Histidine-tryptophan-ketoglutarate solution maximally preserves endothelium-derived hyperpolarizing factor-mediated function during heart preservation: comparison with University of Wisconsin solution.
BACKGROUND
The University of Wisconsin (UW) solution is used widely in heart preservation but has been demonstrated to be detrimental to the endothelial function. The present study compares the effect of histidine-tryptophan-ketoglutarate (HTK) and UW solutions on endothelium-derived hyperpolarizing factor (EDHF)-mediated function in porcine small coronary arteries.


METHODS
An isometric force study was performed in a myograph and the membrane potential of a single smooth muscle cell was measured electrophysiologically. Small coronary arteries (diameter 457 +/- 15 microm) were incubated with UW (n = 8), HTK (n = 7) or Krebs solution (n = 15) at 4 degrees C for 4 hours. After washout, in the presence of indomethacin (Indo; 7 micromol/liter), N(G)-nitro-l-arginine (l-NNA; 300 micromol/liter) and oxyhemoglobin (HbO; 20 micromol/liter), bradykinin (BK; -10 to -6.5 log M)-induced relaxation was compared in U46619 (-8 log M) pre-contraction. EDHF-mediated hyperpolarization was elicited by BK (-6.5 log M) in the presence of Indo, l-NNA and HbO.


RESULTS
BK-induced, EDHF-mediated relaxation was reduced from 93.6 +/- 2.8% to 79.7 +/- 4.6% after UW preservation (p = 0.01 by unpaired t-test and p = 0.005 by 2-way analysis of variance [ANOVA]), whereas HTK incubation did not decrease EDHF-mediated relaxation (87.0 +/- 6.5%, p = 0.3 by unpaired t-test and p = 0.6 by 2-way ANOVA, compared with control, and p = 0.001 by 2-way ANOVA, compared with UW). EDHF-mediated hyperpolarization (10.3 +/- 1.6 mV) was attenuated by UW exposure (3.4 +/- 0.6 mV, [p = 0.002] vs control), but not by HTK exposure (8.3 +/- 1.1 mV, [p = 0.3] vs control).


CONCLUSIONS
HTK is superior to UW solution in protecting EDHF-mediated endothelial function in porcine small coronary arteries. The present findings supports the use of HTK solution in heart preservation.
Yang
Qin
Q
Department of Surgery, The Chinese University of Hong Kong, Hong Kong, and Wuhan Central Hospital, Wuhan University, Wuhan, China.
Zhang
Rong-Zhen
RZ
Yim
Anthony P C
AP
He
Guo-Wei
GW
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005947:Glucose; D005978:Glutathione; D006321:Heart; D016027:Heart Transplantation; D007328:Insulin; D008353:Mannitol; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D011189:Potassium Chloride; D011343:Procaine; D011887:Raffinose; D013552:Swine
D001685:Biological Factors; C039984:Bretschneider cardioplegic solution; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; C067410:endothelium-dependent hyperpolarization factor; D008353:Mannitol; D011343:Procaine; D000493:Allopurinol; D011189:Potassium Chloride; D005978:Glutathione; D005947:Glucose; D000241:Adenosine; D011887:Raffinose