Effect of diltiazem on coronary blood flow of the heart with experimental coronary sclerosis and on regional myocardial blood flow of the heart with acute myocardial ischemia

Effects of 3-acetoxy-2,3-dihydro-5[2-(dimethyl-amino)ethyl]-2-(p-methoxyphenyl)-1,5-benzothiazepin-4 (5H)-one hydrochloride (diltiazem) on coronary circulation of the heart with experimental coronary sclerosis induced by i.v. allylamine (Group A), and on regional myocardial blood flow in acutely-induced ischemic myocardium (Group S) were studied in anesthetized open-chest dogs. Regional myocardial blood flow was continuously measured with heated cross thermocouple method and following results were obtained: 1. In Group A coronary blood flow and coronary flow resistance remained unchanged essentially after the injection of diltiazem, whereas coronary blood flow markedly rose and coronary flow resistance decreased in the normal heart. 2. Local blood flow in both of the inner and outer thirds of the ischemic myocardium was not affected by diltiazem in Group S. In the normal myocardium, however, it increased definitely. 3. From these findings it is concluded that the clinical effectiveness of diltiazem is independent of its vasodilator properties.     

The effect of diltiazem on ST-segment elevation and myocardial blood flow distribution during pacing-induced ischemia

The purpose of this study was to determine if diltiazem can reduce the severity of pacing-induced ischemia independently of increases in overall and microregional ischemic blood flow. Sixteen anesthetized dogs were subjected to atrial pacing and had their left anterior descending coronary arteries (LAD) occluded until significant ST-elevation occurred. Cessation of pacing resulted in abolition of ST-segment elevation. ST-elevation as well as hemodynamics were measured during 5 min periods of pacing + LAD stenosis before, and 10, 40 and 70 min after treatment with intracoronary (i.c., just distal to the stenosis) diltiazem (1.8 micrograms/kg), i.v. diltiazem (180 micrograms/kg) or saline. Myocardial blood flow was measured using radioactive microspheres under baseline conditions, pacing, pacing + stenosis, and pacing + stenosis + drug (70 min post-drug). Both i.c. and i.v. diltiazem significantly and similarly reduced pacing-induced ST-elevation at 40 and 70 min post-drug with the highest measured reductions occurring for both at 70 min (50-60% reduction). Overall ischemic regional myocardial blood flow was unaffected by i.c. and i.v. diltiazem. Diltiazem given i.v. resulted in reduced flow in the lightly ischemic region and increased flows in the subepicardial half of the severely ischemic region. Diltiazem given i.c. resulted in a reduced subepicardial flow in the lightly ischemic region with no other changes occurring in the other regions. Thus, both i.c. and i.v. diltiazem can reduce the severity of pacing-induced ischemia and, in the doses given, in an equivalent fashion. Diltiazem also seems to be able to reduce severity of ischemia in a manner independent of increases in ischemic region flow and in fact can reduce flow in marginally ischemic tissue.     

Effect of intracoronary diltiazem on ST-segment elevation and myocardial blood flow during pacing-induced ischemia

This study was performed to determine if diltiazem can reduce the severity of pacing-induced ischemia independently of its peripheral hemodynamic effects and of increases in ischemic region blood flow. Twelve anesthetized dogs were subjected to atrial pacing and had their left anterior descending coronary arteries (LAD) occluded gradually until ischemia ensued (greater than 10 mV epicardial ST-segment elevation). Cessation of pacing resulted in abolition of ST-segment elevation. ST-segment elevation, as well as peripheral and coronary hemodynamics, was measured during 5-min periods of pacing + LAD stenosis before and 0, 30, and 60 min after treatment with intracoronary (just distal to the stenosis) saline or 1.8 micrograms/kg diltiazem. Myocardial blood flow was measured using radioactive microspheres during pacing, pacing + stenosis, and pacing + stenosis + drug treatment at 60 min. Diltiazem significantly reduced ST-segment elevation approximately 50% at 0, 30, and 60 min compared with elevations seen in animals treated with saline as well as predrug values. No changes in blood pressure, heart rate, or LAD flow occurred with diltiazem. Overall ischemic tissue flow and its transmural distribution were not different with diltiazem compared with saline treatment. Thus, diltiazem can decrease the severity of pacing-induced ischemia independently of its peripheral effects and of increased ischemic region blood flow.     

