Liang 2021 Biomed Pharmacother
Liang L, Zhang G, Cheng C, Li H, Jin T, Su C, Xiao Y, Bradley J, Peberdy MA, Ornato JP, Mangino MJ, Tang W (2021) High-resolution respirometry for evaluation of mitochondrial function on brain and heart homogenates in a rat model of cardiac arrest and cardiopulmonary resuscitation. Biomed Pharmacother 142:111935. |
Β» PMID: 34467895 Open Access Β»
Liang Lian, Zhang Guozhen, Cheng Cheng, Li Hui, Jin Tao, Su Chenglei, Xiao Yan, Bradley Jennifer, Peberdy Mary A, Ornato Joseph P, Mangino Martin J, Tang Wanchun (2021) Biomed Pharmacother
Abstract: The physiology and physiopathology process of mitochondrial function following cardiac arrest remains poorly understood. We aimed to assess mitochondrial respiratory function on the heart and brain homogenates from cardiac arrest rats. The expression level of SIRT1/PGC-1Ξ± pathway was measured by immunoblotting. 30 rats were assigned to the CA group and the sham group. Rats of CA were subjected to 6 min of untreated ventricular fibrillation (VF) followed by 8 min of cardiopulmonary resuscitation (CPR). Mitochondrial respiratory function was compromised following CA and I/R injury, as indicated by CIL (451.46 Β± 71.48 vs. 909.91 Β± 5.51 pmol/min*mg for the heart and 464.14 Β± 8.22 vs. 570.53 Β± 56.33 pmol/min*mg for the brain), CI (564.04 Β± 64.34 vs. 2729.52 Β± 347.39 pmol/min*mg for the heart and 726.07 Β± 85.78 vs. 1762.82 Β± 262.04 pmol/min*mg for the brain), RCR (1.88 Β± 0.46 vs. 3.57 Β± 0.38 for the heart and 2.05 Β± 0.19 vs. 3.49 Β± 0.19, for the brain) and OXPHOS coupling efficiency (0.45 Β± 0.11 vs. 0.72 Β± 0.03 for the heart and 0.52 Β± 0.05 vs. 0.71 Β± 0.01 for the brain). However, routine respiration was lower in the heart and comparable in the brain after CA. CIV did not change in the heart but was enhanced in the brain. Furthermore, both SIRT1 and PGC-1Ξ± were downregulated concurrently in the heart and brain. The mitochondrial respiratory function was compromised following CA and I/R injury, and the major affected respiratory state is complex I-linked respiration. Furthermore, the heart and the brain respond differently to the global I/R injury after CA in mitochondrial respiratory function. Inhibition of the SIRT1/PGC-1Ξ± pathway may be a major contributor to the impaired mitochondrial respiratory function. β’ Keywords: Cardiac arrest, High-resolution respirometry, Ischemia-reperfusion injury, Mitochondrial respiratory function, SIRT1/PGC-1Ξ± pathway β’ Bioblast editor: Plangger M β’ O2k-Network Lab: US VA Richmond Mangino MJ
Labels: MiParea: Respiration
Pathology: Cardiovascular
Stress:Ischemia-reperfusion
Organism: Rat
Tissue;cell: Heart, Nervous system
Preparation: Homogenate
Coupling state: LEAK, ROUTINE, OXPHOS
Pathway: N, S, CIV, ROX
HRR: Oxygraph-2k
2021-09, O2k-brief