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Circulation. 2019 Aug 20;140(8):627-640. doi: 10.1161/CIRCULATIONAHA.119.039932. Epub 2019 Jul 29.

Donor Simvastatin Treatment in Heart Transplantation.

Author information

1
Transplantation Laboratory (A.I.N., E.J.H., R.T., R.K., K.D., S.O.S., K.B.L.), University of Helsinki and Helsinki University Hospital, Finland.
2
Department of Cardiothoracic Surgery (A.I.N., S.O.S., K.B.L.), University of Helsinki and Helsinki University Hospital, Finland.
3
Translational Immunology Program Research Programs Unit (A.I.N., E.J.H., R.T., R.K., K.D., M.K., S.O.S., K.B.L.), University of Helsinki and Helsinki University Hospital, Finland.
4
Medical and Clinical Genetics (M.K.), University of Helsinki and Helsinki University Hospital, Finland.
5
Institute for Molecular Medicine Finland, University of Helsinki (M.K.).
6
Department of Cardiology (J.L.), University of Helsinki and Helsinki University Hospital, Finland.
7
Päijät-Häme Central Hospital, Department of Surgery, Lahti, Finland (J.J.J.).
8
Transplantation and Liver Surgery (I.H.), University of Helsinki and Helsinki University Hospital, Finland.
9
Pathology (A.R.-S.), University of Helsinki and Helsinki University Hospital, Finland.

Abstract

BACKGROUND:

Ischemia-reperfusion injury may compromise the short-term and long-term prognosis after heart transplantation. Experimental studies show that simvastatin administered to the organ donor is vasculoprotective and inhibits cardiac allograft ischemia-reperfusion injury.

METHODS:

Eighty-four multiorgan donors were randomly assigned to receive 80 mg of simvastatin (42 donors) via nasogastric tube after declaration of brain death and upon acceptance as a cardiac donor, or to receive no simvastatin (42 donors). The primary efficacy end point was postoperative plasma troponin T and I levels during the first 24 hours after heart transplantation. Secondary end points included postoperative hemodynamics, inflammation, allograft function, rejections and rejection treatments, and mortality.   Results: Organ donor simvastatin treatment significantly reduced the heart recipient plasma levels of troponin T by 34% (14 900 ± 12 100 ng/L to 9800 ± 7900 ng/L, P=0.047), and troponin I by 40% (171 000 ± 151 000 ng/L to 103 000 ± 109 000 ng/L, P=0.023) at 6 hours after reperfusion, the levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) by 36% (32 800 ± 24 300 ng/L to 20 900 ± 15 900 ng/L; P=0.011) at 1 week, and the number of rejection treatments with hemodynamic compromise by 53% within the first 30 days (P=0.046). Donor simvastatin treatment did not affect donor lipid levels but was associated with a specific transplant myocardial biopsy gene expression profile, and a decrease in recipient postoperative plasma levels of CXCL10 (C-X-C motif chemokine 10), interleukin-1α, placental growth factor, and platelet-derived growth factor-BB. Postoperative hemodynamics, biopsy-proven acute rejections, and mortality were similar. No adverse effects were seen in recipients receiving noncardiac solid organ transplants from simvastatin-treated donors.

CONCLUSIONS:

Donor simvastatin treatment reduces biomarkers of myocardial injury after heart transplantation, and-also considering its documented general safety profile-may be used as a novel, safe, and inexpensive adjunct therapy in multiorgan donation.

CLINICAL TRIAL REGISTRATION:

URL: https://www.clinicaltrials.gov. Unique identifier: NCT01160978.

KEYWORDS:

heart transplantation; ischemia; reperfusion; statins

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