Effect of Hypoxia-Reoxygenation on Endothelial Function in Porcine Cardiac Microveins

Background The cardiac venous system possesses up to 30% of total coronary vascular resistance and the effect of hypoxia-reoxygenation (H-R) and St Thomas (ST) cardioplegic solution on the vein is unknown. We investigated the effects of H-R, with or without ST, on endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in porcine cardiac microveins under clinically relevant temperatures. Methods The microveins (diameter 200 to 450 μM) mounted in a myograph were subjected to hypoxia (Po2< 5 mm Hg) for 30 minutes in Krebs solution (n = 8) or for 60 minutes in Krebs (n = 8) or in ST at 37°C (n = 8) or 4°C (n = 8), followed by 30-minute reoxygenation. The microvein was precontracted with thromboxane A2 mimetic U46619 (−7 log M) and the EDHF-mediated relaxation was induced by bradykinin (−10 to −6 log M) in the presence of indomethacin, NG-nitro-L-arginine, and oxyhemoglobin before and after H-R. Results The maximal EDHF-mediated relaxation was significantly reduced after 30-minute hypoxia (38.7 ± 2.0% vs 61.1 ± 2.3%, n = 8, p< 0.001) or 60-minute hypoxia in either Krebs or ST at 37°C (Krebs: 27.8 ± 1.2% vs 56.6 ± 2.5%, n = 8, p< 0.001; ST: 23.8 ± 4.1% vs 57.1 ± 1.5%, n = 8, p< 0.001). The relaxation was significantly less after prolonged H-R in Krebs (p< 0.001). Incubation in Krebs or ST at 4°C also reduced the EDHF-mediated relaxation (Krebs: 25.3 ± 3.3%, n = 8, p< 0.001; ST: 29.1 ± 4.4%, n = 8, p< 0.001) and there were no significant differences between Krebs and ST regarding the relaxation at either 37°C or 4°C (p> 0.05). Conclusions We conclude that (1) H-R impairs EDHF-mediated relaxation in the coronary microveins with more severe injury during prolonged H-R and (2) ST does not provide protection to the EDHF-mediated relaxation impaired by H-R at either 37°C or 4°C.