The protective effects of L-carnitine on myocardial ischaemia-reperfusion injury in patients with rheumatic valvular heart disease undergoing CPB surgery are associated with the suppression of NF-κB pathway and the activation of Nrf2 pathway

Clin Exp Pharmacol Physiol. 2019 Nov;46(11):1001-1012. doi: 10.1111/1440-1681.13155. Epub 2019 Aug 26.

Abstract

Myocardial ischaemia-reperfusion injury (MIRI) is a main pathophysiologic change following CPB surgery. L-carnitine, a natural amino acid, is able to transport fatty acids for generating energy and has a protective effect on MIRI. We aim to investigate the protective effect of L-carnitine on MIRI in patients with rheumatic valvular heart disease (RVHD) performed CPB surgical operation and the underlying mechanism. In this study, patients were randomized to three groups. L-carnitine was added to the crystalloid cardioplegic solution for experimental group 1 (6 g/L) and experimental group 2 (12 g/L), whereas no L-carnitine was used in the control group. Our results showed that L-carnitine significantly attenuated myocardial injury after surgery in these patients. L-carnitine decreased serum markers of myocardial injury including CK-MB, cTnI, hs-cTnT and IMA. L-carnitine increased left ventricular ejection fraction (LVEF) but reduced wall motion score index (WMSI) after operation. L-carnitine also inhibited myeloperoxidase (MPO) activity and inflammatory cytokines in the myocardium of patients after unclamping the aorta. Additionally, L-carnitine increased levels of superoxide dismutase (SOD) and catalase (CAT) while decreased levels of malondialdehyde (MDA) and protein carbonyl content in the myocardium of patients after unclamping the aorta. Moreover, L-carnitine suppressed the activation of nuclear factor kappa B (NF-κB) and activated nuclear factor erythroid 2-related factor 2 (Nrf2). There was also no significant difference in these indices between two experimental groups after unclamping the aorta. Taken together, L-carnitine had a protective effect against CPB-induced MIRI in patients with RVHD, which might be related to its modulation of NF-κB and Nrf2 activities.

Keywords: L-carnitine; cardiopulmonary bypass surgery; myocardial ischaemia-reperfusion injury; oxidative stress; rheumatic valvular heart disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Carnitine / pharmacology*
  • Female
  • Heart Valve Diseases / surgery*
  • Humans
  • Male
  • Middle Aged
  • Myocardial Reperfusion Injury / etiology*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / prevention & control*
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / metabolism*
  • Oxidative Stress / drug effects
  • Postoperative Period

Substances

  • Biomarkers
  • NF-E2-Related Factor 2
  • NF-kappa B
  • NFE2L2 protein, human
  • Carnitine