The Role of Potassium Channels in Relaxant Effect of Levosimendan in Rat Small Mesenteric Arteries

Summary We investigated both the effect of levosimendan and the role of various potassium channels in KCl-precontracted rat small mesenteric arteries. Levosimendan (10⁻⁶−10⁻³ M) or cromakalim (CRO, 10⁻⁷−10⁻⁴ M) produced concentration-dependent relaxation responses in small mesenteric arteries precontracted by 30 mM KCl. The relaxant responses to levosimendan in KCl-precontracted arteries did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of rat small mesenteric arterial segments with ATP-dependent potassium channel (KATP) blocker glibenclamide (GLI, 10⁻⁶ M) for 30 min significantly inhibited the relaxant responses to both levosimendan and CRO. Neither the Ca²⁺-activated potassium channel (KCa) blocker iberiotoxin (10⁻⁷ M) nor the voltage-dependent potassium channel (KV) blocker 4-aminopyridine (5 mM) incubation for 30 min caused significant alterations in relaxant responses to levosimendan in KCl-precontracted small mesenteric arteries. These findings suggested that levosimendan-induced relaxation responses in isolated rat small mesenteric arteries were neither depended on endothelium nor inhibited by the blockers of KV or KCa but, they rather seem to depend on the activation of KATP.     

不同部位的人体冠状动脉搭桥材料血管释放一氧化氮和内皮超极化因子差异的实验研究

目的:本研究通过直接检测人体乳内动脉(IMA)、大隐静脉(SV)与桡动脉(RA)内皮细胞释放的一氧化氮(NO)浓度以及平滑肌细胞膜电位信号,对比不同部位的人体冠状动脉搭桥材料血管释放一氧化氮和内皮超极化因子(EDHF)的差异.方法:将冠状动脉搭桥手术(CABG)常用的不同部位搭桥材料血管分为4组:乳内动脉组(n=15)、桡动脉组(n=6)、大隐静脉组(n=23),以及压力扩张后的大隐静脉组[简称PV组,n=9,将肝素生理盐水注入大隐静脉管腔,压力维持在100～600 mmHg(1 mmHg=0.133 kPa)].分别将长度为5 mm的血管片放置于37℃血管灌流室中,加入乙酰胆碱(log M-8~log M-5)和缓激肽(log M-10~log M-7),以激发内皮细胞释放一氧化氮与EDHF.应用一氧化氮测定仪与膜电位记录仪,直接检测桥血管释放的一氧化氮与平滑肌细胞膜电位信号,研究其一氧化氮释放动力学与EDHF介导的超极化反应.结果:①一氧化氮基础释放浓度:乳内动脉组显著高于大隐静脉组与桡动脉组;而桡动脉组的一氧化氮基础释放水平明显高于大隐静脉组.②在乙酰胆碱的激发下,乳内动脉组释放的一氧化氮总量明显超过桡动脉组和大隐静脉组;在缓激肽(log M-8、log M-7)的激发下,乳内动脉组和大隐静脉组均较桡动脉组升高.③PV组一氧化氮的基础释放与刺激性释放均显著减少.④乳内动脉组由EDHF调节的平滑肌细胞超极化幅度明显高于大隐静脉组与桡动脉组.桡动脉组与大隐静脉组相比,由乙酰胆碱激发、EDHF介导的平滑肌细胞超极化幅值亦明显增高,差异均有统计学意义(P<0.05~0.01).结论:①从内皮细胞一氧化氮与EDRF介导的内皮细胞功能角度评价,乳内动脉最佳,而桡动脉明显优于大隐静脉;②压力扩张会损害大隐静脉一氧化氮介导内皮细胞功能,导致大隐静脉桥远期通畅率低下.     