Effect of molsidomine on coronary collateral blood flow in acute myocardial ischemia

The actions of molsidomine, a new antianginal agent, on coronary collateral blood flow and myocardial oxygen consumption were studied in anesthetized dogs with acute ligation of the distal third of the left anterior descending coronary artery. Molsidomine (50 and 100 μg/kg, i.v.) produced a significant decrease in myocardial oxygen consumption, however no change occurred in collateral blood flow. These results suggest that the beneficial actions of molsidomine in myocardial ischemia are primarily due to a decrease in oxygen demand.     

冠状动脉介入术中地尔硫的即刻降压效果

目的 :观察地尔硫在冠状动脉介入术中的即刻降压效果。方法 :5 1例术中高血压病人经动脉或静脉注射地尔硫 (0 .2～ 0 .3mg·kg- 1) ,3min推注完毕 ,记录即刻 ,5 ,10 ,2 0 ,30min血压和心率变化。结果 :地尔硫能使收缩压从注射前的 (2 5 .1± 2 .5 )kPa降至注射后即刻的 (2 0 .1± 2 .4 )kPa(P<0 .0 1)。 10min后逐渐回升 ,30min时为 (2 3.2±2 .5 )kPa ,仍明显低于用药前 (P <0 .0 1) ;舒张压由注射前的 (12 .7± 1.5 )kPa降至即刻的 (10 .4±1.3)kPa(P <0 .0 1) ,10min后逐渐回升 ,30min时为 (11.5± 1.3)kPa ,仍低于用药前 (P <0 .0 1)。结论 :经动脉或静脉注射地尔硫能迅速有效地控制冠状动脉介入术中的高血压 ,有利于手术的顺利进行。     

The potentiation of the activity of adenosine on coronary blood flow, blood pressure and heart rate by inosine in the dog.

The activity of adenosine and inosine on coronary blood flow and arterial blood pressure was investigated in anaesthetized and thoracotomized dogs. The following results were obtained. 1. Individual adenosine administration caused an increase in coronary blood flow. However, this adenosine activity was significantly strengthened when the same dose of adenosine was applied simultaneously with inosine in doses of 3.2, 5.6 and 10.0 mg/kg body weight i.v. The duration of the effect of adenosine on the coronary blood flow was also potentiated by inosine. 2. The hypotensive effect resulting from 0.2 mg adenosine/kg i.v. was significantly strengthened by simultaneous inosine application (3.2, 5.6 and 10.0 mg/kg i.v.). The activities on the blood pressure of increments in the individual adenosine dosages (0.2, 0.4 and 0.6 mg/kg i.v.) were significantly potentiated by 10 mg inosine/kg body weight i.v. 3. The heart rate was not modified by 0.2 mg adenosine/kg i.v. However, the same adenosine dosage plus inosine (3.2, 5.6 and 10.0 mg/kg i.v.) applied simultaneously led to bradycardia. Increasing adenosine doses (0.2, 0.4 and 0.6 mg/kg i.v.) applied simultaneously with inosine (10.0 mg/kg body weight i.v.) led to a dose dependent retardation of the heart rate. 4. The possible reasons for the potentiation of the effect of adenosine by inosine were discussed.     

巴曲酶对抗狗心脏缺血/再灌损伤(英文)

目的:研究巴曲酶(Bat)对狗心脏缺血/再灌损伤的影响。方法:狗冠脉左前降枝结扎30 min后恢复血液灌注,于缺血前(Bat-Ⅰ组)或缺血后再灌前15min(Bat-Ⅱ组)静脉注射Bat(1 Bu·kg~(-1))。测定dp/dt_(max)和LVEDP及血浆CK和LDH及心肌MDA含量,观察心肌病理形态学改变。结果:I/R组动物缺血或再灌后死亡率高达65.0％,心肌损伤明显。Bat-Ⅰ和Bat-Ⅱ组动物的死亡率分别为30.0％和28.6％,P<0.05,心肌损伤减轻;血浆CK、LDH含量,LVEDP及心肌MDA含量降低; dp/dt_(max)和-dp/dt_(max)增加。结论:Bat可明显拮抗狗心脏缺血/再灌注损伤,改善心功能。     

