Effect of 11,12-epoxyeicosatrienoic acid as an additive to St. Thomas' cardioplegia and University of Wisconsin solutions on endothelium-derived hyperpolarizing factor-mediated function in coronary microarteries: influence of temperature and time.
BACKGROUND
We examined the effect of 11,12-epoxyeicosatrienoic acid (EET(11,12)) added to St. Thomas' Hospital (ST) solution or University of Wisconsin (UW) solution on endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation under clinically relevant temperature and exposure time.


METHODS
Porcine coronary microarteries (200 to 450 microm) were incubated with Krebs' solution (control), ST with or without EET(11,12) (300 nmol/L) at 22 degrees C for 1 hour as well as at 4 degrees C for 1 or 4 hours, and UW with or without EET(11,12) at 4 degrees C for 4 hours. The EDHF-mediated relaxation was induced by bradykinin (-10 to approximately -6.5 log M) in the precontraction evoked by U(46619) (10 nmol/L) or U(46619) (1 nmol/L) plus endothelin-1 (6 nmol/L).


RESULTS
The EDHF-mediated relaxation was reduced after exposure to UW (79.7% +/- 4.6% versus 93.6% +/- 2.8%, p = 0.01) at 4 degrees C for 4 hours. One-hour exposure to ST under 22 degrees C or 4 degrees C decreased the relaxation (75.2% +/- 7.6% versus 96.7% +/- 1.6%, p < 0.05) or the sensitivity to bradykinin (-8.04 +/- 0.15 versus -8.50 +/- 0.20 log M, p < 0.05). The relaxation increased to 86.8% +/- 5.3% by addition of EET(11,12) to ST (1 hour at 22 degrees C, p < 0.05) but was unchanged when added to either ST or UW at 4 degrees C for 1 or 4 hours.


CONCLUSIONS
As an additive to ST solution, EET(11,12) may partially restore EDHF-mediated endothelial function under moderate hypothermia but had no significant effect under profound hypothermia when added to either ST or UW solution. Further investigation is necessary to improve the effect.
Yang
Qin
Q
Department of Surgery, Division of Cardiothoracic Surgery, Chinese University of Hong Kong, Hong Kong SAR, China.
Zhang
Rong-Zhen
RZ
Yim
Anthony P C
AP
He
Guo-Wei
GW
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology*; D000493:Allopurinol / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001685:Biological Factors / Q000494:pharmacology*; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D002314:Cardioplegic Solutions / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology*; D006324:Heart Arrest, Induced; D007328:Insulin / Q000494:pharmacology*; D019188:Organ Preservation Solutions; D011336:Probability; D011887:Raffinose / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013552:Swine; D013696:Temperature; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D001685:Biological Factors; D002314:Cardioplegic Solutions; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; C067410:endothelium-dependent hyperpolarization factor; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; D000493:Allopurinol; D015126:8,11,14-Eicosatrienoic Acid; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose