Gabapentin alleviates myocardial ischemia-reperfusion injury by increasing the protein expression of GABAARδ.

Gabapentin is a commonly used analgesic in the clinic to reduce opioid consumption. It is well known that gabapentin can reduce cerebral ischemia-reperfusion injury (IRI). However, it remains unclear whether gabapentin can reduce myocardial IRI. Before the performance of myocardial ischemia and reperfusion (I/R), rats received gabapentin without or with an intravenous injection of PI3K inhibitor (LY294002), or an intraspinal injection of lentivirus-mediated GABAARδ-shRNA. The myocardial IRI were evaluated by calculating the infarction area, arrhythmia score and myocardial apoptosis. The activity of PI3K/Akt and the expression of GABAARδ were quantified by western blotting. The effect of gabapentin on myocardial I/R was further demonstrated in vitro by establishing oxygen-glucose deprivation and reoxygenation in cardiomyocytes. After I/R in vivo, there were significant increases in infarction area, arrhythmia and Bax protein expression in the myocardium, as well as a decrease of GABAARδ in the spinal cord. Meanwhile, I/R also decreased the protein expression of PI3K/Akt and Bcl-2. Gabapentin pretreatment successfully attenuated IRI including reducing the myocardial infarction area and apoptosis. This effect was abolished by both the systemic inhibition of PI3K/Akt and the intraspinal suppression of GABAARδ. However, gabapentin pretreatment failed to prevent cellular injury induced by OGD/R in cardiomyocytes. Therefore, the myocardial protective effect of gabapentin may be attributed to activating PI3K/Akt in the myocardium and upregulating GABAARδ in the spinal cord. Gabapentin achieved a potent protective effect on the myocardium during the course of routine clinical treatment.