984

[Value of the measurement of the alveolo-arterial PO2 difference in moderate hyperoxia (FIO2 = 0.40) in chronic respiratory insufficiency].

Alveolo-arterial difference in PO2 (AaDO2) during moderate hyperoxia (FIO2 = 0.40) and shunt-effect (Qs/Qt) were measured in 219 patients with chronic lung disease of various aetiologies. In particular, the series included 79 chronic bronchitics, 35 cases of "primary" emphysema, 40 cases of sarcoidosis and 36 cases of diffuse interstitial pulmonary fibrosis ( DIPF ). Alveolar PO2 was calculated from the equation of alveolar air. Ventilatory parameters were measured under stable conditions using a Fleisch metabograph . Shunt-effect (in moderate hyperoxia) was calculated from the classical equation. AaDO2 in chronic bronchitis was on average 118.3 +/- 30.7 mmHg, significantly higher (p less than 0.005) than in the emphysema patients: 99.2 +/- 22.3 mmHg. The same difference between the two groups was found for shunt-effect (p less than 0.005). In sarcoidosis, AaDO2 and Qs/Qt were only slightly raised on average: 83.6 +/- 22.0 mmHg and 7.2 +/- 3.7% respectively. By contrast, in DIPF , AaDO2 was very high (124.9 +/- 35.7 mmHg) as was Qs/Qt (14.8 +/- 6.9%). The measurement (in moderate hyperoxia) of AaDO2 and Qs/Qt, which are fairly representative of ventilation-perfusion inequalities, may thus make a contribution to the physiopathological differentiation between chronic bronchitis and emphysema. The frank increase in AaDO2 and Qs/Qt in DIPF emphasises the importance of ventilation-perfusion inequalities in the development of hypoxaemia in such patients. For all the cases studied, there was a very satisfactory correlation between AaDO2 in moderate hyperoxia and PaO2 at rest in ordinary air (r = -0.64, p less than 0.001). Similarly, there was a satisfactory correlation between Qs/Qt in moderate hyperoxia and PaO2 at rest in ordinary air (r = -0.53, p less than 0.01).

Blood Pressure↗
PubMed1983

Effects of the calcium antagonist diltiazem on action potentials, slow response and force of contraction in different cardiac tissues.

Action potential duration in human and guinea-pig ventricular myocardium is reduced by diltiazem greater than or equal to 10 mumol/l. A reduction of action potential amplitude and maximum upstroke velocity is observed only at high concentrations of diltiazem (30 mumol/l). In depolarized myocardium (rabbit SA- and AV-node, guinea-pig papillary muscle depolarized by (K+)0 = 27 mmol/l) diltiazem greater than or equal to 0.3 mumol/l reduces amplitude and maximum upstroke velocity of the calcium-dependent action potentials. The decrease in maximum upstroke velocity of the slow response in depolarized guinea-pig papillary muscle is enhanced by elevation of the stimulation frequency, as are the negative inotropic effects (use-dependence). In contrast to nifedipine diltiazem also delays the recovery of the maximum upstroke velocity of the slow response after stimulus-induced inactivation. The reduction of maximum upstroke velocity induced by nifedipine is independent of the rate of activation whereas the blockade induced by diltiazem consists of a small blockade during rest and a profound use-dependent blockade.

Action Potentials↗
PubMed1983

Pulmonary hemodynamics in idiopathic pulmonary fibrosis and other interstitial pulmonary diseases.

65 patients with interstitial lung diseases were subdivided into two groups: idiopathic pulmonary fibrosis (IPF) and other interstitial pulmonary diseases (OIP) according to histopathological, immunological and follow-up findings. Arterial blood gases and pulmonary hemodynamics at rest and during steady-state exercise were compared in these two groups (IPF = 31 patients, OIP = 34 patients). The resting PaO2 was significantly lower in the IPF group (p less than 0.001) and regularly worsened during exercise in this group (from 69.6 +/- 11.6 to 56.0 +/- 9.4 mm Hg, p less than 0.001) whereas it did not vary significantly in the OIP group (from 79.2 +/- 13.1 to 75.3 +/- 14.1 mm Hg, NS). Pulmonary artery mean pressure (PPA) was higher in the IPF group (p less than 0.001) as were all indices of pulmonary vascular resistance (PVR). During exercise, PPA markedly increased in the IPF group (from 21.7 +/- 7.8 to 45.3 +/- 16.2 mm Hg) but modestly in the OIP group (from 15.5 +/- 3.7 to 28.3 +/- 9.8 mm Hg). The best relationships were found between PPA, PVR and PaO2, which suggests that pulmonary arterial hypertension in these diseases is not only due to anatomical factors but also to alveolar and arterial hypoxia. Arterial blood gases and pulmonary hemodynamics at rest and during exercise may be of interest for the discrimination of 'true' interstitial fibrosis (IPF) from other interstitial lung diseases (OIP).

