Cyclosporine A Plus Ischemic Postconditioning Improves Neurological Function in Rats After Cardiac Resuscitation

Attenuation of neuronal apoptosis helps maintain neurological function in patients after cardiac arrest. After ischemia-reperfusion, both cyclosporin A (CsA) and ischemic postconditioning independently protect mitochondria and thus reduce nerve injury. This study employed a rat model to evaluate the neuroprotective effect of combining ischemic postconditioning with CsA after cardiopulmonary resuscitation (CPR).

Rats were apportioned equally to model control, postconditioned, CsA-treated, or CsA + postconditioned groups. Asphyxial cardiac arrest was imposed using modified Utstein-style guidelines. In the appropriate groups, postconditioning was implemented by ischemia and reperfusion (clamping and loosening the left femoral artery); CsA treatment was delivered with a single intravenous dose. Neurological deficits were scored at different times after CPR. Histological evaluation and electron microscopy were used to evaluate tissue damage, and TUNEL and flow cytometry were used to measure the apoptotic rate of hippocampal neurons and size of the mitochondrial permeability transition pore (mPTP) opening.

The apoptotic rate was significantly lower in the postconditioned and CsA-treated groups compared with the model control and lowest in the CsA + postconditioned group. By histological evaluation and electron microscopy, the least damage was observed in the CsA + postconditioned group. The neurological deficit score of the CsA + postconditioned group was significantly higher than that of the CsA-treated group, but the size of the mPTP openings of these two groups was comparable.

Ischemic postconditioning combined with CsA exerted a better neuroprotective effect after CPR than did either postconditioning or CsA alone. Inhibiting the opening of the mPTP is not the only neuroprotective mechanism.