Markova 2017 MiP2017
Sepsis was induced by fecal peritonitis in 8 anesthetized, mechanically ventilated and instrumented pigs of both sexes and continued for 24 hours. In 8 control pigs, an identical experiment but without sepsis induction was performed. In vitro analysis of cardiac function included evaluation of myocardial contractility, electrophysiology, and mitochondrial respiration. Mitochondrial oxygen consumption was measured with O2k-FluoRespirometer in 2 ml chambers at 37°C. Samples from the left ventricle (1.5 – 2.0 mg) were permeabilized by saponin . Using SUIT protocol (G, M, P, D, c, S, Rot, Ama, As+Tm, Azd) standard respiratory states (LEAK, OXPHOS, and ROX), were characterized. Oxygen consumption was corrected on ROX and expressed per mg of tissue wet weight; data were statistically analyzed.
Septic pigs developed typical hyperdynamic circulation with increased cardiac output and peripheral vasodilatation. Contraction force was reduced in the septic hearts, probably due to defective calcium handling. Mitochondrial respiration was significantly suppressed. Oxygen consumption in the LEAK state and in the presence of ADP and Complex I and II substrates (OXPHOS I+II) was significantly reduced by sepsis and this reduction was mainly due to inhibition of Complex II (OXPHOS II), Complex I respiration was not affected. Cytochrome c oxidase (Complex IV) respiration was also decreased in sepsis.
In summary, decreased contraction and impaired calcium release from sarcoplasmic reticulum were accompanied by decreased mitochondrial respiration. However, question remains what is the primary event of sepsis-induced myocardial depression.
Labels: MiParea: Respiration Pathology: Sepsis
Organism: Pig Tissue;cell: Heart
Coupling state: LEAK, OXPHOS Pathway: N, S, CIV, NS, ROX HRR: Oxygraph-2k
- Markova M(1,2), Jarkovska D(1,2), Horak J(2,3), Nalos L(1,2), Benes J(2,4), AL-Obeidallah M(1,2,5), Sviglerova J(1,2), Kuncova J(1,2), Matejovic M(2,3), Stengl M(1,2)
- Dept Physiology
- Biomedical Center, Fac Medicine Pilsen CHU
- Dept Internal Medicine I, Fac Medicine Pilsen CHU Teaching Hospital
- Dept Anesthesia Intensive Care Medicine, Fac Medicine Pilsen CHU Teaching Hospital
- Dept Cardiac Surgery, Teaching Hospital, Pilsen; Czech Republic. - [email protected]
- Canto C, Garcia-Roves PM (2015) High-resolution respirometry for mitochondrial characterization of ex vivo mouse tissues. Curr Protoc Mouse Biol. 5:135-53.