三七绒根提取物(76017)对心血管的作用

三七绒根提取物(76017)为三七绒根乙醇提出物的有效成分,毒性较低,给小白鼠静注LD_(50)为836±17mg/kg。 给麻醉猫静注76017 25～50 mg/kg,3～5分钟内冠脉流量最高增加79％(P<0.05),血压呈暂时性下降,心率也略减慢,心肌耗氧量减少,比给药前平均降低24.3％(P<0.05)。 在家兔离体心脏灌流实验中,当2％76017 0.1和0.2ml注入灌流系统时,小剂量组给药后1分钟,冠脉流量平均增加17.5％;大剂量组给药后5分钟和7.5分钟分别增加48％和43％,(P<0.05),心率也稍减慢(P>0.05)。小剂量组心肌收缩振幅在5分钟内最高增加48％(P<0.05)。 在家兔离体器官血管灌流的实验中,当2％76017 0.1和0.2ml注入灌流系统,记录5分钟内的峰值,小剂量组兔肾、耳及后肢的流量分别增加50,57和32％;而大剂量组分别增加70,64和33％。     

三七提出物对心脏的药理作用

三七绒根提取物“76017”(简称17号)按1∶20000的浓度加入灌流液中,能增加离体豚鼠心脏冠脉流量。搏动心脏用17号后,冠脉流量增加84.04%,同时心肌收缩力增强,但心率变化不大;在用垂体后叶素收缩冠脉的基础上,用17号灌流,冠脉流量增加83.78%;纤颤心脏用17号灌流,冠脉流量增加65.06%。麻醉犬冠状静脉窦流出量测量。经十二指肠投予17号100mg/kg,冠脉流量增加57.03%,并能持续3小时以上,同时呈现心率减慢和血压降低。血氧测定结果,在冠脉流量增加高峰期,心肌耗氧量增加64.03%。心肌匀浆耗氧量测定。0.1%的17号抑制以丙酮酸为底物之耗氧量,增加以琥珀酸为底物之耗氧量。在实验性心肌梗塞模型上,静脉注入17号10mg/kg,未见到对心肌缺血性损害有保护作用,静脉注入心得安0.5 mg/kg,则有明显的保护作用。     

右美托咪定地佐辛单独或联合用药对腔镜下胃癌根治患者术后苏醒期的影响

目的 评价右美托咪定、地佐辛单独或联合用药对全麻腔镜胃癌根治患者术后苏醒期的影响。方法 选择2015年3月至2016年6月安徽省立医院收治的腔镜胃癌根治术患者80例,随机分为对照组（C组）、右美托咪定组（DEX组）、地佐辛组（DEZ组）和右美托咪定+地佐辛组（DD组）,每组20例。DEX、DD组于麻醉诱导前15分钟时静脉注射右美托咪定,DEZ组和DD组关腹时静脉注射地佐辛,C组关腹时静脉注射生理盐水。记录入PACU（T₀）、吸痰拔管（T₁）、拔管后5分钟（T₂）及10分钟（T₃）的平均动脉压（MAP）、心率（HR）;记录拔管后10分钟（T₃）、30分钟（T₄）、60分钟（T₅）的VAS、Ramsay评分。结果 同C组相比,T₀～T₃时DEX、DEZ、DD组MAP降低,DEX和DD组HR减慢（P<0.05）,T₃～T₅时DEX、DEZ和DD组VAS评分降低,Ramsay镇静评分增加（P<0.05）。同C组比较,其他各组躁动率和寒战发生率显著降低（P<0.05）,DD组与其他各组比较,躁动率和寒战发生率显著降低（P<0.05）。结论 右美托咪定、地佐辛单独或复合用药可使腔镜胃癌根治患者术后苏醒期血流动力学平稳,拔管后躁动和寒战发生率降低,复合用药效果更佳。     

剖宫产术前后预防性应用奥硝唑3种方法的比较

目的 探讨剖宫产术预防性应用奥硝唑的方法。方法 随机将146例剖宫产产妇分为术前给药A组(A₁组50例,单次给药;A₂42例,术前术后双次给药)和术后连续给药B组(52例)。结果 A组术后平均体温低于B组(P<0.01),退热时间短于B组(P<0.05),人均抗菌药用量A组均少于B组(P<0.001)。结论 术前应用奥硝唑优于术后应用奥硝唑。     