Effect of obzidan on cerebral blood flow in acute cerebral ischemia

The effect of obsidan on the local cerebral circulation was studied in cats with normal brain circulation and under acute cerebral ischemia. It was demonstrated that obsidan (0.2 mg/kg) increased local cerebral circulation, while on being given in a dose of 1 mg/kg it lowered it in cats with normal brain circulation. In animals with stroke (both on the side with normal circulation and on the side of cerebral ischemia) obsidan (0.2 mg/kg) significantly decreased the local cerebral circulation and destroyed autoregulation of the brain circulation.     

Effect of bromocriptine on cardiac function and coronary blood flow

The present study was designed to investigate the effects of bromocriptine, a dopamine receptor agonist, on systemic and coronary hemodynamics and to determine the mechanisms involved in the action of this compound. Intravenous infusion of bromocriptine (1 microgram/kg/min for 20 min) to pentobarbital-anesthetized dogs produced significant decreases in blood pressure, heart rate, total peripheral resistance, peak dP/dt, left ventricular pressure, and coronary blood flow. There were significant increases in stroke volume and coronary vascular resistance, whereas the index of contractility was unaffected. Cardiac output was decreased 30 min after the termination of bromocriptine infusion. The cardiovascular actions of bromocriptine were significantly antagonized by the dopamine receptor antagonist, sulpiride. Bromocriptine also failed to exert these effects when administered to animals that were treated with ganglionic blocking agents. These results suggest that the hypotensive action of bromocriptine is mainly due to a decrease in total peripheral resistance. In addition, the actions of bromocriptine on cardiac function are the result of activation of presynaptic dopamine receptors and the drug does not have any direct action on the myocardium.     

ET-A receptor activity restrains coronary blood flow in the failing heart

Circulating levels of the potent vasoconstrictor peptide endothelin-1 (ET-1) are increased in congestive heart failure (CHF). Coronary blood flow and myocardial oxygen consumption (MVO2) are decreased in some models of CHF. This study tested the hypothesis that ET-1 induced coronary vasoconstriction limits oxygen availability in the failing heart. The effects of selective ET-A receptor blockade with BQ610 (5 microg/min, intracoronary) and selective ET-B receptor blockade with BQ788 (5 microg/min, intracoronary) on coronary blood flow were examined at rest and during graded treadmill exercise in 8 dogs in which congestive heart failure (CHF) had been produced by rapid ventricular pacing for three to four weeks. In animals with CHF, ET-B receptor blockade caused no change in left ventricular (LV) pressure or coronary blood flow. In contrast, ET-A blockade with BQ610 resulted in modest significant increases of coronary blood flow at rest (from 22.4 +/- 2.1 to 27.9 +/- 3.0 mL/min) and during two exercise stages (from 26.9 +/- 2.0 to 30.7 +/- 1.9 during stage 1 exercise and from 28.5 +/- 2.0 to 31.7 +/- 1.3 mL/min during stage 2; all P < 0.05), with an upward shift in the relationship between coronary flow and rate-pressure product. The increase in coronary flow produced by ET-A blockade was not associated with an increase of either myocardial oxygen uptake or LV dP/dt. Thus, although ET-A receptor blockade caused a modest increase in coronary flow, this did not result in an increase of MVO2, implying that ET-A-mediated coronary vasoconstriction did not limit oxygen uptake by the failing heart.     

