Altered endothelium-derived hyperpolarizing factor-mediated endothelial function in coronary microarteries by St Thomas' Hospital solution.
OBJECTIVE
We examined the effect of St Thomas' Hospital solution on endothelium-derived hyperpolarizing factor-mediated function in the porcine coronary microarteries with emphasis on the effect of temperature and washout time.


METHODS
Microartery rings (diameter, 200-450 micrometers) were studied in myograph. The arteries were incubated in St Thomas' Hospital or Krebs solution (control) at 4 degrees C for 4 hours followed by 45 minutes (group Ia) or 90 minutes washout (group Ib) or at 22 degrees C for 1 hour followed by 45 minutes (group IIa) or 90 minutes washout (group IIb) and precontracted with -8.5 log M U 46619. The endothelium-derived hyperpolarizing factor-mediated relaxation to bradykinin was studied when endothelium-derived nitric oxide and prostaglandin I2 were inhibited with the presence of 7 micromol/L indomethacin and 300 micromol/L NG-nitro-L -arginine.


RESULTS
After exposure to St Thomas' Hospital solution, the maximal endothelium-derived hyperpolarizing factor-mediated relaxation (percentage of the precontraction) was significantly reduced at either temperature after washout for 45 minutes (group Ia, 42.7% +/- 3.5% vs 69.0% +/- 5.3%; n = 9; P =.000; and group IIa, 12.3% +/- 1.6% vs 56.1% +/- 4. 4%; n = 8; P =.000) but fully recovered after washout for 90 minutes. The U46619-induced contraction force was also significantly reduced after washout for 45 minutes (P <.001) but fully recovered at 90 minutes.


CONCLUSIONS
Under profound and moderate hypothermia, St Thomas' Hospital solution impairs endothelium-derived hyperpolarizing factor-mediated relaxation and smooth muscle contraction in the coronary microarteries. These effects exist during the reperfusion period for at least 45 minutes after exposure to St Thomas' Hospital solution and may account for the possible myocardial dysfunction during reperfusion.
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Z D
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Cardiovascular Research Laboratory, Grantham Hospital, and Division of Cardiothoracic Surgery, Department of Surgery, University of Hong Kong, Aberdeen, Hong Kong.
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G W
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D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001639:Bicarbonates / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology*; D001920:Bradykinin / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D011464:Epoprostenol / Q000502:physiology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D013552:Swine; D013696:Temperature; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D001639:Bicarbonates; D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; C041711:St. Thomas' Hospital cardioplegic solution; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D009569:Nitric Oxide; D012965:Sodium Chloride; D011189:Potassium Chloride; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D008274:Magnesium; D002122:Calcium Chloride; D001920:Bradykinin; D007213:Indomethacin