Increased ATP production during long-term brain ischemia in rats in the presence of propentofylline

Abstract

Forty adult rats were subjected to stepwise two- and four-brain vessel occlusion and propentofylline 25 mg/day per kilogram body weight was intraperitoneally administered for 1 week or 3 weeks. Adenosine 5'-triphosphate, creatine phosphate, adenosine 5'-diphosphate and adenosine were determined in rat parietotemporal cortex by high-pressure liquid chromatography; lactate and pyruvate were measured spectrophotometrically. Stepwise and permanent long-term brain vessel occlusion gradually reduced the concentration of energy-rich phosphates and induced a marked increase in the concentration of adenosine, a parameter of ischemia. Three weeks of propentofylline treatment resulted in a significant increase in cerebral adenosine 5'-triphosphate concentration from 2.16 +/- 0.15 [(-)-propentofylline] to 2.70 +/- 0.24 nmol/mg wet weight during four-vessel occlusion (+25%). This was associated with an enhancement of the adenosine 5'-triphosphate/adenosine 5'-diphosphate ratio (+33%), mainly because of the significant reduction in adenosine 5'-diphosphate concentration. Propentofylline did not prevent the increase in lactate concentration during permanent brain vessel occlusion, but significantly reduced the tissue concentration of adenosine. In summary, the results demonstrate that continuous propentofylline administration over 3 weeks induced a striking increase in rat cortical adenosine 5'-triphosphate concentration during long-term brain vessel occlusion. Thus, propentofylline may have possible neuroprotective effects and could be used in the treatment of patients with chronic cerebrovascular disorders.