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 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.


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 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).


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 degrees C or 4 degrees C.
Dong
Ying-Ying
YY
Department of Surgery, The Chinese University of Hong Kong, Hong Kong.
Wu
Min
M
Yim
Anthony P C
AP
He
Guo-Wei
GW
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates; D001685:Biological Factors / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002122:Calcium Chloride; D002314:Cardioplegic Solutions; D003331:Coronary Vessels; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D007552:Isotonic Solutions; D008274:Magnesium; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology; D010313:Partial Pressure; D011189:Potassium Chloride; D012965:Sodium Chloride; D013552:Swine; D014664:Vasodilation / Q000187:drug effects
D001639:Bicarbonates; D001685:Biological Factors; D002314:Cardioplegic Solutions; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; C041711:St. Thomas' Hospital cardioplegic solution; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D012965:Sodium Chloride; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D008274:Magnesium; D002122:Calcium Chloride; D001920:Bradykinin