犬冠状动脉节段阻力的α-肾上腺素能调节

在14条麻醉开胸犬,分别在搏动的与心室纤颤(VF)的心脏观察了电刺激左侧星状神经节(LSGS)和冠状动脉内注入去甲肾上腺素(NE)对冠状动脉节段阻力的作用。冠状动脉内给心得宁2.5mg 阻断心肌的β_1-肾上腺素能受体。冠状动脉左旋支恒流灌注。测量左旋支灌注压与左族支远端冠状动脉压。不论在搏动的或VF的心脏,NE和LSGS均使心肌内小冠状动脉阻力和冠状动脉总阻力显著增加;而对心外膜大冠状动脉阻力并无明显作用。该结果表明,α-肾上腺素能活动主要收缩心肌内小冠状动脉。     

迷走神经与乙酰胆碱对缩窄的犬冠状动脉节段阻力的影响

在麻醉开胸犬,用电起搏维持心率恒定,研究了电刺激颈迷走神经(VNS)及冠状动脉内注入乙酰胆碱(ACh)对缩窄的冠状动脉的节段阻力及血流量的影响。在左旋支主干造成不同程度的冠状动脉缩窄。分别测定左旋支血流量(CBF_(cx))、主动脉压和主旋支远端冠状动脉压,记录心电图。实验发现,在冠状动脉临界狭窄和重度狭窄时,VNS 或冠脉给ACh 引起心外膜大冠状动脉阻力及冠状动脉主旋支总阻力增大,CBF_(cx)减少;随着缩窄程度加重,这些改变也愈明显,然而,心肌内小冠状动脉阻力却无显著改变。     

β-肾上腺素能激动剂对犬冠状动脉节段阻力的影响

在麻醉开胸犬研究了冠状动脉内注入异丙肾上腺素对冠状动脉节段阻力的作用。冠状动脉内预先给心得宁2.5mg 以阻断心脏的β_1-肾上腺素能受体。冠状动脉左旋支恒流灌注,测量左旋支近端压及其远端小冠状动脉压,记录心电图。冠状动脉内给异丙肾上腺素后,冠状动脉左旋支总阻力及心肌内小冠状动脉阻力分别由4.54±0.77(M±SD)和4.20±0.75下降至3.95±0.69(P<0.05)和3.43±0.66mmHg·min/ml(P<0.05),而心外膜大冠状动脉阻力反趋增大,由0.35±0.11上升至0.53±0.34mmHg·min/ml(P>0.05)。实验证明,β-肾上腺素能活动时在体犬冠状血管的直接作用主要是舒张心肌内小冠状动脉,使其阻力显著减低,而心外膜大冠状动脉阻力趋向继发性增大。     

在正常和冠状动脉狭窄犬中扩张胃对冠脉血流动力学的影响

饱餐和扩张胃对心血管的影响早已引起人们的注意,但结论是不一致的。以往的实验都是在正常冠脉的动物上进行。本文在造成冠脉狭窄的情况下进行观察。在22条开胸狗的左旋支上,用微米狭窄器造成临界狭窄和重度狭窄。把一个气球送入胃中并充气600ml连续观察30min。正常冠脉组在扩张胃的最初15min内(前期)冠脉流量增多,主动脉压升高,血管总阻力下降,冠脉扩张;在扩张胃后15分钟(后期)无显著变化。冠脉临界狭窄组,前期冠脉流量增多,血管总阻力下降,冠脉扩张;后期流量减少,壁内血管阻力增加,冠脉收缩。冠脉重度狭窄组,前期冠脉流量无明显增加;后期流量显著减少,血管总阻力及心外膜、壁内血管阻力均增加,提示左旋支血管各段都发生收缩。 我们认为,餐后心绞痛的发作可能主要是在原有冠脉狭窄基础上冠脉流量进一步减少的结果。     

犬冠状动脉狭窄与心肌需氧代谢的关系

本文在实验性开胸犬上,用一个微米缩窄器定量造成冠脉左旋支三种狭窄程度,并测量了血液动力学、血气和冠状窦pH、乳酸值。 冠脉轻度狭窄时,左旋支每分血流量(CBF)未下降;而乳酸值增加。临界狭窄时,CBF轻度下降,心肌耗氧量(MVO_2)随之下降而乳酸值增加。重度狭窄时,CBF、MVO_2、心肌供氧/耗氧比值和冠状窦pH值均下降;而氧提取率和乳酸值增加。冠脉狭窄大于75％后,狭窄程度与心肌供氧有明显相关(r=-0.92);而与心肌耗氧呈弱相关(r=-0.58)。     

