Cardioprotective effect of Interleukin-11 against warm ischemia-reperfusion injury in a rat heart donor model

Tomoki Sakata, Hiroki Kohno, Tomohiko Inui, Hiroki Ikeuchi, Yuki Shiko, Yohei Kawasaki, Shota Suzuki, Shota Tanaka, Masanori Obana, Kiyotake Ishikawa, Yasushi Fujio, Goro Matsumiya

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Abstract

Shortage of donor organs for heart transplantation is a worldwide problem. Donation after circulatory death (DCD) has been proposed to expand the donor pool. However, in contrast to the donation after brain death that undergoes immediate cold preservation, warm ischemia and subsequent reperfusion injury are inevitable in DCD. It has been reported that interleukin-11 (IL-11) mitigates ischemia-reperfusion injury in rodent models of myocardial infarction and donation after brain death heart transplantation. We hypothesized that IL-11 also offers benefit to warm ischemia in an experimental model of cardiac transplantation that resembles DCD. The hearts of naïve male Sprague Dawley rats (n = 15/group) were procured, subjected to 25-min warm ischemia, and reperfused for 60 min using Langendorff apparatus. IL-11 or saline was administered intravenously before the procurement, added to maintenance buffer, and infused via perfusion during reperfusion. IL-11 group exhibited significantly better cardiac function post-reperfusion. Severely damaged mitochondria was found in the electron microscopic analysis of control hearts whereas the mitochondrial structure was better preserved in the IL-11 treated hearts. Immunoblot analysis using neonatal rat cardiomyocytes revealed increased signal transducer and activator of transcription 3 (STAT3) phosphorylation at Ser727 after IL-11 treatment, suggesting its role in mitochondrial protection. Consistent with expected activation of mitochondrial respiration by mitochondrial STAT3, immunohistochemical staining demonstrated a higher mitochondrial cytochrome c oxidase subunit 2 expression. In summary, IL-11 protects the heart from warm ischemia reperfusion injury by alleviating mitochondrial injury and could be a viable therapeutic option for DCD heart transplantation.

Original languageEnglish
Article number176145
JournalEuropean Journal of Pharmacology
Volume961
DOIs
StatePublished - 15 Dec 2023

Keywords

  • Donation after circulatory death
  • Ex-vivo organ perfusion
  • Heart transplantation
  • Interleukin-11
  • Ischemia reperfusion injury
  • Mitochondrial damage

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