Abstract
Purpose The endothelium has a pivotal role in the maintenance of cardiac function after heart transplantation, mainly by controlling the coronary circulation. Brain death (BD) as well as ischemia/reperfusion (IR) injury compromise vascular endothelium and thereby myocardial protection. Beneficial effects of conditioned medium (CM) from mesenchymal stem cells (MSCs) against IR injury have been demonstrated. We hypothesized that physiological saline supplemented CM could protect vascular grafts of BD rats from IR injury. Methods Rat MSCs derived CM was used for conservation purposes. We detected 28 factors involved in inflammation, oxidative stress and apoptosis. Donors were either subjected to sham operation or BD by inflation of a subdural balloon for 5.5h. Then, thoracic aortic rings from BD rats were isolated and immediately mounted after preparation in an organ bath chamber (BD group) or underwent 24h cold ischemic preservation in physiological saline supplemented either with a vehicle (BD-IR group) or CM (BD-IR+CM group). Immunohistochemical staining for myeloperoxidase (MPO), nitrotyrosine (NT), caspase-8, -9, and -12 was performed. Results Characterization of BD donors: Compared to the sham group, BD leads to significantly impaired hemodynamic parameters, higher aortic MPO, NT, caspase-8, -9, and -12 contents. Organ bath experiments: The preservation of BD-IR aortic rings with CM significantly improved IR-induced decreased maximum endothelium dependent vasorelaxation (Rmax) to acetylcholine compared to the vehicle treated BD-IR group (Rmax to acetylcholine: BD 81±2 vs BD-IR 50±3 vs BD-IR+CM 72±2%, p Conclusion Endothelial dysfunction during IR injury is improved by preservation of vascular grafts from BD rats with CM. This protective effect may partly arise from a reduction of inflammation and nitro oxidative stress responses, and inhibition of caspase-8 and -9 mediated apoptosis.
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