治疗高血压药物的研究 海南岛萝芙木根总硷对狗冠脉血流的影响

气泡流量计法测定麻醉狗冠脉血流量。给药前11只狗血压、冠脉血流量及冠状血管阻力的平均数±标准差分别为:83±13毫米汞柱,80±14毫升/100克心肌/分及1.06±0.28毫米汞柱/(毫升/100克心肌/分)。静脉注射萝芙木根总硷0.2毫克/公斤后,血压降低了原水平的30—40%,对冠脉血流无明显影响,而冠脉阻力则显著降低。冠状动脉内注射0.1毫米未引起变化。因此认为萝芙木根总硷能使冠状动脉扩张,对高血压病人冠状循环机能不全情观可能有益。     

苯乙肼对狗冠脉血流动力的作用

开胸狗18只,用轉子流速計連續测量冠状动脉左旋枝流量。冠状动脉內注射苯乙肼25微克/公斤或股靜脉滴注5毫克/公斤都增加冠脉流量,降低冠脉阻力,扩張冠脉。苯乙肼5毫克/公斤/天連續皮下注射5天(“苯乙肼化”)則冠脉流量略减少而冠脉阻力稍增高,因此扩張冠脉不是它治疗心絞痛的基础。苯乙肼不加强5-羥基色胺和去甲腎上腺素的扩張冠脉作用,也不对抗脑垂体后叶素的收縮冠脉作用,它对利血平化狗的作用与正常者无明显差別,且其作用快而短,說明它不是通过抑制单胺氧化酶而产生其心血管效应。推测苯乙肼急性給药的扩張冠脉作用可能是它本身直接作用于腎上腺素能受体的結果;注射5天后能节約心肌耗氧,提示它治疗心絞痛可能与影响心肌代謝有关。     

常咯啉对狗冠脉循环和心肌梗塞后室性心律失常的作用

麻醉开胸狗7只,静注常咯啉7mg/kg,血压和左心室作功显著减低,冠脉血流量和主动脉血流量减少不显著,而冠脉阻力有减低趋势。在左心室作功减低时,心肌对氧、乳酸和丙酮酸的利用无明显影响。麻醉开胸结扎左冠状动脉前降支24小时后的清醒狗6只,静脉推注常咯啉5mg/kg对心肌梗塞后室性心律失常有明显的治疗效果,有效时间约半小时左右。对窦性心律的 P-R,QRS 和 Q-T 间期无明显改变。因常咯啉能有效控制狗急性心肌梗塞后的室性心律失常,值得临床试用。     

左旋精氨酸在冠脉搭桥术中心肌保护效果研究

目的:通过在心脏停搏液中添加适量左旋精氨酸来观察其在冠脉搭桥术中心肌保护效果。方法:选择2008年1月～2010年1月在我院行冠状动脉旁路移植术患者20例,随机分为2组,每组10例,对照组:常规心肌保护液组,不添加左旋精氨酸。实验组,心肌保护液中加入7.5g/L左旋精氨酸。测患者术前(T1)、术后6小时(T2)、术后12小时(T3)、术后24小时(T4)、术后48小时(T5)血浆中TNF-α、IL-6、IL-8及cTn I含量。记录临床观察指标。结果:两组血浆TNF-α、IL-6、IL-8、cTn I浓度术前无统计学意义(P>0.05),术后各时点TNF-α、IL-6、IL-8、cTn I浓度显著升高且实验组均低于对照组(P<0.05)。临床观察指标除血管活性药物应用情况实验组优于对照组(P<0.05)外无明显差异。结论:在心脏停搏液中加入L-精氨酸,可有效保护缺血心肌,减轻心肌再灌注损伤程度。     

乙酰胆碱对离体大鼠缺血/复灌心脏的保护作用及其机制

目的:探讨乙酰胆碱(ACh)预处理抗心肌缺血复灌(I/R)损伤作用及其与线粒体渗透性转换孔和/或线粒体ATP敏感性钾通道的关系。方法:采用离体大鼠心脏Langendorff灌流方法进行全心停灌30min,复灌120min复制I/R模型。测定心室力学指标和复灌各时间点冠脉流出液中乳酸脱氢酶(LDH)含量。实验结束测定心肌组织formazan含量的变化。结果:与单纯I/R组相比,ACh(0.1μmol/L,5min)预处理明显提高心肌细胞的formazan含量,降低复灌期间冠脉流出液中LDH含量,明显改善I/R所致的左室发展压、左心室内压最大上升和下降速率、心率与发展压乘积和左室舒张末压力的下降,缓解冠脉流量的减少。线粒体渗透性转换孔开放剂苍术苷(20μmol/L,复灌前给药20min)和线粒体ATP敏感性钾通道抑制剂5-羟基癸酸(100μmol/L,缺血前给药20min)能明显减弱ACh的保护作用。结论:在大鼠离体心脏灌流模型上,ACh预处理具有抗心脏缺血/复灌损伤的作用,这种保护作用可能与其抑制线粒体渗透性转换孔的开放和促进线粒体ATP敏感性钾通道的开放有关。     

