Effect of trapidil in ischemia/reperfusion injury of peripheral nerves

Objective: Ischemia plays an important role in the development of pathological changes in nerve tissue, and restoration of blood flow results in injury (ischemia/reperfusion [I/R] injury) mediated by toxic oxygen free radicals. Trapidil is currently used as a coronary artery vasodilating agent and is also used for the prevention of ischemic symptoms of cerebral vasospasm. The purpose of this study was to determine the effects of trapidil on I/R injury and the ischemic tolerance of rat peripheral nerves.

Methods: Preischemia or prereperfusion administration of trapidil (8 mg/kg) was evaluated in the rat sciatic nerve I/R injury model. Nerve tissue samples from the I/R injury site were assayed for malondialdehyde (MDA), nitrites, and nitrates, as markers of I/R injury, and pathological changes were evaluated by electron microscopy.

Results: I/R resulted in an increase in MDA levels, which remained elevated for 2 weeks in control nerves. Rats that received trapidil before ischemia exhibited decreased MDA levels, and rats that received trapidil after the standard 3 hours of ischemia demonstrated increased tolerance to reperfusion, as reflected in significantly decreased MDA levels. Nitrite and nitrate levels in trapidil-treated rats were significantly higher than those in control Animals. Histological evaluations of the sciatic nerve segments demonstrated that preischemia and postischemia trapidil treatments had a sparing effect against the myelin damage and axonal edema that are consistently noted in untreated ischemic reperfused nerves.

Conclusion: The results confirm that pretreatment with trapidil before the ischemic insult or before reperfusion provides marked protection against I/R injury in peripheral nerves.