Protective Role of Dimethyltryptamine in Preserving Donor Heart Function in a Heterotopic Rat Transplantation Model

Preserving donor organ viability during cold storage is critical for successful heart transplantation, as ischemia–reperfusion injury (IRI) adversely affects graft function. N,N-Dimethyltryptamine (DMT), an endogenous sigma-1 receptor ligand, has demonstrated cytoprotective effects under hypoxic and oxidative stress. This study evaluated the effects of DMT on graft recovery in a rat model of heterotopic heart transplantation. Hearts from male Lewis rats were preserved for 1 hour at 4°C in either standard Custodiol solution or Custodiol supplemented with DMT. Both donors and recipients in the treatment group also received DMT. After transplantation, graft function was assessed 60 minutes into reperfusion using pressure–volume analysis, complemented by molecular and histological evaluations. DMT-treated grafts exhibited higher left ventricular systolic pressure, enhanced myocardial contractility and improved diastolic relaxation compared with controls. Gene expression analysis revealed significant modulation of Ddit3, Hif1a and Vldlr, with additional trends in apoptotic and metabolic markers. A strong trend toward reduced cleaved caspase-3 expression and significantly lower p62 immunohistochemical scores further supported attenuation of cellular stress, whereas cardiac troponin I and TNF-α levels were unchanged. These findings indicate that DMT treatment preserves myocardial function and improves early graft performance, potentially through modulation of mitochondrial, metabolic and cellular stress pathways.