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 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 μm) were studied in myograph. The arteries were incubated in St Thomas' Hospital or Krebs solution (control) at 4°C for 4 hours followed by 45 minutes (group Ia) or 90 minutes washout (group Ib) or at 22°C for I hour followed by 45 minutes (group IIa) or 90 minutes washout (group IIb) and precontracted with -8.5 log M U₄₆₆₁₉. 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 μmol/L indomethacin and 300 μmol/L N(G)-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.