Glutathione attenuates coronary constriction to acetylcholine in patients with coronary spastic angina

This study examined the effect of reduced glutathione (GSH), an important antioxidant that restores intracellular redox imbalance and prevents inactivation of endothelial-derived nitric oxide, on the abnormal vasomotor reactivity in spastic coronary arteries. The responses of epicardial diameter of the left coronary arteries to intracoronary infusion of acetylcholine (ACh; 50 microg/min) were measured by quantitative coronary angiography before and during combined intracoronary infusion of GSH (50 mg/min for 6 min) or saline as a placebo in 24 patients with coronary spastic angina and in 28 control patients. All of the spastic coronary arteries showed constrictor response to ACh, whereas the control coronary arteries as a whole showed only minimal diameter changes to ACh. GSH infusion suppressed constrictor response of epicardial diameter to ACh in patients with coronary spastic angina, whereas it had no significant effect in control subjects. Saline infusion did not have any effects. The results indicate that GSH attenuated the constrictor response to ACh in epicardial coronary arteries of patients with coronary spastic angina. GSH may have an important role in the regulation of coronary vasomotor function in patients with coronary spastic angina.     

Thromboxane A2/endoperoxide receptors mediate cholinergic constriction of rabbit lung microvessels.

Using an X-ray television system, we directly measured the internal diameter (ID; 100-1,000 microns) of small pulmonary arteries and analyzed the effects of cyclooxygenase inhibition and thromboxane A2/prostaglandin endoperoxide (TP) receptor blockade on the ID reductions in response to vagal nerve stimulation (VNS; 16 Hz) and injection of acetylcholine (ACh; 0.3 micrograms) in anesthetized rabbits. The ID reductions of the small arteries in response to VNS and ACh were completely abolished by pretreatment with cyclooxygenase inhibitors indomethacin and meclofenamate. Those reductions were also eliminated by pretreatment with TP receptor antagonists AA-2414 and Ono 3708. Both TP receptor antagonists abolished the ID reduction to thromboxane A2 mimetic U-46619 but did not affect the reduction to norepinephrine. The ID reductions in response to VNS and ACh were eliminated by atropine. The reduction in response to VNS was abolished by hexamethonium bromide, whereas the reduction in response to ACh was not altered by hexamethonium bromide. The results indicate that vasoconstrictions of the rabbit small pulmonary arteries in response to VNS and exogenous ACh are mediated by TP receptors as well as muscarinic receptors. The data suggest that during VNS endogenous ACh acts on muscarinic receptors to constrict the small arteries mainly by generating thromboxane A2 or prostaglandin endoperoxide.     

Effects of supplemental oxygen administration on coronary blood flow in patients undergoing cardiac catheterization

Patients with heart disease are frequently treated with supplemental oxygen. Although oxygen can exhibit vasoactive properties in many vascular beds, its effects on the coronary circulation have not been fully characterized. To examine whether supplemental oxygen administration affects coronary blood flow (CBF) in a clinical setting, we measured in 18 patients with stable coronary heart disease the effects of breathing 100% oxygen by face mask for 15 min on CBF (via coronary Doppler flow wire), conduit coronary diameter, CBF response to intracoronary infusion of the endothelium-dependent dilator ACh and to the endothelium-independent dilator adenosine, as well as arterial and coronary venous concentrations of the nitric oxide (NO) metabolites nitrotyrosine, NO(2)(-), and NO(3)(-). Relative to breathing room air, breathing of 100% oxygen increased coronary resistance by approximately 40%, decreased CBF by approximately 30%, increased the appearance of nitrotyrosine in coronary venous plasma, and significantly blunted the CBF response to ACh. Oxygen breathing elicited these changes without affecting the diameter of large-conduit coronary arteries, coronary venous concentrations of NO(2)(-) and NO(3)(-), or the coronary vasodilator response to adenosine. Administering supplemental oxygen to patients undergoing cardiac catheterization substantially increases coronary vascular resistance by a mechanism that may involve oxidative quenching of NO within the coronary microcirculation.     

