KATP通道开放剂JTV-506对大鼠心肌梗死范围的影响

目的　探讨ATP敏感性钾通道开放剂JTV 5 0 6 (JTV)对离体大鼠心功能及心肌梗死范围的影响。方法用Langerdorff装置 ,观察JTV对冠脉灌流量及左心室压力的影响。应用离体大鼠双冠脉分别灌流模型 ,观察药物对心肌梗死面积的影响。结果　JTV在 1μmol·L-1时明显增加冠脉灌流量 ,当达 10 μmol·L-1时左室收缩压明显下降 ,在缺血前加缺血中或缺血时单独应用JTV均可缩小心肌梗死范围 ,此作用可被格列本脲阻断。结论　JTV有明显扩冠作用 ,大剂量可降低心脏收缩功能 ,用不影响心功能的剂量可减小心梗范围 ,此作用与KATP通道开放有关。     

羟苯氨酮保护大鼠心脏对抗心肌缺血-再灌注损伤

目的研究强心扩血管新药羟苯氨酮(oxyphenamone)对心肌缺血-再灌注损伤的保护作用。方法对离体或在体大鼠心脏，阻断冠脉前降支10 min后行再灌注15 min(离体)或30 min(在体)，形成心肌缺血-再灌注损伤模型，从心电图、心肌酶学与心肌超微结构等方面观察药效。结果羟苯氨酮(离体心脏灌流1-10 μmol·L^-1，或静脉注射0.1-1.0 mg·kg^-1)剂量依赖性地明显减少再灌注时的心律失常，对抗损伤所致心肌CPK，LDH与MDA的变化，减轻心肌超微结构损伤。结论羟苯氨酮明显保护离体和在体大鼠心肌对抗冠脉阻断所致缺血-再灌注损伤。     

H2受体介导组胺对大鼠海马缺氧缺糖诱导细胞水肿及活性降低的保护作用

目的探讨组胺对海马脑片缺血诱导细胞水肿及活性降低的作用，以及与受体亚型的关系。方法大鼠海马脑片以缺氧缺糖(OGD)诱导缺血损伤后，实时检测CA1区透光度变化评价细胞水肿；并测定2,3,5-三苯基氯化四氮唑(TTC)产物甲，评价脑片活性。观察不同浓度组胺的作用，以及组胺受体拮抗剂对组胺作用的影响。结果 组胺(0.01～10 μmol·L^-1)明显抑制OGD诱导的海马脑片透光度增加，并提高脑片活性。H₁受体拮抗剂苯海拉明(0.1～10 μmol·L^-1)不影响组胺的作用，H₂受体拮抗剂西咪替丁(0.1～10 μmol·L^-1)则部分拮抗组胺的保护作用。结论组胺对大鼠海马脑片缺血诱导细胞水肿及活性降低有保护作用，该作用与H₂受体有关。     

蚓激酶的心肌保护作用及机制

目的研究蚓激酶对心肌缺血的保护作用，并进一步探讨其可能机制。方法采用结扎大鼠左冠状动脉前降支制备急性心肌缺血模型，观察蚓激酶对心肌缺血的保护作用；应用全细胞膜片钳和激光扫描共聚焦技术，研究蚓激酶对L-型钙电流(I_Ca-L)和细胞内游离钙离子浓度的影响。结果蚓激酶80，40和20 mg·kg^-1剂量组均可缩小心肌梗死面积。膜片钳研究结果表明，当刺激电压为+10 mV时，10和50 μmol·L^-1蚓激酶使I_Ca-L降低共聚焦结果显示，在静息状态下，10 μmol·L^-1蚓激酶对［Ca²⁺］_i无明显影响；但10 μmol·L^-1蚓激酶对60 mmol·L^-1 KCl诱导的［Ca²⁺］_i升高却有明显抑制作用，并且在整个实验过程中(240 s)并未出现明显的峰值。结论蚓激酶对大鼠心肌缺血具有保护作用，其机制可能与抑制I_Ca-L及下调［Ca²⁺］_i有关。     

盐酸氟桂利嗪对大鼠离体心脏的保护作用

目的 探讨盐酸氟桂利嗪对离体大鼠心脏心功能的影响及对缺血再灌注后心脏的保护作用.方法 用Langendorff 装置观察盐酸氟桂利嗪对冠脉灌流量及左心室压力的影响及对缺血25 min,再灌注30 min后心脏功能的影响.结果 盐酸氟桂利嗪在10-5mol/ L时明显增加冠脉灌流量,达10-3 mol/ L时左室收缩压明显降低.与对照组比较,在缺血前应用10-5 mol/ L 及10-3 mol/ L的盐酸氟桂利嗪可以改善缺血再灌注后的心功能.结论 盐酸氟桂利嗪具有明显的扩冠作用,大剂量可降低心脏收缩功能,应用合适的剂量,对缺血再灌注心脏具有保护作用.     