Functional role of potassium channels in the vasodilating mechanism of levosimendan in porcine isolated coronary artery

Levosimendan, a new type of inodilator drugs, is known to activate membrane adenosine 3,5-triphosphate-sensitive potassium (K_ATP) channels in some vascular smooth muscles and causes vasorelaxation. The involvement of potassium channels in the mechanism of the coronary artery relaxing effect of the drug has not been established. In the present study performed in the porcine epicardial coronary artery, the effect of levosimendan (0.009–3.2 M) was compared to cromakalim (0.0125–5 M), the known activator of ATP-sensitive potassium (K_ATP) channels, in the presence of glibenclamide (GLI), an inhibitor of K_ATP channels and tetraethylammonium (TEA), the non-selective inhibitor of potassium channels. The interaction of levosimendan with the specific calcium-activated potassium channel (K_Ca) blocker, iberiotoxin (IBTX), and the voltage-sensitive potassium channel (K_V) blocker, 4-aminopyridine (4-AP), was also studied. All the experiments were performed in the isometric tension of endothelium denuded porcine isolated epicardial coronary arteries precontracted with 20 mM potassium chloride. 1 M GLI decreased the maximum of cromakalim-induced relaxation by 60% but did not affect the action of levosimendan. In contrast, 2 mM TEA decreased only the coronary artery relaxing effect of levosimendan. 100 nM IBTX suppressed the maximum effect of levosimendan by only 15% while 0.5 mM 4-AP significantly shifted the concentration-response curve of the inodilator to the right. 5 mM 4-AP caused a maximum of 33% decrease of levosimendan-induced relaxation. These results indicate that, in porcine isolated epicardial coronary artery, the vasorelaxing mechanism of levosimendan involves the activation of voltage-sensitive and, at large concentrations, calcium-activated potassium channels.     

Comparison of the Effects of Levosimendan and Papaverine on Human Internal Mammary Artery and Saphenous Vein

Purpose  

Internal mammary artery (IMA) and saphenous vein (SV) are two most common vessels used in coronary artery bypass grafting (CABG). In the present study, the effect of levosimendan (a novel inotropic/vasodilator compound) and papaverine are compared, using IMA and SV obtained from CABG patients.     

The Effect of Hydrogen Peroxide in Human Internal Thoracic Arteries: Role of Potassium Channels,Nitric Oxide and Cyclooxygenase Products

Introduction We investigated both the effect and the role(s) of potassium channels, nitric oxide (NO) and cyclooxygenase (COX) products in the effect of hydrogen peroxide (H₂O₂) in human internal thoracic artery (ITA) rings. Materials and methods Samples of redundant ITA obtained from patients undergoing a coronary artery bypass graft surgery were cut into 3 mm wide rings and suspended in 20 ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. Results H₂O₂ (10⁻⁷–10⁻⁴ M) produced concentration-dependent relaxation responses in human ITA precontracted by phenylephrine. The relaxant responses to H₂O₂ did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of human ITA rings with superoxide dismutase (50 U/ml) did not affect the relaxant responses to H₂O₂, while 1,000 U/ml catalase caused a significant decrease. Incubation of endothelium-intact or endothelium-denuded human ITA rings with voltage-dependent potassium channel blocker 4-aminopyridine (5 mM) significantly inhibited the relaxant responses to H₂O₂. COX inhibitor indomethacin (10⁻⁵ M) also caused a significant inhibition. Incubation with ATP-dependent potassium channel blocker glibenclamide (10⁻⁶ M) or Ca²⁺-activated potassium channel blocker iberiotoxin (10⁻⁷ M) or NO synthase (NOS) blocker -nitro-l-arginine methyl ester (10⁻⁴ M) did not alter relaxant responses of ITA rings to H₂O₂. Conclusion The findings of the present study suggested that H₂O₂-induced relaxation responses in human ITA were neither dependant on the endothelium nor blocked by NOS inhibition but they rather seem to depend on the activation of voltage-dependent potassium channels and COX.     

