Maarman 2015 Abstract MiPschool Cape Town 2015

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Characterisation of mitochondrial function in a model of pulmonary hypertension-induced right ventricular failure.

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Maarman G, Sliwa K, Lecour S (2015)

Event: MiPschool Cape Town 2015

Pulmonary hypertension (PH) is characterized by increased mean pulmonary artery pressure causes increased right ventricular (RV) afterload and failure, which leads to death [1]. PH causes mitochondrial dysfunction and this impacts the function of the RV [2-4]. Researchers are now focussing on novel cardioprotective therapies for PH, but the full extent of mitochondrial dysfunction in PH is not described and this could influence the efficacy of drugs that target the mitochondrial milieu [2-4]. Our aim was to characterize RV mitochondrial respiration in model of PH-induced RV failure. Male Long Evans rats, were injected with monocrotaline (MCT, 80mg/kg i.p, n=6) and control rats (CON) (n=6) received saline injections. After 28 days, mitochondria were isolated from RV sections. Mitochondrial respiration was assessed using an Oroboros Oxygraph-2k, with glutamate+malate or succinate as substrates and rotenone as inhibitor. When glutamate and malate were used as substrates: MCT hearts had a 21% lower RV state 2 (p< 0.02), 20% lower RV state 3 (p< 0.02), a 23% lower RV state 4 (p< 0.02) and unchanged RV RCI compared to controls. When succinate was used as a substrate and rotenone as inhibitor: MCT hearts had a 52% lower RV state 3 (p< 0.002), a 43% lower RV state 2 (p< 0.03), a 33% lower RV state 4 (p< 0.04) and RV RCI was similar between groups. Our data suggest that PH-induced RV failure is associated with a reduction of mitochondrial respiration through complexes I and II in both RV and LV sections (data not shown). This supports the importance of developing cardioprotective therapies that can correct or augment mitochondrial respiration.


O2k-Network Lab: ZA Cape Town Smith J


Labels: MiParea: Respiration, Instruments;methods, Patients, mt-Awareness  Pathology: Cardiovascular 

Organism: Rat  Tissue;cell: Heart  Preparation: Isolated mitochondria 


Coupling state: LEAK, OXPHOS  Pathway: N, S, NS  HRR: Oxygraph-2k 


Affiliations

Inst South Africa Newlands, ESSM UCT Dept Human Biol Sports Sc, Univ Cape Town, South Africa.- gerald.maarman@uct.ac.za

References

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