Protective effect of hyperpolarized preservation solution combining sodium-hydrogen exchange inhibitor and potassium channel opener on donor heart / 第二军医大学学报

Objective: To study whether sodium-hydrogen exchange inhibitor(NHEI) can enhance the protective effect of hyperpolarized preservation solution containing potassium channel opener (PCO), and the effect was compared with that of Celsior solution. Methods: After equilibrated on a crystalloid-perfused Langendorff model for 30 min, rabbit hearts were divided into four groups: (1) Cel group: receiving another 30 min of equilibration, 8 h cold storage with Celsior solution and 1 h reperfusion; (2) Pin group: arrested and stored with pinacidil (a type of PCO) hyperpolarizing cardioplegia; (3) Cel+Car group: receiving the same treatment as Cel group except that 10 μmol/L cariporide (a type of NHEI) was administered during the second equilibration period and reperfusion; and (4) Pin+Car group: receiving cariporide treatment and hyperpolarized arrest and storage. Results: Recovery rate of systolic function in the Pin+Car group was significantly higher than that in the Pin group ([87.4±11.9]% vs [69.0±7.2]%, P0.05). No significant differences were found in any parameters between Cel group and Cel+Car group. There were no differences in coronary flow among all groups. Conclusion: NHEI can greatly enhance the protective effect of PCO hperpolarized preservation solution on the donor heart, and the combination of them has a comparable protective effect to Celsior solution.

Effects of Pinacidil, Tetrathylammonium and Glibenclamide on Hypoxic Vasoconstriction in Isolated Perfused Rabbit Lungs / 대한마취과학회지

BACKGROUND: This study investigated the effects of the K+ channel opener, pinacidil on hypoxic pulmonary vasoconstriction in isolated perfused rabbit lungs. In order to evaluate the vasodilatation mechanism of K+ channel opener, we also studied the effects of two K+ channel blocker, tetraethylammonium (TEA), a Ca2+ activated K+ channel blocker and glibenclamide (GLB), an ATP-sensitive K+ channel blocker. METHODS: Isolated lungs from white rabbits were ventilated with a normoxic gas (21%O2-5%CO2-74%N2) and a hypoxic gas (3%O2- 5%CO2-92%N2) alternatively, and then perfused with blood-containing perfusate solution. After a hypoxic pressor response (HPR) had been obtained, various drugs were added to the perfusate reservoir to achieve the predetermined circulating concentration, and the influences of the drugs on HPR were then tested. RESULTS: Pinacidil (0.3-6.0 mcM) produced a dose-dependent pulmonary vasodilation on hypoxic ventilation challenge. TEA (1 mM) caused pulmonary vasoconstriction in normoxic ventilation and potentiated a hypoxic pressor response. When the hypoxic pressor response was potentiated by TEA, pinacidil (1.0, 3.0 mcM) reduced the contraction, but GLB did not cause pulmonary vasoconstriction under normoxic ventilation, potentiate a hypoxic pressor response. CONCLUSIONS: Piacidil is capable of opposing the pulmonary responses of acute hypoxia. Moreover the effects of TEA and GLB suggest that HPV might be mediated through Ca2+ activated K+ channels, not through ATP-sensitive K+ channels.

Effects of Pinacidil, a Potassium-Channel Opener, on Biodistribution of Thallium-201 in Tumor-Bearing Mice / 대한핵의학회잡지

PURPOSE: Thallium behaves similarly to potassium in vivo. Potassium channel opener (K-opener) opens ATP-sensitive K+/-channel located at cell membrane, resulting in potassium efflux from cytosol. We have previously reported that K-opener can alter biokinetics of Tl-201 in cultured cells and in vivo. Malignant tumor cells have high Na-K ATPase activity due to increased metabolic activities and dedifferentiation, and differential delineation of malignant tumor can be possible with Tl-201 imaging. K-opener may affect tumoral uptake of Tl-201 in vivo. To investigate the effects of pinacidil (one of the potent K-openers) on the localization of the tumor with Tl-201 chloride, we evaluated the changes in biodistribution of Tl-201 with pinacidil treatment in tumor-bearing mice. MATERAL AND METHODS: Balb/c mice received subcutaneous implantation of murine breast cancer cells in the thigh and were used for biodistribution study 3 weeks later. 100 microgram of pinacidil dissolved in 200 microliter DMSO/PBS solution was injected intravenously via tail vein at 10 min after 185 KBq (5 microcurie) Tl-201 injection. Percentage organ uptake and whole body retention ratio of Tl-201 were measured at various periods after injection, and values were compared between control and pinacidil-treated mice. RESULTS: Pinacidil treatment resulted in mild decrease in blood levels of Tl-201, but renal uptakes were markedly decreased at 30-min, 1- and 2-hour, compared to control group. Hepatic, intestinal and muscular uptake were not different. Absolute percentage uptake and tumor to blood ratios of Tl-201 were lower in pinacidil treated mice than in the control group at all time points measured. Whole body retention ratio of Tl-201 was lower in pinacidil treated mice (58+/-4%), than in the control group (67+/-3%) at 24 hours after with injection of 100 microgram pinacidil. CONCLUSION: K-opener did not enhance, but rather decreased absolute tumoral uptake and tumor-to-blood ratios of Tl-201. Decreased whole body retention ratio and renal uptake were observed with pinacidil treatment in tumor-bearing mice.

Activation of the Cardiac ATP-Sensitive K+Channel by KR-30816,Newly Synthesized Potassium Channel Opener

BACKGROUND: The effects of a newly synthesized potassium channel opener, KR-30816((-)(nitro-2-hydroxymethyl-2-methy-2H-1-benzopyran-4-y1)pyridine oxide) on the action potential of papillary muscles of guinea pigs and the ATP-sensitive potassium channel current(IKATP) of single ventricular muscle cells of rats were examined to make clear its action mechanism of the KATPchannel. METHODS: We used the conventional microelectrode and the excised inside-out patch configuration. RESULTS: KR-30816 caused a shortening of the action potential duration in dose-dependent manner, which was inhibited by glibenclamide(3microM). Before run-down of the K+channel, KR-30816 activated the cardiac ATP-sensitive K+ channel only in the presence of ATP and shifted the dose-response relation curve between [ATP]i and the channel activity to the right in parallel. After run-down of the KATP channel, KR-30816 did not after the channel opening either in the absence or in the presence of UDP. CONCLUSION: These results suggest that KR-30816 antagonizes the inhibitory effect of ATP on the KATPchannel in a competitive manner, thereby enhancing the channel openings.