中国萝芙木碱Verticillatine对麻醉狗和猫心功能与血流动力学的影响

Verticillatine(Vt)0.5～1.0mg/kg iv,能使麻醉狗的血压下降,心率减慢,cl,LVSP LV dp/dt max,LVWI,TPR降低,作用随剂量增加而加强。冠脉阻力稍降低,但心肌氧利用率和氧耗减少。颈内动脉和股动脉血流增加,阻力减少。给麻醉猫iv Vt和六羟季铵1.0 mg/kg后,BP,LVP和LV dp/dt max降低,但LV dp/dt/p和LVEDP无明显变化。说明Vt能降低心脏后负荷,对前负荷无明显影响。     

中国萝芙木碱Verticillatine对麻醉狗和猫心功能与血流动力学的影响

Verticillatine(Vt)0.5～1.0mg/kg iv,能使麻醉狗的血压下降,心率减慢,cl,LVSP LV dp/dt max,LVWI,TPR降低,作用随剂量增加而加强。冠脉阻力稍降低,但心肌氧利用率和氧耗减少。颈内动脉和股动脉血流增加,阻力减少。给麻醉猫iv Vt和六羟季铵1.0 mg/kg后,BP,LVP和LV dp/dt max降低,但LV dp/dt/p和LVEDP无明显变化。说明Vt能降低心脏后负荷,对前负荷无明显影响。     

麝香保心分散片对冠脉结扎犬血流动力学的影响

目的研究麝香保心分散片对冠脉结扎犬血流动力学的影响。方法采用麻醉犬开胸结扎左冠状动脉前降支 (LAD)产生急性心肌梗死 (AMI)模型 ,测定AMI 3h犬的心脏血流动力学参数。结果十二指肠给予麝香保心分散片 ,能明显增加心输出量 (CO)和搏出量 ,增加心肌血流量 ,降低冠脉阻力 ,增加左室收缩内压 (LVSP)及室内压最大上升和下降速率 (±dp/dtmax) ,轻度减慢心率 ,明显降低左室舒张末期压 (LVEDP) ,增加冠脉结扎犬心脏指数 (CI)及搏功 ,降低总外周阻力 ,对平均动脉压有下降趋势。结论麝香保心分散片主要以改善心肌收缩和舒张功能 ,增加缺血心肌供血等环节 ,发挥抗心肌缺血作用     

葛根素的药理及临床应用

葛根素(puerarin)是中药葛根的主要有效成分之一,近10多年来对葛根素进行了许多研究,本文对其的临床前药理和临床研究作一概述.1 葛根素的药理作用1.1 对血压和心率的影响 葛根素具有降血压和减慢心率的作用.葛根素使正常Wis-tar大鼠、清醒自发高血压大鼠(SHR)、正常猫、正常及急性心肌梗死犬的血压和心率均明显或显著降低和减慢;对利血平化及右室旁路犬血压也显著降低;对清醒高血压犬也有一定的降压作用,对猴也引起心率减慢及相应的Q-T间期的延长.但葛根素的作用机制尚不清楚.离体和整体的经典实验说明葛根素对β-肾上腺素受体有明显阻断作用.对于受体水平,葛根素能显著降低细胞膜β-受体的最大结合容量,抑制受体与标记配体结合,阻断肾上腺素对细胞膜腺苷酸环化酶活性的激动作用,因而认为葛根素是β-受体阻滞剂.但该论点并未被其他学者所证实,这可能与两者采用剂量不同有关.1.2 对血流量的影响iv葛根素对正常和利血平化犬均显著增加冠脉血流量和降低冠脉血管阻力;对急性心肌梗死犬可降低主动脉压,但对缺血区侧枝冠脉血流量并不减少;在右室旁路制备犬使主动脉压恢复到给药前水平时,葛根素降低侧枝血管阻力、增加缺血区和非缺血区血流量的作用更加明显,并且减低冠脉血管阻力的作用比减低全身血管阻力     

地奥心血康对犬心肌缺血及血流动力学的影响

本文研究地奥心血康对结扎冠状动脉所造成的犬急性心肌缺血及心脏血流动力学的影响。地奥心血康１００ｍｇ／ｋｇ，ｉｖ，能明显减少心肌缺血范围，减轻缺血损伤程度；可使心率明显减慢，血压、心输出量、左室内压、左室作功、心肌耗氧量、冠状动脉阻力和总外周阻力下降，冠状动脉血流量增加。提示该药有抗心肌缺血作用，并能改善心脏血流动力学。     