Vagally and acetylcholine-mediated constriction in small pulmonary vessels of rabbits

Using a new X-ray TV system, we analyzed effects of vagal nerve stimulation (VNS; 1-30 Hz) and intravenous injection of acetylcholine (Ach; 0.3-0.9 microgram) on the internal diameter (ID; 100-1,500 microns) of small pulmonary arteries and veins in anesthetized rabbits. In selective segments of the arteries, ID decreased abruptly and maximally by 50-70% in a specific stimulus frequency to the vagal nerve and a dose of ACh. The vasoconstrictor sites were distributed near the branching points of the arteries, particularly those downstream, and their numbers increased with an increase in the stimulus frequencies and ACh doses. The relative frequencies of occurrences were 15.3% with VNS (30 Hz) and 5.3% with ACh (0.9 microgram). In nonselective segments with VNS, ID decreased frequency dependently by 0, 4, 12, and 26% at 1, 4, 15, and 30 Hz, respectively, and with ACh, decreased dose dependently by 21 and 35% with 0.3 and 0.9 microgram, respectively. The vasoconstriction in response to VNS and ACh was attenuated by atropine, enhanced by eserine, and not affected by phentolamine. That vasoconstriction to VNS was abolished by hexamethonium. No selective constriction was found in veins and the ID was decreased uniformly by 1-2% with VNS and ACh.     

Transcardiac adiponectin gradient is independently related to endothelial vasomotor function in large and resistance coronary arteries in humans

Adiponectin, an adipocyte-derived protein, has been shown to have vasculoprotective effects. This study examined the possible relationship between coronary vasomotor function and the transcardiac gradient of adiponectin, reflecting adiponectin utilization and/or accumulation in the coronary vascular bed. The epicardial diameter and blood flow response of the left anterior descending coronary artery to intracoronary infusions of ACh was analyzed in 108 consecutive subjects who had a normal coronary angiogram and left ventriculogram. Adiponectin levels were measured by ELISA in plasma obtained from the aortic root (Ao) and the anterior interventricular vein (AIV). Adiponectin levels in the AIV were lower than levels in the Ao. In multivariate linear regression analysis, the transcardiac gradient of adiponectin (Ao - AIV levels) showed a positive correlation with increases in epicardial coronary diameter and coronary blood flow in response to ACh that was independent of traditional coronary risk factors. The transcardiac gradient of adiponectin was not significantly associated with the coronary dilator response to isosorbide dinitrate and the coronary flow response to sodium nitroprusside. In other groups of patients with coronary spastic angina (n = 41) or microvascular angina (n = 32) who had impaired coronary vasomotor responses, there was no significant gradient of adiponectin between the Ao and AIV. The transcardiac gradient of adiponectin may modulate endothelial vasomotor function in large and resistance coronary arteries and may play a role in the pathogenesis of diseases presenting with coronary vasomotor dysfunction.     

Pathophysiological plasma ET-1 levels antagonize beta-adrenergic dilation of coronary resistance vessels in conscious dogs

On the basis of in vitro experiments showing that endothelin (ET)-1 interferes with smooth muscle ATP-sensitive K(+) (K(ATP)) channel opening, which is pivotal in beta-adrenergic coronary dilation, we hypothesized that pathophysiological plasma ET-1 levels impair beta-adrenergic dilation of resistance coronary vessels. In conscious instrumented dogs, graded intravenous doses of dobutamine caused the expected inotropic responses. As myocardial O(2) consumption (MVo(2)) increased, the disproportionate rise in coronary sinus (CS) Po(2) indicates that increases in coronary blood flow (CBF) exceeded metabolic requirements, consistent with beta-adrenergic dilation. ET-1 intravenous infusions, to reach pathophysiological plasma levels, reduced slopes of the Po(2)-MVo(2) and CBF-MVo(2) relations. In contrast, the first derivative of left ventricular pressure over time responses to dobutamine were not impaired during ET-1 delivery. Clazosentan, an ET(A) receptor blocker, prevented reduction of the slope of Po(2)-MVo(2) and CBF-MVo(2) relations. After ganglionic blockade to exclude reflex influences, ET-1 still reduced slopes of Po(2)-MVo(2) and CBF-MVo(2) relations. To assess effects of ET-1 on endothelium-dependent and -independent coronary vascular responses, intracoronary ACh and nitroglycerin were given to directly target coronary vessels. CBF responses to ACh and nitroglycerin were maintained during ET-1 delivery. In contrast, responses to intracoronary K(ATP) channel-dependent dilators adenosine and lemakalim were impaired by ET-1. In conclusion, pathophysiological levels of ET-1 impaired beta-adrenergic dilation of resistance coronary vessels through an ET(A) receptor-dependent process. In contrast, left ventricular inotropic responses to dobutamine were not impaired during ET-1 delivery. Our data suggest that ET-1 may interfere with smooth muscle K(ATP) channels to impair beta-adrenergic coronary dilation.     

