[Protective effects of naftidrofuryl oxalate against hypoxia-induced death]

To analyze the effects of naftidrofuryl oxalate (LS-121) on the central nervous system exposed to critical hypoxia, survival duration was employed as a parameter of the protective effects of the drug against hypoxia-induced death. In the control group (no drug administration), the electroencephalogram (EEG) was flattened promptly after changing to hypoxia from aerobic conditions, and it was impossible to recognize precisely what time the EEG disappeared because of vigorous body movements. Arterial blood pressure (BP) was clearly recognized, and rats never recovered after BP decreased to 0 mmHg, although the electrocardiogram (ECG) was still recorded. Thus, survival duration recognized by measuring the time from the onset of hypoxia to the time when BP became 0 mmHg was considered to be a good indicator. After LS-121 (10 mg/kg) administration, survival duration was significantly prolonged compared to the control. Combination therapy of LS-121 (25 mg/kg) and bifemelane hydrochloride (BI) (25 mg/kg) also revealed the prolongation of survival duration. Neither idebenone (10 mg/kg) nor nicergoline (10 mg/kg) showed significant changes in survival duration. These findings suggest that LS-121, either with or without BI, could improve cerebrovascular disorders induced by hypoxia.