Limb Ischemic Postconditioning Alleviates Postcardiac Arrest Syndrome through the Inhibition of Mitochondrial Permeability Transition Pore Opening in a Porcine Model.

Abstract

OBJECTIVE:

Previously, the opening of mitochondrial permeability transition pore (mPTP) was confirmed to play a key role in the pathophysiology of postcardiac arrest syndrome (PCAS). Recently, we demonstrated that limb ischemic postconditioning (LIpostC) alleviated cardiac and cerebral injuries after cardiac arrest and resuscitation. In this study, we investigated whether LIpostC would alleviate the severity of PCAS through inhibiting mPTP opening.

METHODS:

Twenty-four male domestic pigs weighing 37 ± 2 kg were randomly divided into three groups: control, LIpostC, and LIpostC+atractyloside (Atr, the mPTP opener). Atr (10 mg/kg) was intravenously injected 30 mins prior to the induction of cardiac arrest. The animals were subjected to 10 mins of untreated ventricular fibrillation and 5 mins of cardiopulmonary resuscitation. Coincident with the beginning of cardiopulmonary resuscitation, LIpostC was induced by four cycles of 5 mins of limb ischemia and then 5 mins of reperfusion. The resuscitated animals were monitored for 4 hrs and observed for an additional 68 hrs.

RESULTS:

After resuscitation, systemic inflammation and multiple organ injuries were observed in all resuscitated animals. However, postresuscitation systemic inflammation was significantly milder in the LIpostC group than in the control group. Myocardial, lung, and brain injuries after resuscitation were significantly improved in the LIpostC group compared to the control group. Nevertheless, pretreatment with Atr abolished all the protective effects induced by LIpostC.

CONCLUSION:

LIpostC significantly alleviated the severity of PCAS, in which the protective mechanism was associated with the inhibition of mPTP opening.

• Authors: Zhengquan Wang, Lifeng Wu, Jiefeng Xu, Jindan Gao, Sen Ye, Zilong Li, Yuanzhuo Chen, Xiangyu Zhang
• Journal: BioMed research international (Biomed Res Int) Vol. 2020 Pg. 9136097 ( 2020) ISSN: 2314-6141 [Electronic] United States
• PMID: 32382579 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Zhengquan Wang et al.

Chemical References

• Mitochondrial Permeability Transition Pore
• Atractyloside

Topics

• Animals
• Atractyloside (pharmacology)
• Disease Models, Animal
• Ischemic Postconditioning
• Male
• Mitochondrial Permeability Transition Pore (metabolism)
• Post-Cardiac Arrest Syndrome (metabolism, pathology, prevention & control)
• Swine