小剂量右美托咪定对剖宫产术中寒战的预防效果及安全性

目的 探讨小剂量右美托咪定预防剖宫产术中寒战的有效性和安全性。方法 选择2015年12月至2016年8月合肥市第三人民医院60例ASA I-II级剖宫产患者，依据随机数字表随机分成Dex0.1组、Dex0.3组、对照组，各20例，3组患者均行连续硬膜外麻醉，硬膜外麻醉阻滞完善后，Dex0.1组和Dex0.3组分别从静脉缓慢输注负荷剂量的右美托咪定0.1 μg/kg和0.3 μg/kg，输注时间10 min，对照组输注生理盐水。观察各组产妇麻醉前（T₀）、给药后5分钟（T₁）、给药后10分钟（T₂）、给药后30分钟（T₃）的平均动脉压、心率、自主呼吸、氧饱和度、及寒战发生情况和新生儿1、5、10 min的Apgar评分。结果 3组患者自主呼吸和氧饱和度比较，差异无统计学意义（P>0.05）；3组患者平均动脉压和心率在T₀、T₃时组间比较，差异无统计学意义（P>0.05），平均动脉压（MAP）和心率（HR）在T₁、T₂时组间比较如下：Dex0.1组与生理盐水组比较，差异无统计学意义（P>0.05），Dex0.3组与Dex0.1组、生理盐水组比较，平均动脉压和心率下降，其中T₁时Dex0.3组MAP（82±9）mmHg，HR（83±10）次/分，Dex0.1组MAP（86±8）mmHg，HR（86±9）次/分，生理盐水组MAP（87±6）mmHg，HR（89±8）次/分；T₂时Dex0.3组MAP（81±7）mmHg，HR（82±10）次/分，Dex0.1组MAP（86±8）mmHg，HR（88±10）次/分，生理盐水组MAP（85±7）mmHg，HR（90±10）次/分，差异有统计学意义（P<0.05）；Dex0.3组与生理盐水组和Dex0.1组比较，寒战发生率及寒战时长显著降低：Dex0.3组、Dex0.1组、生理盐水组寒战发生率分别为15%、45%和50%，寒战时长Dex0.3组、Dex0.1组、生理盐水组分别为（7.8±3.0）min、（10.0±2.9）min和（10.2±3.1）min，差异具有统计学意义（P<0.05）；3组Apgar评分比较差异无统计学意义（P>0.05）。结论 小剂量右美托咪定可以安全且有效预防剖宫产术中寒战的发生，0.3 μg/kg为一适宜剂量。     

脑心通胶囊对缬沙坦在大鼠体内药动学的影响

目的 研究脑心通胶囊对缬沙坦在大鼠体内药动学的影响。方法 建立液相色谱-串联质谱（LC-MS/MS）法检测缬沙坦血药浓度,并进行专属性考察、回收率试验、基质效应、稳定性试验等方法学验证;24只SD雄性大鼠,随机均分为3组,每组8只,分别为缬沙坦组（A组）,缬沙坦和脑心通胶囊单次给药组（B组）,脑心通胶囊给药7 d后,第8天ig给予缬沙坦和脑心通胶囊组（C组）,于给药前及给药后不同时间点由大鼠眼眶静脉丛采血,采用液相色谱-串联质谱（LC-MS/MS）法测定血浆中缬沙坦的质量浓度,DAS2.0软件统计分析,得到缬沙坦的药动学参数。结果 成功建立LC-MS/MS法检测缬沙坦血药浓度方法,方法学验证符合药动学相关规范要求。口服缬沙坦在大鼠体内的药动学属于一室模型。B组C_max明显低于A组,但差异无统计学差异;B组t_1/2显著高于A组（P<0.05）;C组t_max、t_1/2、AUC_0-tn、AUC_0-∞均显著高于A组（P<0.05、0.01）,K_e显著低于A组（P<0.05）;C组AUC_0-tn、AUC_0-∞显著高于B组（P<0.05）。结论 大鼠经连续ig给药脑心通胶囊后,可显著延缓缬沙坦在大鼠体内的达峰时间,并使缬沙坦在大鼠体内的生物利用度升高。     

