PROPOFOL BLOCK OF CARDIAC SODIUM CURRENTS IN RAT ISOLATED MYOCARDIAL CELLS IS INCREASED AT DEPOLARIZED RESTING POTENTIALS

1. The effect of propofol on cardiac whole-cell sodium currents and single sodium channels in rat isolated ventricular myocytes was examined using patch-clamp techniques. 2. Propofol caused a block of the whole-cell sodium current, the potency of block depending on the holding potential. When cells were held at -90 mV, the EC₅₀ was 2.8 μg/mL. When cells were held more hyperpolarized (at -140 mV), the EC50 increased to 44.0 μg/mL. 3. Although the degree of block produced by the same concentration of propofol was different at different holding potentials, the time course of onset and recovery from block was the same. 4. The current/voltage relationship for the sodium current showed a pronounced block of peak current by propofol (40–50 % block of the maximum current by 30 μg/mL propofol), with a minimal shift in the voltage dependence of activation and no shift in reversal potential. 5. The voltage dependence of the steady state inactivation curve was shifted to more hyperpolarized potentials by propofol (shift of 18 and 8 mV by 30 and 10 μg/mL propofol, respectively). 6. Single channel records showed that propofol caused a shortening of the mean channel open time (from a mean of 0.59 to 0.38 ms by 10 μg/mL propofol), but no change in the channel amplitude. 7. It is concluded that propofol produces a block of sodium currents in cardiac myocytes at concentrations that are comparable to those that may be attained during anaesthesia.     

INCREASED BLOOD PRESSURE AND CHANGES IN MEMBRANE LIPIDS ASSOCIATED WITH CHRONIC ETHANOL TREATMENT OF RATS

1. Changes in membrane fluidity have been proposed to contribute to the pathogenesis of ethanol-induced hypertension possibly through changes in membrane lipid patterns, but reports are inconsistent. 2. In a controlled trial we documented ethanol-induced changes in blood pressure and composition of membrane lipids in ethanol-fed rats. 3. Systolic blood pressure increased significantly in the ethanol-treated rats (9.3 mmHg, s.e.m. 2.9) compared with the control group (—1.3 mmHg, s.e.m. 2.6). Mean cholesterol content in red cell membranes did not differ significantly between ethanol-fed and control rats. Phospholipids of aorta, red cells and kidney showed a significant decrease in the polyunsaturated to saturated fatty acid ratio, while membrane phospholipids from the heart showed a significant increase in the polyunsaturated to saturated fatty acid ratio with ethanol treatment. 4. In univariate regression blood pressure was significantly negatively related to levels of arachidonic acid in the kidney (P= 0.0013) and to linoleic acid in the aorta (P= 0.0341) and red cells (P= 0.0289). Blood pressure was not significantly related to fatty acids in the heart nor to membrane cholesterol or phospholipids. 5. Differences in fatty acid composition of phospholipids between controls and ethanol-fed rats are consistent with altered membrane fluidity. Altered membrane function is a potential mechanism involved in ethanol-induced hypertension.     

INCREASED CARDIAC ANGIOTENSIN-CONVERTING ENZYME IN RATS WITH CHRONIC HEART FAILURE

1. Chronic heart failure was induced in rats by ligation of the left coronary artery to produce a left ventricular myocardial infarct. 2. Cardiac angiotensin-converting enzyme (ACE) was estimated by radioligand binding in myocardial homogenates and by autoradiography studies of radioligand binding to ACE in heart sections. 3. Radioligand binding studies demonstrated an increase in binding sites in animals with myocardial infarction, compared with sham operated animals. Mean increases were 457% in right atrium, 295% in left atrium, 326% in right ventricle, 187% in left ventricle and 530% in the region of the left ventricular infarct, compared with the sham left ventricle. 4. Autoradiography studies confirmed tissue homogenate binding studies, demonstrating (i) a marked increase in ligand binding in the infarct area and (ii) an increase in binding density in the hypertrophied myocardium of right and left atrium, and right and left ventricle. 5. The induction of cardiac ACE in the myocardium of rats with chronic heart failure may participate in the pathophysiology of cardiac hypertrophy.     