Modification by severe hypoxia and diltiazem of dog coronary artery contractions in vitro

The contractions induced by prostaglandin (PG) F2 alpha and by Ca2+ in helical strips of canine coronary arteries exposed to Ca2+-free medium under severe hypoxia and stimulated by PGF2 alpha or K+ were augmented by the return to normoxia. Inhibition under hypoxia was ranked as follows: Ca2+-induced contractions in the strips stimulated by PGF2 alpha greater than Ca2+-induced contractions in the K+-depolarized strips greater than PGF2 alpha-induced contractions in the Ca2+-free medium. The inhibition of arterial contractions during severe hypoxia was not influenced by removal of the endothelium. Treatment with indomethacin attenuated the inhibitory effect of hypoxia on Ca2+-induced contractions in arteries stimulated by PGF2 alpha or serotonin but affected neither the Ca2+-induced contractions in the strips depolarized by excess K+ or the PGF2 alpha-induced contractions in Ca2+-free medium. Diltiazem attenuated the Ca2+-induced contractions in arteries stimulated by PGF2 alpha or K+ but did not attenuate the PGF2 alpha-induced contractions in the Ca2+-free medium during hypoxia or normoxia. Diltiazem also inhibited the contractions caused by re-oxygenation. In conclusion, severe hypoxia inhibited the contractions induced by Ca2+ in the presence of PGF2 alpha receptor activation more than those associated with membrane depolarization. The PGF2 alpha-induced contractions in the Ca2+-free medium (possibly due to the release of intracellularly stored Ca2+) may be relatively resistant to severe hypoxia. The hypoxia-induced inhibition of contractions due to Ca2+ in PGF2 alpha-stimulated arteries could be associated partly with the release of PGI2 but not with endothelium-derived relaxing factor(s).     

Effect of vasoactive intestinal peptide on myocardial contractility and coronary blood flow in the dog: comparison with isoproterenol and forskolin

The effects of intracoronary injections of vasoactive intestinal peptide (VIP) on left ventricular (LV) dp/dt, coronary blood flow (CBF), and myocardial oxygen consumption (MVO2) were compared with isoproterenol (ISO) and forskolin in 18 dogs using a preparation in which cardiac output, mean systemic arterial pressure, and heart rate were fixed. In eight dogs in which the effects of VIP and ISO were compared using doses ranging from 2 x 10(-12) to 2 x 10(-8) mol, both agents significantly increased LV dp/dt at doses greater than or equal to 6.6 x 10(-10) mol. At maximal doses (2 x 10(-9) to 2 x 10(-8) mol) the effect of ISO was significantly greater than VIP. Both VIP and ISO significantly increased CBF at all doses, but at maximal doses the effect of VIP on CBF was significantly greater than ISO. The increase in CBF relative to the increase in MVO2, an index of direct coronary vasodilation, was significantly greater for VIP compared with ISO. In 10 additional dogs the effects of VIP and ISO were compared with forskolin given in doses ranging from 2 x 10(-9) to 2 x 10(-7) mol. At maximal doses (2 x 10(-7) mol) the increase in LV dp/dt was similar to VIP but significantly less than ISO, whereas the increase in CBF was similar to ISO but significantly less than VIP. The increase in CBF relative to the increase in MVO2 was significantly greater for forskolin compared with ISO, indicating a direct vasodilator effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

红细胞分布宽度与冠心病冠状动脉病变的相关性研究

目的：探讨红细胞分布宽度（ RDW）与冠状动脉粥样硬化性心病（冠心病）冠状动脉病变程度的相关性。方法将697例患者根据冠脉造影结果分为冠心病组453例和非冠心病组244例,比较2组患者的临床资料,并对冠心病危险因素进行多元logistic回归分析。结果冠心病组RDW水平高于非冠心病组,多元logistic回归分析显示RDW值与冠心病独立相关;以冠脉病变支数将所有患者分为4组进行RDW值比较,发现随着病变支数增加,RDW值逐渐升高;多元逐步回归分析显示RDW值与冠心病冠脉病变严重程度独立相关,RDW值越高,冠脉病变越严重（β＝0？．282, P ＝0．000）。结论 RDW与冠心病冠脉病变严重程度密切相关,RDW升高可能是冠心病冠脉病变严重程度的一个预测指标。     