茄秧治疗心血管疾病的研究 1.茄秧对血流动力和心肌耗氧量的影响

茄秧为茄科植物食用茄(Solanaceae Melongena L.)地上部分全草,用水醇法制成100%(生药)注射液。本文测定了在密闭容器内小鼠耗氧量的动态变化。从盐水、心得安和茄秧三组动物死亡临界氧分压分别为7.1±0.8%、6.8±0.5%和6.4±0.5%,死亡时间分别为24.3±3.4、31.4±4.6和32.7±4.6分钟,茄秧与心得安相近明显降低小鼠氧代谢。在减压或常压下该药均增加小鼠耐缺氧作用。给狗静注茄秧注射液1.5克/公斤,冠脉流量显著增加,流量峰值比给药前增加199. 5 % , 1-3 0分钟流量均值比给药前增加123.3%,流量增加持续时间均在30分钟以上。给药后动静脉氧差由9.5ml%降至5.Iml0%,心肌氧利用率由著降低(P<0.01)。该药能明显增加离休豚鼠心峡冠脉流量。用Rb~(86)示踪法证明,该药能显著增加心叽营养性血流量,静注4克/公斤该药可使家兔血压下降29.2%,股动脉流量增加59%能使离体兔耳灌注流量增加38～43% ,具有镇静作用。该药毒性较小,小鼠腹腔给药LD_(50)为85 .9±3.5克/公斤。在药理实验基础上,经临床90例证明,该药对冠心病心绞痛和高血压有明显治疗作用。     

小剂量乙酰半胱氨酸治疗慢性肝损伤作用及其机制

目的 研究小剂量乙酰半胱氨酸（N-acetylcysteine,NAC）对CCl₄所致慢性肝损伤的疗效及其作用机制。方法 将大鼠分为正常对照组、模型组、小剂量NAC低、中、高剂量组和阳性对照组。小剂量NAC低、中、高剂量组分别给予45,90,180 mg·kg^-1,阳性对照组给予阿拓莫兰54 mg·kg^-1,正常对照组和模型组腹腔注射等容积灭菌生理盐水。采用CCl₄复制大鼠慢性肝损伤模型,末次给药后24 h麻醉大鼠,腹主动脉取血,检测血清ALT、AST含量以及肝组织中SOD、MDA、GSH和Hyp含量,观察肝脏组织病理学变化,免疫组化检测肝组织Nrf2、HO-1的表达。结果 与正常组比较,模型组大鼠血清ALT、AST、MDA和Hyp含量明显升高（P<0.01）,SOD、GSH虽有下降趋势,但结果无统计学差异,Nrf2、HO-1蛋白表达均增加,但差异无统计学意义。与模型组比较,小剂量NAC低、中、高剂量组ALT、AST水平明显降低（P<0.01）,低、中剂量组SOD、GSH、Hyp含量差异均有显著性（P<0.01或P<0.05）,高剂量组GSH、Hyp含量差异均有显著性（P<0.01或P<0.05）,各剂量组MDA均有下降趋势,但无统计学意义,低、中、高剂量组Nrf2、HO-1蛋白表达均增加,其中低剂量组差异有统计学意义（P<0.01或P<0.05）。结论 小剂量乙酰半胱氨酸对CCl₄诱导大鼠慢性肝损伤具有较好的治疗作用,其作用机制可能通过Nrf2/HO-1通路发挥抗氧化应激作用。     

高三尖杉酯碱在大鼠及小鼠的代谢

本文报告³H-高三尖杉酯碱在正常大鼠、小鼠和荷瘤小鼠体内的吸收、分布和排泄。给大鼠静注后,t_1/2(α)和(β)分别为2.1和53.7分钟。静注后15分钟,以骨髓、肾和肝的放射性最高。荷瘤小鼠体内的放射性分布情况与正常大鼠的趋势相仿。静注后24小时,自大鼠尿排泄剂量的42.2%,在粪中排出6.3%,其中原形药放射性占剂量的15.9%。静注后48小时,自胆汁排泄剂量的57.7%,其中原形药放射性占剂量的20.2%。该碱经肌注也可被迅速吸收入血。     