牡荆素对麻醉犬血流动力学及心肌耗氧量的影响

目的研究牡荆素对麻醉犬血流动力学及心肌耗氧量的影响。方法杂种犬30只,人工呼吸下开胸,给药后观察其心率（HR）、血压（MAP）、心输出量（CO）、冠脉血流量（CBF）、左室压（LVP）及血氧含量。计算冠脉阻力（CVR）和体循环总外周阻力（TPR）等血流动力学指标。采用多普勒超声血流仪测定麻醉犬冠脉流量和心输出量,用血气分析仪测定血氧含量。结果牡荆素可减慢心率和左心室内压,并显著增加麻醉犬冠脉血流量和心输出量,降低总外周血管阻力和冠脉阻力,提高心搏出量、心搏指数及心脏指数。结论牡荆素可显著改善麻醉犬血流动力学参数。     

生脉输液对麻醉犬血流动力学及心肌耗氧量的影响

目的研究生脉输液对麻醉犬血流动力学及心肌耗氧量的影响。方法将杂种犬36只,随机分为6组(每组6只):对照组、阳性药组(硝酸甘油注射液组和生脉注射液组)、生脉输液高、中、低三个剂量组。人工呼吸下开胸,观察用药前后不同时间点麻醉犬的冠脉流量(CBF)、心输出量(CO)、冠脉阻力(CAVR)、总外周阻力(TPVR)、心搏出量(SV)、心搏指数(SI)、心脏指数(CI)、左室作功(LVSW)、心肌血流量(MBF)、心肌耗氧指数(MOCI)、耗氧量(VO2)、心肌氧利用率(MOUR)等指标的变化。结果与对照组比较,生脉输液(200,100 mg生药.kg-1)能显著增加麻醉犬冠状动脉和主动脉的血流量、增加心肌血流量,降低总外周血管阻力和冠状动脉阻力,提高心搏出量和心肌氧利用率。结论生脉输液对麻醉犬血流动力学参数有改善作用,具有良好的抗心肌缺血作用。     

人参茎叶皂甙对狗心脏血流动力学的影响

实验表明人参茎叶皂甙(GSL)50mg/kg i.v.可使狗左室泵功能和心肌收缩性发生程度不同的改变,可使 LVP,CO,CI,TPVR,BP,HR,耗氧量,(dp/dt)max,(dp/dt)/CPIP等下降,PF,SI,t-(dp/dt)max 等上升。这些结果与目前掌握的人参根总皂甙对狗血流动力学的影响基本一致。     

红花总黄素对缺血心肌的影响及机制研究

目的观察红花总黄素对实验性缺血心肌的影响,并探讨其机制。方法采用异丙肾上腺素(10mg·kg-1)制备大鼠急性心肌缺血模型,观察血流动力学指标变化(MBP、LVSP、LVEDP、±dp/dtmax等)。同时,分别观测家兔给药前,给药后15、30、60min的冠脉流量(CF)和心肌耗氧量(MVO2)。结果红花总黄素各组对心肌缺血大鼠血流动力学有明显改善作用。红花总黄素各组给药后15min均表现出不同程度的增加心脏冠脉流量,心肌耗氧量明显减少。结论红花总黄素抑制心肌缺血引起的心功能减弱,其机制与其能明显增加冠脉流量和减少心肌耗氧量有关。     

羟苯氨酮对麻醉狗心脏血流动力学与心肌氧消耗的影响*

目的:研究强心扩血管新药羟苯氨酮对心肌氧消耗的影响。方法:用多导生理记录仪和电磁流量计测定麻醉开胸狗心脏血流动力学参数,用血气分析仪测定动脉与冠状窦血氧含量,计算心肌氧代谢参数。结果:羟苯氨酮iv 0．5～4mg·kg~(-1)轻度减慢心率,中度降低血压、左室作功、冠脉阻力与总外周血管阻力,短暂增加心输出量与冠脉流量,明显降低心肌氧摄取率与氧消耗量。结论:羟苯氨酮降低心肌氧消耗与心脏负荷,增加心肌供血,有利于对心肌缺血的治疗。     

Coronary collateral blood flow in acute myocardial ischemia is not increased by dihydropyridine-induced coronary vasodilatation

The effect of two dihydropyridine derivatives, nifedipine and felodipine, on myocardial blood flow distribution 1 h after ligation of the left anterior descending coronary artery (LAD) was studied in open-chest dogs by means of radioactive microspheres. The myocardium normally perfused from the LAD was first labeled with 125I-labeled microspheres injected directly into the LAD before ligation. Microspheres used for blood flow measurements were given in the left atrium. An intravenous infusion rate of 0.3 nmol/kg/min felodipine slightly depressed mean aortic blood pressure (approximately 5 mm Hg) and decreased coronary vascular resistance in normal myocardium. Nifedipine, at three times the dose of felodipine, had a comparable hypotensive effect, but the decrease in coronary vascular resistance was not statistically significant. The two dihydropyridines were also compared in a dose range that was four times higher. The mean arterial blood pressure reduction (approximately 30% for both drugs) was counterbalanced by inflation of an intraaortic balloon to avoid a drastic decrease in afterload and coronary perfusion pressure. Under these circumstances, felodipine and nifedipine decreased coronary vascular resistance and increased blood flow to nonischemic myocardium comparably. However, in severely ischemic, truly collateral-dependent myocardium without admixture of interdigitating healthy myocardium, the blood flow was unaffected after administration of both felodipine and nifedipine. Although felodipine was three times more potent than nifedipine with regard to vasodilatation in the normal myocardium, the difference in vascular selectivity between the two agents did not influence the effect on the "true" collateral blood flow in acute myocardial ischemia.     

