Hypoxia-reoxygenation, St. Thomas cardioplegic solution, and nicorandil on endothelium-derived hyperpolarizing factor in coronary microarteries.
BACKGROUND
We investigated effects of hypoxia-reoxygenation (H-R) with and without St. Thomas solution under clinically relevant temperatures and effects of nicorandil on endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in porcine coronary microarteries.


METHODS
In a myograph, rings of porcine microarteries (diameter 200 to 450 microm) were subjected to hypoxia (PO2 < 5 mm Hg) for 30 minutes in Krebs at 37 degrees C, or for 60 minutes in Krebs and St. Thomas solution with or without nicorandil (0.1 microM) at 37 degrees C or 4 degrees C, followed by 30-minute reoxygenation. The EDHF-mediated relaxation by bradykinin (-10 to approximately -6 logM) with inhibitors of nitric oxide and prostacyclin was studied.


RESULTS
The maximal EDHF-mediated relaxation was reduced after hypoxia for 30 minutes (59.9%% +/- 1.6% versus 81.2%% +/- 3.5%, p < 0.05) or 60 minutes (44.4% +/- 6.0% versus 82.7% +/- 7.4%, p < 0.001) in Krebs or St. Thomas (28.9% +/- 1.8% versus 78.1% +/- 3.0%, p < 0.001) at 37 degrees C and at 4 degrees C (Krebs: 49.3% +/- 3.0%, p < 0.001; ST: 43.1% +/- 2.6%, p < 0.001) and it was less in St. Thomas solution at 37 degrees C than at 4 degrees C (p < 0.001). The reduced relaxation was recovered by nicorandil (Krebs at 37 degrees C: 81.7% +/- 3.4%, p < 0.001; St. Thomas at 37 degrees C: 71.0% +/- 7.9%, p <0.001; St. Thomas at 4 degrees C: 85.3% +/- 3.3%, p < 0.001).


CONCLUSIONS
We conclude that (1) H-R impairs EDHF-mediated relaxation in the coronary microarteries with more injury during prolonged H-R, and this can be partially eliminated by St. Thomas at 4 degrees C but not at 37 degrees C; and (2) as an additive, nicorandil may fully restore EDHF-mediated endothelial function after prolonged H-R.
Dong
Ying-Ying
YY
Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.
Wu
Min
M
Yim
Anthony P C
AP
He
Guo-Wei
GW
D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D001685:Biological Factors / Q000037:antagonists & inhibitors*; D002122:Calcium Chloride / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects; D004347:Drug Interactions; D008274:Magnesium / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D020108:Nicorandil / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001639:Bicarbonates; D001685:Biological Factors; C041711:St. Thomas' Hospital cardioplegic solution; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D020108:Nicorandil; D012965:Sodium Chloride; D011189:Potassium Chloride; D008274:Magnesium; D002122:Calcium Chloride