右美托咪定辅助臂丛麻醉的镇静效果及安全性

目的 观察右美托咪定辅助臂丛麻醉的镇静效果和安全性。方法 选取2014年2月至2015年10月上海交通大学医学院附属第九人民医院行臂丛麻醉手术的120例患者为研究对象,采用随机双盲法分为A、B、C组,每组40例。A组术前予静脉注射咪达唑仑0.04 mg/kg;B组在阻滞前10 min静脉泵入0.5μg/kg右美托咪定,10 min泵完;C组在阻滞前10 min静脉泵入0.5μg/kg右美托咪定,10 min泵完,同时术前静脉注射咪达唑仑0.04 mg/kg。记录3组患者给药前（T₀）、给药10 min后（T₁）、20 min后（T₂）、30 min后（T₃）、60 min后（T₄）以及手术结束时（T₅）的心率（HR）、平均动脉压（MAP）、血氧饱和度（SpO₂）及警觉/镇静（OAA/S）评分。结果 与B、C两组比较,A组患者的感觉完全阻滞时间、运动完全阻滞时间显著缩短,差异有统计学意义（F=5.133、5.849,P=0.007、0.004）。与给药前（T₀）HR、MAP和OAA/S评分相比,A组仅T₁时显著降低,C组T₁～T₄均显著降低（P均<0.05）;B组各个时刻均保持平稳（P均>0.05）;组间上述各指标比较,A组患者T₁时刻低于B组,C组患者T₁～T₄时刻均低于B组,且T₂～T₄时刻低于A组（P均<0.05）;3组的SpO₂比较,差异无统计学意义（P>0.05）;C组患者术中因心率减慢而给予阿托品治疗的例数多于A、B两组,差异有统计学意义（χ²=7.50,P=0.02）。结论 右美托咪定辅助臂丛神经阻滞具有较高的镇静效果和安全性能。     

缬草乙醇提取物(VES)对心血管的作用

缬草(Valeriana officinalis L.)为败酱科植物缬草的根及根茎,临床用作镇静剂。近年来有人曾报道缬草对心血管系统有一定的影响。我们将天津医药工业研究所提取的缬草乙醇提取物(以下简称VES)进行了下列实验研究。 实验材料、方法及结果 将缬草用石油醚及二氯甲烷提取后,剩下不溶解的固体,再用乙醇提取,然后将乙醇蒸去,即得淡黄色粉末,称为缬草乙醇提取物,易溶于水,其水溶液称为VES。     

Blockade of angiotensin II type 1 receptors suppressed free radical production and preserved coronary endothelial function in the rabbit heart after myocardial infarction.

The hypothesis that blockade of angiotensin II type 1 (AT1) receptors after myocardial infarction prevents coronary endothelial vasomotor dysfunction by suppressing oxygen free radical production was examined. Rabbits underwent coronary ligation or a sham operation with or without infusion of valsartan, an AT 1 receptor blocker. Two weeks after the operation, the heart was isolated from each rabbit and perfused with buffer in the Langendorff mode, and coronary flow responses to acetylcholine and sodium nitroprusside were assessed. The ratio of heart weight to body weight and the lipid peroxide level in the myocardium were increased by 30 and 50%, respectively, 2 weeks after infarction. The coronary flow response to acetylcholine (10(-8) to 10(-5) M) was reduced by 50% in the hearts with infarction compared with the sham controls, although coronary flow responses to sodium nitroprusside were similar. The coronary flow response to acetylcholine in the hearts with infarction was restored by concurrent infusion of N -2-mercaptopropionyl-glycine, a free radical scavenger. Valsartan (10 mg/kg/d) infused after infarction prevented both ventricular remodeling and elevation of the tissue lipid peroxide level and preserved coronary flow response to acetylcholine. In conclusion, long-term AT1 receptor blockade after infarction protects the coronary arteries from endothelial vasomotor dysfunction through suppression of free radical production.     