Widespread Myocardial Delivery of Heart-Derived Stem Cells by Nonocclusive Triple-Vessel Intracoronary Infusion in Porcine Ischemic Cardiomyopathy: Superior Attenuation of Adverse Remodeling Documented by Magnetic Resonance Imaging and Histology

Single-vessel, intracoronary infusion of stem cells under stop-flow conditions has proven safe but achieves only limited myocardial coverage. Continuous flow intracoronary delivery to one or more coronary vessels may achieve broader coverage for treating cardiomyopathy, but has not been investigated. Using nonocclusive coronary guiding catheters, we infused allogeneic cardiosphere-derived cells (CDCs) either in a single vessel or sequentially in all three coronary arteries in porcine ischemic cardiomyopathy and used magnetic resonance imaging (MRI) to assess structural and physiological outcomes. Vehicle-infused animals served as controls. Single-vessel stop-flow and continuous-flow intracoronary infusion revealed equivalent effects on scar size and function. Sequential infusion into each of the three major coronary vessels under stop-flow or continuous-flow conditions revealed equal efficacy, but less elevation of necrotic biomarkers with continuous-flow delivery. In addition, multi-vessel delivery resulted in enhanced global and regional tissue function compared to a triple-vessel placebo-treated group. The functional benefits after global cell infusion were accompanied histologically by minimal inflammatory cellular infiltration, attenuated regional fibrosis and enhanced vessel density in the heart. Sequential multi-vessel non-occlusive delivery of CDCs is safe and provides enhanced preservation of left ventricular function and structure. The current findings provide preclinical validation of the delivery method currently undergoing clinical testing in the Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC) trial of CDCs in heart failure patients.     

降钙素基因相关肽对不同程度冠脉狭窄时的心脏功能的影响

本实验观察了冠脉内注射降钙素基因相关肽（ＣＧＲＰ０．３μｇ／ｋｇ）对正常及不同程度冠脉狭窄犬的心功能的影响。结果表明正常犬冠脉内注射ＣＧＲＰ后,平均动脉压（ＭＡＰ）下降１．２ｋＰａ（Ｐ＜０．０５）,同时,心率（ＨＲ）、心输出量（ＣＯ）、左室收缩压峰值（ＬＶＳＰ）均不同程度增加;左室舒张末压（ＬＶＥＤＰ）轻度降低。在中度狭窄３０ｍｉｎ后,冠脉内注射ＣＧＲＰ对ＨＲ、ＭＡＰ无明显影响;而重度狭窄后注射ＣＧＲＰ,ＭＡＰ由狭窄时降低逐渐增高,ＨＲ由增快而变慢。ＣＯ、ＬＶＳＰ均显著增高,ＬＶＥＤＰ降低,此作用较冠脉狭窄前更为明显。提示ＣＧＲＰ扩张冠脉动脉,增加冠脉血流量和心排血量,增强心肌收缩力,对缺血心脏功能有保护作用。     

A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese

Coronary spasm plays an important role in the pathogenesis of not only variant angina but also ischemic heart disease in general. However, the precise mechanism(s) by which coronary spasm occurs remains to be elucidated. Coronary spasm may arise from interactions between environmental and genetic factors. Endothelial derived nitric oxide (NO) has been implicated in the control of vascular tone. We have recently shown that both basal and acetylcholine (ACh)-induced NO activities are impaired in the coronary arteries of patients with coronary spasm. The purpose of this study has been to elucidate the possible variants that occur in the coding region of the endothelial nitric oxide synthase (eNOS) gene and that may be associated with coronary spasm. After initial screening in the entire 26 coding regions of the eNOS gene, we found a missense Glu298Asp variant in exon 7 in patients with coronary spasm. We subsequently performed a larger scale study involving 113 patients with coronary spasm and 100 control subjects, who were all diagnosed by intracoronary injection of ACh. The analysis revealed a significant difference in the distribution of the variant between the coronary spasm group (21.2%) and control group (9.0%; P=0.014 for dominant effect). Thus, we have found the missense Glu298Asp variant in the eNOS gene by the analysis of its entire 26 coding regions. The variant is significantly associated with coronary spasm. Received: 2 February 1998 / Accepted: 9 April 1998