P109Cardioprotective effect of dipeptidyl peptidase-4 inhibitor during ischemia-reperfusion injury is via prevention of cardiac mitochondrial dysfunction

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Abstract

Dipeptidyl peptidase-4 (DPP-4) inhibitor has been used to treat type-2 diabetes mellitus. Despite its benefits on glycemic control, the effects of DPP-4 inhibitor on the heart during ischemia-reperfusion (I/R) are not known. We tested the hypothesis that during I/R, 1) DPP-4 inhibitor attenuates cardiac arrhythmias and reduces the infarct size, and 2) the cardioprotective effects of DPP-4 inhibitor is via its prevention of cardiac mitochondrial dysfunction.

Methods

Fourteen pigs were randomized to receive either DPP-4 inhibitor (vildagliptin, Vil) 50 mg or normal saline (NSS) intravenously prior to a 90-min left anterior descending artery occlusion, followed by a 120-min reperfusion. The hemodynamics, cardiac electrophysiological parameters, and the infarct size were determined. Since I/R is known to cause severe oxidative stress and cardiac mitochondrial dysfunction, rat cardiac mitochondria were used to elucidate the cardioprotective mechanisms of DPP-4 inhibitor.

Results

Compared to the NSS group, DPP-4 inhibitor attenuated effective refractory period (ERP) shortening, decreased the number of premature ventricular contractions and arrhythmia score, increased the ventricular fibrillation threshold (VFT) during I/R, and also decreased the infarct size (Figure). In cardiac mitochondria, DPP-4 inhibitor significantly decreased the reactive oxygen species production and prevented mitochondrial depolarization caused by severe oxidative stress (Figure).

Conclusions

During I/R, DPP-4 inhibitor stabilizes cardiac electrophysiology by preventing the ERP shortening, decreasing arrhythmias, increasing the VFT, and decreasing the infarct size. This cardioprotective effect could be due to its prevention of cardiac mitochondrial dysfunction caused by severe oxidative stress during I/R.

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