Effects of trapidil and nitroglycerin on coronary circulation in conscious dogs

Effects of trapidil and nitroglycerin (glyceryl trinitrate) on coronary blood flow or epicardial coronary diameter were studied in conscious dogs, instrumented with a Doppler flow probe or a pair of ultrasonic dimension crystals on the left circumflex coronary artery. Bolus intravenous injections of trapidil (0.5, 1.0 and 2.0 mg/kg i.v.) increased coronary blood flow, dose-dependently, such being comparable at the peak value seen with nitroglycerin (5, 10 and 20 micrograms/kg i.v.). Coronary blood flow following the intravenous administration of trapidil or nitroglycerin increased biphasically and returned to pre-drug levels in 1.4 +/- 0.2 min (trapidil 1 mg/kg i.v.) or 1.0 +/- 0.1 min (nitroglycerin 10 micrograms/kg i.v.), while the mean coronary diameter increased monophasically and approached the control level 5 min after drug administration. The first peak was observed before the maximal decrease in aortic pressure and the second peak was associated with concomitant increases in heart rate and myocardial contractility induced by a sudden hypotension. Propranolol, a beta-blocker, did not modify the initial peak but attenuated markedly the second peak (P less than 0.05) in case of trapidil (1.0 mg/kg i.v.) or nitroglycerin (10 micrograms/kg i.v.), which corresponded with reduced changes in reflex tachycardia and positive inotropism. Therefore, the direct effects of trapidil and nitroglycerin on coronary circulation of conscious dogs are an initial transient dilatation of the resistance vessels followed by a continuation of the dilatation of the conductance coronary vessels.     

Effects of intravenous diltiazem on cardiocirculatory dynamics and cardiac output distribution in conscious spontaneously hypertensive rats

The effects of the calcium channel blocker, diltiazem hydrochloride (DZ), on conscious, resting spontaneously hypertensive rats (SHR) were evaluated and compared with results from parallel studies on Wistar-Kyoto (WKY) controls. DZ was administered as a continuous, cumulative infusion at rates equal to 0.40, 2.00, and 10.00 mg/kg/h (each dose was administered for 15 min). Parallel volume infusion (saline) controls were simultaneously conducted using volume infusion rates identical to those used in DZ studies (0.015, 0.100, and 0.500 ml/min). Three hours prior to study, animals were instrumented under halothane anesthesia for measurement of left ventricular, arterial, and central venous pressures; heart rate and arterial blood gases; and for injection of radioactive microspheres and subsequent determination of cardiac output, regional blood flows, and cardiac output distribution. All data were collected at control (C) before initiation of infusion, and at the end of each 15-min infusion period in each animal. At C and compared with WKY, SHR had increased heart rate (392 vs. 280 beats/min), mean arterial pressure (155 vs. 100 mm Hg), left ventricular peak systolic pressure (200 vs. 132 mm Hg), and systemic vascular resistance (0.3 vs. 0.2 mm Hg/ml/min/kg), and reduced stroke volume (1.8 vs. 2.2 ml/beat/kg); but no difference in cardiac output, left ventricular end diastolic pressure, or central venous pressure was found. At C, SHR tended to have increased blood flow and reduced vascular resistance in the coronary circulation and increased vascular resistance in the cutaneous, renal, bronchial arterial, hepatic arterial, testicular, and cerebral circulations. Infusion of DZ increased cardiac output and stroke volume and decreased heart rate, left ventricular and arterial pressures, and systemic vascular resistance in SHR. Similar changes of substantially smaller magnitude were observed in WKY. DZ increased flow and reduced resistance in the coronary and skeletal muscle circulations of SHR to a greater extent than in WKY. DZ also normalized vascular resistance in previously elevated regions. These results suggest that acute intravenous infusion of DZ at doses ranging between 2 and 5 mg/kg is capable of normalizing cardiovascular hemodynamics and regional blood flow distribution in SHR.     

