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.     

尼可地尔治疗冠心病心绞痛21例

本文报道口服国产尼可地尔治疗冠心病心绞痛患者21例,21例患者完成全过程观察。尼可地尔对控制心绞痛发作疗效有效率为86％,对冠心病高血压患者兼有降压作用。进行STI检查发现2/3患者的PEP/LVET比值缩短,4例患者进行放射性核素检查,LVEF测定均有增加,这反映收缩力及心功能得到改善,心电图改善不多。本文研究显示尼可地尔有解聚血小板的作用,这与抗心绞痛、防止心肌梗塞有益,并优于硝酸甘油。临床观察证明尼可地尔对心率无明显影响。该药吸收快、作用迅速、副作用轻微,长期服用安全范围大,有其一定实用价值。     

Calcium antagonists in the treatment of hypertension in patients with ischaemic heart disease

Are lives saved or heart attacks prevented by antihypertensive therapy, as a result of blood pressure reduction alone, or because of other properties of the antihypertensive medications which are independent of blood pressure lowering? Long-acting calcium antagonists seem to be as effective as thiazide diuretics and angiotensin-converting enzyme (ACE) inhibitors in preventing all-cause mortality and stroke in patients with hypertension, but are probably inferior to ACE inhibitors in preventing coronary artery disease. In patients with symptomatic coronary artery disease, calcium antagonists are generally as effective as β-blockers in relieving angina and improving exercise time-to-onset of angina or ischaemia. Unstable angina or myocardial infarction require treatment with a β-blocker, with an ACE inhibitor added when necessary for blood pressure control or if there is significant left ventricular (LV) dysfunction. If β-blockers are contraindicated and if there is no LV dysfunction, a non-dihydropyridine calcium antagonist can be substituted.     

Study of the efficacy of nicorandil in patients with ischaemic heart disease using Exercise-Tl-201 myocardial tomography

Summary The effect of nicorandil on myocardial perfusion in ischaemic heart disease has been studied using exercise-load Tl-201 myocardial SPECT (Ex-SPECT). Ex-SPECT was carried out in 12 patients with previous myocardial infarction (OMI) and 9 with angina pectoris (AP) before and after administration of nicorandil 15 mg/day, for three or more weeks; % Tl uptake and the washout rate in infarcted or ischaemic areas were calculated from short axial images using the Bull's eye method.In the OMI group, % Tl uptake and washout rates in the infarction areas improved significantly from 52.4% and 0.25 before nicorandil to 60.4% and 0.38 after it. In the AP group, too, % Tl uptake and washout rates showed a significant improvement from 56.9% and 0.10 before to 69.1% and 0.33 after administration. Six subjects who had not received the drug, and who showed negative washout rates, had high improvement rates when nicorandil was administered, suggesting that the drug could increase myocardial perfusion during exercise loading as well as suppressing coronary spasm.Ex-SPECT was done in 4 subjects before and after nicorandil and after subsequent surgical treatment (PTCA or CABG) and the effects of the two therapies were compared. The washout rate was improved from 0.01 to 0.34 by administration of nicorandil, and a notable increase in coronary artery blood flow was achieved compared to the level after surgical treatment, i.e. 0.50.It was concluded that, normal dosages of nicorandil have a powerful direct effect of dilating the coronary arteries without any influence on preload or afterload.     

The role of nicorandil in the treatment of myocardial ischaemia

Nicorandil is an anti-anginal agent that has been used in the United Kingdom for over 6 years and is becoming increasingly popular. It induces coronary and peripheral vasodilatation via a dualistic mode of action, mediated by the opening of potassium-ATP channels (K(ATP)) and its nitrate effect by stimulation of adenyl cyclase, with an increase in cGMP levels. Comparison to nitrates and other anti-anginal agents have shown it to be of equal efficacy in relieving ischaemic symptoms. Recent evidence suggests a role for nicorandil as a myocardial preconditioning agent but this may be limited by systemic vasodilatation. There is ongoing research into its role in improving the long-term outcome of patients with ischaemic heart disease (IHD). It has been shown to be of proven efficacy in the treatment of IHD and further research will clarify other uses of this agent.     

