The effect of irradiation on cardiac function was assessed using an isolated working rat heart preparation. The animals were given single doses of X-rays in the range 15-30 Gy to their hearts. Cardiac output (CO = aortic flow + coronary flow), heart weight and body weight were followed for a period of 10 months after treatment. Irradiation led to a decrease in cardiac function. This reduction was dose-dependent and progressive with time after treatment. The shape of the Frank-Starling curves constructed for irradiated hearts suggests a loss of contractile function of the myocardium. Coronary flow rates measured in 'working' hearts and in 'Langendorff' hearts were not significantly changed by the irradiation treatment. The isolated working rat heart preparation proved to be a simple and suitable animal model for the investigation of irradiation-induced cardiotoxicity.

The primary defence mechanism of myocytes against peroxides and peroxide-derived peroxyl and alkoxyl radicals is the glutathione redox cycle. The purpose of the present study was to increase the turnover rate of this cycle by stimulating the glutathione peroxidase catalysed reaction (2GSH-->GSSG), the glutathione reductase catalysed reaction (GSSG-->2GSH), or both. Neonatal rat heart cell cultures were subjected to a standardized protocol of oxidative stress using 80 mumol.l-1 cumene hydroperoxide (CHPO) for 0-90 min. The consequences of this protocol were described in terms of cellular concentrations of GSH, GSSG, NADPH and ATP, formation of malondialdehyde (MDA), release of GSSG and of ATP catabolites, depression of contraction frequency, cellular calcium overload, and enzyme release. Trolox-C, an analogue of vitamin E, accelerated the glutathione peroxidase reaction leading to lowering of GSH concentration and the GSH/GSSG ratio, less MDA formation, diminished negative chronotropy, delayed calcium overload, and less enzyme release. Glucose was used to accelerate the glutathione reductase reaction by supplying NADPH, leading to higher GSH concentration and a higher GSH/GSSG ratio, less MDA formation, diminished negative chronotropy, unchanged development of calcium overload, and less enzyme release. As a full turn of the glutathione redox cycle involves both the peroxidase and the reductase reactions, the combination of Trolox-C and glucose was superior to either of the two alone: 90 min following addition of CHPO together with Trolox-C and glucose, the GSH concentration and the GSH/GSSG ratio were almost normal, MDA formation was extremely low, calcium overload was markedly delayed, and enzyme release hardly occurred at all. Cells remained beating in the observation period of 30 min. We conclude that the capacity of the glutathione redox cycle to withstand oxidative stress can be increased by stimulation of either the peroxidase reaction or the reductase reaction, and that optimal redox cycling is achieved by stimulation of both reactions.

Comparison of in vivo cardiac function with ex vivo cardiac performance of the rat heart after thoracic irradiation Franken, N.A.P.; Camps, J.A.J.; van Ravels, F.J.M.; van der Laarse, A.; Pauwels, E.K.J.; Wondergem, J. General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Download date: 12 May 2018T he British Journal of Radiology, 70 (1997Radiology, 70 ( ), 1004Radiology, 70 ( -1009Radiology, 70 ( © 1997 The British Institute of RadiologyComparison of in vivo cardiac function with ex vivo cardiac performance of the rat heart after thoracic irradiation 1,2N A P FRANKEN, 3J A J CAMPS, 1F J M VAN RAVELS, 4A VAN DER LAARSE, 3E K J PAUWELS and 1J WONDERGEM Departments of 1Clinical Oncology, 3Diagnostic Radiology and Nuclear Medicine, and 4Cardiology, University Hospital Leiden, and 2Department of Radiotherapy, Academic Medical Center, University of Amsterdam, The Netherlands Abstract. The aim of the study was to compare in vivo cardiac function with ex vivo cardiac performance after local heart irradiation in the same rat. Left ventricular ejection fraction (LVEF) was measured in vivo by radionuclide ventriculography in Sprague-Dawley rats up to 16 months after a single dose of 20 Gy. Four days after in vivo measurements, cardiac performance was determined ex vivo, using the isolated working rat heart preparation. After irradiation, cardiac performance measured ex vivo deteriorated more rapidly than the in vivo measured LVEF. Within 4 months post-treatment, ex vivo cardiac output and stroke volume started to decrease and declined continuously throughout the observation period of 16 months. The reduction in stroke volume was already significant ( p<0.04) at 4 months post-treatment, whereas the decline in cardiac output was significant ( p<0.05) at 12 months post-treatment. In vivo, no change in LVEF was observed during the first 12 months post-treatment. Thereafter, LVEF decreased rapidly from 65±2% to 46±8% ( p<0.01), at 16 months post-treatment. Up to 12 months post-irradiation, LVEF was not correlated to ex vivo cardiac output. At 16 months post-treatment, when clinical symptoms of heart failure become evident, a positive relation between both parameters was found. The lack of correlation between the in vivo and ex vivo measurements of cardiac function during the firs...

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