尼群的平对麻醉犬冠脉流量、心肌耗氧量、二氧化碳产生率的影响

尼群的平20μg/kg iv显著降低麻醉犬血压的过程,冠状窦流量明显增加。持续3h,冠状窦氧含量增加,氧摄取率、心肌耗氧量、二氧化碳产生率降低,持续了3h以上,说明该剂适用于高血压伴心肌缺血。     

Comparative effects of two slow channel calcium entry blockers, FR 34235 and nifedipine, on true coronary collateral blood flow

The effect of a new dihydropyridine calcium entry blocker, FR 34235, on coronary collateral blood flow was compared with that of nifedipine in anesthetized dogs following acute ligation of the left anterior descending coronary artery. A special technique was used to separate true coronary collateral blood flow from overlap flow due to interdigitation of normally perfused tissue contained within the ischemic region. During infusion of doses of both agents, which produced nearly equivalent decreases (15-20 mm Hg) in mean arterial pressure, flow was significantly increased in normal myocardium; however, no change in collateral perfusion to ischemic myocardium was observed. When blood pressure was returned to control by an aortic cuff, blood flow to the normal region further increased. Transmural flow to the ischemic region was also significantly increased by both compounds. Nifedipine increased collateral flow primarily to the subepicardium, whereas FR 34235 increased collateral perfusion to the subepicardium, midmyocardium, and subendocardium. These results suggest that dihydropyridine calcium entry blockers may increase collateral blood flow to ischemic myocardium if drug-induced hypotension is minimized. In addition, FR 34235 has a more favorable effect on the transmural distribution of blood flow than nifedipine.     

Collateral blood flow following acute coronary artery occlusion: comparison of a new intracellular calcium antagonist (KT-362) and diltiazem

The effects of a new intracellular calcium antagonist, KT-362 (150 and 300 micrograms/kg per min), on hemodynamics and collateral function (retrograde pressure and flow, radioactive microspheres) distal to an acute coronary artery occlusion were studied in anesthetized dogs and compared with the effects of the structurally related classical calcium channel blocker, diltiazem (15 and 30 micrograms/kg per min), and a saline-treated control group. In the saline series, there were no changes in systemic hemodynamics or coronary collateral blood flow over the 90-min ischemic period. KT-362 reduced mean aortic pressure, heart rate, and dP/dt whereas diltiazem only decreased aortic blood pressure. When blood pressure was controlled by a distal aortic cuff, heart rate was significantly reduced in both groups and dP/dt was reduced in the KT-362 series and increased in diltiazem-treated dogs. In both drug-treated groups, retrograde pressure and flow were significantly increased only when aortic pressure was controlled. Regional myocardial tissue blood flow in the nonischemic or ischemic region did not change significantly after KT-362 treatment despite its hypotensive actions, and in the presence of a constant aortic pressure, transmural collateral blood flow and the ischemic/nonischemic blood flow ratio tended to increase. In contrast, diltiazem treatment resulted in a significant decrease in the ischemic/nonischemic blood flow ratio in the absence of blood pressure control. In the presence of constant aortic pressure, blood flow to the nonischemic area was markedly increased by diltiazem whereas subendocardial blood flow was significantly increased in the ischemic area.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of protection of ischemic myocardium by verapamil in conscious dogs

To determine whether coronary dilation and decreased myocardial oxygen requirements resulting from administration of verapamil, a calcium and slow current antagonist, protect ischemic myocardium in conscious dogs, we studied 15 treated and 15 control animals after coronary occlusion. Verapamil (0.2–0.7 mg/kg/h) was given by continoous infusion for 17 h beginning 5 h after the initial plasma creatine kinase (CK) elevation after coronary occlusion. Observed infarct size and infarct size predicted before verapamil were estimated from hourly plasma CK values and infarct size was estimated also from myocardial CK depletion measured directly, 24 h after occlusion. Changes in heart rate, blood pressure, and frequency of premature ventricular complexes (recorded every 30 min) after occlusion were similar in treated and control dogs. Coronary flow after verapamil, measured with radioactively labeled microspheres, did not increase in ischemic zones but increased by 90% in normal myocardium (p < 0.05). The differences between observed and predicted infarct size estimated from plasma CK changes in treated and controls were similar (3.0±2.2 (S.E.) and 2.0±1.4 CK-g-eq), and myocardial CK depletion was also comparable in the two groups (25 ± 2% and 23 ±2%). Thus although verapamil, administered five hours after the initial plasma CK elevation, increased coronary flow in normal myocardium, it did not augment flow in ischemic tissue or limit the extent of infarction.     