Effect of diltiazem and propranolol on myocardial ischaemia during unrestricted daily life in patients with effort-induced chronic stable angina pectoris

Summary To examine the effect of diltiazem 60 mg thrice daily and propranolol 80 mg thrice daily on myocardial ischaemia during unrestricted daily life, we have studied 14 patients with established effort-induced chronic stable angina pectoris in a double-blind crossover study.Ambulatory electrocardiographic monitoring was performed using frequency modulated (FM) tape recorder after 2 weeks of placebo therapy and at the end of each 4 week treatment period for a minimum of 24 h.The mean (±SEM) number of episodes of ST-segment depression greater than 1 mm during placebo treatment were 97±28, and these fell to 54±27 during diltiazem treatment (p<0.05) and to 12±6 during propranolol treatment (p<0.02).The maximal depth of ST-segment depression in 24 h, which indicates the severity of the episode, was 3.3±0.4 mm during placebo, 2.5±0.2 mm during diltiazem (p<0.05), and 1.6±0.5 mm during propranolol (p<0.01). Both diltiazem and propranolol treatment produced significant reduction in the total area of ST-segment depression observed during 24 h.A uniform reduction in the mean heart rate during the 24 h was observed during propranolol therapy and not during diltiazem therapy.Both diltiazem and propranolol treatment improved indices of myocardial ischaemia during daily normal unrestricted life, as measured by ambulatory ST-segment monitoring in patients with established chronic stable angina pectoris. Their differing effects on heart rate suggest that they act by different mechanisms.     

尼可地尔对急性心肌梗塞患者血流动力学的影响

11例急性心肌梗塞患者(男10女1,年龄62±SD9 yr)于发病3d内入院,用尼可地尔15-20mgpo,监测服药前、后的血流动力学变化,结果显示服用尼可地尔后心率减慢,血压、右心房压、肺楔嵌压、体循环及全肺阻力下降,心脏指数增加(P<0.05);药物作用于服药后1-2h最明显,4h仍有作用。示该药可改善患者的血流动力学指数。     

KATP通道介导的油茶皂甙对在体大鼠心肌产生的缺血预适应样保护作用

目的：研究油茶皂甙（SQS）对大鼠心肌产生的缺血预适应样保护作用及与KATP通道的关系。方法：以ISO诱发大鼠心肌缺血损伤为模型，使用KATP通道特异性阻断剂gliberclamide(GLI5mg.kg^-1).实验分为四组，分别为生理盐水对照组（NS组）、ISO诱发损伤组（I／R组）、SQS组（I／R＋SQS0.2mg.kg^-1)和GLI组（I／R＋GLI＋SQS）。在注射ISO前，从阴茎静脉预适应注射各被试药物或NS，每天1次，连续3d，末次给药后立即皮下多点注射ISO。NS组皮下注射等量NS。分别测定大鼠ECG及末次给药后血清CPK活性，FFA和腺苷含量。结果：预适应ivSOQS能有效地保护ISO所致大鼠心肌损伤；先ivGLI后再给予SQS，则SQS对心肌损伤的保护作用明显减弱，结论：SQS对ISO所致心肌缺血大鼠可产生药理性预适应保护作用，该作用可能由KATP通道所介导。     

硝酸甘油和尼可地尔对缺血区冠脉循环作用的比较

采用实验性冠脉狭窄犬模型,冠脉内恒流灌注硝酸甘油和尼可地尔(均为1μg·kg~(-1)·min~(-1)).发现硝酸甘油有两种作用:灌注5min时能扩张冠脉狭窄段(R_L)及狭窄远端小动脉(R_s),增加冠脉血流量(CBF),改善心肌缺血;但灌注10min后.却引起R_L的增加、CBF的减少,使冠状静脉全血粘度(Hb)、血细胞比容(Hct)增加。加重心肌缺血和恶化冠脉循环。尼可地尔能持久和缓和地扩张冠脉.使R_S降低,CBF增加,降低冠状静脉的Hb、Hct.改善缺血区冠脉循环。     