不同钾通道阻滞剂对大鼠血管平滑肌的影响

目的：研究几种不同钾通道阻滞剂对血管平滑肌的影响。方法：大鼠离体胸主动脉条张力记录法。结果：BaCl₂,4-AP,CsCl和TEA均能浓度依赖的引起大鼠离体胸主动脉条收缩, 其中BaCl₂引起血管收缩的作用明显强于其它3种化合物,EC₅₀值为90　μmol.L^-1。而E-4031、索他洛尔和格列本脲对血管张力没有影响;此外E-4031、索他洛尔和4-AP还可抑制去甲肾上腺素引起的血管收缩。结论：E-4031、索他洛尔和格列本脲在正常治疗浓度下对血管平滑肌的张力影响不大;并提示不同的钾通道阻滞剂其组织选择性存在明显差异。     

环维黄杨星D抗心房纤颤的作用及其电生理机制

环维黄杨星D(CVB-D)对CaCl₂-Ach诱发小鼠在体心房纤颤和乌头碱、哇巴因或肾上腺素所致豚鼠离体心房纤颤,有明显的剂量依赖性抑制作用,且作用强度与胺碘酮(Ami)相似。CVB-D0.3～100μmol·L^-1降低离体右心房自律性。对离体左心房,CVB-D0.3μmol·L^-1抑制肾上腺素引起的异常自律性,延长有效不应期和动作电位时程,降低兴奋性;高浓度时,可降低V_max,延长冲动传导时间。Ami0.3～30μmol·L^-1有相似的电生理作用,但对V_max无明显的影响。提示CVB-D可试用于心房纤颤的患者。     

白藜芦醇对麻醉大鼠颈动脉窦压力感受器的作用

在隔离灌流左侧颈动脉窦区的麻醉大鼠上观察了白藜芦醇对颈动脉窦压力感受器活动的影响。隔离灌流麻醉大鼠的颈动脉窦区，同时记录窦神经放电，并绘制压力感受器活动的机能曲线。白藜芦醇(30， 60及120 μmol·L^-1)隔离灌流颈动脉窦区时，压力感受器活动的机能曲线向右下方移位，曲线的斜率以及窦神经放电的最大积分值显著下降，且其变化呈一定的剂量依赖性。预先应用NO合酶抑制剂(L-NAME， 100 μmol·L^-1)可完全消除白藜芦醇对压力感受器活动的抑制作用；预先应用钙通道的开放剂(Bay K8644， 500 nmol·L^-1)可以取消白藜芦醇的抑制作用；预先应用正矾酸钠(sodium orthovanadate， 1 mmol·L^-1)后，对白藜芦醇抑制压力感受器活动的作用无影响。白藜芦醇对大鼠颈动脉窦压力感受器活动有抑制作用，此作用可能与局部NO的释放及减弱牵张敏感性通道介导的钙离子内流有关。     

强心扩血管药羟苯氨酮对离体心肌与血管的作用

为阐明强心扩血管药羟苯氨酮对心肌与血管的直接影响,采用离体心脏,离体心肌与血管制备,以心肌张力、心率、冠脉流量及血管平滑肌张力为观察指标。结果显示:给离体大鼠心脏灌流羟苯氨酮0.1～1μmol·L^-1可使心肌收缩力和冠脉流量明显增加,心率轻度减慢。羟苯氨酮剂量依赖性地增加豚鼠乳头肌和左房肌张力,并减慢右房频率。羟苯氨酮(1～50μmol·L^-1)非竞争性地对抗KCl,5-HT和CaCl₂致狗冠状动脉,基底动脉和肠系膜动脉的收缩,显示它有松弛血管平滑肌的作用。与磷酸二酯酶抑制剂类药物米力农作比较,两者的正性肌力作用与扩血管作用相似。然而,羟苯氨酮减慢心搏频率,米力农则增加心率。提示羟苯氨酮有直接正性肌力、负性频率与扩血管作用。     

