Effect of 11,12-epoxyeicosatrienoic acid as an additive to st. thomas’ cardioplegia and university of wisconsin solutions on endothelium-derived hyperpolarizing factor–mediated function in coronary microarteries: influence of temperature and time

Background We examined the effect of 11,12-epoxyeicosatrienoic acid (EET11,12) added to St. Thomas’ Hospital (ST) solution or University of Wisconsin (UW) solution on endothelium-derived hyperpolarizing factor (EDHF)–mediated relaxation under clinically relevant temperature and exposure time. Methods Porcine coronary microarteries (200 to 450 μm) were incubated with Krebs’ solution (control), ST with or without EET11,12 (300 nmol/L) at 22°C for 1 hour as well as at 4°C for 1 or 4 hours, and UW with or without EET11,12 at 4°C for 4 hours. The EDHF-mediated relaxation was induced by bradykinin (−10 to approximately −6.5 log M) in the precontraction evoked by U46619 (10 nmol/L) or U46619 (1 nmol/L) plus endothelin-1 (6 nmol/L). Results The EDHF-mediated relaxation was reduced after exposure to UW (79.7% ± 4.6% versus 93.6% ± 2.8%, p = 0.01) at 4°C for 4 hours. One-hour exposure to ST under 22°C or 4°C decreased the relaxation (75.2% ± 7.6% versus 96.7% ± 1.6%, p< 0.05) or the sensitivity to bradykinin (−8.04 ± 0.15 versus −8.50 ± 0.20 log M, p< 0.05). The relaxation increased to 86.8% ± 5.3% by addition of EET11,12 to ST (1 hour at 22°C, p< 0.05) but was unchanged when added to either ST or UW at 4°C for 1 or 4 hours. Conclusions As an additive to ST solution, EET11,12 may partially restore EDHF-mediated endothelial function under moderate hypothermia but had no significant effect under profound hypothermia when added to either ST or UW solution. Further investigation is necessary to improve the effect.