尼可地尔对急性ST段抬高型心肌梗死患者直接经皮 冠状动脉介入术后临床效果的影响

目的 观察冠状动脉联合外周静脉应用尼可地尔对急性ST段抬高型心肌梗死（STEMI）患者直接经皮冠 状动脉介入（PPCI）治疗术后心肌微循环及短期预后的影响。方法 100例接受PPCI治疗的急性STEMI患者,根据 不同给药方式分为尼可地尔组和对照组,每组各50例。尼可地尔组于PPCI术中开通靶血管即刻予冠状动脉注射尼 可地尔并静脉持续泵入24 h,对照组于PPCI术中予冠脉注射生理盐水并静脉持续泵入24 h。主要观察指标为PPCI 术后即刻冠脉血流及心肌血流灌注情况,包括介入术后TIMI血流分级、校正TIMI帧计数（CTFC）、再灌注心律失常、 ST段回落、肌酸激酶同工酶（CK-MB）达峰时间及峰值,次要观察指标为住院期间主要不良心血管事件（MACE）及左 心室射血分数（LVEF）。结果 2组内手术前后肝肾功能、心率、血压变化差异无统计学意义（均P＞0.05）。与对照 组相比,PPCI术后尼可地尔组再灌注心律失常发生比例、慢血流/无复流比例、住院期间MACE比例、CTFC、CK-MB 峰值降低;TIMI 3 级血流患者比例、CK-MB 达峰时间提前至 14 h 内的比例、ST 段回落的比例均明显增加（均 P＜ 0.05）。2组患者住院期间LVEF差异无统计学意义（P＞0.05）。结论 冠脉联合外周静脉应用尼可地尔有助于实现 STEMI患者PPCI术后梗死血管的血运重建,减少慢血流/无复流的发生,限制梗死面积,增加心肌血流灌注,改善心 肌微循环和短期预后。     

地奥心血康胶囊联合尼可地尔治疗冠心病心肌缺血的临床研究

目的探讨地奥心血康胶囊联合尼可地尔治疗冠心病心肌缺血的疗效。方法选取天津市静海区医院在2015年7月—2016年7月收治的冠心病心肌缺血患者161例,随机分成对照组(80例)和治疗组(81例)。对照组口服尼可地尔片,1片/次,3次/d。治疗组在对照组的基础上口服地奥心血康胶囊,2粒/次,3次/d。两组患者均规律治疗6周。评价两组患者临床疗效,同时比较治疗前后两组患者ST段压低次数、心肌耗氧量和心肌缺血总负荷、N-末端脑钠肽前体(NT-pro BNP)水平和不良反应差异。结果治疗后,对照组和治疗组的总有效率分别为81.25%、97.53%;两组比较差异具有统计学意义(P0.05)。治疗后,两组患者ST段压低次数、心肌耗氧量和心肌缺血总负荷均明显降低(P0.05);且治疗组这些指标均明显低于对照组患者(P0.05)。治疗后,两组NT-pro BNP水平均显著降低,同组治疗前后差异有统计学意义(P0.05);治疗后,治疗组NT-pro BNP水平明显低于对照组,两者比较差异具有统计学意义(P0.05)。治疗期间,对照组不良反应发生率为16.25%,显著高于治疗组的4.94%,两组比较差异具有统计学意义(P0.05)。结论地奥心血康胶囊联合尼可地尔治疗冠心病心肌缺血具有显著的临床疗效,可显著改善患者心肌缺血的预后,具有一定的临床推广应用价值。     