Adolescent↗
PubMed1981

Prognostic value of pulmonary artery pressure in chronic obstructive pulmonary disease.

In 175 patients with chronic obstructive lung disease (157 chronic bronchitic and 18 emphysematous patients) exhibiting moderate to severe airway obstruction (mean FEV1/vital capacity = 40.2 +/- 11.1%), cumulative survival rates calculated by the actuarial method were compared in subgroups according to the initial level of mean pulmonary artery pressure, pulmonary volumes, and arterial blood gases. Patients were catheterised between 1968 and 1972 and were followed for at least five years. The results emphasise the high prognostic value of PAP since survival rates after four and seven years were significantly lower in the subgroup with PAP greater than 20 mmHg (2.7 kPa). Certain other parameters ("driving" pressure across the pulmonary circulation, FEV1 and Paco2) appear to be equally good at predicting survival as PAP in these obstructed patients. The effect of age should be taken into account in prognostic studies such as ours since survival rates were significantly lower in patients over 60 years of age. In 64 patients who underwent a second right heart catheterisation at least three years after the first (average delay: 5.5 +/- 2 years), the prognostic value of changes in PAP, arterial blood gases, and pulmonary volumes was studied but with the exception of Pao2 was unremarkable. Further studies are needed in this field.

Adult↗
PubMed1981

[The prognostic significance of pulmonary arterial hypertension in chronic obstructive airway disease (author's transl)].

In 175 cases of chronic obstructive airway disease (most often chronic bronchitis) with severe ventilatory deficit in the majority of cases, the prognostic value of mean pulmonary arterial pressure (PAP) and other respiratory function parameters (FEV1, blood gases) was studied by calculation of survival rates using the actuarial method. The patients were cathetherised between 1968 and 1972 and the maximum period of follow-up is 10 years. The results demonstrated the definite prognostic value of PAP : 4 and 7 year survival rates were markedly different according to whether initial PAP was above or below 20 mmHg. However other haemodynamic (motor pressure through the pulmonary circulation) and non-haemodynamic (FEV1, PaCO2) parameters also would appear to be as useful as PAP in predicting survival in such patients. The prognosis is particularly bad in patients with severe pulmonary arterial hypertension (PAP greater than 30 mmHg). In this type of study, it is essential to bear in mind the influence of age. Survival rates differed significantly according to whether the subjects were over 60 years in age initially.

Adult↗
PubMed1980

Aspartate-beta-semialdehyde dehydrogenase from Escherichia coli. Purification and general properties.

Aspartate-beta-semialdehyde dehydrogenase, from an Escherichia coli mutant derepressed for the biosynthesis of L-lysine, has been purified to homogeneity. Its isoelectric point is pH 4.3. This enzyme has a molecular weight of 77000 and is composed of two identical or highly similar subunits of molecular weight 38000 +/- 2000. Their N-terminal amino-acid sequence is Met-Lys-Asx-Val-Gly-. Three cysteine residues per subunit were detected: two are reactive in the native enzyme and one is partially protected by the substrate. Formation of an acyl-enzyme intermediate was also detected. Correlation of the 1H nucleár magnetic resonance spectrum of [4-2H]NADPH produced from [4-2H]NADP+ indicated that aspartate beta-semialdehyde dehydrogenase transfers the pro-S hydrogen from NADPH (class B dehydrogenase). A short comparison with the corresponding yeast enzyme is given.

Amino Acid Sequence↗
PubMed1980

Aspartate-beta-semialdehyde dehydrogenase from Escherichia coli. Affinity labeling with the substrate analogue L-2-amino-4-oxo-5-chloropentanoic acid: an example of half-site reactivity.

The substrate binding site of aspartate-beta-semialdehyde dehydrogenase from Escherichia coli was studied by affinity labeling with L-2-amino-4-oxo-5-chloropentanoic acid. The substrate analogue irreversibly inactivates the enzyme with pseudo-first-order kinetics and with a half-of-the-sites reactivity. The substrate aspartate beta-semialdehyde protects the enzyme against the inactivation. A single group is labeled at the active site and is concluded to be the side-chain of a histidine residue. The amino acid sequence around the active site residue was established from a peptic digest of the labeled enzyme: Phe-Val-Gly-Gly-Asp-(modified residue)-Thr-Val-Ser.

