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Differential inflammatory responses of the native left and right ventricle associated with donor heart preservation.

Publication ,  Journal Article
Lei, I; Huang, W; Ward, PA; Pober, JS; Tellides, G; Ailawadi, G; Pagani, FD; Landstrom, AP; Wang, Z; Mortensen, RM; Cascalho, M; Platt, J ...
Published in: Physiol Rep
September 2021

BACKGROUND: Dysfunction and inflammation of hearts subjected to cold ischemic preservation may differ between left and right ventricles, suggesting distinct strategies for amelioration. METHODS AND RESULTS: Explanted murine hearts subjected to cold ischemia for 0, 4, or 8 h in preservation solution were assessed for function during 60 min of warm perfusion and then analyzed for cell death and inflammation by immunohistochemistry and western blotting and total RNA sequencing. Increased cold ischemic times led to greater left ventricle (LV) dysfunction compared to right ventricle (RV). The LV experienced greater cell death assessed by TUNEL+ cells and cleaved caspase-3 expression (n = 4). While IL-6 protein levels were upregulated in both LV and RV, IL-1β, TNFα, IL-10, and MyD88 were disproportionately increased in the LV. Inflammasome components (NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC), cleaved caspase-1) and products (cleaved IL-1β and gasdermin D) were also more upregulated in the LV. Pathway analysis of RNA sequencing showed increased signaling related to tumor necrosis factor, interferon, and innate immunity with ex-vivo ischemia, but no significant differences were found between the LV and RV. Human donor hearts showed comparable inflammatory responses to cold ischemia with greater LV increases of TNFα, IL-10, and inflammasomes (n = 3). CONCLUSIONS: Mouse hearts subjected to cold ischemia showed time-dependent contractile dysfunction and increased cell death, inflammatory cytokine expression and inflammasome expression that are greater in the LV than RV. However, IL-6 protein elevations and altered transcriptional profiles were similar in both ventricles. Similar changes are observed in human hearts.

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Published In

Physiol Rep

DOI

EISSN

2051-817X

Publication Date

September 2021

Volume

9

Issue

17

Start / End Page

e15004

Location

United States

Related Subject Headings

  • Ventricular Dysfunction, Right
  • Ventricular Dysfunction, Left
  • Tissue Donors
  • Organ Preservation Solutions
  • Myocardial Ischemia
  • Middle Aged
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Inflammation Mediators
 

Citation

APA
Chicago
ICMJE
MLA
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Lei, I., Huang, W., Ward, P. A., Pober, J. S., Tellides, G., Ailawadi, G., … Tang, P. C. (2021). Differential inflammatory responses of the native left and right ventricle associated with donor heart preservation. Physiol Rep, 9(17), e15004. https://doi.org/10.14814/phy2.15004
Lei, Ienglam, Wei Huang, Peter A. Ward, Jordan S. Pober, George Tellides, Gorav Ailawadi, Francis D. Pagani, et al. “Differential inflammatory responses of the native left and right ventricle associated with donor heart preservation.Physiol Rep 9, no. 17 (September 2021): e15004. https://doi.org/10.14814/phy2.15004.
Lei I, Huang W, Ward PA, Pober JS, Tellides G, Ailawadi G, et al. Differential inflammatory responses of the native left and right ventricle associated with donor heart preservation. Physiol Rep. 2021 Sep;9(17):e15004.
Lei, Ienglam, et al. “Differential inflammatory responses of the native left and right ventricle associated with donor heart preservation.Physiol Rep, vol. 9, no. 17, Sept. 2021, p. e15004. Pubmed, doi:10.14814/phy2.15004.
Lei I, Huang W, Ward PA, Pober JS, Tellides G, Ailawadi G, Pagani FD, Landstrom AP, Wang Z, Mortensen RM, Cascalho M, Platt J, Eugene Chen Y, Lam HYK, Tang PC. Differential inflammatory responses of the native left and right ventricle associated with donor heart preservation. Physiol Rep. 2021 Sep;9(17):e15004.

Published In

Physiol Rep

DOI

EISSN

2051-817X

Publication Date

September 2021

Volume

9

Issue

17

Start / End Page

e15004

Location

United States

Related Subject Headings

  • Ventricular Dysfunction, Right
  • Ventricular Dysfunction, Left
  • Tissue Donors
  • Organ Preservation Solutions
  • Myocardial Ischemia
  • Middle Aged
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Inflammation Mediators