Cardioprotective effect of dipeptidyl peptidase-4 inhibitor during ischemia-reperfusion injury

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitor is a new anti-diabetic drug for type-2 diabetes mellitus patients. Despite its benefits on glycemic control, the effects of DPP-4 inhibitor on the heart during ischemia-reperfusion (I/R) periods are not known. We investigated the effect of DPP-4 i...

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Main Authors: Chinda K., Palee S., Surinkaew S., Phornphutkul M., Chattipakorn S., Chattipakorn N.
Format: Article
Language:English
Published: 2014
Online Access:http://www.ncbi.nlm.nih.gov/pubmed/3502482
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spelling th-cmuir.6653943832-10782014-08-29T09:17:43Z Cardioprotective effect of dipeptidyl peptidase-4 inhibitor during ischemia-reperfusion injury Chinda K. Palee S. Surinkaew S. Phornphutkul M. Chattipakorn S. Chattipakorn N. Background: Dipeptidyl peptidase-4 (DPP-4) inhibitor is a new anti-diabetic drug for type-2 diabetes mellitus patients. Despite its benefits on glycemic control, the effects of DPP-4 inhibitor on the heart during ischemia-reperfusion (I/R) periods are not known. We investigated the effect of DPP-4 inhibitor on cardiac electrophysiology and infarct size in a clinically relevant I/R model in swine and its underlying cardioprotective mechanism. Methods: Fourteen pigs were randomized to receive either DPP-4 inhibitor (vildagliptin) 50 mg or normal saline intravenously prior to a 90-min left anterior descending artery occlusion, followed by a 120-min reperfusion period. The hemodynamic, cardiac electrophysiological and arrhythmic parameters, and the infarct size were determined before and during I/R. Rat cardiac mitochondria were used to study the protective effects of DPP-4 inhibitor on cardiac mitochondrial dysfunction caused by severe oxidative stress induced by H2O2 to mimic the I/R condition. Results: Compared to the saline group, DPP-4 inhibitor attenuated the shortening of the effective refractory period (ERP), decreased the number of PVCs, increased the ventricular fibrillation threshold (VFT) during the ischemic period, and also decreased the infarct size. In cardiac mitochondria, DPP-4 inhibitor decreased the reactive oxygen species (ROS) production and prevented cardiac mitochondrial depolarization caused by severe oxidative stress. Conclusions: During I/R, DPP-4 inhibitor stabilized the cardiac electrophysiology by preventing the ERP shortening, decreasing the number of PVCs, 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. © 2013 Elsevier Ireland Ltd. All rights reserved. 2014-08-29T09:17:43Z 2014-08-29T09:17:43Z 2013 Article 01675273 10.1016/j.ijcard.2012.01.011 22285447 IJCDD http://www.ncbi.nlm.nih.gov/pubmed/3502482 http://www.scopus.com/inward/record.url?eid=2-s2.0-84879120827&partnerID=40&md5=b6838335acad6635c9157ce8aac28201 http://cmuir.cmu.ac.th/handle/6653943832/1078 English
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
language English
description Background: Dipeptidyl peptidase-4 (DPP-4) inhibitor is a new anti-diabetic drug for type-2 diabetes mellitus patients. Despite its benefits on glycemic control, the effects of DPP-4 inhibitor on the heart during ischemia-reperfusion (I/R) periods are not known. We investigated the effect of DPP-4 inhibitor on cardiac electrophysiology and infarct size in a clinically relevant I/R model in swine and its underlying cardioprotective mechanism. Methods: Fourteen pigs were randomized to receive either DPP-4 inhibitor (vildagliptin) 50 mg or normal saline intravenously prior to a 90-min left anterior descending artery occlusion, followed by a 120-min reperfusion period. The hemodynamic, cardiac electrophysiological and arrhythmic parameters, and the infarct size were determined before and during I/R. Rat cardiac mitochondria were used to study the protective effects of DPP-4 inhibitor on cardiac mitochondrial dysfunction caused by severe oxidative stress induced by H2O2 to mimic the I/R condition. Results: Compared to the saline group, DPP-4 inhibitor attenuated the shortening of the effective refractory period (ERP), decreased the number of PVCs, increased the ventricular fibrillation threshold (VFT) during the ischemic period, and also decreased the infarct size. In cardiac mitochondria, DPP-4 inhibitor decreased the reactive oxygen species (ROS) production and prevented cardiac mitochondrial depolarization caused by severe oxidative stress. Conclusions: During I/R, DPP-4 inhibitor stabilized the cardiac electrophysiology by preventing the ERP shortening, decreasing the number of PVCs, 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. © 2013 Elsevier Ireland Ltd. All rights reserved.
format Article
author Chinda K.
Palee S.
Surinkaew S.
Phornphutkul M.
Chattipakorn S.
Chattipakorn N.
spellingShingle Chinda K.
Palee S.
Surinkaew S.
Phornphutkul M.
Chattipakorn S.
Chattipakorn N.
Cardioprotective effect of dipeptidyl peptidase-4 inhibitor during ischemia-reperfusion injury
author_facet Chinda K.
Palee S.
Surinkaew S.
Phornphutkul M.
Chattipakorn S.
Chattipakorn N.
author_sort Chinda K.
title Cardioprotective effect of dipeptidyl peptidase-4 inhibitor during ischemia-reperfusion injury
title_short Cardioprotective effect of dipeptidyl peptidase-4 inhibitor during ischemia-reperfusion injury
title_full Cardioprotective effect of dipeptidyl peptidase-4 inhibitor during ischemia-reperfusion injury
title_fullStr Cardioprotective effect of dipeptidyl peptidase-4 inhibitor during ischemia-reperfusion injury
title_full_unstemmed Cardioprotective effect of dipeptidyl peptidase-4 inhibitor during ischemia-reperfusion injury
title_sort cardioprotective effect of dipeptidyl peptidase-4 inhibitor during ischemia-reperfusion injury
publishDate 2014
url http://www.ncbi.nlm.nih.gov/pubmed/3502482
http://www.scopus.com/inward/record.url?eid=2-s2.0-84879120827&partnerID=40&md5=b6838335acad6635c9157ce8aac28201
http://cmuir.cmu.ac.th/handle/6653943832/1078
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