Effects of intravenous epinine administration on left ventricular systolic performance, coronary hemodynamics, and circulating catecholamines in patients with heart failure.

Twenty-six patients with mild to moderate heart failure were studied to determine the effects of epinine infusion (at a rate producing plasma levels similar to those measured after oral administration of 100 mg of the prodrug ibopamine) on left ventricular (LV) function (14 patients), and coronary flow and circulating catecholamines (12 patients). The only significant hemodynamic change at an infusion rate of 0.5 microgram/kg/min was a 9% (p less than 0.05) decrease in systemic vascular resistance (SVR). At an infusion rate of 1 microgram/kg/min (mean free epinine plasma levels 14.3 +/- 3.7 ng/ml), heart rate (HR), dP/dtmax (1,405 +/- 255 to 1,490 +/- 320 mm Hg, NS), (dP/dt)/DP40, and the relaxation rate remained unchanged, but the ejection fraction (EF) increased from 32 to 38% (p less than 0.001), cardiac output (CO) increased, and SVR decreased by 22% (p less than 0.05). In a separate group of 12 patients, epinine infusion at rates of 0.5-1 microgram/kg/min produced no significant changes in coronary blood flow or myocardial oxygen uptake. At these infusion rates, arterial norepinephrine (NE) and dopamine (DA) levels decreased slightly and arterial and coronary sinus epinephrine increased. In conclusion, epinine, at concentrations similar to those achieved during therapeutic use of ibopamine, had negligible effect on myocardial contractility and relaxation rate in heart failure patients. Cardiac pump function was improved by a decrease in SVR rather than by inotropic stimulation. The data also suggest that these low concentrations of epinine may modulate the sympathetic nervous system, but further studies are needed to determine whether this effect could have clinical significance.     

Effects of bepridil hydrochloride on cardiocirculatory dynamics, coronary vascular resistance, and cardiac output distribution in normal, conscious rats

The purpose of this study was to characterize the cardiocirculatory effects of bepridil hydrochloride (BP) in the normal, conscious rat. Animals were instrumented under halothane anesthesia for right atrial, left ventricular, arterial, and venous pressure recordings. The radioactive-microsphere technique was used to measure regional blood flow and cardiac output before (control) and during intravenous (i.v.) infusion of either BP at three dosage levels (3.0, 6.0, 12.0 mg/kg) or vehicle (VH) at infusion rates matching those of the BP protocol (0.0408 ml/min). The predominant effects of BP (cumulative dose = 9.0 mg/kg i.v.) in the conscious rat were reduced coronary vascular resistance and heart rate. BP showed selectivity for the coronary circulation since systemic vascular resistance was not significantly reduced until a cumulative i.v. dosage of 21.0 mg/kg was administered. BP had few effects on other regions of the peripheral circulation. BP (21 mg/kg) reduced blood flow and increased vascular resistance in the arterial circulations of four of six skeletal muscles studied although opposite effects occurred in two of six muscles studied. BP had no significant effect on blood flow or vascular resistance in the other major arterial circulations. The results of this study show that BP is a selective coronary vasodilator that also reduces the primary indices of myocardial oxygen demand. These results suggest that the clinical therapeutic antianginal efficacy of BP occurs through a combined effect to increase myocardial oxygen supply and to reduce myocardial oxygen demand.     

Central and peripheral haemodynamic effects of L-NAME infusion in healthy volunteers

AIMS: To evaluate the effects of the intravenous administration of the nitric oxide synthesis inhibitor N(g)nitro-L-arginine methyl ester (L-NAME) in healthy volunteers. METHODS: L-NAME (0.25, 0.5 and 0.75 mg/kg over 8 min) was infused in 13 healthy male volunteers. Finally, subjects were infused with either L- or D-arginine. RESULTS: L-NAME resulted in dose-dependent falls in heart rate 60 bpm (55-64 bpm) to 49 bpm (46-52 bpm) (P<0.01) and increased mean arterial pressure 77.0 mmHg (73.2-80.8 mmHg) to 90.0 mmHg (87.1-92.8 mmHg) (P<0.01). The cardiac output was significantly reduced after each L-NAME infusion, and systemic vascular resistance increased linearly over the dosage range. Cardiac stroke volume was significantly reduced only following 0.75 mg/kg/min L-NAME: from 100 ml (91.3-108.7 ml) to 83 ml (74.7-91.4 ml); P<0.01. Forearm blood flow was unchanged at any dosage. L-arginine but not D-arginine infusion reversed the haemodynamic effects of L-NAME. CONCLUSIONS: Contrasting with the profound dose-dependent effects of L-NAME had significant effects on central haemodynamics but no discernible effects on peripheral blood flow.     