通心舒胶囊联合尼可地尔治疗冠心病心绞痛的临床研究

目的研究通心舒胶囊联合尼可地尔片治疗冠心病心绞痛的临床疗效。方法选取2017年12月—2019年5月在华中阜外医院治疗的冠心病心绞痛患者92例为研究对象,将所有患者随机分为对照组和治疗组,每组各46例。对照组患者口服尼可地尔片,1片/次,3次/d;治疗组在对照组治疗的基础上口服通心舒胶囊,2粒/次,3次/d。两组患者均连续口服4周。观察两组的临床疗效和心电图疗效,比较两组的临床症状、心功能指标、心肌酶指标、血液流变学指标。结果治疗后,对照组和治疗组的临床疗效总有效率分别为78.26%、93.48%,两组比较差异有统计学意义(P0.05)。治疗后,对照组和治疗组的心电图疗效总有效率分别为80.43%、93.48%,两组比较差异有统计学意义(P0.05)。治疗后,两组心绞痛持续时间、发作次数显著降低,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组心绞痛持续时间、发作次数明显低于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患者左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)明显降低,左室射血分数(LVEF)明显升高,同组治疗前后比较差异有统计学意义(P0.05);且治疗组患者心功能指标明显优于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患者血清酸激酶MB型同工酶(CK-MB)、肌酸激酶(CK)水平显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组患者血清心肌酶指标水平明显低于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患者全血黏度(WBV)、血浆黏度(PV)、纤维蛋白原(FIB)水平均明显降低,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组患者血液流变学指标水平明显低于对照组,两组比较差异有统计学意义(P0.05)。结论通心舒胶囊联合尼可地尔片治疗冠心病心绞痛具有较好的临床疗效,可改善临床症状、心功能指标、心肌酶指标、血液流变学指标,具有一定的临床推广应用价值。     

灯盏生脉胶囊联合尼可地尔治疗冠心病心绞痛的临床研究

目的 探讨灯盏生脉胶囊联合尼可地尔片治疗冠心病心绞痛的临床疗效。方法 选取2020年1月—2021年3月平煤神马医疗集团总医院治疗的124例冠心病心绞痛患者为研究对象,按照随机数字方法分为对照组（62例）和治疗组（62例）。对照组患者口服尼可地尔片,5 mg/次,3次/d。治疗组患者在对照组基础上口服灯盏生脉胶囊,2粒/次,3次/d。两组患者均连续治疗14 d。观察对比两组患者的临床疗效、心电图疗效、心绞痛发作次数及持续时间。同时比较两组治疗前后SF-36量表评分、基质金属蛋白酶相关指标、炎性因子水平、氧化应激指标的变化情况。结果 治疗后,治疗组总有效率是95.16%,显著高于对照组的79.03%（P<0.05）。治疗后,治疗组心电图疗效总有效率是95.16%,显著高于对照组的80.65%（P<0.05）。治疗后,两组心绞痛发作次数及心绞痛持续时间均显著降低（P<0.05）,且治疗后治疗组心绞痛发作情况改善优于对照组（P<0.05）。治疗后两组SF-36量表评分均升高（P<0.05）;治疗后治疗组SF-36量表评分高于对照组（P<0.05）。治疗后,两组患者白细胞介素-18（IL-18）、肿瘤坏死因子（TNF-α）、可溶性细胞间黏附分子（sICAM-1）均较治疗前显著降低（P<0.05）;治疗后,治疗组炎症因子水平低于对照组（P<0.05）。治疗后,两组超氧化物歧化酶（SOD）均较治疗前显著升高,但脂质过氧化物（LPO）、丙二醛（MDA）均降低（P<0.05）;治疗后,治疗组SOD水平较对照组升高,LPO、MDA水平较对照组降低（P<0.05）。治疗后,两组基质金属蛋白酶抑制因子1（TIMP-1）均有所升高,但基质金属蛋白酶-9（MMP-9）有所降低（P<0.05）;治疗后,治疗组TIMP-1水平高于对照组,但MMP-9水平低于对照组（P<0.05）。结论 灯盏生脉胶囊联合尼可地尔片治疗可以提高冠心病心绞痛患者临床疗效,有效改善患者心绞痛发作次数及心绞痛持续时间,提高日常生活质量,改善炎性反应、氧化应激反应,值得临床广泛应用。     

