(701.9) Effect of Pre-Conditioning with Copolymer-Based Cell Membrane Stabilizer Poloxamer 188 on Adult Mouse Coronary Artery Endothelial Layer Integrity after Prolonged Hypoxia/Reoxygenation

Poster Board Number: B153

Insha Maknojia (Vanderbilt University), Matthew Hampton (Vanderbilt University), Zhu Li (Vanderbilt University), Matthew Barajas (Vanderbilt University), Matthias Riess (TVHS VA Medical Center, Vanderbilt University)

Prolonged ischemia followed by reperfusion can cause significant tissue damage and cell death. This ischemia/reperfusion (IR) injury can be alleviated by administration of Copolymer-based Cell Membrane Stabilizers (CCMS), like the tri-block Poloxamer (P)188, thought to be able to seal gaps in cell membranes and/or tight junctions and, thus, repair leaks attributable to severe cellular stress. We have previously tested post-conditioning, i.e. the administration of P188 upon reperfusion/reoxygenation, to attenuate IR injury in various models. Here, we hypothesized that pre-conditioning, i.e. its administration before simulated ischemia (hypoxia), has a protective effect on endothelial cell layer integrity as assessed by Trans-Endothelial Electrical Resistance (TEER).

Confluent adult mouse coronary artery endothelial cell (ECs) layers were pre-treated with 0, 30, 100, 300, 1,000, or 2,000 µM P188 during plating of cells before simulated IR with a 24-hour hypoxic followed by a 2-hour reoxygenation (HR) period. EC monolayer barrier integrity was assessed by TEER.

In contrast to mere post-conditioning, pre-conditioning dose-dependently attenuated HR injury compared to control/normoxia (Fig 1) even after prolonged HR for 24+2 hrs.

These results suggest that CCMS may indeed elicit its cardioprotective effect, in part, through protection of the EC layer. However, more research is needed to determine optimal dosage and timing for CCMS administration.

Supported, in part, by Merit Review Award I01 BX003482 from the U.S. Department of Veterans Affairs Biomedical Laboratory Ramp;amp;D Service; Training in Perioperative Science Award [5T32 GM108554] from the National Institutes of Health; a Starter Grant from the Society of Cardiovascular Anesthesiologists; and by institutional funds.