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. 2023 Feb 7:36:10742.
doi: 10.3389/ti.2023.10742. eCollection 2023.

Effects of T3 Administration on Ex Vivo Rat Hearts Subjected to Normothermic Perfusion: Therapeutic Implications in Donor Heart Preservation and Repair

Iordanis Mourouzis  1 , Dimitris Kounatidis  1 , Vassiliki Brozou  1 , Dimitris Anagnostopoulos  1 , Athanasia Katsaouni  1 , Athanasios Lourbopoulos  1 , Constantinos Pantos  1
Affiliations

Effects of T3 Administration on Ex Vivo Rat Hearts Subjected to Normothermic Perfusion: Therapeutic Implications in Donor Heart Preservation and Repair

Iordanis Mourouzis et al. Transpl Int. .

Abstract

The present study investigated the effects of triiodothyronine (T3) administration in ex vivo model of rat heart normothermic perfusion. T3 is cardioprotective and has the potential to repair the injured myocardium. Isolated hearts were subjected to normothermic perfusion (NP) with Krebs-Henseleit for 4 h with vehicle (NP) or 60 nM T3 in the perfusate (NP + T3). Left ventricular end diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), perfusion pressure (PP) and percentage of change of these parameters from the baseline values were measured. Activation of stress induced kinase signaling was assessed in tissue samples. Baseline parameters were similar between groups. LVEDP was increased from the baseline by 13% (70) for NP + T3 vs. 139% (160) for NP group, p = 0.048. LVDP was reduced by 18.2% (5) for NP + T3 vs. 25.3% (19) for NP group, p = 0.01. PP was increased by 41% (19) for NP + T3 vs.91% (56) for NP group, p = 0.024. T3 increased activation of pro-survival Akt by 1.85 fold (p = 0.047) and AMPK by 2.25 fold (p = 0.01) and reduced activation of pro-apoptotic p38 MAPK by 3fold (p = 0.04) and p54 JNK by 4.0 fold (p = 0.04). Administration of T3 in normothermic perfusion had favorable effects on cardiac function and perfusion pressure and switched death to pro-survival kinase signaling.

Keywords: cold cardioplegia; heart; kinase signalling; normothermic perfusion; thyroid hormone.

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Conflict of interest statement

The following patent is relevant to the work in this manuscript: PCT/4972/2021. Pharmaceutical composition comprising L-triiodothyronine (T3) for use in the treatment of tissue hypoxia and sepsis. CP and IM are the inventors and hold royalties in relation to this patent. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic diagram showing the experimental design of the study. (A) Experiments performed to compare Cold Cardioplegia (CC) to normothermic perfusion (NP), (B) Experiments performed to investigate the effects of triiodothyronine (T3) in rat hearts with NP.
FIGURE 2
FIGURE 2
Left ventricular end-diastolic pressure (LVEDP, (A), left ventricular developed pressure [LVDP, (B)] and perfusion pressure [PP, (C)] in hearts preserved with cold cardiop legia (CC, n = 10) and hearts with normothermic perfusion (NP, n = 10). Values represent Means, bars stand for standard deviation. *p < 0.05, ***p; 0.001.
FIGURE 3
FIGURE 3
Left ventricular end-diastolic pressure [LVEDP, (A)], and perfusion pressure [PP, (B)] in hearts subjected to normothermic perfusion in Langendorff apparatus for 210 min after an initial period of 30 min perfusion (stabilization period). At the end of stabilization, KH buffer was supplemented either with vehicle (NP, n = 10) or with 60 nM T3 (NP + T3, n = 8). Values represent Means, bars stand for standard deviation. The respective non-linear fit-curves with the 95% Confidence Intervals produced with non-linear fit analysis are shown with dotted lines.
FIGURE 4
FIGURE 4
Representative western blots and densitometric assessment in arbitrary units of the ratio of phosphorylated Akt to total Akt expression (A), phosphorylated AMPK to total AMPK expression (B), phosphorylated p54 and p46 JNKs to total JNKs expression (C) and phosphorylated p38 MAPK to total p38 MAPK expression (D) in hearts at the end of normothermic perfusion supplemented either with vehicle (NP) or with 60 nM T3 (NP + T3). Data represent Means from n = 5 hearts per group. Bars stand for standard deviation. *p < 0.05, **p < 0.01.
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References

    1. Khush KK, Cherikh WS, Chambers DC, Harhay MO, Hayes D, Jr., Hsich E, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-Sixth Adult Heart Transplantation Report - 2019; Focus Theme: Donor and Recipient Size Match. J Heart Lung Transpl (2019) 38(10):1056–66. 10.1016/j.healun.2019.08.004 - DOI - PMC - PubMed
    1. Lepoittevin M, Giraud S, Kerforne T, Barrou B, Badet L, Bucur P, et al. Preservation of Organs to Be Transplanted: An Essential Step in the Transplant Process. Int J Mol Sci (2022) 23(9):4989. 10.3390/ijms23094989 - DOI - PMC - PubMed
    1. Minor T, von Horn C. Rewarming Injury after Cold Preservation. Int J Mol Sci (2019) 20(9):2059. 10.3390/ijms20092059 - DOI - PMC - PubMed
    1. Messer S, Ardehali A, Tsui S. Normothermic Donor Heart Perfusion: Current Clinical Experience and the Future. Transpl Int (2015) 28(6):634–42. 10.1111/tri.12361 - DOI - PubMed
    1. Minasian SM, Galagudza MM, Dmitriev YV, Karpov AA, Vlasov TD. Preservation of the Donor Heart: from Basic Science to Clinical Studies. Interact Cardiovasc Thorac Surg (2015) 20(4):510–9. 10.1093/icvts/ivu432 - DOI - PubMed

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