Gender Differences in Pain and Biomechanical Responses After Acid Sensitization of the Human Esophagus

Our aims were to investigate gender differences to multimodal stimulations of the esophagus after experimentally induced sensitization. Thirty healthy age-matched subjects, 13 males and 17 females, were included. Pain evoked by mechanical and thermal stimuli was assessed before and after perfusion of the lower esophagus with 0.1 N hydrochloric acid. Males were more sensitive to the baseline mechanical stimuli (P < 0.01) and tolerated a lower volume of acid (P = 0.04). After acid perfusion, males were more sensitive than females to distensions (cross-sectional area P = 0.001 and volume P = 0.001). Acid perfusion sensitized both males (P = 0.03) and females (P = 0.04) to heat stimulation but not to cold stimulation (males, P = 0.09; females, P = 0.8). The referral areas for pain evoked by mechanical and thermal stimuli were larger in females compared with males both before and after acid perfusion (P = 0.002). In females only the referred pain area increased to heat stimulations (P = 0.02). Acid infusion resulted in a more hyperreactive esophagus (P = 0.03) but the hyperreactivity was not gender-dependent. In conclusion, males were more sensitive to mechanical and chemical esophageal stimuli and showed acid-evoked mechanical hyperalgesia. Females had significantly larger referred pain areas to the stimulations. The differentiated response to peripheral and central pain mechanisms may explain the gender-related differences seen in several gastrointestinal disorders.     

ATP敏感性钾通道对狗的冠状动脉的调节

目的　探讨冠状动脉震颤发生的条件及和ATP敏感性钾通道的关系。方法　用优降糖诱发冠状动脉震颤后分别用尼可的尔、硝酸甘油观察两药对震颤的影响。结果　优降糖 3mg/kg可诱发冠状动脉震颤 ,且此现象在细小的动脉表达得更为强烈 ;震颤不能被硝酸甘油抑制 ,但可被尼可的尔终止。结论　ATP敏感性钾通道的阻滞可发生冠状动脉的震颤 ,且在细小动脉中尤为突出 ,当内皮细胞产生NO减少时震颤也将增强。     

Free Internal Mammary Artery Graft Reimplantation on the Same Vessel in Repeat Coronary Revascularization

We describe the case of a 62-year-old man who needed a 3-vessel coronary artery bypass reoperation and mitral valve replacement. The patient''s existing free left internal mammary artery graft was not functioning because of a critical stenosis in the native vessel just after the distal anastomosis. The free graft itself was in perfect condition, and we decided to reuse it. Because the course of the graft was so tortuous, we concluded that skeletonization would yield the extra length needed for reimplantation. After reimplanting the graft, we performed venous grafting and mitral valve replacement. The patient was well and had no signs of ischemia at 29 months postoperatively.There have been few reports on recycling internal mammary artery grafts in repeat coronary artery bypass grafting. To our knowledge, ours is the first report of the reimplantation of a free internal mammary artery graft on the same vessel. We describe the procedure and our decision-making process.     

人巨细胞病毒活动性感染患者颈动脉超声检查分析

目的：探讨人巨细胞病毒（HCMV）活动性感染患者的颈动脉超声特点。方法：应用免疫荧光法检测外周血白细胞HCMV-PP65作为HCMV活动性感染的指标，观察56例HCMV活动性感染相关性和171例非HCMV活动性感染相关性动脉粥样硬化患者的颈动脉超声结果，同时比较年龄、高血压、糖尿病、吸烟等血管危险因素。结果：HCMV活动性感染组年龄、高血压、高脂血症、糖尿病、吸烟等危险因素以及内膜增厚和斑块形成的发生率均与非HCMV活动性感染组无显著差异，HCMV活动性感染组颈内动脉同时存在≥2种不同类型斑块的发生率显著高于非HCMV活动性感染组（52．94％比12．5％，P〈0．01）。结论：颈内动脉同时存在≥2种不同类型斑块可能与HCMV活动性感染相关。