Anti-inflammatory and metabolic effects of remote ischemic preconditioning and postconditioning on the contractile performance of the diaphragm in endotoxemic rats

Tork, Ola M.; Dawood, Amal F.; Sadek, Nermeen B.; Mahmoud, Manal M.; Rashed, Laila A.; Selim, Samah

doi:10.4103/1687-4625.182555

Anti-inflammatory and metabolic effects of remote ischemic preconditioning and postconditioning on the contractile performance of the diaphragm in endotoxemic rats

Authors

Abstract

Background
Respiratory failure is a major cause of mortality during septic shock and is due in part to the decreased ventilatory muscles contraction. These muscles depend mainly on fatty acid oxidation as an important source of ATP. We investigated the effects of remote ischemic preconditioning and postconditioning (RpostC) on the contractile functions of the diaphragm in relation to metabolic functions during systemic inflammation in lipopolysaccharide (LPS)-induced endotoxemia model.
Materials and methods
A total of 24 adult male albino rats were divided equally into four groups: (i) the control group (group 1); (ii) LPS group (group 2), in which rats were treated with a single intraperitoneal injection of LPS (0.8 mg/kg intraperitoneal single dose); (iii) preconditioned group (group 3), in which remote ischemic preconditioning was induced with three ischemia/reperfusion cycles of the right hind limbs just before LPS injection; and (iv) postconditioned group (group 4), in which remote ischemic postconditioning was induced as in group 3 just after LPS injection. The animals were killed 5 days after the treatment. Among all groups, the contractility of the diaphragm was examined and the gene expressions of the carnitine palmitoyl transferase 1β (0β), the nuclear receptor peroxisome proliferator-activated receptor-α (α), peroxisome proliferator-activated receptor γ coactivator-1α (α), and the nuclear factor erythroid 2-related factor 2 () - the master of antioxidant response element - by real-time reverse transcription-PCR in the rat diaphragm tissue were determined; in addition, the serum levels of inflammatory markers, tumor necrosis factor α (TNFα) and interleukin-6, and lipids were measured.
Results
Both types of remote ischemic, preconditioning and postconditioning, significantly improved the contractile performance of the diaphragm ( < 0.001) compared with rats in the LPS group. These improvements were accompanied with significant elevation in the diaphragmatic expression of PPARα, PGC-1α, and CPT-1β, together with decreased serum lipids. In addition, there was a significant improvement in Nrf2 with a reduction in serum TNFα and interleukin-6.
Conclusion
Our results showed that the improvement of contractile performance of the diaphragm during sepsis was related to the improvement in the expression of nuclear hormone receptors involved in fat oxidation and modulation in oxidative stress and its consequences on inflammatory response. On the basis of these findings, we can suggest that early rational postconditioning interventions may be one of the promising strategies in the management of sepsis.

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