Abstract
BackgroundCytostatic drugs are effective in cancer treatment but some have significant cardiotoxic side effects, including heart failure (HF). The aim of this study was to investigate the effect of high‐dose cyclophosphamide (CTX) on fiber and microvasculature (MV) structure of the heart.MethodsEight male New Zealand White rabbits (2.9 ± 0.1 kg) were randomly allocated into two groups receiving either 70 mg/kg of CTX (n=4) or sterile 0.9% NaCl (n=4; control) iv once a week for three weeks. Hearts were harvested one week after the last treatment, weighted, and the coronary arterial tree filled with fluorescent casting resin for structural analysis applying our imaging cryomicrotome.ResultsThe heart mass of CTX treated rabbits was significantly lower than normal (13.8 ± 0.4 vs. 17.1 ± 0.5; p = 0.04). All hearts were prepared for imaging; however, currently only 1 control and 1 CTX heart has been imaged. Consistent with the loss in heart mass, the preliminary results from the CTX heart showed ventricular dilatation and severe thinning of the ventricle walls. Heart fibers are normally densely arranged; however, the CTX heart consisted of loosely arranged fibers. Also, large transmural vessels are normally radially oriented, a characteristic lost in the CTX heart.ConclusionsCTX induces HF resulting in loss of fiber and MV structural organization.Supported by ZonMw 916.11.171
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