人参皂甙Rb1降低细胞内Ca2+作用的机制

使用荧光探针Fura-2/AM,采用双波长荧光分光光度法观察到,人参皂甙Rb₁(10,50,100μmol·L^-1)能剂量依赖性减少新生鼠脑细胞内钙浓度,并能增加由硫酸亚铁及半胱氨酸所降低的膜流动性,Rb₁(10μmol·L^-1)能使离体大鼠尾动脉去甲肾上腺素量—效曲线右移,最大效应降低;Rb₁(10,100μmol·L^-1)能降低离体鼠基底动脉5-HT所引起的收缩。使用全细胞膜片钳技术发现人参皂甙Rb₁(50,100μmol·L^-1)对钙电流无明显影响;Rb₁在低剂量能增加大鼠突触体Na⁺-K⁺ATPase及Ca²⁺-Mg²⁺ATPase活性。从而揭示Rb₁降低胞内钙含量可能通过增加ATP酶活性而产生。     

ATP敏感性钾通道SUR2B/Kir6.1亚型选择性开放剂纳他卡林的心血管药理学作用特征

目的研究SUR2B/Kir6.1亚型KATP通道开放剂纳他卡林的心血管药理学作用。方法(1)血流动力学测定:戊巴比妥钠腹腔注射麻醉大鼠,从颈总动脉插管至左心室,连接八导生理记录仪记录心功能的变化。(2)制备大鼠离体工作心脏,观察纳他卡林对其心功能的影响。(3)制备大鼠尾动脉血管条,用去甲肾上腺素预收缩后,观察累积给予纳他卡林对血管张力的影响。结果纳他卡林10-8～10-4mol.L-1对大鼠离体工作心脏功能无影响;对大鼠尾动脉血管条具有内皮细胞依赖性舒张作用。麻醉大鼠,纳他卡林0.5、2、8mg.kg-1静脉注射可剂量依赖性降低血压,纳他卡林8mg.kg-1抑制心脏的收缩和舒张功能,其效应可被格列苯脲和L-NAME拮抗。结论纳他卡林对心脏无直接作用,可通过舒张血管降低血压;纳他卡林的心血管药理学作用与其选择性开放KATP通道、促进内皮细胞释放NO有关。     

Endothelin-1-induced reduction of myocardial infarct size by activation of ATP-sensitive potassium channels in a rabbit model of myocardial ischaemia and reperfusion.

1. This study examined whether endothelin-1 (ET-1) reduces infarct size in a rabbit model of acute coronary artery occlusion (60 min) and reperfusion (120 min). In addition, we investigated whether the observed cardioprotective effect of ET-1 was due to the activation of ATP-sensitive potassium (KATP) channels by using two selective antagonists, glibenclamide and sodium 5-hydroxydecanoate (5-HD). 2. In the anaesthetized rabbit, infarct size (expressed as a percentage of the area at risk) after 60 min of coronary artery occlusion followed by 2 h of reperfusion was 55 +/- 4% (n = 11). ET-1 (0.3 nmol kg-1), administered as a bolus injection into the left ventricle, had no effect on infarct size (62 +/- 2%, n = 4). A lower dose of ET-1 (0.03 nmol kg-1) resulted in a significant reduction in infarct size (infarct size 43 +/- 3%; P < 0.05, n = 16). The higher dose (0.3 nmol kg-1), but not the lower dose of ET-1 caused a significant rise in blood pressure, pressure rate index and hence, myocardial oxygen consumption. 3. The reduction in infarct size afforded by ET-1 (0.03 nmol kg-1) was abolished by pretreatment of rabbits with the KATP channel inhibitors, glibenclamide (0.3 mg kg-1) and 5-HD (5 mg kg-1), (infarct size 59 +/- 3 and 63 +/- 4% respectively; n = 4-9). 4. We propose that ET-1 reduces infarct size by opening KATP channels.     

尼可地尔对豚鼠心肌细胞膜及线粒体膜电位的影响

研究KATP通道开放剂尼可地尔 (Nic)对豚鼠心肌细胞膜和线粒体膜电位的影响 .用激光共聚焦显微镜和特异性荧光探针 ,观察不同剂量的Nic及KATP通道阻滞剂格列本脲 (Gli)引起急性分离的豚鼠心肌细胞膜电位 ,线粒体膜电位荧光值的变化 .Nic1mmol·L- 1引起细胞膜电位在 1min内迅速超极化〔膜电位荧光值减少 ( 75± 12 ) %〕 ,Gli 3μmol·L- 1可阻断其变化 ;0 .1和 1mmol·L- 1Nic可使线粒体膜电位去极化和膜电位荧光值在 1,2 ,5min分别增加( 12± 3) %和 ( 32± 8) % ,( 2 5± 6) %和 ( 39± 9) % ,( 34± 6) %和 ( 4 5± 12 ) % ;3μmol·L- 1Gli可抑制其变化 .结果说明低浓度Nic只引起线粒体膜电位去极化 ,高浓度Nic还可使细胞膜电位发生超极化 ,引起KATP通道开放     

Reduction by prostaglandin E1 or prostaglandin E0 of myocardial infarct size in the rabbit by activation of ATP-sensitive potassium channels.

