Activation of JAK-STAT and nitric oxide signaling as a mechanism for donor heart dysfunction

Abstract

Background-Donor heart dysfunction (DHD) precluding procurement for transplantation occurs in up to 25% of brain dead (BD) donors. The molecular mechanisms of DHD remain unclear. We investigated the potential role of myocardial interleukin (IL)-6 signaling through the JAK2-STAT3 pathway which can lead to the generation of nitric oxide (NO) and decreased cardiac myocyte contractility.

Ginkgo biloba extract EGb761 attenuates brain death-induced renal injury by inhibiting pro-inflammatory cytokines and the SAPK and JAK-STAT signalings

“…Bulcao et al . have demonstrated that the expression level of phosphorylated STAT3 increases up to five-fold in DBD grafts with donor heart dysfunction as compared to normal grafts39. Takahiro et al .…”

Advances in heart transplantation: The year in review

“…They proposed that this pathway, which is known to cause myocardial dysfunction, could be a therapeutic target to improve donor heart function. 3 Yang and Yu 4 studied the effect of adding pinacidil, an adenosine triphosphate-sensitive potassium channel opener, to a hyperpolarizing cardioplegic agent in rats. They found that potassium channel modulation improved energy stores and decreased myocardial damage.…”

The implications of brain death in donor lung injury: investigation and blockade of the endothelin axis

“…[163] Systemic venous and CNS derived IL-6 is significantly higher at brain death than at admission to the intensive care unit (ICU) in TBI patients that progress to BD. [143] Brain death induces the production of IL-6 in multiple organs, including the kidney, [201] heart, [202] liver [203] and lung. [173] IL-6 signalling induces nitric oxide synthase in cardiac myocytes [202] and contributes to early haemodynamic compromise in the donor via direct negative inotropy.…”

“…[143] Brain death induces the production of IL-6 in multiple organs, including the kidney, [201] heart, [202] liver [203] and lung. [173] IL-6 signalling induces nitric oxide synthase in cardiac myocytes [202] and contributes to early haemodynamic compromise in the donor via direct negative inotropy. [199,204] IL-6 mRNA and protein are elevated in non-structural donor heart dysfunction.…”

“…[199,204] IL-6 mRNA and protein are elevated in non-structural donor heart dysfunction. [202] Damman et al recently investigated IL-6 related renal acute phase protein synthesis in rats. [163] As expected, IL-6 was upregulated after brain death.…”