Electrical stimulation prolongs the survival days of leukemic mice treated with methotrexate

To investigate effects of electrical stimulation on survival days of leukemic mice treated with methotrexate (MTX), L1210-bearing mice were treated by MTX and calcium folinate (leucovorin) rescue therapy (MTX: 400 mg/kg, followed by leucovorin at the dose of 7.5 mg/kg at 8, 15 and 24 hr after MTX) under electrical stimulation (foot shock: shock amplitude, 0.4 mA; voltage, 60-100 V/cm; shock duration, 5 sec; frequency, 0.5 Hz) of various lengths. The survival days were significantly prolonged by 6-hr electrical stimulation in combination with MTX, while plasma MTX concentrations and pharmacokinetic parameters such as the area under the curve (AUC-12 hr) and clearance (CL) were not significantly altered. Psychological stress did not alter the efficacy of MTX in the communication box paradigm. Amplified efficacy of MTX was shown in a length-dependent manner when electrical stimulation of various lengths were applied to L1210-bearing mice.