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Biomedical subjects

C Holubarsch

Publications and source records attributed to C Holubarsch.

At least 91 records · Page 5Linked to original sources
PubMed1986

Myothermal economy of rat myocardium, chronic adaptation versus acute inotropism.

By means of rapid planar Hill type antimony-bismuth thermophiles the initial heat liberated by papillary muscles was measured synchronously with developed tension for control (C), pressure-overload (GOP), and hypothyrotic (PTU) rat myocardium (chronic experiments) and after application of 10(-6) M isoproterenol or 200 10(-6) M UDCG-115. Economy of force production was analyzed by the ratio of initial heat versus developed tension-time integral. This ratio was found to be reduced by 34% in GOP and by 43% in PTU myocardium (P less than 0.01, respectively) indicating increased economy of force production. In contrast, isoproterenol increased initial heat versus tension-time integral by 70% (P less than 0.01) indicating reduced economy of force production. No change in this ratio was found for UDCG-115. The presented data indicates that long and short term modulation of myocardial energetic costs of force generation is possible. The basic mechanisms for these myocardial alterations are discussed.

Animals↗
PubMed1986

Acute effects of nitrates on left ventricular performance and energetics.

Left ventricular myocardial performance and efficiency were analyzed on the basis of two new energetic parameters in patients with coronary heart disease. The myocardial energy consumed during one cardiac cycle is related on the one hand to the work performed (E1) and on the other to the stress-time integral (E2). E1 was obtained by analysis of the pressure-volume integral divided by the left ventricular muscle mass. E2 was obtained as follows: The stress-time integral was analyzed from pressure-volume data and wall thickness using an ellipsoidal calculation model. In order to transfer the stress-time integral into energy units, the value is multiplied by a constant factor which was obtained experimentally in myothermal studies. In patients with coronary heart disease, a single dose of nitroglycerin (1.6 mg s.l.) reduced the total energy sigma (E1 + E2) from 6.1 mcal/g to 4.7 mcal/g (n = 10; P less than 0.01). The efficiency of myocardial contraction (E1/sigma (E1 + E2] was not changed significantly. These data explain quantitatively the beneficial effect of preload and afterload reduction due to nitroglycerin.

Energy Metabolism↗
PubMed1985

The economy of isometric force development, myosin isoenzyme pattern and myofibrillar ATPase activity in normal and hypothyroid rat myocardium.

Hypothyroidism was induced in Wistar-Kyoto rats by adding propylthiouracil to the drinking water (0.8 mg/ml). Initial heat, total activity-related heat, and resting heat rate were measured in left ventricular papillary muscle preparations of propylthiouracil-treated and control rats contracting isometrically at 12 beats/min (21 degrees C), using Hill type, planar vacuum-deposited bismuth and antimony thermopiles. In the propylthiouracil preparations, relative to control, time-to-peak tension increased from 288 +/- 27 (mean +/- SD) to 411 +/- 25 msec (P less than 0.001), dp/dtmax decreased from 38.3 +/- 9.5 to 20.4 +/- 3.5 g X mm-2/sec (P less than 0.001), and peak developed tension decreased from 6.11 +/- 1.75 to 4.64 +/- 0.89 g X mm-2 (P less than 0.05). In the propylthiouracil preparations, initial heat was significantly (P less than 0.001) reduced by 27 or 43% when normalized to peak twitch tension or tension-time integral, respectively. In experiments where the papillary muscles were tetanized, the slope of the linear function of total activity-related heat versus tension-time integral was decreased by 43% (P less than 0.001) in the propylthiouracil preparations, indicating an improved economy of isometric tension maintenance. The predominant myosin isoenzyme of the left ventricular wall, as well as the papillary muscle myocardium, was the V3 variety in the propylthiouracil animals, in contrast to V1 in the controls. Myofibrillar actomyosin calcium-magnesium-stimulated adenosine triphosphatase activity was significantly (P less than 0.02) decreased from 55 +/- 18 (control) to 31 +/- 8 nmol inorganic phosphate ion/mg X min (propylthiouracil).(ABSTRACT TRUNCATED AT 250 WORDS)

Actomyosin↗
PubMed1985

[Regression of heart hypertrophy. Criteria of regression from the viewpoint of the clinician].