Affinity Labels↗
PubMed1980

Affinity labeling of the Escherichia coli aspartate-beta-semialdehyde dehydrogenase with an alkylating coenzyme analogue. Half-site reactivity and competition with the substrate alkylating analogue.

3-Chloroacetylpyridine-adenine dinucleotide phosphate (clac3PdADP+, a NADP+ alkylating analogue, irreversibly inactivates aspartate-beta-semialdehyde dehydrogenase with pseudo-first-order kinetics. NADP+ and NADPH, but not the substrate, protected the enzyme from inactivation. The pH dependence of the inactivation kinetics was determined. Incorporation of 1 mol cl[14C]-ac3PdADP+/dimer totally inactivates the enzyme. Successive alkylation by the coenzyme analogue and by the substrate analogue, L-2-amino-4-oxo-5-chloropentanoic acid, was studied. After inactivation with the coenzyme analogue, no incorporation of the substrate analogue was detected. However, when the enzyme was first inactivated with the substrate analogue, the protein could subsequently be alkylated with the coenzyme analogue. The binding of NADP+ and NADPH to aspartate-beta-semialdehyde dehydrogenase was determined by fluorescence.

Affinity Labels↗
PubMed1979

Course of pulmonary hemodynamics in patients with chronic obstructive pulmonary disease.

Eighty-five patients with chronic obstructive pulmonary disease, mainly chronic bronchitis (71 patients), who had arterial hypoxemia and moderate to severe obstruction of the airways underwent at least two right cardiac catheterizations in a clinical steady state, with a delay of three years or more between the first and the last catheterization. The average delay was 60 +/- 19 months (range, 36 to 119 months). Patients were regularly examined (quarterly clinical and functional checkups). The changes in pulmonary hemodynamic data were small. In the group of 53 patients with an initial mean pulmonary arterial pressure of 20 mm Hg or less, this pressure varied from 15.4 +/- 3.1 to 18.3 +/- 6.6 mm Hg (P less than 0.001); in the group of 32 patients with an initial mean pulmonary arterial pressure greater than 20 mm Hg, this pressure varied from 27.7 +/- 6.0 to 31.0 +/- 9.3 mm Hg (P less than 0.05). The mean pulmonary arterial pressure increased by 5 mm Hg or more in only 28 patients. In these patients with hemodynamic "worsening," the final arterial oxygen pressure (PaO2) was lower and the final arterial carbon dioxide tension was higher than in the remaining patients. A significant negative correlation (r = -0.39; P less than 0.001) was observed between changes in PaO2 and mean pulmonary arterial pressure. There was a generally good agreement between the course of pulmonary hemodynamics (mean pulmonary arterial pressure), on the one hand, and the clinical, radiologic (transverse diameter of the heart), and electrocardiographic evolution, on the other hand. In the 33 patients who died, a relatively long survival was observed after the first episode of right-sided heart failure or after ascertaining pulmonary hypertension.

Adult↗
PubMed1978

3-Chloroacetylpyridine adenine dinucleotide phosphate, an alkylating analogue of NADP+.

An alkylating analogue of NADP+ the 3-chloroacetylpyridine adenine dinucleotide phosphate was prepared from 3-diazoacetylpyridine adenine dinucleotide phosphate which was obtained by enzymatic transglucosidation of NADP+. The 3-diazoacetylpyridine adenine dinucleotide phosphate proved to be more unstable when compared to the corresponding NAD+ analogue. The alkylation of several dehydrogenases using this alkylating analogue is mentioned.

Alkylation↗
PubMed1977

Regional pulmonary function in sarcoidosis.

In 26 subjects with a confirmed histological diagnosis of thoracic sarcoidosis regional lung function was studied with Xenon 133. All subjects also underwent overall lung function studies including CO steady state (TCO SS) and single breath (TCO SB) diffusing capacity. Regional ventilation (Vr) was on the average increased in stages I (isolated hilar adenopathies) and II (pulmonary infiltration) and appeared normal in stage III (pulmonary fibrosis). Regional perfusion (Qr) was on the average normal in stages I and II and decreased in stage III. There were no appreciable differences between average values in stages I and II. Abnormalities of Vr and Qr were frequently found in individual cases. A distinction was made between the total number of abnormalities and deficiency abnormalities. The total number of abnormalties was high in all three stages. Deficiency abnormalities were relatively rare in stages I and II, and frequent in stage III. The correlation between radiological and regional functional abnormalities was low. TCO SB/VA was found significantly lower (P less than 0.005) in subjects with regional deficiency abnormalities (mostly perfusion abnormalities). These data probably indicate that a lowered diffusing capacity may be due to the loss of pulmonary capillaries and not only to ventilation - perfusion disparities.

Adolescent↗