Immunity and Stress Responses Are Induced During Ex Situ Heart Perfusion

Abstract

Background: Ex situ heart perfusion (ESHP) preserves the donated heart in a perfused, beating condition preventing cold storage–related ischemia and provides a platform to evaluate myocardial viability during preservation. However, myocardial function declines gradually during ESHP. Extracorporeal circulation systems are associated with the induction of systemic inflammatory and stress responses. Our aim was to evaluate the incidence of inflammation and induction of endoplasmic reticulum stress responses during an extended period of ESHP. Methods: Cardiac function, myocardial tissue injury, markers of inflammation, oxidative stress, and endoplasmic reticulum stress were assessed in healthy pig hearts, perfused for 12 hours either in nonworking mode (non-WM=7) or working mode (WM, n=6). Results: Cardiac function declined during ESHP but was significantly better preserved in the hearts perfused in WM (median 11-hour cardiac index/1-hour cardiac index: WM=27% versus non-WM=9.5%, P =0.022). Myocardial markers of endoplasmic reticulum stress were expressed higher in ESHP hearts compared with in vivo samples. The proinflammatory cytokines and oxidized low-density lipoprotein significantly increased in the perfusate throughout the perfusion in both perfusion groups. The left ventricular expression of the cytokines and malondialdehyde was induced in non-WM, whereas it was not different between WM and in vivo. Conclusions: Myocardial function declines during ESHP regardless of perfusion mode. However, ESHP in WM may lead to superior preservation of myocardial function and viability. Both inflammation and endoplasmic reticulum stress responses are significantly induced during ESHP and may contribute to the myocardial functional decline, representing a potential therapeutic target to improve the clinical donor heart preservation.

Damage-Associated Molecular Patterns in Myocardial Infarction and Heart Transplantation: The Road to Translational Success

“…A better strategy to study the involvement of DAMPs and PRRs in IRI following HTx may be found in using ex vivo heart machine perfusion (EVHP). Using healthy, physiologically relevant, pig hearts or rejected transplant hearts in the EVHP system allows to better reflect the human situation and to study inflammatory mechanisms and effect of therapeutics in more detail ( 197 , 198 ). Additionally, ischemia time is an important factor in IRI and transplantation outcome ( 199 ).…”

The tumor microenvironment may trigger lymphoproliferation in cardiac myxoma

“…Chronic inflammation, fibroblastic proliferation, dystrophic calcification, and even ossification within the CM have also been described [4] . These tumors are histologically benign, slow-growing neoplasms of unclear histogenesis, but may be associated with heart failure and/or cardiac arrhythmias [6] , [7] , [8] – 9] . They are most commonly sporadic, but up to 10% are associated with the Carney complex with a familial inheritance pattern [10] , [11] , [12] – 13] .…”

Heart transplant advances: Ex vivo organ-preservation systems

“…19 Finally, a durable "working-mode" perfusion platform has been elusive but would offer more direct assessment of function during perfusion, as well as potentially reducing some of the inflammatory response seen in Langendorff retrograde aortic perfusion. 20 In conclusion, ex vivo heart perfusion has already enabled significant expansion of the donor pool, the use of hearts that would otherwise have been excluded due to geographic or donor-related factors, and to date shows comparable outcomes with the standard of care.…”