1. This study examined whether pretreatment of rabbits with infusions of prostaglandin E1 (PGE1) or prostaglandin E0 (PGE0) (which were terminated prior to the onset of ischaemia) reduce myocardial infarct size arising from coronary artery occlusion (60 min) and reperfusion (120 min). In addition, we investigated whether the observed cardioprotective effects of these two prostaglandins were due to the activation of ATP-sensitive potassium (KATP) channels. 2. In the anaesthetized rabbit, infarct size (expressed as a percentage of the area at risk) after 60 min of coronary artery occlusion followed by 2 h of reperfusion was 59 +/- 4% (n = 10). PGE1 or PGE0 treatment (1.0 micrograms kg-1 min-1), administered as 1 h pretreatments (0.05 ml min-1, i.v.), significantly reduced infarct size to 44 +/- 6% (n = 6) or 42 +/- 1% (n = 6), respectively. PGE1 or PGE0 pretreatment resulted in a significant reduction in mean arterial blood pressure, which returned to baseline within 15 min of discontinuation of the infusion (i.e. prior to LAL ligation). 3. The reduction in infarct size afforded by PGE1 was abolished by pretreatment of rabbits with the KATP channel blockers, glibenclamide (60 +/- 4%; n = 8) or 5-hydroxydecanoate (58 +/- 6%; n = 6). Similarly, glibenclamide also largely attenuated the reduction in infarct size afforded by PGE0 (52 +/- 3%; n = 8). 4. We propose that a 1 h pretreatment of PGE1 or PGE0 reduces infarct size by activating protein kinase C resulting in the opening of KATP channels.     

The role of myocardial KATP-channel blockade in the protective effects of glibenclamide against ischaemia in the rat heart

Glibenclamide preserves postischaemic myocardial function in the isolated, erythrocyte perfused, working rat heart model. This study addresses the possible involvement of KATP channels in this beneficial action of glibenclamide. We hypothesized that if glibenclamide improved postischaemic cardiac function by blocking of KATP channels, opening of these KATP channels should result in the opposite, namely detrimental effects on postischaemic heart function. Postischaemic functional loss and coronary blood flow were recorded during treatment with glibenclamide (4 micromol x l(-1); n = 5), the KATP channel openers pinacidil (1 micromol x (l-1); n = 5) and diazoxide (30 micromol x l(-1); n = 5), the combination of glibenclamide with pinacidil (n = 5) and glibenclamide with diazoxide (n = 5), and vehicle (n = 8). Both pinacidil and diazoxide significantly increased coronary blood flow 2-3 times, which was abolished by glibenclamide pre- and postischaemically. This confirms that under both flow conditions glibenclamide significantly blocks KATP channels in the coronary vasculature. The 12 min. global ischaemic incident resulted in a cardiac functional loss of 22.2 +/- 2.9% during vehicle. Glibenclamide reduced the cardiac functional loss to 4.3 +/- 1.2% (P < 0.01). Interestingly, both pinacidil and diazoxide reduced the cardiac functional loss to 4.0 +/- 1.5% (P < 0.01) and 2.9 +/- 1.4% (P < 0.001), respectively. The combination pinacidil+glibenclamide resulted in additional protection compared with the individual components (0.6 +/- 0.1 versus 4.0 +/- 1.5%, P < 0.05). Thus, in contrast to its effect on coronary vascular tone, the glibenclamide-induced improvement of postischaemic cardiac function may not be mediated through blockade of the KATP channel. Alternative mechanisms may be operative, such as uncoupling of the mitochondrial respiratory chain, thereby preconditioning the hearts against stunning.     