The slow-channel calcium blocking agent, nitrendipine, and coronary collateral blood flow

The effects of a new dihydropyridine slow-channel calcium blocking agent, nitrendipine, on hemodynamics and myocardial blood flow in normal and ischemic areas distal to either an acute or chronic coronary artery occlusion were studied in anesthetized dogs. Nitrendipine produced significant and dose-related decreases in mean aortic blood pressure and increases in flow through the nonobstructed coronary artery. In acute coronary artery occlusion experiments, only small changes in perfusion of the ischemic zone were observed following nitrendipine. On the other hand, in dogs with a chronic coronary artery occlusion and well-developed collateral circulation, nitrendipine produced significant and dose-related increases in subepicardial perfusion within the central ischemic zone. No change in subendocardial blood flow during drug-induced hypotension was observed, but when aortic pressure was held constant, there was an increase in subepicardial, subendocardial, and overall transmural myocardial perfusion. The data demonstrate that nitrendipine improves oxygen supply to collateral-dependent myocardium via an increase in coronary collateral blood flow in a model of chronic coronary occlusion.     

Cardioprotective effects of YM934, an ATP-sensitive potassium channel opener, on stunned myocardium in anesthetized dogs.

The effects of YM934 [2-(3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazin-4-yl) pyridine N-oxide], an adenosine triphosphate (ATP)-sensitive potassium channel opener, on stunned myocardium were examined. Forty eight anesthetized dogs were subjected to 15 min of left anterior descending (LAD) coronary artery occlusion followed by 3 hours of reperfusion. To elucidate the possible contribution of the cardioprotective property of YM934 to stunned myocardium, a nonhypotensive dose of YM934 was directly injected into the LAD coronary artery before the ischemic insults. Intracoronary artery infusion (i.c.) of YM934 (0.1 microg/kg/min) produced a marked improvement in post-ischemic regional contractile dysfunction. The effects were not associated with improvement of hemodynamics, including regional myocardial blood flow during ischemia, heart rate and mean arterial blood pressure. The anatomic areas at risk expressed as a percentage of the left ventricle and regional myocardial blood flow were not significantly different between groups. The cardioprotective effect of YM934 was completely blocked by pretreatment with an ATP-sensitive potassium channel blocker, glibenclamide (1.0 mg/kg i.v. bolus). These results suggest that YM934 exerts cardioprotective effect on stunned myocardium through opening myocardial ATP-sensitive potassium channels.     

Alpha-human atrial natriuretic peptide, carperitide, reduces infarct size but not arrhythmias after coronary occlusion/reperfusion in dogs

Carperitide, a recombinant form of alpha-hANP, possesses potent diuretic, natriuretic, and vasodilatory activity, and inhibits the renin-aldosterone system and sympathetic nervous activity. However, its beneficial effects on ischemic myocardium have not been studied fully. We examined carperitide's effects on infarct size, hemodynamics, and arrhythmia frequency in anesthetized dogs (n = 20) subjected to a 90-min coronary artery occlusion/6-h reperfusion protocol. Intravenous infusion of carperitide (0.2 microg/kg/min) commenced 15 min after occlusion and continued during occlusion/reperfusion. Ventricular fibrillation developed in two of 10 control versus three of 10 treated dogs (p = NS). Hemodynamics, collateral blood flow to the ischemic wall measured 10 min after occlusion, and extent of area at risk were comparable for the two groups. Infarct size/area at risk was smaller in treated than in control dogs (4.5 +/- 2.1% vs. 27.8 +/- 7.8%, respectively; p < 0.05). During occlusion, carperitide tended to increase collateral blood flow (+39%) and significantly decreased left ventricular systolic pressure (-13%) and end-diastolic pressure (-40%) compared with baseline. In control dogs, collateral blood flow tended to decrease (-8.3%), whereas most hemodynamic parameters did not change significantly with respect to baseline. The number of arrhythmias recorded during occlusion/reperfusion was similar in the two groups. Intravenous administration of carperitide limited infarct size, but did not reduce incidence of ventricular arrhythmias after 90-min coronary occlusion/6-h reperfusion in anesthetized dogs. Although the beneficial effects of carperitide may be attributable to concomitant changes in hemodynamics and collateral blood flow, the precise mechanisms require further investigation.