(P272) CORONARY VASCULAR RESISTANCE, FLUID PROVISION, AND THE ENDOTHELIAL GLYCOCALYX DURING EX-SITU HEART PERFUSION: THE ROLE OF PLASMA PROTEINS AS A POTENTIAL VASCULAR PROTECTANT

Background: Ex-situ heart perfusion (ESHP) is an advanced transportation method for donor hearts that enables more physiologic preservation of the organ outside the body compared to standard ice storage via provision of oxygen and nutrients. However, function still declines during machine perfusion. We have previously observed loss of coronary vascular resistance leading to supraphysiologic coronary flow during ESHP, alongside shedding of the endothelial glycocalyx (EGX), suggesting that vascular damage is endured. It is also known that fluid provision during surgery can yield deposition of EGX components into plasma. Plasma proteins, particularly albumin, are known to interact with and stabilize the EGX, which in turn functions to regulate vascular resistance. Therefore, we hypothesized that supplementation of plasma proteins during ESHP could ameliorate loss of resistance and EGX damage.

METHODS AND RESULTS: The hearts of yorkshire pigs weighing 45-55kg were procured and subject to ESHP for 12 hours using a 1:1 mixture of donor whole blood and Krebs-Heinseleit buffer (KHB) with albumin. We varied fluids provision during procurement, as well as the presence of plasma proteins during ESHP in 4 groups: high fluids group (n=6), provided 2.5-3.0L of fluids during surgery with 8% albumin KHB during ESHP; low fluids group (n=5), provided 500mL of fluids with 8% albumin KHB during ESHP; high albumin group (n=5), provided 500mL of fluids with 16% albumin KHB during ESHP; and plasma group (n=6), provided 500mL of fluids with donor plasma instead of KHB (same ratio to donor whole blood). Coronary flow alongside other functional parameters were measured once every two hours, with samples of the perfusion solution obtained for analysis of glycocalyx markers. By 3 hours of perfusion, indexed coronary flow (iCF) was significantly elevated within the high fluids group compared to all other groups and remained so throughout (p < 0.05). Perfusate hyaluronan was significantly elevated at perfusion start in the high fluids group vs. all other groups (p < 0.05), with plasma and high-albumin groups remaining low by mid perfusion. Syndecan-1 was significantly increased at early, mid, and late perfusion in the high fluids group compared to plasma group (p < 0.05 each).

Conclusion: Avoidance of fluids during procurement enables improved preservation of coronary tone during ESHP, potentially via preservation of the EGX. Damage to the EGX during short term perfusion can be prevented supplementation of plasma or albumin.