received mediastinal irradiation for the treatment of neoplasms .... Blood samples were taken immediately after (0.5±24 h) and on days 2, 3,. 4, 5, 6, 7, 9, 12 and ...
Ó Springer-Verlag 2000
J Cancer Res Clin Oncol (2000) 126:27±32
ORIGINAL PAPER
N. A. P. Franken á E. Strootman á L. Hollaar A. van der Laarse á J. Wondergem
Myocardial enzyme activities in plasma after whole-heart irradiation in rats
Received: 15 March 1999 / Accepted: 12 July 1999
Abstract Plasma levels of myocardial enzymes present after local heart irradiation were studied in a rat model. The purpose was to investigate whether, within days after irradiation, these enzyme levels change to such an extent that they may be helpful in assessing the severity of cardiac damage after radiotherapy. Therefore, activities of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and a-hydroxybutyrate dehydrogenase (a-HBDH) were determined in the plasma and left ventricular myocardium of rats following local heart irradiation with a single dose of 20 Gy. A dose of 20 Gy is known to cause irreversible cardiac damage and to reduce survival times of the animals. Cardiac enzyme assays were performed directly after and twice daily for up to 2 weeks after radiation. Plasma CK, LDH, AST and a-HBDH levels were increased between 2 h and 24 h after irradiation. Plasma ALT levels remained unchanged. Myocardial enzyme levels, measured between 24 h and 16 days after radiation, did not dier between irradiated and control animals, although acute (®rst 12 h) reductions were observed in the irradiated group. The elevated enzyme levels in plasma appeared to correlate with the acutely reduced myocardial enzyme levels. Although irradiation with a dose of 20 Gy induced acute rises of cardiac enzyme levels in plasma, it is doubtful that fractionated radiation, as applied clinically for treatment of solid tumors, will induce plasma N.A.P. Franken1 á E. Strootman á J. Wondergem (&) Department of Clinical Oncology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands L. Hollaar á A. van der Laarse Department of Cardiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands Present address: Department of Radiotherapy, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands
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enzyme elevations that are large enough to indicate the extent of cardiac damage occurring acutely or chronically. Key words Heart irradiation á Plasma enzyme levels á Myocardial enzyme levels á Rat Abbreviations CK creatine kinase á LDH lactate dehydrogenase á AST aspartate aminotransferase á ALT alanine aminotransferase á a-HBDH a-hydroxybutyrate dehydrogenase
Introduction Although radiotherapy has been shown to be a successful modality in the treatment of cancer, considerable eorts are being undertaken to improve the ecacy of this therapy. Besides research on its antitumor eect, much emphasis is placed on eects on normal tissue to gain insight into the mechanisms responsible for the development of adverse eects and/or late complications as a result of radiotherapy. Early identi®cation of plasma or tissue factors that can be used for detecting pathological processes leading to complications in normal tissues is important. Individual information on the radioresponse of the organ or tissue at risk, already obtained during treatment, oers the possibility of ``early'' intervention to reduce the severity or to delay the development of the ``expected'' late complications. Clinical studies have demonstrated that patients who received mediastinal irradiation for the treatment of neoplasms frequently develop cardiovascular complications long after radiotherapy (Gomez et al. 1983; Morgan et al. 1985; Young et al. 1990). When a large portion of the heart is located in the radiation ®eld, as in the treatment of Hodgkin's disease, a dose of up to 40 Gy in 20 fractions over a 4-week period is well tolerated, but at doses above that a rapid increase in cardiac abnormalities have been reported (Stewart et al. 1995). When small heart volumes are treated (volume
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