Effects of high-dose cyclophosphamide in the isolated rabbit heart

Evidence of acute cardiomyopathy in high-dose cyclophosphamide (Cytoxan) therapy has been described in patients receiving immunosuppression prior to bone marrow transplantation. Deaths attributable to Cytoxan cardiomyopathy have been documented in cumulative dosages, ranging from 144 to 270 mg/kg body weigh give in a 4-10 day period. The general clinical course observed in these cases includes: progressive voltage drop on EKG, normal serum CPK, pericardial effusion and refractory congestive heart failure. Unlike cardiac complications from the anthracycline derivatives, this problem appears to be an acute phenomenon. Published deaths occur within 15 days after the initial dose of Cytoxan. The effects of high-dose Cytoxan were studied in 30 isolated rabbit hearts using a modified Langendorff preparation. Cyclophosphamide significantly depressed peak left ventricular dP/dt and LV systolic pressure in doses of 200 mg/kg body weight at the 0.0000 level. This effect was sustained in hearts electronically paced to control loading conditions (p < 0.0000). Decreased calcium in the perfusate without pacing depressed heart rate (p < 0.0000) peak left ventricular dP/dt (p < 0.0020). Success of the bone marrow transplantation patient has been directly linked to the expertise of nursing support. High-dose cyclophosphamide is the most frequently used agent in preparative immunosuppression, with additional agents added as the patient condition warrants. Since the phenomena of cardiac complications may be an acute condition with this drug, the importance of nursing observations and intervention cannot be overstressed. Data obtained in this study with an animal model suggests depression of myocardial contractility. Methods to assess the critical state of the myocardium in patients receiving this agent would continue to add to the body of nursing knowledge.