Examination of the left ventricle damage in cyclophosphamide monotherapy with DSC in animal models

Lots of cytotoxic drug have cardiac toxic effect, but besides some other drugs, cyclophosphamide has got a similar cardiac toxic effect but its mechanism less clear. Limit value of cyclophosphamide which causes severe cardiac toxicity is also not known. The purpose of this study was to introduce at the first time the calorimetry in the diagnosis of cyclophosphamide-induced cardiomyopathy in an experimental animal model and to try to assign a limit value of cyclophosphamide which can cause cardiac muscle damage. Adult guinea pigs (n = 55, in 11 different groups) were injected intraperitoneally with the dose of cyclophosphamide that comparable to the human dosage. Animals were euthanized; left ventricle cardiac muscle samples were analysed by a SETARAM micro-calorimeter. The denaturation temperatures were measured, and the calorimetric enthalpies were calculated based on the areas under thermal absorption curves. The thermal parameters of denaturation of the samples show that several times administered cyclophosphamide can damage myosin head and actin first, and with increasing dose the full actomyosin complex gets damaged. With the results of our study, we can get closer to understand the pathophysiology and get more data about of the limit value of cyclophosphamide-induced cardiomyopathy.