Tumour necrosis factor‐α contributes to improved cardiac ischaemic tolerance in rats adapted to chronic continuous hypoxia. (28th March 2015)

• Record Type: Journal Article
• Authors: Chytilová, A.; Borchert, G. H.; Mandíková‐Alánová, P.; Hlaváčková, M.; Kopkan, L.; Khan, Md. A. Hye; Imig, J. D.; Kolář, F.; Neckář, J.
• Is Part Of: Acta physiologica. Volume 214:Number 1(2015:May)
• Page Start: 97
• Page End: 108
• Publication Date: 2015-03-28
• Subjects: Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.12489
• Languages: English
• ISSNs: 1748-1708

Abstract

<abstract abstract-type="main" id="apha12489-abs-0001"> <title>Abstract</title> <sec id="apha12489-sec-0001" sec-type="section"> <title>Aim</title> <p>It has been demonstrated that tumour necrosis factor‐alpha (TNF‐<italic>α</italic>) <italic>via</italic> its receptor 2 (TNFR2) plays a role in the cardioprotective effects of preconditioning. It is also well known that chronic hypoxia is associated with activation of inflammatory response. With this background, we hypothesized that TNF‐<italic>α</italic> signalling may contribute to the improved ischaemic tolerance of chronically hypoxic hearts.</p> </sec> <sec id="apha12489-sec-0002" sec-type="section"> <title>Methods</title> <p>Adult male Wistar rats were kept either at room air (normoxic controls) or at continuous normobaric hypoxia (CNH; inspired O<sub>2</sub> fraction 0.1) for 3 weeks; subgroups of animals were treated with infliximab (monoclonal antibody against TNF‐<italic>α</italic>; 5 mg kg<sup>−1</sup>, i.p., once a week). Myocardial levels of oxidative stress markers and the expression of selected signalling molecules were analysed. Infarct size (tetrazolium staining) was assessed in open‐chest rats subjected to acute coronary artery occlusion/reperfusion.</p> </sec> <sec id="apha12489-sec-0003" sec-type="section"> <title>Results</title> <p>CNH increased myocardial TNF‐<italic>α</italic> level and expression of TNFR2; this response was abolished by infliximab treatment. CNH reduced myocardial infarct size from 50.8 ± 4.3% of the area at risk in normoxic animals to 35.5 ± 2.4%. Infliximab abolished the protective effect of CNH (44.9 ± 2.0%). CNH increased the levels of oxidative stress markers (3‐nitrotyrosine and malondialdehyde), the expression of nuclear factor <italic>κ</italic>B and manganese superoxide dismutase, while these effects were absent in infliximab‐treated animals. CNH‐elevated levels of inducible nitric oxide synthase and cyclooxygenase 2 were not affected by infliximab.</p> </sec> <sec id="apha12489-sec-0004" sec-type="section"> <title>Conclusion</title> <p>TNF‐<italic>α</italic> plays a role in the induction of ischaemia‐resistant cardiac phenotype of CNH rats, possibly <italic>via</italic> the activation of protective redox signalling.</p> </sec> </abstract>