Inhibition of phosphodiesterase 4 attenuates myocardial ischemia/reperfusion injury by inhibiting cardiomyocytes apoptosis

Abstract

The effects of selective inhibitors of phosphodiesterase type 4 (PDE4), rolipram on gastric and brain ischemia/reperfusion injuries were investigated. However, the effects of rolipram on myocardial ischemic/reperfusion (I/R) are not fully understood. Here, it was investigated whether rolipram has protective effects on in vitro and in vivo myocardial I/R. Treatment with rolipram on H9c2 cells significantly inhibited cell death during I/R in a concentration-dependent manner. Rolipram also exerted a profound protective effect on apoptosis by decreasing the apoptosis-induced protein Bax and increasing the inhibitory protein Bcl-2 during I/R. Furthermore, rolipram suppressed the caspase-3 activity in cardiomyocytes exposed to I/R. To further investigate the role of rolipram on in vivo myocardial I/R, in vivo myocardial I/R model was established by ligating left anterior descending artery (LAD) for 1 h followed by 1 h of reperfusion. Compared to ischemic control group, administration of rolipram reduced infarct size and lactate dehydrogenase (LDH) level against myocardial I/R injury model. These findings indicate that rolipram has protective effect against I/R injury in cardiomyocytes. This beneficial effect is partly dependent on decreased Bax, caspase-3 as well as increased Bcl-2.