Int J Med Sci 2022; 19(6):1036-1046. doi:10.7150/ijms.73151 This issue Cite

Research Paper

Viable Allogeneic Mitochondria Transplantation Improves Gas Exchange and Alveolar-Capillary Permeability in Rats with Endotoxin-Induced Acute Lung Injuries

Yu-Li Pang1, Shi-Yuan Fang2, Tzu-Ting Cheng3, Chien-Chi Huang3,4, Ming-Wei Lin4, Chen-Fuh Lam3,5*✉, Kuen-Bao Chen6*✉

1. Department of Anesthesiology, Chi Mei Medical Center, Tainan 710, Taiwan.
2. Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
3. Department of Anesthesiology, E-Da Hospital and E-Da Cancer Hospital, Kaohsiung 824, Taiwan.
4. Department of Medical Research, E-Da Hospital and E-Da Cancer Hospital, Kaohsiung 824, Taiwan.
5. School of Medicine, I-Shou University College of Medicine, Kaohsiung 824, Taiwan.
6. Department of Anesthesiology, China Medical University Hospital, Taichung 404, Taiwan.
*Equal contributions in this work.

Citation:
Pang YL, Fang SY, Cheng TT, Huang CC, Lin MW, Lam CF, Chen KB. Viable Allogeneic Mitochondria Transplantation Improves Gas Exchange and Alveolar-Capillary Permeability in Rats with Endotoxin-Induced Acute Lung Injuries. Int J Med Sci 2022; 19(6):1036-1046. doi:10.7150/ijms.73151. https://www.medsci.org/v19p1036.htm
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Abstract

Graphic abstract

Background: Acute lung injuries (ALI) cause disruption of the alveolar-capillary barrier and is the leading cause of death in critically ill patients. This study tested the hypothesis that the administration of freshly isolated viable allogeneic mitochondria can prevent alveolar-capillary barrier injuries at the endothelial level, as mitochondrial dysfunction of the pulmonary endothelium is a critical aspect of ALI progression.

Methods: ALI was induced by intratracheal lipopolysaccharide instillation (LPS, 1mg/kg) in anesthetized rats. Mitochondria (100 µg) were isolated from the freshly harvested soleus muscles of naïve rats and stained with a green fluorescence MitoTracker™ dyne. A mitochondria or placebo solution was randomly administered into the jugular veins of the rats at 2 h and 4 h after ALI induction. An arterial blood gas analysis was done 20 h later. The animals were then sacrificed and lung tissues were harvested for analysis.

Results: An IVIS Spectrum imaging system was used to obtain ex vivo heart-lung block images and track the enhancement of MitoTracker™ fluorescence in the lungs. Mitochondria transplantation significantly improved arterial oxygen contents (PaO2 and SaO2) and reduced CO2 tension in rats with ALI. Animals with mitochondrial transplants had significantly higher ATP concentrations in their lung tissues. Allogeneic mitochondria transplantation preserved alveolar-capillary barrier function, as shown by a reduction in protein levels in the bronchoalveolar lavage fluid and decreased extravasated Evans blue dyne and hemoglobin content in lung tissues. In addition, relaxation responses to acetylcholine and eNOS expression were potentiated in injured pulmonary arteries and inflammatory cells infiltration into lung tissue was reduced following mitochondrial transplantation.

Conclusions: Transplantation of viable mitochondria protects the integrity of endothelial lining of the alveolar-capillary barrier, thereby improving gas exchange during the acute stages of endotoxin-induced ALI. However, the long-term effects of mitochondrial transplantation on pulmonary function recovery after ALI requires further investigation.

Keywords: ATP, ARDS, endothelial function, hyaline membrane, pulmonary artery


Citation styles

APA
Pang, Y.L., Fang, S.Y., Cheng, T.T., Huang, C.C., Lin, M.W., Lam, C.F., Chen, K.B. (2022). Viable Allogeneic Mitochondria Transplantation Improves Gas Exchange and Alveolar-Capillary Permeability in Rats with Endotoxin-Induced Acute Lung Injuries. International Journal of Medical Sciences, 19(6), 1036-1046. https://doi.org/10.7150/ijms.73151.

ACS
Pang, Y.L.; Fang, S.Y.; Cheng, T.T.; Huang, C.C.; Lin, M.W.; Lam, C.F.; Chen, K.B. Viable Allogeneic Mitochondria Transplantation Improves Gas Exchange and Alveolar-Capillary Permeability in Rats with Endotoxin-Induced Acute Lung Injuries. Int. J. Med. Sci. 2022, 19 (6), 1036-1046. DOI: 10.7150/ijms.73151.

NLM
Pang YL, Fang SY, Cheng TT, Huang CC, Lin MW, Lam CF, Chen KB. Viable Allogeneic Mitochondria Transplantation Improves Gas Exchange and Alveolar-Capillary Permeability in Rats with Endotoxin-Induced Acute Lung Injuries. Int J Med Sci 2022; 19(6):1036-1046. doi:10.7150/ijms.73151. https://www.medsci.org/v19p1036.htm

CSE
Pang YL, Fang SY, Cheng TT, Huang CC, Lin MW, Lam CF, Chen KB. 2022. Viable Allogeneic Mitochondria Transplantation Improves Gas Exchange and Alveolar-Capillary Permeability in Rats with Endotoxin-Induced Acute Lung Injuries. Int J Med Sci. 19(6):1036-1046.

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