Transplantation of donor hearts after circulatory or brain death in a rat model

Shiliang Li; Sivakkanan Loganathan; Sevil Korkmaz; Tamás Radovits; Peter Hegedűs; Yan Zhou; Matthias Karck; Gábor Szabó

doi:10.1016/j.jss.2014.12.038

Transplantation of donor hearts after circulatory or brain death in a rat model

J Surg Res. 2015 May 1;195(1):315-24. doi: 10.1016/j.jss.2014.12.038. Epub 2014 Dec 24.

Authors

Shiliang Li¹, Sivakkanan Loganathan², Sevil Korkmaz³, Tamás Radovits⁴, Peter Hegedűs⁵, Yan Zhou⁶, Matthias Karck³, Gábor Szabó³

Affiliations

¹ Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. Electronic address: lishiliangcom@hotmail.com.
² Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany; Department of Anesthesiology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
³ Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.
⁴ Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
⁵ Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany; Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
⁶ Department of Otolaryngology, Union Hospital of Tongji Medical College, Hua-Zhong University of Science and Technology, Wuhan, China.

PMID: 25592272
DOI: 10.1016/j.jss.2014.12.038

Abstract

Background: Heart transplantation represents the only curative treatment for end-stage heart failure. Presently, the donor pool is restricted to brain-dead donors. Based on the lack of suitable donors and the increasing number of patients, we investigated some molecular pathomechanisms of the potential use of hearts after circulatory determination of death (DCDD) in transplantation.

Materials and methods: Rats were either maintained brain death for 5 h by inflation of a subdurally placed balloon catheter (n = 6) or subjected to cardiac arrest by exsanguinations (n = 6). Additionally, a control group was used (n = 9). Then the hearts were perfused with a cold preservation solution (Custodiol), explanted, stored at 4°C in Custodiol, and heterotopically transplanted.

Results: Brain death was associated with decreased left-ventricular contractility (dP/dtmax: 4895 ± 505 versus 8037 ± 565 mm Hg/s; ejection fraction: 27 ± 5 versus 44 ± 5%; Emax: 2.2 ± 0.3 versus 4.2 ± 0.3 mm Hg/μL; preload recruitable stroke work: 59 ± 5 versus 96 ± 6 mm Hg; 5 h after brain death versus before brain death; P < 0.05) and impaired cardiac relaxation (dP/dtmin: -4734 ± 575 versus -9404 ± 550 mm Hg/s and prolonged Tau, P < 0.05) compared with controls. After transplantation, significantly decreased systolic function and prolonged Tau were observed in brain-dead and DCDD groups compared with those in controls. Tumor necrosis factor-alpha, cyclooxygenase-2, nuclear factor-κB, inducible-NOS, and caspase-3 messenger RNA and protein-levels were significantly increased in the brain-dead compared with both control and DCDD groups. Additionally, marked myocardial inflammatory cell infiltration, edema, necrosis, and DNA-strand breaks were observed in the brain-dead group.

Conclusions: Our results show that despite the similar functional outcome in DCDD and brain-dead groups, brain-dead hearts showed marked myocardial inflammatory cell infiltration, edema, necrosis, DNA-strand breaks, and increased transcriptional and posttranscriptional expression for markers of apoptosis and inflammatory signaling pathways.

Keywords: Brain death; Donation after circulatory declaration of death; Graft function; Heart transplantation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain Death*
DNA Breaks
Heart Transplantation*
Male
Models, Animal
Myocardium / metabolism
Myocardium / pathology
Random Allocation
Rats, Inbred Lew
Ventricular Function, Left