Regression of ventricular hypertrophy has been studied in cases of valvular disease after valve replacement, as well as in hypertension under drug treatment. All studies have focussed on the left ventricle. The right heart chamber has not been quantitatively assessed. Regression has been found in both conditions in the range of 15-40% of initial left ventricular muscle mass. In hypertrophic cardiomyopathy consistent results have not been obtained. The ECG, correlating with muscle mass only loosely, is but a semiquantitative, albeit reliable indicator of regression. Vectorcardiography seems to be useful and deserves further study and application. Echocardiography has been validated for both TM- and 3D-mode and allows quantitative estimation of LV-mass during regression. Further improvement can be achieved through the subcostal approach. Left ventriculography remains standard of comparison, but can be considered valid only if angulated biplane technique is used. Repeated application of this technique is limited, unless digital subtraction angiography is used. This technique, however, has not been applied for serial studies of LV-mass during the process of regression. Computed tomography and nuclear magnetic resonance have been used for estimation of muscle mass. The capability of NMR seems particularly high. First results are presented and show excellent quantitation of LV-mass.

Cardiomegaly↗
PubMed1985

[Induced platelet aggregation in patients with coronary heart disease as well as trained and untrained control persons].

Induced in vitro platelet aggregation (adrenaline and collagen) and serum lipid levels were investigated in 21 postinfarction patients, in 11 of these patients subsequent to therapy with 46 +/- 14 mg nifedipine per os daily for one week and in 21 untrained, 16 endurance-trained, and 17 non-endurance-trained healthy male control subjects. Plasma catecholamine levels at rest (patients) and oxygen uptake capacity (control subjects) were determined in subgroups. Mean platelet aggregation was increased in patients (p less than 0.05) and was decreased both in endurance-trained subjects (p less than 0.05) and in the group of 11 patients subsequent to therapy with nifedipine (p less than 0.01), but platelet aggregation was slightly higher in non-endurance-trained individuals. Adrenaline-induced platelet aggregation correlated positively with collagen-induced aggregation (r = 0.72), with LDL-cholesterol fraction (r = 0.51) and negatively with oxygen uptake capacity (r = -0.49). Patients with increased LDL-cholesterol levels also showed increased plasma catecholamine levels (r = 0.49 and r = 0.43). Low aerobic capacity (oxygen uptake capacity), high LDL-cholesterol levels and plasma catecholamine concentrations indicate an increased induced platelet sensitivity in vitro.

Adult↗
PubMed1984

A myothermal analysis of the myosin crossbridge cycling rate during isometric tetanus in normal and hypothyroid rat hearts.

Hypertrophied rabbit heart papillary muscles (thyrotoxicosis), with a high V1/V3 myosin isoenzyme ratio and contractile protein ATPase activity, have a high velocity of unloaded shortening and a decrease in the myothermal economy of isometric twitch force development and dissipation; in hypertrophied hearts (pressure overload) with a low V1/V3 isoenzyme ratio and ATPase activity, the converse was found to be true (Am J Cardiol 1979; 44:947-953; Fed Proc 1982; 41:192-198). In the present study the confounding problem of internal shortening, which takes place during force development and dissipation in the isometric twitch, is minimized by carrying out measurements of the rate of heat liberation during the plateau phase of tetanic force maintenance. The studies are further extended to another species (rat) where the V1/V3 myosin isoenzyme ratio is altered by treating the animal with propyl thiouracil added to the drinking water (PTU); here the contractile protein alteration occurs with myocardial atrophy rather than hypertrophy. High resolution, rapid temperature measurements are made in tetanically stimulated isometrically contracting rat heart papillary muscles from normal (high V1/V3 ratio) and PTU treated (low V1/V3 ratio) rats to assess the relationship between contractile protein performance (crossbridge cycling rate) in the intact muscle and that under controlled conditions in isolated myofibrils. In papillary muscles from the normal heart the crossbridge cycling rate (+/- SEM) during force maintenance was 6.53 (+/- 1.73) cycles/second compared with 3.13 (+/- 0.24) and 0.53 (+/- 0.17) cycles s-1 in the myofibril at high and low ionic strength, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1983

Force generation in experimental tetanus, KCl contracture, and oxygen and glucose deficiency contracture in mammalian myocardium.

We studied the amount and time-course of tension recovery after quick releases (0.25 mm) during experimental tetanus, potassium chloride contracture (KCl), hypoxic contracture (H) as well as joint glucose and oxygen deficiency contracture (HG) in left ventricular papillary muscles of rat and right ventricular papillary muscles of cat myocardium. Both in experimental tetanus and KCl contracture, the tension recovery was finished within 200 ms after the release, and was 77% and 60% of initial tension fall, respectively. The Q10 value for the time constant of half of recovery tension was 2.5, and the time constants differed by the same factor between rat and cat myocardium. In H or HG contracture, we never could find any significant tension recovery process during the first 200 ms after a release, neither in late nor in very early stages of contracture tension generation. However, when longer observation periods (90 s) after a release were monitored, a slow tension recovery was observed which was at least 18% of initial tension fall. This data indicates fast, calcium-mediated cross-bridge cycling in experimental tetanus and KCl contracture. In contrast, the very slow tension recovery in H and HG contracture, which is consistent with recent myothermal data, can be interpreted as rigorlike cross-bridges with a very slow cycling rate, a long time of attachment in force-generating position and low energy turnover.