Effects of the novel beta-adrenergic partial agonist alifedrine on cardiac performance in dogs with acute ischemic left ventricular failure

Acute ischemic left ventricular failure was induced in dogs by coronary embolization with plastic microspheres, resulting in reduced cardiac output (CO), increased left ventricular end-diastolic pressure (LVEDP), pulmonary capillary pressure (PCP), and total peripheral resistance (TPR). Intravenous (i.v.) administration of alifedrine, a beta-adrenergic partial agonist (0.3 mg/kg as bolus and 0.3 mg/kg/h as infusion), significantly improved performance of the failing heart. Left ventricular contractility was increased up to 50%, heart rate (HR) up to 28%, and CO up to 30%. LVEDP, PCP, and TPR were markedly decreased. Myocardial oxygen consumption was increased only to a minor degree despite the positive inotropic effect; coronary flow was augmented up to 26%. Thus, alifedrine in this model markedly improved left ventricular function by balanced stimulation of the myocardium and reduction of pre- and afterload.     

Deterioration of the protein kinase C-K(ATP) channel pathway in regulation of coronary flow in hypercholesterolaemic rabbits

We studied the effect of experimental hypercholesterolaemia/atherosclerosis on changes in coronary flow and cardiac function, induced by protein kinase C and ATP-sensitive K(+) (K(ATP)) channel modulators in isolated Langendorff-perfused rabbit hearts. Both phorbol 12-myristate-13-acetate (PMA) and phorbol 12,13-dibutyrate (PDB, 0.1 microM each), activators of protein kinase C, decreased, whereas staurosporine, (0.1 microM), a protein kinase C inhibitor, increased coronary flow and left ventricular dP/dt, an index of ventricular contractility. Glyburide (5-50 microM), a K(ATP) channel inhibitor, blocked the effect of staurosporine. The phorbol esters were without effect in the presence of pinacidil (5 microM), a K(ATP) channel activator. Neither the protein kinase C modulators nor glyburide produced any effect on coronary flow and left ventricular contractility, when the hearts were prepared from animals either maintained on a cholesterol (1.5%)-enriched diet or treated with lovastatin (5 mg/kg/day per os). Treatment with farnesol (1 mg/kg twice a day for 7 days intravenously) restored the reactivity of hearts from either hypercholesterolaemic or lovastatin-treated animals to protein kinase C modulators. We conclude that non-cholesterol mevalonate products are necessary for the functional integrity of the protein kinase C-K(ATP) channel pathway in the rabbit heart.     

乙酰肉毒碱和肉毒碱抗乏氧性心衰及其与强心甙合用的对比研究

Experiments on Langendorff's guinea pig heart showed that, when 0.1M acart (acetylcarnitine) or cart (carnitine) was given at 1 ml/min for 5 min, both prevented heart failure from hypoxia. The beneficial effects of acart were more powerful than those of cart.In isolated rabbit right atria, when acart or cart (0.05 ml of 0.04 M) was followed by strophanthin K (3.75 μg), acart+strophanthin K increased significantly contraction amplitude, but cart+strophanthin K didnot. Acart or cart (0.1 ml of 0.04 M)were found to significantly shorten the duration of rhythm disorder-induced by strophanthin K (50 μg). The duration of rhythm-disorder in the former (1.17±0.44 min) was significantly shorter than that in the latter (2.67±0.33 min).LD₅₀ of acart and cart in mice were 1228 mg/kg and 974 mg/kg, respectively.It is concluded that acart was more effective and less toxic than cart in the treatment of heart failure.