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Connective tissue content and myocardial stiffness in pressure overload hypertrophy A combined study of morphologic, morphometric, biochemical, and mechanical parameters

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Summary

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.

Zusammenfassung

Linksventrikuläre Myokardproben von Goldblatt-II-(4 und 8 Wochen post operationem) und spontanhypertensiven Ratten (SHR; Alter 40 und 80 Wochen) wurden histologisch und morphometrisch untersucht. Von denselben Herzen wurden zudem die Dehnbarkeit des linksventrikulären Papillarmuskels mittels Ruhe-Dehnungs-Kurven sowie der Kollagenanteil der gesamten linken Ventrikelwandung mittels Hydroxyprolinkonzentration bestimmt. Neben der zu erwartenden Hypertrophie der Myozyten fanden wir in beiden Hypertrophiemodellen eine Myokardfibrose. Das Ausmaß der Fibrose nahm mit der Dauer des Bestehens der Hypertension zu. In späteren Studien wurden zusätzlich degenerative Veränderungen an Myozyten beobachtet.

Morphometrische Bestimmungen und Hydroxyprolinkonzentration weisen einen Anstieg des Kollagengehaltes des druckbelasteten linken Ventrikels nach. Morphometrische und chemische Ergebnisse stehen im Einklang mit der myokardialen Dehnbarkeit—gemessen am isolierten Papillarmuskel derselben Herzen. Diskrepanzen, die im 40-Wochen-Stadium der SHR-Gruppe auftreten, müssen auf Unterschiede im Verteilungsmuster des Kollagens auf Interstitium, perivaskuläre Räume und Wände der Blutgefäße zurückgeführt werden. Der Vergleich histologischer, chemischer und physiologischer Ergebnisse zeigt 1., daß die Herzhypertrophie bei Goldblatt- und SH-Ratten von Myokardfibrose begleitet ist, und 2., daß Veränderungen der passiv-elastischen Eigenschaften des Myokards besser vom morphometrischen als vom chemischen Resultat widergespiegelt werden.

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  1. K. -U. Thiedemann

    Present address: Anatomisches Institut der Universität Tübingen, 7400, Tübingen

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  1. Physiologisches Institut (II), Universität Tübingen, Tübingen, Germany

    Ch. Holubarsch, I. Medugorac & R. Jacob

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Supported by the Deutsche Forschungsgemeinschaft.

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Thiedemann, K.U., Holubarsch, C., Medugorac, I. et al. Connective tissue content and myocardial stiffness in pressure overload hypertrophy A combined study of morphologic, morphometric, biochemical, and mechanical parameters. Basic Res Cardiol 78, 140–155 (1983). https://doi.org/10.1007/BF01906668

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