Animals↗
PubMed1982

Heat production during hypoxic contracture of rat myocardium.

Contracture due to hypoxia, to both oxygen and glucose deficiency, and to potassium chloride was induced in rat left ventricular papillary muscle preparations. Under contracture conditions, the sum of resting heat plus contracture heat was measured using Hill-type, planar vacuum-deposited thermopiles. On the basis of the measured total and initial heat output and the corresponding tension-time integral during single twitches under control conditions (Lmax, 21 degrees C, stimulus frequency 12/min), the expected heat output during contracture was calculated, assuming that the contracture tension is maintained by the same calcium-induced cross-bridge cycling as occurs in the single twitch response. With potassium chloride, the contracture tension was 1.33 +/- 0.27 g/mm2, a value which is similar to those found in hypoxic contracture and in contracture due to both oxygen and glucose deficiency. There was no significant difference between measured and calculated values for resting heat plus contracture heat (8.40 +/- 2.84 mW/g measured, 8.55 +/- 2.50 mW/g calculated); there was a linear correlation (r = 0.99) between predicted and measured values (P less than 0.05). The measured value for resting plus contracture heat in hypoxic contracture was 1.88 +/- 0.37 mW/g, whereas a value of 4.80 +/- 1.09 mW/g (P less than 0.005) was calculated on the basis of the twitch heat per tension-time integral and contracture tension (1.09 +/- 0.31 g/mm2). Contracture tension was 1.80 +/- 0.78 g/mm2 in contracture due to oxygen and glucose deficiency, whereas the value for resting plus contracture eat was 1.61 +/- 0.56 mW/g. The calculated resting plus contracture heat value for this preparation was significantly higher (7.45 +/- 3.75 mW/g; P less than 0.05). There was no significant regression between predicted and measured resting heat plus contracture heat in the hypoxic contracture preparations (slope not different from zero). In contracture due to oxygen and glucose deficiency, the linear regression had a slope of 6.06 (P less than 0.05). The results suggest that the potassium chloride contracture relies on cross-bridge cycling as in a twitch contraction, whereas hypoxic contracture and that due to oxygen and glucose deficiency may be explained by cross-bridge formations with no, or very low, heat production, i.e., contracture tensions due to hypoxia and to oxygen and glucose deficiency are maintained by rigor-like cross-bridge formation or by slowly cycling cross-bridges with a long time of cross-bridge attachment.

Animals↗
PubMed1979

Gastritis, intestinal metaplasia and dysplasia versus benign ulcer in stomach and duodenum and gastric carcinoma -- a histotopographical study.

In histological examination of gastrectomy specimens from patients with duodenal ulcer, gastric ulcer, and early and advanced cancer, both chronic atrophic gastritis and intestinal metaplasia were identified in 54% of the cases with duodenal ulcer. At 90 to 100%, respectively, these mucosal changes were approximately twice as frequent with gastric ulcer and early and advanced gastric cancer. Mild dysplasia occurred in 54% of the cases with duodenal ulcer; occurred somewhat more frequently with gastric ulcer, in 75% of the cases; and in almost all cases with early and advanced gastric cancer, at 90% and 100%, respectively. Whereas 27% of the cases with duodenal ulcer, 62% with gastric ulcer, and 90% and 95% of the respective cases with early and advanced gastric cancer showed moderate dysplasia, only severe dysplasia in early gastric cancer (40%) and advanced gastric (81%) was clearly more frequent in comparison to duodenal ulcer (9%) and gastric ulcer (12%). In the cases with duodenal ulcer chronic atrophic gastritis and intestinal metaplasia were limited mostly to the antrum; with gastric ulcer and cancerous stomach disorders, they also occurred in other stomach sections. Mild and moderate dysplasia conformed to the same distribution pattern. Severe dysplasia, which was only detected in two ulcer cases, was not only substantially more frequent in cases with early and advanced gastric cancer, but also showed a clear topographic relationship to cancer localization in the stomach.

Aged↗
PubMed1977

[Histo-topography of gastric mucosa changes in benign and malignant stomach diseases].

