Does Cyclophosphamide Enhance Myocardial Depression Induced by Volatile Anesthetics in Isolated Hearts ?

Cyclophosphamide is the most commonly used alkylating agent for anti cancer chemotherapy and immunosuppression. Halothane and sevoflurane are volatile anesthetics and halothane has been demonstrated to enhance cyclophosphamide toxicity. However, the interaction between sevoflurane and cyclophosphamide has not yet been investigated. We evaluated the effects of cyclophosphamide on myocardial depression by sevoflurane and halothane in isolated rat hearts. Seventy-two isolated rat hearts were placed in a Langendorff perfusion system. The heart rate was maintained at 300 bpm. Perfusion pressure was maintained at 60 mmHg. The left ventricular end-diastolic pressure was kept constant at 5 mmHg throughout the study. Halothane and sevoflurane were equilibrated for 20 minutes in the solution through a calibrated vaporizer. After stabilization, the heart was perfused with a solution equilibrated with 1 minimum alveolar concentration (MAC) of halothane or sevoflurane in combination with cyclophosphamide at a concentration of 0, 20, 200 or 2 0 0 0μM for 10 minutes. Systolic left ventricular pressure (SLVP) and the maximum left ventricular rate of pressure development (LV max dP/dt) were examined. At baseline measurement, there were no significant differences in SLVP and LV max dP/dt for the three groups. In combination with cyclophosphamide at the concentration of 20μM, halothane, not sevoflurane, reduced SLVP and LV max dP/dt. When the concentration of cyclophosphamide rose to a therapeutic level, halothane increased myocardial depression with cyclophosphamide, but sevoflurane did not. Halothane produced lower SLVP and LV max dP/dt than sevoflurane at only high concentrations of cyclophosphamide. These findings lead to the hypothesis that halothane markedly induces myocardial depression when the concentrations of cyclophosphamide rise to toxic levels. In conclusion, Halothane increased myocardial depression more than sevoflurane did when co-administrated with cyclophosphamide. Our findings suggest that sevoflurane is an adequate anesthetic for patients undergoing cyclophosphamide therapy.