Histidine–tryptophan–ketoglutarate solution maximally preserves endothelium-derived hyperpolarizing factor–mediated function during heart preservation: comparison with University of Wisconsin solution

Abstract

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 μm) were incubated with UW ( n = 8), HTK ( n = 7) or Krebs solution ( n = 15) at 4°C for 4 hours. After washout, in the presence of indomethacin (Indo; 7 μmol/liter), N G-nitro- l-arginine ( l-NNA; 300 μmol/liter) and oxyhemoglobin (HbO; 20 μmol/liter), bradykinin (BK; −10 to −6.5 log M)-induced relaxation was compared in U 46619 (−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.