The incidence and distribution of chronic gastritis, chronicatrophic gastritis and epithelial dysplasia I-III have been investigated in 50 resected stomachs of patients suffering from duodenal ulcer, gastric ulcer, early or advanced gastric cancer. Only in gastric cancer epithelial dysplasia III has been frequently observed, particularly in the neighbourhood of gastric cancer. Distribution of chronic-atrophic gastritis was similar to the distribution of dysplasia I and II. These mucosal lesions were detectable with the same frequency in patients with or without gastric cancer.

Chronic Disease↗
PubMedDate not supplied

Influence of endothelin 1 on human atrial myocardium--myocardial function and subcellular pathways.

The influence of endothelin 1 on isometrically contracting human atrial muscle strip preparations was investigated under physiological conditions (37 degrees C, 1 Hz, Ca2+ 2.5 mM). Endothelin dose-dependently increased isometric tension from 3 x 10(-10) M to 1 x 10(-7) M. At 1 x 10(-7) M the inotropic effect of endothelin was maximum with isometric tension being increased by 32 +/- 6% (n = 11, p < 0.05). At 1 x 10(-7) M endothelin the positive inotropic effect was preceded by a transient negative inotropic effect with a decline in tension by -5 +/- 1% (n = 11, p < 0.05). Endothelin prolonged time from peak tension to 50% relaxation (RT50) by 29 +/- 5%. With BQ123 a competitive antagonist of the ETA receptor positive inotropic effect and the prolongation of relaxation was significantly reduced and initial negative a inotropic effect was abolished, indicating a ETA receptor mediated effect. Preincubation with phorbolmyristateacetate (10(-5) M) to downregulate proteinkinase C (PKC) eliminated the positive inotropic effect of endothelin. Similarly, N-5,5-dimethylamiloride (10(-5) M) which inhibits Na+/H(+)-exchanger activity, abolished the positive inotropic effect of ET. However, with either PMA or DMA the initial transient negative inotropic effect was still present (-13 +/- 7%, n = 9, p < 0.05 and -3 +/- 1%, n = 6, p < 0.05). Furthermore, both substances did not abolish the prolongation of twitch time parameters observed under endothelin. After preincubation with PMA, endothelin prolonged RT50 by 18 +/- 6% and with DMA by 11 +/- 2%. Using the photoprotein aequorin as an indicator for intracellular calcium concentrations showed that the positive inotropic effect was mainly mediated by an increase of systolic intracellular calcium concentrations. Thus, the present data indicate that the positive inotropic effect of endothelin in human atrial myocardium results from activation of PKC with a subsequent activation of the Na+/H(+)-exchanger. However, the initial negative inotropic effects as well as the prolongation of relaxation seem to result from a different intracellular mechanism of endothelin.

Aequorin↗
PubMedDate not supplied

[Evaluation of elasticity by means of length-tension relationships in a model of isolated ventricular myocardium from rat and cat papillary muscle under conditions of contracture (author's transl)].

Increase of Ca2+ concentration to 7.5 mM in the presence of 10 mM or 20 mM caffeine shifted length-tension relationships of 5 rat trabecular muscles and 5 cat papillary muscles to higher tensions. At 1max diastolic tension was enhanced from (formula: see text), for all measured points of stress-strain relationships after the increase of diastolic tension by caffeine and Ca2+ as well as under control conditions. The function E = f (sigma) = b (sigma - c) was computed by linear regression analysis (0.99 greater than r2 greater than 0.96). The average value of constant b was 13.89 +/- 2.01 in control curves of rat trabecular muscles and 13.42 +/- 1.98 in curves with 10 mM caffeine and 7.5 mM Ca2+. Likewise, in cat papillary muscles 20 mM caffeine and 7.5 mM Ca2+ did not alter the stiffness constant b in a statistically significant manner (control: 16.63 +/- 3.03, caffeine: 16.43 +/- 3.02). The results demonstrate that the stiffness constant b cannot indicate acute variations of the length-tension relationships due to caffeine and Ca2+ and may result in overestimating of myocardial distensibility. However, if the tangent modulus (E) is related to strain (epsilon), the alterations of diastolic elasticity are detectable. Mathematical considerations of these experimental results imply a new base for evaluation of diastolic elasticity of the heart by means of the tangent modulus (E). These results are of substantial importance in clinical evaluation of distensibility of myocardial tissue, as the tangent modulus related to wall stress apparently is not appropriate to realize alterations in "passive" myocardial properties due to contracture.

Animals↗