Effect of etafenone on total and regional myocardial blood flow.

The distribution of blood flow to the subendocardial, medium and subepicardial layers of the left ventricular free wall was studied in anaesthetized dogs under normoxic (A), hypoxic (B) conditions and under pharmacologically induced (etafenone) coronary vasodilation (C). Regional myocardial blood flow was determined by means of the particle distribution method. In normoxia a transmural gradient of flow was observed, with the subendocardial layers receiving a significantly higher flow rate compared with the subepicardial layers. In hypoxia induced vasodilation this transmural gradient of flow was persistent. In contrast a marked redistribution of regional flow was observed under pharmacologically induced vasodilation. The transmural gradient decreased. In contrast to some findings these experiments demonstrate that a considerable vasodilatory capacity exists in all layers of the myocardium and can be utilized by drugs. The differences observed for the intramural distribution pattern of flow under hypoxia and drug induced vasodilation support the hypothesis that this pattern reflects corresponding gradients of regional myocardial metabolism.     

Effect of endothelin on systemic and regional hemodynamics in rats

In this study we analyzed the changes in systemic haemodynamics induced by endothelin, 1 nmol/kg, given as an i.v. bolus to anaesthetized rats. Endothelin induced a dramatic decrease in cardiac output whereas the total peripheral resistance increased more than two times. In addition, renal blood flow decreased while renal vascular resistance increased to a similar extent. A marked decrease in blood flow to the splanchnic organs was also observed. In conclusion, endothelin seems to modulate peripheral vasomotor tone, at least under certain conditions.     

Effect of intracoronary captopril on coronary blood flow and regional myocardial function in dogs

To evaluate the cardiac effect of an inhibitor of angiotensin-converting enzyme, the effect of intracoronary (i.c.) captopril on coronary blood flow and regional myocardial function was examined in the anesthetized open-chest dog. Blood flow of the left circumflex coronary artery (LCX), left ventricular pressure (LVP), aortic pressure (AoP) and regional myocardial segment length were measured continuously. Captopril i.v. (0.3 mg/kg) produced an immediate reduction in AoP and an increase in percent shortening of myocardial segments followed by a decrease in coronary vascular resistance and increases in heart rate and LVdP/dt. Reductions in LCX flow induced by i.c. angiotensin were attenuated and i.c. bradykinin-induced increases in LCX flow were augmented after captopril. On the contrary, i.c. infusion of captopril (0.01 mg/min) into the LCX caused no change in hemodynamic variables and myocardial shortening although responses to angiotensin I and bradykinin were markedly modified. These results suggest that captopril may have no direct cardiac effect.     

Effect of dehydroemetine on myocardial circulation and contractility in vivo

The effects of dehydroemetine on myocardial haemodynamics and contractility were studied in anaesthetised cats. Doses of 3 and 5 mg/kg caused a fall in blood pressure, heart rate, myocardial blood flow, ‘cardiac effort index’, left ventricular systolic pressure and maximum rate of rise of left ventricular pressure, without affecting myocardial vascular resistance and heat production. These doses, as well as a 1-mg/kg dose, also caused electrocardiographic changes suggestive of disturbed generation and spread of electrical activity of the heart. None of the effects of dehydroemetine was prevented by previous adminisstration of propanolol or atropine or by vagotomy. It is concluded that the only primary effect of the drug on the heart is a depression of the myocardium and that any observed reduction in coronary blood flow is secondary to this.     

The effects of neuropeptide Y on myocardial contractility and coronary blood flow.

1. This study was designed to assess the effects of exogenous neuropeptide Y (NPY) on cardiac contractility and coronary blood flow (CBF) in anaesthetized dogs and to evaluate the effect of NPY on the responses to sympathetic and parasympathetic stimulation and to inotropic agents. 2. Bolus doses of NPY (500 micrograms), administered via the femoral vein, increased mean arterial pressure. The pressor effect was associated with reductions in heart rate, CBF and cardiac contractility. 3. The effects of NPY (500 micrograms) on contractility and CBF were compared with that of vasopressin (VP) (1 unit). For similar reductions in CBF, NPY and VP had similar negative inotropic effects. Thus, it is likely that the negative inotropic response to NPY is not due to a direct effect of NPY on the heart muscle but is largely due to coronary vasoconstriction. 4. In the presence of NPY (500 micrograms, i.v.), there was an inhibition of the positive inotropic response to stimulation of the left cardiac sympathetic nerve (2 or 5 Hz, 0.05 ms). NPY also inhibited the negative inotropic response and chronotropic response to vagal stimulation (2, 3 or 5 Hz, 0.05 ms). 5. Dose-response curves were obtained for the inotropic, chronotropic and pressor responses to cumulative infusions of noradrenaline (n = 6) and dobutamine (n = 6). NPY had no effect on these dose-response curves. 6. The effect of NPY on the responses to salbutamol and impromidine was assessed. NPY did not alter the positive inotropic, chronotropic or depressor responses to these agonists.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of tranquilizers on the course of myocardial ischemia and on myocardial resistance to hypoxia in coronary artery occlusion

