Novel vs clinical organ preservation solutions: improved cardiac mitochondrial protection

Abstract

BackgroundHeart transplantation remains the gold standard for end-stage heart failure, with current ex vivo organ storage times limited to 4 to 6 h before critical tissue damage occurs. Many preservation solutions exist in an attempt to limit both ischemic and reperfusion damage. In order to compare the effects of various storage solutions, mitochondrial function can be used to provide a sensitive analysis of cellular metabolic function.MethodsExperimental plates were seeded with cardiac myoblasts and kept in suspended animation for either 4 or 8 h at either 4o or 21 °C, in Celsior®, Perfadex®, or Somah storage solutions. Cells were then reanimated for 1 h at 37 °C to simulate a reperfusion or clinical transplant scenario. Cellular bioenergetics were measured immediately thereafter to examine biochemical differences between preservation solutions and their effectiveness on preserving metabolic function.ResultsThe oxygen consumption rates of Somah solution were significantly higher than Celsior® and Perfadex® at 4 °C, with the exception of Perfadex® at 4o for 4 h. This effect was sustained up to 8 h. At 21 °C, oxygen consumption rates of Somah solution are significantly higher than Celsior® and Perfadex® at basal conditions after 4 h, but this effect is not sustained after 8 h.ConclusionsThe purpose of this experiment was to study the efficacy of various preservation solutions on a mitochondrial level. The significantly higher oxygen consumption rates of Somah at 4 °C suggests that Somah solution may have the ability to protect cellular mitochondrial integrity, improve transplanted organ function by reducing ischemic-reperfusion injury, and thereby improve transplant outcomes. Given that Somah offers benefits over Celsior® and Perfadex® at 4 °C, it should be a target in future organ preservation solution research.Electronic supplementary materialThe online version of this article (doi:10.1186/s13019-017-0564-x) contains supplementary material, which is available to authorized users.

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Ice, ice, maybe? Is it time to ditch the igloo cooler? Benefits of machine perfusion preservation of donor hearts

“…The graft is then placed in precooled preservation solution, stored in insulated containers and then immersed with ice. While extensive research has been conducted on the composition of preservation solutions to include impermeants, substrates, buffers, membrane stabilizers and other components, the main benefit seems to be reduction of allograft metabolism and slowing adenosine triphosphate (ATP) depletion under hypothermic conditions . While the loss of ATP is slowed by this technique, depletion to nonviable levels is inevitable, limiting the ischemic interval particularly for cardiac transplantation .…”

“…While extensive research has been conducted on the composition of preservation solutions to include impermeants, substrates, buffers, membrane stabilizers and other components, the main benefit seems to be reduction of allograft metabolism and slowing adenosine triphosphate (ATP) depletion under hypothermic conditions. 15 While the loss of ATP is slowed by this technique, depletion to nonviable levels is inevitable, limiting the ischemic interval particularly for cardiac transplantation. 16,17 Although ischemic intervals of up to 6 h are considered acceptable, the risk of primary graft failure and mortality begins to increase after 3 h, nearly doubling by 6 h, particularly for older donors.…”