Potential of adenosine receptor agonists for the prevention and treatment of coronary artery disease and acute myocardial infarction

Adenosine is an ubiquitously produced autocoid which mediates its effects via four receptor subtypes (A₁, A_2A, A_2B and A₃) which show a relatively widespread tissue distribution. Adenosine itself is upregulated in vascular tissue in response to hypoxia and induces vasodilation as a homeostatic response. The vasodilator effects of adenosine are exploited clinically, where it is used as a pharmacological vasodilator during stress testing. More recently, it has become clear that adenosine and adenosine agonists possess significant potential for cardioprotection. Thus, given prior to an ischaemic insult, adenosine and adenosine A₁ receptor agonists can reduce infarct size, reduce arrhythmia and improve post-ischaemic cardiac function. In addition, when given during myocardial ischaemia just prior to reperfusion, adenosine and adenosine A_2A receptor agonists can inhibit neutrophil adhesion, activation and infiltration into post-ischaemic myocardium, thereby inhibiting lethal reperfusion injury and further salvaging myocardial tissue. There is also some evidence that stimulation of adenosine A₃ receptors can protect myocardium. The realisation that adenosine analogues possess cardioprotective activity has stimulated research to identify subtype selective analogues with the optimal profile for use in acute myocardial infarction (MI) and cardiac surgery. Several compounds have reached the stage of early clinical development and hold significant promise as future therapies. In addition to direct cardioprotective effects, adenosine A₁ selective agonists may also indirectly benefit the heart via their metabolic effects. Thus, adenosine A₁ receptor stimulation results in a marked suppression of lipolysis in adipose tissue, which in turn leads to a reduction in the levels of circulating free fatty acids, triglycerides and very low density lipoproteins. Triglycerides are now accepted as an independent risk factor for mortality from coronary artery disease. Thus, the potential exists for the development of orally-active selective A₁ receptor agonists for the treatment of hypertriglyceridaemic patients to reduce the incidence of primary or secondary coronary events. Progress is being made in the design of such A₁ selective agonists.Therefore, the next decade should see advances in the therapeutic application of adenosine agonists in the porphylactic treatment of coronary artery disease and in acute MI.     

Clopidogrel in the treatment of ischaemic heart disease

Clopidogrel is an effective antiplatelet agent that has undergone rigorous assessment in the setting of ischaemic heart disease over the last decade. There is extensive evidence for the use of this drug in patients undergoing percutaneous coronary intervention, in those with stable ischaemic heart disease and also in those with acute coronary syndromes. This article examines the use of clopidogrel in patients with ischaemic heart disease.     

尼可地尔合用KB-R7943对缺血再灌注损伤离体大鼠心脏的保护作用

目的研究ATP敏感性钾通道开放药尼可地尔合用钠钙交换阻滞药KB-R7943对缺血再灌注损伤离体大鼠心脏的作用。方法离体大鼠心脏通过改良Langendorff装置灌流,减少灌流量造成缺血45 min后再灌注2 h建立大鼠心肌缺血再灌注损伤模型,分模型组、尼可地尔组、KB-R7943组、尼可地尔+KB-R7943组,每组10只。TTC染色观察心肌梗死面积,比色法检测冠脉灌流液中过氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,电镜观察心肌超微结构。结果与模型组比较,尼可地尔组和KBR7943组的心肌梗死面积均减小、冠脉灌流液中SOD活性升高、MDA含量下降(P<0.05);与模型组相比,尼可地尔+KB-R7943组的心肌梗死面积、冠脉灌流液中SOD活性和MDA含量改变均非常显著(P<0.01),心肌超微结构损伤减轻,均较尼可地尔组和KB-R7943组有显著改善(P<0.05)。结论尼可地尔合用KB-R7943可显著缩小心肌梗死面积,提高冠脉灌流液中SOD活性,减少MDA含量,减轻心肌超做结构损伤,对缺血再灌注损伤大鼠心脏有保护作用。     