It was shown that meprobamate and phenazepam protect the myocardium from hypoxia and decrease myocardial ischemia during coronary occlusion. Phenibut and mebicar reduce the tolerance to ischemia and increase the degree of ischemic injury to the heart. Diazepam has no effect on these processes.     

Effect of a new alpha 2-adrenoceptor antagonist on poststenotic coronary resistance and myocardial function

The effect of the alpha 2-adrenoceptor antagonist 4-fluoro-2-(imidazoline-2-ylamino)-isoindoline maleate (BDF 8933) on poststenotic end-diastolic distal coronary resistance and poststenotic myocardial function (sonomicrometry) was investigated under control conditions and during cardiac sympathetic nerve stimulation (CSNS = electrical stimulation of the left ventrolateral cervical cardiac nerve). In 7 vagotomized, open-chest dogs end-diastolic distal coronary resistance was determined. This variable was essentially unchanged after administration of the agent. In additional 6 dogs regional myocardial function was measured as systolic wall thickening (SWT). CSNS increased SWT of the posterior circumflex-perfused myocardium from 12.7 +/- 4.6% to 21.9 +/- 8.4% (p less than 0.05) under control conditions. With a severe stenosis on the left circumflex coronary artery, SWT was reduced to 5.4 +/- 4.0% and further decreased to 2.1 +/- 5.1% (p less than 0.05) during CSNS. After i.v. injection of 150 micrograms/kg BDF 8933, poststenotic myocardial function at rest was 4.2 +/- 4.2%, and 5.6 +/- 3.6% during CSNS. Regarding to the systemic effects BDF 8933 significantly increased peak left ventricular pressure in all 13 dogs. Thus, the new alpha 2-adrenoceptor antagonist BDF 8933 at the chosen dosage prevents sympathetically induced myocardial ischemia, but increases left ventricular afterload resistance.     

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.     

Effect of endothelin on regional hemodynamics and renal function in awake normotensive rats

The effects of endothelin on regional hemodynamics and renal function were studied in awake normotensive rats. Intravenous injection of endothelin (700 pmol/kg) transiently lowered mean blood pressure (from 108 +/- 2 to 84 +/- 2 mm Hg, p less than 0.01), due to a reduction in total vascular resistance (38 +/- 1%, p less than 0.01), and increased stroke volume (29 +/- 5%, p less than 0.01) and heart rate (from 399 +/- 18 to 447 +/- 18 bpm, p less than 0.05); mesenteric and renal blood flow was reduced (37 +/- 13, p less than 0.05 and 63 +/- 5%, p less than 0.01), whereas carotid blood flow was increased (78 +/- 5%, p less than 0.01). This effect was followed by long-lasting hypertension due to increased total vascular resistance (112 +/- 19%, p less than 0.01); stroke volume, mesenteric, and renal blood flow were reduced (34 +/- 5, 41 +/- 4, and 58 +/- 4%, respectively, p less than 0.05) and carotid blood flow returned to basal levels. Bilateral nephrectomy enhanced the initial hypotensive effect. Pretreatment with nifedipine blocked the hypertensive effect, whereas bilateral nephrectomy did not. A subpressor dose of endothelin (70 pmol/kg) had no effect on stroke volume, mesenteric blood flow, glomerular filtration rate, and plasma renin activity; carotid blood flow was transiently increased (48 +/- 16%, p less than 0.05), then returned to basal levels; renal blood flow decreased (22 +/- 6 and 15 +/- 4% at 30 s and 10 min, respectively p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Enhancement of coronary conductance by alpha-human atrial natriuretic polypeptide without effects on myocardial contractility

