Effect of trapidil in ischemia/reperfusion injury of peripheral nerves

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.

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.

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.

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