Protective effect of mitochondrial KATP activation in an isolated gracilis model of ischemia and reperfusion in dogs

Adenosine triphosphate-sensitive potassium channel (KATP) openers protect ischemic myocardium by direct protection of cardiac myocytes, which is thought to be a result of activation of mitochondrial KATP (mKATP). KATP is expressed in skeletal muscle, and the purpose of this study was to determine the effect of the mKATP opener BMS-191095 on infarct size in an isolated gracilis model of ischemia and reperfusion in dogs. The right and left gracilis muscles were isolated in anesthetized dogs except for the artery and vein supplying these muscles (pedicle). BMS-191095 (0.4 mg) or vehicle were infused directly into the artery supplying each gracilis muscle (each animal had one drug-treated and one vehicle-treated muscle). The pedicle was completely occluded for 5 hours followed by 48 hours of reperfusion, after which infarct size was determined. In the vehicle-treated gracilis muscles, significant necrosis was observed (82% +/- 3% of gracilis muscle). BMS-191095 significantly reduced the infarct size in the contralateral gracilis muscle (55% +/- 6%). Reflow into the gracilis muscle was significantly greater in BMS-191095-treated muscles. BMS-191095 appears to reduce damage in ischemic/reperfused skeletal muscle, suggesting that mKATP activation is an important protective mechanism in this tissue.     

Nicorandil attenuates myocardial dysfunction associated with transient ischemia by opening ATP-dependent potassium channels.

The objective of this study was to determine whether ATP-dependent potassium channel activation is involved in the mechanism by which nicorandil reduces postischemic contractile dysfunction produced by a brief period of ischemia (myocardial stunning). Barbital-anesthetized dogs were subjected to 15-min left anterior descending (LAD) coronary artery occlusion followed by 3-h reperfusion. Saline or nicorandil (100 micrograms/kg + 25 micrograms/kg/min) were infused 15 min before and throughout occlusion with or without addition of the KATP channel antagonist, glibenclamide 0.3 mg/kg as an intravenous (i.v.) bolus. Regional myocardial blood flow was measured by radioactive microspheres, and left ventricular (LV) segment function was measured by sonomicrometry. There were no significant differences between the groups in area-at-risk size or collateral blood flow. In contrast, nicorandil significantly reduced mean aortic blood pressure (BP) and the rate-pressure product (RPP) which persisted throughout the occlusion period. In addition, nicorandil markedly accelerated recovery of segment shortening in the ischemic/reperfused region as compared with control dogs. Pretreatment of dogs with glibenclamide blocked none of the hemodynamic effects of nicorandil, but it did prevent improvement in reperfusion segment function. The small dose of glibenclamide used had no effect on hemodynamics or the degree of stunning. Thus, these results suggest that nicorandil attenuates stunning in anesthetized dogs by a direct cardioprotective effect as a result of KATP channel activation in ischemic myocardium.     

Inhibition by glibenclamide of negative chronotropic and inotropic responses to pinacidil, acetylcholine, and adenosine in the isolated dog heart.

The blocking effects of glibenclamide on the chronotropic and inotropic responses to K+ channel openers pinacidil (ATP-sensitive) and acetylcholine (ACh) or adenosine (receptor-operated) were investigated in the isolated, blood-perfused canine atrium or ventricle. Glibenclamide (0.1-3 mumol) induced no significant cardiac effects. Cumulative administration of pinacidil (0.03-3 mumol) dose-dependently decreased sinus rate much less than the contractile force of the atrial and ventricular muscles. Glibenclamide similarly inhibited the negative chronotropic and inotropic responses to pinacidil in a dose-related manner. A high dose of glibenclamide (3 mumol) slightly but significantly attenuated the negative chronotropic and inotropic responses to ACh and adenosine but not to verapamil. These results demonstrate that glibenclamide inhibits the negative chronotropic and inotropic responses to the ATP-sensitive K+ channel opener pinacidil and the receptor-operated K+ channel openers ACh and adenosine but more selectively antagonizes the responses to pinacidil in the dog heart and suggest that in contrast to ACh and adenosine, an ATP-sensitive K+ channel opener has a greater effect on the ventricle than on the sinoatrial node.     