The effect of synthetic human atrial 28-amino acid peptide (alpha-human atrial natriuretic polypeptide, alpha-hANP) on coronary circulation and cardiac functions was examined in open-chest dogs. Intravenous injection of alpha-hANP increased coronary and systemic conductance, and coronary and aortic blood flow with a significant fall in blood pressure. Continuous infusion of alpha-hANP into the left anterior descending coronary artery (LAD) increased LAD blood flow in a dose-dependent manner. The linear regression analysis revealed the relationship of logit (changes in mean coronary conductance (delta MCC] = 1.45 x log (coronary plasma concentration of alpha-hANP) + 7.51 (r = 0.87, n = 29). REC50 of alpha-hANP was 5.1 microM, where REC50 was the concentration to increase MCC to a half maximum MCC during reactive hyperemia after a 30-s coronary occlusion. alpha-hANP increased coronary conductance with no changes of myocardial oxygen consumption (MVO2) when blood pressure remained constant. Indices of myocardial contractility measured with a strain gauge arch, myocardial force (F), max dF/dt and LV max dp/dt, were not altered by either bolus intravenous injection or continuous intracoronary infusion of alpha-hANP. These results indicated a direct increase by alpha-hANP of coronary and systemic vascular conductance.     

左旋荷包牡丹碱对猪冠状动脉条收缩效应的影响

目的 观察左旋荷包牡丹碱（L－dicentrine,L-D)对K^ ,5-HT Hist,Ca^2 引起的猪冠状动脉条收缩效应的影响。方法 利用猪冠状动脉条的离体实验法,观察对其收缩的影响。结果 L－D对K^ ,5-HT,Hist,Ca^2 诱发的猪冠状动脉平滑肌的收缩有显的拮抗作用,量效曲线显示：L－D呈现非竞争性拮抗方式。在无Ca^2 液中,L－D能抑制5－HT诱发的猪冠状动脉收缩,说明5－HT对猪冠状动脉依赖细胞内Ca^2 所致的收缩有明显的抑制作用,而对外Ca^2 所致的收缩无明显的影响。结论 L－D具有松弛猪冠状动脉条的作用,同时也提示冠状动脉平滑肌可能存在5－HT受体。     

峨眉唐松草碱对冠状循环及冠脉螺旋条收缩反应的影响

MAF 17μM,50μM增加离体豚鼠心脏冠脉流量,分别为12.9％及20.4％,同时,均伴有负性心力及频率作用。MAF 50mg/kg,ip使小鼠心脏营养性血流量增加13％,当MAF(50mg/kg,ip)与so(2.5mg/kg,sc)合用时,有一定程度的加强后者增加血流量的作用(增加14.3％),而当其与CaCl_2(300 mg/kg,ip)联用时,又明显减弱CaCl_2增加心肌营养性血流量的作用(减少14.9％)。在离体冠脉螺旋条,MAF还可明显抑制高K~+去极化所致收缩反应,CaCl_2又可逆转此抑制效应,以上结果提示其扩张冠脉、负性心力及负性频率作用,可能与阻钙内流有一定关系。 此外,MAF 30μM抑制去甲肾上腺素及苯福林所致冠脉条的依剂量性收缩,这可能是由于阻止了激动α受体引起收缩反应时所需CaCl_2内流所致。     

