POTENTIAL COMPLICATIONS ASSOCIATED WITH NORMOTHERMIC LONIDAMINE INFUSION AND WITH SYSTEMIC ACIDOSIS IN DOGS RECEIVING LONIDAMINE DURING WHOLE-BODY HYPERTHERMIA (WBH)

The vascular toxicosis of lonidamine (40 mg/h) or vehicle infusion was investigated in six dogs. Vasculitis and thrombosis were observed in veins infused with lonidamine but not in veins infused with vehicle. T his finding suggests that it may not be possible to use lonidamine inf usion to circumvent therapeutic limitations associated with the oral l onidamine formulation currently used in patients. We also investigated the systemic toxicosis of lonidamine (400 mg/m(2) rapid intravenous b olus) or vehicle in six other dogs that developed systemic acidosis (p H less than or equal to 7.0) during whole body hyperthermia (42 degree s C x 90 min). Gross and histologic haemorrhage was observed in all do gs; however, haemorrhagic lesions in acidotic dogs receiving lonidamin e + WBH were more severe than changes observed in acidotic dogs receiv ing vehicle + WBH. These observations confirm the results of in vitro studies which suggest that the combined effect of lonidamine and hyper thermia is enhanced under acidic conditions. Furthermore, these findin gs indicate that acid-base status of patients receiving lonidamine dur ing WBH must be monitored carefully to avoid serious complications.