Donor Simvastatin Treatment is More Effective in Donors with Low Plasma Levels of Arginine

Abstract

<h3>Purpose</h3> Brain death may lead to a severe impairment of endothelial function and affect graft function. Recent study shows that simvastatin treatment to the organ donor decreases plasma biomarker levels of myocardial injury and heart failure and reduces the number of acute rejection episodes with hemodynamic compromise early after heart transplantation. However, the mechanisms of donor simvastatin treatment remain unknown. Therefore, we analyzed the plasma metabolomics of brain-dead heart transplant donors with or without simvastatin treatment to examine the molecular background of the beneficial effects. <h3>Methods</h3> In a prospective, double-blinded randomized controlled trial, 84 multiorgan donors were randomly assigned to receive either 80 mg of simvastatin (n=42) via nasogastric tube or to receive no simvastatin (n=42). Plasma samples from 84 human brain-dead multi-organ donors were collected immediately before organ procurement. We profiled over 100 targeted metabolites using mass spectrometry. <h3>Results</h3> We found that arginine and tryptophan were weakly negatively correlated with simvastatin treatment. Univariate Cox regression analysis showed that low levels of arginine were significantly associated with acute rejection and graft-related mortality (Figure 1 A,B). Additionally, we saw that donor simvastatin treatment significantly reduced the number of acute rejections by 41% (p=0.012) in low arginine group within the first year (Figure 1C). There was no difference in donor demographics between the groups. However, there was a statistically significantly higher need for mechanical circulatory support for hearts from donors with low arginine levels. <h3>Conclusion</h3> This study shows that donor simvastatin treatment could be more efficient in brain-dead heart transplant donors with low arginine. Further analysis will be conducted by exploring the interplay between arginine and simvastatin in detail. The complete results will be presented at the ISHLT2022 congress.