Effects of the new potassium channel opener JTV-506 on coronary vessels in vitro and in vivo

The vascular effects of JTV-506 ((-)-(3S,4R)-2.2-bis(methoxymethyl)- 4-[(1,6-dihydro-l-methyl-6-oxo-3-pyridazinyl)amino]-3-hydroxychroman+ ++-6- carbonitrile hemihydrate, CAS 170148-29-5), a new potassium channel opener, was evaluated in isolated coronary arteries and anesthetized dogs. JTV-506 (1 nmol/l-3 mumol/l) produced a concentration-dependent relaxation in porcine isolated epicardial large coronary arteries precontracted with KCl (30 mmol/l), phenylephrine (3 mumol/l), histamine (3 mumol/l), serotonin (5-HT; 300 nmol/l), prostaglandin F2 alpha (PGF2 alpha; 10 mumol/l), U-46619 (100 nmol/l), endothelin-1 (ET-1; 30 nmol/l) and Bay K-8644 (100 nmol/l). JTV-506 was 2.5-8.5 and 13.3-81.5 times more potent than levcromakalim (CAS 94535-50-9) and nicorandil (CAS 65141-46-0), respectively, but was less potent than nifedipine (CAS 21829-25-4). JTV-506 and levcromakalim produced almost a complete relaxation in arteries precontracted with various kinds of vasoconstrictor, except for KCl. In contrast, nifedipine produced about 80-90% relaxation in arteries, precontracted with PGF2 alpha, U-46619 and ET-1. Thus, this potassium channel opener can be characterized as an agonist-nonselective vasorelaxant. The relaxing effects of JTV-506 and levcromakalim on coronary arteries precontracted with 30 mmol/l KCl was competitively antagonized by 3 mumol/l glibenclamide, an ATP-sensitive potassium (KATP) channel blocker. In canine isolated epicardial large coronary arteries, 10 mumol/l JTV-506, 10 mumol/l levcromakalim, 100 mumol/l nicorandil and 0.1 mumol/l nifedipine eliminated 10 mmol/l 3,4-diaminopyridine-induced rhythmic contractions. In anesthetized dogs, when administered directly into the coronary artery, JTV-506 induced dose-dependent increases in coronary arterial diameter and coronary blood flow. These results suggest that JTV-506 elicits coronary vasorelaxation through activation of the KATP channel. It is expected that JTV-506 might be useful in the treatment of coronary vasospasm in angina pectoris.     

Cardioprotective effects of nicorandil in rabbits anaesthetized with halothane: potentiation of ischaemic preconditioning via KATP channels

1. The roles of ATP-sensitive K+ channels (KATP channels) in ischaemic or pharmacological preconditioning in the rabbit heart remain unclear. Infarct limitation by ischaemic preconditioning was abolished by the KATP channel blocker glibenclamide under ketamine/xylazine anaesthesia, but not under anaesthesia induced by pentobarbital. Infarct limitation by the KATP channel opener pinacidil was detected under ketamine/xylazine anaesthesia, but not under pentobarbital anaesthesia. Thus, these effects appear to be anaesthetic dependent. 2. In the present study, we examined whether nicorandil (a KATP channel opener nitrate) exhibits cardioprotective actions under halothane anaesthesia, another commonly used volatile anaesthetic. Control animals were subjected to 40 min coronary occlusion and 120 min reperfusion. Before 40 min ischaemia, the nicorandil group received nicorandil (100 microg/kg per min, i.v., for 10 min), the 5' preconditioning (PC) group received 5 min ischaemia/20 min reperfusion, the 2.5'PC group received 2.5 min preconditioning ischaemia/20 min reperfusion, the nicorandil +2.5'PC group received both nicorandil and 2.5 min ischaemia/20 min reperfusion, the nicorandil +2.5'PC + 5-hydroxydecanoate (5HD) group received both nicorandil and 2.5 min ischaemia/20 min reperfusion in the presence of 5-hydroxydecanoate (5HD; a KATP blocker) and the 5HD group received 5 mg/kg, i.v., 5HD alone. Myocardial infarct size in control (n = 7), nicorandil (n = 5), 5'PC (n = 8), 2.5'PC (n = 5), nicorandil + 2.5'PC (n = 5), nicorandil + 2.5'PC + 5HD (n = 5) and 5HD (n = 4) groups averaged 44.4 +/- 3.6, 41.7 +/- 5.7, 17.8 +/- 3.2,* 34.1 +/- 4.8, 21.3 +/- 4.2,* 39.1 +/- 5.6 and 38.9 +/- 5.0% of the area at risk, respectively (*P <0.05 vs control). 3. Thus, nicorandil alone did not have an infarct size-limiting effect in halothane-anaesthetized rabbits. However, the results suggest that even when nicorandil alone does not demonstrate a direct cardioprotective effect, it may enhance ischaemic preconditioning via KATP channels. Key words: ATP-sensitive K+ (KATP) channel, ischaemic preconditioning, myocardial infarction, nicorandil, rabbit.