慢性孵育β淀粉样肽25-35对培养大鼠海马神经元电压依赖性外向钾通道亚型mRNA表达的影响

目的研究慢性孵育β淀粉样肽_25-35(β-AP_25-35)对海马神经元电压依赖性外向钾通道亚型mRNA表达的影响。方法用RT-PCR方法检测mRNA的表达,用光密度扫描法半定量测定表达变化。结果在正常培养的海马神经元上延迟整流(Kv2.1,Kv1.5),瞬间外向(A型)(Kv4.2,Kv1.4),钙激活的大电导(rSlo)钾通道亚型均有表达。β-AP_25-35 3 μmol·L^-1孵育细胞24 h后,Kv2.1 mRNA的表达明显上调,其它亚型则无显著性变化;β-AP_25-35上调Kv2.1 mRNA的作用主要发生在β-AP_25-35应用后48 h内;60 h后Kv2.1 mRNA表达水平显著下调。结论Kv2.1转录水平的上调可能参与β-AP_25-35选择性地增加海马神经元上延迟整流钾电流(I_K)的作用。     

慢性摄入吗啡和U50488H对鼠心к-受体的影响

本研究观察了大鼠慢性摄入吗啡和U50488H对心脏κ-受体结合特性的影响。慢性吗啡处理9d后,大鼠对吗啡产生升温效应耐受性,同时心肌κ-受体的K_d和B_(max)均增加,提示慢性吗啡处理后心肌κ-受体数目上调,但亲和力降低。而慢性U50488H处理4d后即产生完全的降温效应耐受性,同时心肌κ-受体的K_d增加,B_(max)无明显改变,提示慢性U50488H处理后心肌κ-受体亲和力下降。结果表明,大鼠μ和κ阿片耐受引起心肌κ-受体的调节机制是不同的。     

藻酸双酯钠对冠心病患者心脏功能的影响

藻酸双酯钠200mg加入10％葡萄糖500ml中iv drip,qd,治疗冠心病32例,男20例,女12例,平均年龄58±10y,14d为一疗程。结果显示,治疗后患者的心脏功能、血脂和血液流变学指标均有显著改善(P<0.05),心肌耗氧量明显降低(P<0.05)。     

PROSTAGLANDIN SYNTHETASE INHIBITION WITH INDOMETHACIN RECTAL SUPPOSITORIES IN THE TREATMENT OF ACUTE AND CHRONIC URINARY CALCULUS OBSTRUCTION

The effect of indomethacin suppositories on both acute urinary colic and urinary calculus, resistant or refractory to conventional therapy with analgesics and spasmolytics was investigated. Fifty-five patients with acute urinary colic refractory to treatment with repeated injections of antispasmodics and analgesics had dramatic or complete pain relief after receiving indomethacin suppositories (100 mg) (P less than 0.01). Fifteen of the 55 patients passed urinary stones within 30 days of treatment with indomethacin. Three out of 30 other patients with renal or ureteric stones were treated with indomethacin suppositories (100 mg) twice daily. Twenty-one of the 30 patients passed their stones within 30 days of treatment. It is concluded that indomethacin suppositories can relieve acute urinary colic resistant to treatment with analgesic/antispasmodic drugs, and facilitate expulsion of urinary calculi. The mechanism of action of indomethacin is discussed in terms of its analgesic and anti-inflammatory effects and its prostaglandin synthesis inhibition.     

THE INTERACTION OF EPHEDRINE WITH β-ADRENOCEPTORS IN TRACHEAL, CARDIAC AND SKELETAL MUSCLES

Three beta-adrenoceptor mediated effects were measured in vitro on tissues from guinea-pig: (a) relaxation of the trachea (mainly beta 2), (b) increase in the force of contraction of the papillary muscle (beta 1), and (c) depression of the subtetanic contractions of the soleus muscle (beta 2). The relaxant effect of ephedrine on the trachea was weak but was resistant to reserpine pretreatment. There was no appreciable agonistic effect of ephedrine on the soleus muscle. Ephedrine per se had a marked positive inotropic effect on the papillary muscle with a pD2 of about 6.0. This effect disappeared completely after pretreatment with reserpine. Ephedrine inhibited the response to isoprenaline. The apparent pA2 was about 4.8 in all tissues studied.     

HYPOTHESIS: AN ANGIOTENSIN CONVERTING ENZYME/GENOTYPE,PRESENT IN ONE IN THREE CAUCASIANS,IS ASSOCIATED WITH AN INCREASED MORTALITY RATE

• 1 This review argues that the deletion (D) allele of an insertion (I)/deletion polymorphism of the angiotensin I-converting enzyme (ACE) gene is a marker for a variant associated with increased ACE expression, as well as myocardial infarction (MI) and other life-threatening conditions.
• 2 By examination of I/D frequency in different age groups of individuals having well-known risk factors, it appears that homozygosity for the D allele may be associated with an increased risk of premature death in subjects at high-risk of cardiovascular events. For the risk factor hypertension, the odds ratio for DD vs II in patients aged ≥60 years was 6.6.
• 3 Besides in MI itself, the DD genotype appears to be also more prevalent in MI patients who develop restenosis several months after balloon angioplasty, patients with various forms of heart failure, those with ventricular hypertrophy and diabetic patients who develop nephropathy.
• 4 Particular genotypes of other components of the renin-angiotensin system may add to the risk conferred by the ACE DD genotype.
• 5 Emerging evidence therefore suggests that the ACE genotype may eventually be placed on the list of common, well-known risk factors for fatal cardiovascular events.

