Effect of hypoxia-reoxygenation on endothelial function in porcine cardiac microveins

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.

The microveins (diameter 200 to 450 microM) 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 degrees C (n = 8) or 4 degrees 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.

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 degrees 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 degrees 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 degrees C or 4 degrees C (p > 0.05).

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 degrees C or 4 degrees C.