Altered endothelium-derived hyperpolarizing factor-mediated endothelial function in coronary microarteries by St Thomas' Hospital solution

Objectives: We examined the effect of St Thomas' Hospital solution on endot helium-derived hyperpolarizing factor-mediated function in the porcine coro nary microarteries with emphasis on the effect of temperature and washout t ime, Methods: Microartery rings (diameter, 200-450 mu m) were studied in my ograph, The arteries were incubated in St Thomas' Hospital or Krebs solutio n (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 wi th -8.5 log M U-46619. The endothelium-derived hyperpolarizing factor-media ted relaxation to bradykinin was studied when endothelium-derived nitric ox ide and prostaglandin I-2 were inhibited with the presence of 7 mu mol/L in domethacin and 300 mu mol/L N-G-nitro-L-arginine. Results: After exposure t o St Thomas' Hospital solution, the maximal endothelium-derived hyperpolari zing factor-mediated relaxation (percentage of the precontraction) was sign ificantly 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 wa shout for 90 minutes. The U-46619-induced contraction force was also signif icantly reduced after washout for 45 minutes (P < .001) but fully recovered at 90 minutes. Conclusion: Under profound and moderate hypothermia, St Tho mas' Hospital solution impairs endothelium-derived hyperpolarizing factor-m ediated relaxation and smooth muscle contraction in the coronary microarter ies. These effects exist during the reperfusion period for at least 45 minu tes after exposure to St Thomas' Hospital solution and may account for the possible myocardial dysfunction during reperfusion.