Summary
Dexamethasone (6 mg/kg) given intravenously to anesthetized cats exerted no significant hemodynamic effect on control open-chest cats or in cats subjected to acute myocardial ischemia by coronary artery ligature. However, dexamethasone normalized elevated S-T segments toward preischemic values, and prevented much of the increase in plasma CPK activity following coronary artery ligation. Moreover, dexamethasone prevented loss of CK activity within ischemic myocardial tissue five hours after the onset of ischemia. Dexamethasone also reduced the extent of ischemic damage as assessed by a nitro-blue tetrazolium staining technique, providing anatomic verification of the reduced ischemic damage. Moreover, dexamethasone prevented the swelling and vacuolization of myocardial lysosomes in the ischemic region, indicating a stabilization of lysosomal membranes within the heart. These data indicate that lysosomal disruption is an important consequence of myocardial ischemia and that early treatment with dexamethasone prevents the loss of myocardial lysosomal and cellular enzymes as reflected in normalization of the ECG and plasma CK activity of ischemic cats. In this way, dexamethasone may act to retard the spread of the developing infarct within the ischemic myocardium.
Zusammenfassung
Intravenöse Verabfolgung von Dexamethason (6 mg/kg) hatte keine signifikanten hämodynamischen Effekte, weder bei Kontrollkatzen mit offenem Thorax noch bei Katzen mit akuter myokardialer Ischämie infolge Koronararterienligatur. Jedoch machte Dexamethason eine ischämisch bedingte ST-Hebung rückgängig und wirkte in starkem Maße vorbeugend gegenüber dem Anstieg der Plasma-CPK-Aktivität nach Koronararterienunterbindung. Darüber hinaus verhinderte Dexamethason 5 Stunden nach dem Einsetzen der Ischämie den Verlust der CK-Aktivität im ischämischen Myokardgewebe. Auch reduzierte Dexamethason das Ausmaß der ischämischen Schädigung bei Bewertung auf der Grundlage der Nitroblau-Tetrazolium-Technik. Darüber hinaus verhinderte Dexamethason die Schwellung und Vakuolisierung myokardialer Lysome in der ischämischen Region als Hinweis auf eine Stabilisierung lysosomaler Membranen im Herzen. Diese Ergebnisse zeigen, daß die strukturelle Zerstörung der Lysosomen eine wichtige Konsequenz der myokardialen Ischämie darstellt und daß eine frühe Behandlung mit Dexamethason den Verlust von lysosomalen und zellulären Enzymen des Myokards verhindert, was in einer Normalisierung des Ekg und der Plasma-Aktivität der ischämischen Katzen zum Ausdruck kommt. Auf diese Art und Weise dürfte Dexamethason einer Ausbreitung der Infarzierung im ischämischen Myokard entgegenwirken.
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With 6 figures and 1 table
Supported in part by grants from the W. W. Smith Foundation and by Organon, Inc.
Summer Research Fellow of the Ischemia-Shock Research Center
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Lefer, A.M., Crossley, K., Grigonis, G. et al. Mechanism of the beneficial effect of dexamethasone on myocardial cell integrity in acute myocardial ischemia. Basic Res Cardiol 75, 328–339 (1980). https://doi.org/10.1007/BF01907581
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DOI: https://doi.org/10.1007/BF01907581