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Protection of Myocardial Ischemia–Reperfusion by Therapeutic Hypercapnia: a Mechanism Involving Improvements in Mitochondrial Biogenesis and Function

  • Laiting Chi
  • Nan Wang
  • Wanchao Yang
  • Qi Wang
  • Dengming Zhao
  • Tian Sun
  • Wenzhi LiEmail author
Original Article
  • 76 Downloads

Abstract

Previous studies proposed that acidic reperfusion may be a protective strategy for myocardial ischemia–reperfusion therapy with potential of clinical transformation. In this study, we investigated whether therapeutic hypercapnia could mimic acidosis postconditioning in isolated hearts with a 30-min left coronary artery ligation–reperfusion model in rats. Therapeutic hypercapnia (inhalation 20% CO2 for 10 min) is cardioprotective with a strict therapeutic time window and acidity: it reduced the infarct ratio and serum myocardial enzyme and increased the myocardial ATP content. Furthermore, mitochondrial morphology damage, the loss of mitochondrial membrane potential, and the formation of mitochondrial permeability transition pore were effectively inhibited, indicating the improvements in mitochondrial function. The expression of the mitochondrial biogenesis regulators was upregulated simultaneously. These findings indicated therapeutic hypercapnia in animals can mimic ex vivo acidosis postconditioning to alleviate myocardial ischemia–reperfusion injury. The effect is related to improvement in mitochondrial function and regulation of the mitochondrial biogenesis pathway.

Keywords

Myocardial ischemia–reperfusion Hypercapnia Mitochondrial biogenesis Acidosis Postconditioning 

Abbreviations

AMPK

AMP-activated protein kinase

cTnI

Cardiac troponin I

IR

Ischemia–reperfusion

MAP

Mean arterial pressure

MPTP

Mitochondrial permeability transition pores

NBC

Na+–bicarbonate cotransporter

NCE

Na+–Ca2+ exchanger

NHE

Na+–H+ exchanger

NMR

Nuclear magnetic resonance

PCI

Percutaneous coronary intervention

PGC-1α

Peroxisome proliferator–activated receptor γ coactivator-1α

pHi

Intracellular pH

PI3K

Phosphatidylinositol 3 kinase

PKC

Protein kinase C

TEM

Transmission electron microscopy

TFAM

Mitochondrial transcription factor A

TTC

2,3,5-triphenyltetrazolium chloride

ROS

Reactive oxygen species

∆Ψm

Mitochondrial membrane potential

Notes

Acknowledgments

The authors greatly appreciate the technical assistance of the Department of Pathology of Harbin Medical University (Harbin, Heilongjiang Province, China) in transmission electron microscope evaluation, Harbin, Heilongjiang Province, China.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All institutional ethical guidelines and national guidelines for the care and use of laboratory animals were followed and approved by the Animal Care Committee of Harbin Medical University, China. No human studies were carried out for this article.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Laiting Chi
    • 1
  • Nan Wang
    • 1
  • Wanchao Yang
    • 1
  • Qi Wang
    • 1
  • Dengming Zhao
    • 1
  • Tian Sun
    • 1
  • Wenzhi Li
    • 1
    Email author
  1. 1.Department of Anesthesiology, The Heilongjiang Province Key Lab of Research on Anesthesiology and Critical Care MedicineSecond Affiliated Hospital of Harbin Medical UniversityHarbinChina

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