薯蓣皂苷对大鼠心肌收缩力影响的研究

目的观察薯蓣皂苷(dioscin,Dio)对大鼠心肌收缩力的影响。方法采用Langendorff逆行主动脉灌流法对大鼠离体心脏进行灌流,利用压力感受器插管法测定左心室相关心功能参数,记录低、中和高3个浓度Dio对左心室收缩压(LVSP)、左心室舒张末期压(LVEDP)、左心室内压最大上升/下降速率(±dp/dt_(max))的影响。利用激光共聚焦显微镜观察Dio对H9c2细胞内Ca~(2+)浓度的影响,并利用多功能酶标仪观察药物对细胞线粒体膜电位的影响。结果 0.1、1μmol·L~(-1)Dio可明显增加LVSP,由(11.55±0.52)、(10.53±0.28)kPa分别增加至(13.08±0.72)、(12.53±0.64)kPa(P<0.01);增加+dp/dt_(max)由(0.38±0.10)、(0.40±0.07)kPa·ms~(-1)分别增加至(0.42±0.11)、(0.43±0.02)kPa·ms~(-1)(P<0.05)。10μmol·L~(-1)Dio则使LVSP由(12.13±0.33)kPa减至(9.46±0.77)kPa(P<0.01),使+dp/dt_(max)由(0.42±0.04)kPa·ms~(-1)降为(0.24±0.04)kPa·ms~(-1)(P<0.01)。0.1、1、10μmol·L~(-1)的Dio可使H9c2细胞中Ca~(2+)相对荧光强度由(16.62±0.89)分别增加至(21.48±0.80)、(25.68±0.69)和(19.84±0.66)(P<0.01)。0.1、1μmol·L~(-1)Dio对H9c2细胞线粒体膜电位无明显影响,而10μmol·L~(-1)Dio会使JC-1单体与聚合物的比值由(1.14±0.03)增加为(1.35±0.06)(P<0.01),即引起线粒体膜电位下降。结论低、中浓度Dio可增加LVSP和+dp/dt_(max),表现正性肌力作用,机制为增加细胞内Ca~(2+)浓度。并且,其在增加细胞内Ca~(2+)浓度的同时并不会引起钙超载,仅高浓度出现。     

Effects of intracoronary propranolol on coronary blood flow and regional myocardial function in dogs

The study was conducted to evaluate the effects of intracoronary administration of dl-propranolol on coronary blood flow and regional myocardial function in anesthetized open-chest dogs. The results were compared with those obtained with d-propranolol, atenolol and lidocaine. Bolus intracoronary injections of dl-propranolol (0.02-2 mg) dose dependently produced transient increases in coronary blood flow and subsequent depression in regional segment shortening which qualitatively resembled those produced by the dextro isomer (0.02-2 mg) and lidocaine (0.2-10 mg). Atenolol (up to 2 mg) was almost devoid of these effects. Isoproterenol-induced responses were abolished by dl-propranolol and atenolol but only incompletely blocked by d-propranolol. These results demonstrate that propranolol at high doses has direct coronary vasodilating and cardiodepressant effects in situ, and indicate that the major part of these effects can be attributed to the membrane-stabilizing action rather than beta-adrenoceptor blockade.     

保心胶囊对急性心肌缺血犬一氧化氮和内皮素的影响

目的探讨中药复方保心胶囊(四逆汤胶囊)对实验性急性心肌缺血犬一氧化氮(NO)和内皮素-1(ET-1)的影响.方法结扎冠状动脉左前降支建立急性心肌缺血犬模型,在心肌缺血前、缺血后30、60和120min,分别观察犬血清NO和血浆ET-1水平的变化,并测定心肌组织NO和ET-1的含量.结果在犬急性心肌缺血过程中,血清和心肌NO水平明显下降,而血浆和心肌ET-1水平明显增高;在保心胶囊治疗组,血清和心肌的NO水平明显升高,ET-1水平明显降低,与缺血组比较有显著性差异(P＜0.05).结论促进NO的产生和抑制ET-1的合成可能是保心胶囊抗心肌缺血性损伤的重要机制之一.     

非选择性内皮素受体拮抗剂对肥厚心肌局部血管紧张素系统的影响

目的：探讨内皮素受体拮抗剂对肥厚心肌局部血管紧张素系统的影响及可能作用机制。方法：24只大鼠随机分为对照组、心肌肥厚组和内皮素受体拮抗剂组。测定左室指数,采用免疫组化法测定心肌组织中血管紧张素受体-1（AT1R）,放射免疫法测定心肌组织血管紧张素Ⅱ（AngⅡ）含量,分光光度法测心肌组织血管紧张素转化酶（ACE）活性,部分心肌组织进行HE、VG染色。结果：与对照组相比,心肌肥厚组左室指数、左室全心比、ACE活性、AngⅡ浓度及AT1R阳性表达率增加均有统计学意义（P〈0.05）。与心肌肥厚组相比,内皮素受体拮抗剂组左室指数、左室全心比、ACE活性、AngⅡ浓度及AT1R阳性表达灰度值降低均有统计学意义（P〈0.05）,但ACE活性、AT1R阳性表达灰度值仍高于对照组（P〈0.05）,而其他指标差异无统计学意义。结论：去甲肾上腺素诱导的心肌肥厚大鼠心肌组织局部血管紧张素系统活化,导致心肌细胞肥大,胶原增生。PD142893可以部分抑制这一作用,内皮素可能参与了血管紧张素系统活化过程。