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C Holubarsch

Publications and source records attributed to C Holubarsch.

97 records · Page 6Linked to original sources
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Connective tissue content and myocardial stiffness in pressure overload hypertrophy. A combined study of morphologic, morphometric, biochemical, and mechanical parameters.

We investigated samples of left ventricular myocardium from Goldblatt II (4 and 8 weeks after operation) and spontaneously hypertensive rats (SHR; 40 and 80 weeks old) by histological and morphometric methods. From the same hearts, the distensibility of the left ventricular papillary muscle was analyzed by means of resting tension curves, and the collagen content of the whole left ventricular wall was determined by means of hydroxyproline concentration. In all groups, myocardial fibrosis was observed to accompany myocardial hypertrophy. The severity of fibrotic lesions increased with the duration of hypertension, and, in late stages, degenerative changes of cardiac myocytes were found. Morphometric determinations and chemical analysis of the hydroxyproline concentration revealed a decrease in myocardial muscle content, which was paralleled by an increase in collagen content when compared to the respective controls. In general, morphometric and chemical findings correlate with increased myocardial stiffness observed during mechanical measurements in isolated papillary muscle preparations from the same hearts. Differences were found, however, between chemical analysis and mechanical measurements in the 40-week-old SHR group, which may result from different patterns of collagen distribution between interstitium, perivascular spaces, and the walls of blood vessels. The comparison between histological, morphometric, chemical, and physiological data shows that (1) cardiac hypertrophy of Goldblatt and SH-rats is accompanied by myocardial fibrosis, and (2) changes in passive elastic properties of myocardium is better reflected in morphometric than in chemical analysis.

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Energetic changes of myocardium as an adaptation to chronic hemodynamic overload and thyroid gland activity.

Pressure-overload cardiac hypertrophy and hypothyroidism were shown to be associated with a decreased maximum shortening velocity of the myocardium. To investigate the nature of these intrinsic myocardial changes, we studied the energetic consequences in left ventricular papillary muscles of the rat by using standard HILL planar vacuum-deposited antimony-bismuth thermopiles. To evaluate the economy of isometric force generation and maintenance, we analyzed the ratio of liberated heat and developed tension or developed tension-time integral in twitches and experimentally induced tetanic contractions. Hypothyroidism was induced by treatment with propylthiouracil (PTU), and hypertension by operative narrowing of the left renal artery of rats according to Goldblatt (GOP). In the myocardium of hypothyroid as well as hypertensive rats, initial heat per peak twitch tension and total activity-related heat per tension-time integral were significantly reduced compared to controls. In tetanic contractions, total activity-related heat per tension-time integral was also decreased in PTU and GOP myocardium when compared to controls. Thus, the economy of force generation and maintenance is improved in the myocardium of the experimental animals. The data is interpreted in terms of altered cross-bridge cycling rates which are shown to be associated with changes in the myosin isoenzyme pattern. The intrinsic changes of the myocardium due to pressure-overload hypertrophy and hypothyroidism are considered to be adaptive rather than pathologic reactions of the myocardium.

Adaptation, Physiological↗
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Diastolic tension of rat cardiac muscle during deficiency of oxygen and glucose. Stress-strain relationships and reversibility.

In the isometrically contracting rat trabecular muscle strip preparation, contracture tension was induced either by 10 min of hypoxia (low contracture tension) or by 30 min of joint oxygen and glucose withdrawal (severe contracture tension) at optimum length. Using stepwise 0.1 mm releases, length-tension relationships were recorded under control and contracture conditions in both types of contracture. Stress-strain relationships were evaluated as well as the linear function of the tangent elastic modulus delta sigma/delta epsilon versus stress sigma. The slope of the delta sigma/delta epsilon = f (sigma) function was not significantly changed in low contracture compared to control conditions (n = 8; p less than 0.001). When reversibility tests were performed by reoxygenation after 10 min hypoxia and reperfusion with oxygen and glucose after 30 min of glucose and oxygen withdrawal, low contracture tension was completely abolished after 15 min, whereas 28% of severe contracture was maintained even after 60 min of reperfusion. Additional morphological studies revealed uniform sarcomere lengths in low contracture, and two populations of sarcomere lengths in the severe contracture. On the basis of the present and earlier results, a model of contracture tension generation is proposed in which cross-bridges between actin and myosin cycle at a very low rate and are attached in a force-generating position for a long time.

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Prospects of X-ray microanalysis in the study of pathophysiology of myocardial contraction.

X-ray microanalysis was used to compare chemically untreated cryosections of quick-frozen myocardial tissue in "caffeine contracture" with cryosections of normal muscle. Our goal was to find out if it is possible by means of this method to detect changes in the calcium compartmentalization of the myocardial cell occurring by changes in its functional state. While it is possible to quantitate calcium in the cisternae of sarcoplasmic reticulum of the control muscle preparation, calcium could never be detected in these compartments of caffeine-contracted muscles. In active microsomal fraction of ventricular myocardium it is possible to quantitate calcium and also to distinguish two components on account of their different ability to accumulate this element. The calcium content is different in the two components of the fraction.

Animals↗
PubMedDate not supplied

Contracture type and fibrosis type of decreased myocardial distensibility. Different changes in elasticity of myocardium in hypoxia and hypertrophy.

Resting length-tension relationships were measured in rat trabecular muscle strips under control (O2) and contracture (N2) conditions as well as in preparations of Goldblatt II (8-week stage) and control rats. For the evaluation of the diastolic elastic properties, diastolic stress at 1max, stress-strain relationships, the relation between tangent modulus delta sigma divided by delta epsilon and stress sigma, and the function ln stress sigma = f (strain epsilon) were calculated and plotted. It was shown that the hypoxic contracture corresponds to the calcium-caffeine contracture--an experimental contracture model already investigated earlier. In contrast to these contracture-induced alterations, Goldblatt II hypertrophied myocardium corresponded to the fibrosis type. This type was already analyzed in an experimental model of myocardium-tendon tandem preparation. Additional investigations of hydroxyproline concentration of the same biological material showed in contrast to other studies that the collagen content may already be increased in this early stage of hypertrophy. Thus, altered distensibility of Goldblatt myocardium is certainly primarily due to increased connective tissue content.

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