The group at C2 of N-ethylnicotinamide determines the vasodilator potencies and mechanisms of action of nicorandil and its congeners in canine coronary arteries

Summary The relaxant mechanisms of action of nicorandil and its congeners (SG-86, SG-103, SG-209 and SG-212) on large coronary arteries were investigated in isolated canine circumflex arteries contracted with 25 mmol/l KCl or 10^–7 mol/l U46619, a thromboxane A₂ analogue. SG-212, SG-86, SG-209 and SG-103 were obtained by replacement of the nitroxy group of nicorandil by bromine, the hydroxy, acetoxy and nicotinoyloxy groups, respectively.Nicorandil (10^–6–10^–3 mol/l), SG-212 (3 × 10^–4 –10^–2 mol/l),SG-209 (10^–4–10^–2 mol/l), SG-103 (3 × 10^–4–10^–2 mol/l), and SG-86 (10^–3–10^–2 mol/l) all produced a concentration-dependent relaxation in KCl- or U46619-contracted arteries. The order of relaxant potency was as follows: Nicorandil » SG-209 > SG-212 = SG-103 > SG-86. The relaxant effect of nicorandil was not affected by glibenclamide but antagonized by methylene blue. In the presence of glibenclamide, the concentration-relaxation curves for SG-209 underwent rightward parallel shifts. The relaxant effect of SG-209, however, was not affected by methylene blue. The concentration-relaxation curves for SG-212 underwent rightward parallel shifts only to a limited extent in the presence of glibenclamide, but they were not affected by methylene blue. The relaxant effect of SG-103 was affected by neither glibenclamide or methylene blue. The relaxant effect of SG-86 was not affected by glibenclamide. The relaxant effect of nicorandil accompanied an increase in cyclic-GMP levels but that of SG-209 did not. These results indicate that the group at C2 of the parent structure of nicorandil and its congeners, i.e., N-ethylnicotinamide determines not only the vasodilator potency but the vasodilator mechanism of action of the compound. Send offprint requests to N. Taira at the above address     

CGRP、K_(ATP)通道和脊神经在鞘内注射吗啡预处理减轻大鼠心肌缺血后损伤中的作用

目的探讨降钙素基因相关肽(CGRP)、ATP敏感性钾离子通道(KATP通道)和脊神经在鞘内注射吗啡预处理对在体大鼠心肌缺血/再灌注损伤中的保护作用。方法♂SD大鼠60只,建立鞘内置管和心肌缺血/再灌注损伤模型,随机分为10组,每组6只:对照组(CON,生理盐水)、二甲亚砜组(DMSO,GLI的溶剂)、CGRP8-37组(CGRP受体阻滞剂,3nmol.kg-1)、格列苯脲组(GLI,KATP通道阻滞剂,0.3 mg.kg-1)、利多卡因组(LID,1%盐酸利多卡因10μl)、鞘内注射吗啡预处理组(MPC,3×1μg.kg-1)、CGRP8-37+MPC组、GLI+MPC组、LID+MPC组、GLI+LID组。观察指标包括:平均动脉压(MAP)、心率(HR),计算平均动脉压和心率乘积(RPP);心肌缺血危险区(AAR)、梗死区(IS)的体积、心肌梗死面积以IS/AAR表示。结果与CON组比较,MPC组、LID组、LID+MPC组和GLI+LID组的IS和IS/AAR均明显下降(P<0.05,P<0.01);与MPC组比较,CGRP8-37+MPC组、GLI+MPC组和LID+MPC组的IS和IS/AAR均明显增加(P<0.01)。结论外周CGRP的释放、KATP通道和脊神经可能参与了鞘内注射吗啡预处理减轻大鼠心肌缺血后损伤的作用。