缺血修饰白蛋白对冠脉慢血流患者的临床意义

目的探讨缺血修饰白蛋白（IMA）水平对冠脉慢血流（CSF）治疗的临床意义。方法根据冠脉造影结果选取无冠状动脉狭窄但伴有冠状动脉血流缓慢者为CSF组（n=37）,以冠脉造影正常者为对照组（n=20）,比较CSF组与对照组IMA水平及CSF组治疗前后矫正的TIMI帧数（CTFC）及IMA水平。结果 CSF组共有78支血管受累,受累血管以右冠和左前降支多见,分别为84%和70%。与对照组比较,CSF组IMA值显著升高（P〈0.01）;CSF组治疗后IMA水平明显低于治疗前水平（P〈0.01）,且与CTFC改善程度呈正相关。结论 IMA检测可反映心肌组织缺血,操作简单,有望成为心肌缺血随访生化标志物。     

葛根素注射液对冠心病心绞痛患者血液流变学的影响

目的了解葛根素对冠心病患者血液流变学的影响。方法对68例冠心病患者进行葛根素治疗，葛根素400mg加入5％葡萄糖注射液250mL中静脉滴注，1次·d^-1，共15d，并进行治疗前后血液流变学观察。同时选取49名查体健康者进行对照研究。结果冠心病患者存在血液流变学指标异常，葛根素治疗后血液流变学各项指标有显著改善。结论血液流变学异常可促进冠心病的发生发展，葛根素治疗后可显著改善冠心病患者血液黏稠度，其疗效可靠，毒副作用小，值得推广。     

A haemodynamic and radionuclide assessment of diltiazem in coronary heart disease.

To obtain multiple dose-response haemodynamic and radionuclide data on i.v. diltiazem, 12 ischaemic patients were studied during routine catheterization. At rest, following a 20 min stable control period, the effects of four doses (0.0625, 0.0625, 0.125 and 0.25 mg kg-1 diltiazem at 5 min intervals) were measured in the 3-5 min following i.v. injection. The exercise effects of the cumulative 0.5 mg kg-1 dosage were assessed by comparing a control and post drug period of supine bicycle exercise. The increase in plasma diltiazem levels correlated linearly with the administered dose and achieved therapeutic levels. There were significant dose-related reductions in systemic arterial blood pressure and vascular resistance index; the heart rate fell and cardiac stroke index increased. The calculated double-product (heart rate X systolic blood pressure) was significantly reduced. The left ventricular filling pressures, ejection fraction and cardiac volumes were unaltered. During supine bicycle exercise, the systemic diastolic blood pressure, heart rate and calculated double-product were reduced without change in other parameters. Over the dose range 0.0625-0.5 mg kg-1, diltiazem acutely increased cardiac stroke index and reduced resting heart rate. These haemodynamic data, taken together with its described coronary vasodilator activity suggest that its role in acute vasospastic angina and during angiographic procedures ought to be explored further.     

苯环利定对犬冠状动脉的作用

目的：研究苯环利定（Ｐｈｅ）对犬冠状动脉的作用．方法：利用冠脉条生物检定，电磁流量计记录犬血流量等技术分别观察Ｐｈｅ对犬冠脉螺旋条和麻醉犬冠状动脉血流量的影响，同时观察Ｐｈｅ受体拮抗剂右美沙芬（Ｄｅｘ）的拮抗效应．结果：Ｐｈｅ０１－１００μｍｏｌ·Ｌ－１量效依赖地使冠脉条收缩，Ｄｅｘ非竞争性拮抗Ｐｈｅ效应．Ｐｈｅ１０ｍｇ·ｋｇ－１使麻醉犬冠脉左旋支主干流量增加，从３３４（３５ｍＬ·ｋｇ－１·ｍｉｎ－１增加到５１０（５８ｍＬ·ｋｇ－１·ｍｉｎ－１．左室内压和血压缓慢升高，Ｄｅｘ５ｍｇ·ｋｇ－１对整体Ｐｈｅ作用有拮抗效应．结论：Ｐｈｅ离体与整体的冠脉调节不同，提示Ｐｈｅ中枢和外周调节效应可能不一致，Ｐｈｅ整体调节的复杂性．