     

tTcm-小分子多肽配合物显像剂的合成及其在小鼠体内的生物分布研究

目的寻求新的心、肾显像剂。方法与结果以巯基乙酸为初始原料,用不同的羧基活化的方法设计合成了5个新的目标配体,其结构经光谱鉴定(IR,¹HNMR,¹³CNMR,MS和元素分析)。将合成的5个新目标配体进行了锝-99m放射性标记,研究了其在小鼠体内的生物分布特征。结论^tTc^m-MVG₂有较高的肾摄取,较长时间的肾滞留,血清除快,且肾与其他组织的活度比值高,具备成为肾功能显像剂的条件;^tTc^m-MVGT,^tTc^m-MVGH和^tTc^m-MPGT均有较高的心肌初始摄取,但心肌滞留不好,血清除慢,心肌与其他组织的活度比值不高,主要从肝、肾中代谢。     

REGIONAL DISTRIBUTION OF THE CARDIAC OUTPUT AND RENAL RESPONSES TO ATRIAL ATRIURETIC PEPTIDE INFUSION IN RABBITS WITH CONGESTIVE HEART FAILURE

1. A biventricular, low-output congestive cardiomyopathy was induced in 19 rabbits by administering adriamycin (16 mg/kg). The effects of alpha-rat atrial natriuretic peptide (ANP) infused at 0.1, 0.2 and 0.4 micrograms/kg per min, were then examined in terms of (i) central haemodynamics (ii) regional blood flow (iii) renal function and (iv) plasma norepinephrine and plasma renin. 2. In this dose range, ANP produced progressive and significant falls in stroke volume, cardiac output and mean arterial pressure, owing to a fall in venous return. The heart rate response to this was blunted. 3. Using radiolabelled microspheres, significant falls in the perfusion of cutaneous, gastrointestinal and musculoskeletal tissues were observed, due to reduced vascular conductances in these beds. These changes were accompanied by activation of the sympathetic nervous system as evidenced by a progressive rise in plasma norepinephrine. A significant increase in plasma renin was only observed with the highest infusion of ANP. 4. Renal blood flow was maintained in the face of a falling mean arterial pressure and cardiac output, but diuretic and natriuretic effects were absent. 5. It was concluded that the dominant influence of ANP infusion in this model of heart failure appeared to be a reduction in cardiac preload with detrimental overall haemodynamic consequences.     

硫酸镁对大鼠海马神经元瞬间外向钾电流和延迟整流钾电流的抑制作用

目的研究硫酸镁(MgSO₄)对大鼠海马神经元瞬间外向钾电流(I_A)和延迟整流钾电流(I_K)的作用。方法 全细胞膜片钳技术。结果MgSO₄可浓度依赖地抑制I_A和I_K,半数抑制浓度IC₅₀分别为6.30和7.60 mmol·L^-1;此外还与电压呈依赖性关系,但不具有频率依赖性。6 mmol·L^-1 MgSO₄非常显著地影响I_A和I_K的激活过程,但不改变二者的斜率因子。另外6 mmol·L^-1 MgSO₄还非常显著地影响I_A的失活过程,但不改变其斜率因子。结论 MgSO₄抑制大鼠海马神经元的I_A和I_K,并改变I_A和I_K的激活过程和失活过程。这可能是其抗缺血缺氧引发的中枢神经系统损伤,具有神经保护作用的机制之一。     

PRO- AND ANTI-ARRHYTHMIC EFFECTS OF A κ OPIOID RECEPTOR AGONIST: A MODEL FOR THE BIPHASIC ACTION OF A LOCAL HORMONE IN THE HEART

1. The effects of kappa opioid receptor stimulation on cardiac rhythm and the underlying signal pathways were investigated in the rat. 2. Stimulation of kappa opioid receptors with 40-50 mumol/L U50 488H, a selective kappa opioid receptor agonist, induced dysrhythmias and increased inositol 1,4,5-trisphosphate (IP3) production in rat isolated, perfused heart. The pro-arrhythmic effects of U50 488H were abolished by 5 mumol/L norbinaltorphimine (nor-BNI), a specific kappa opioid receptor antagonist. 3. The effect of U50 488H on cardiac dysrhythmia and IP3 production were abolished by 1 mmol/L neomycin and streptomycin, phospholipase C (PLC) inhibitors. 4. At 1 mumol/L, U50 488H, which itself has no effect on cardiac rhythm and IP3 production, significantly attenuated the potentiating effect of 1 mumol/L noradrenaline (NA) on dysrhythmias, which were induced by low flow in the isolated heart. The effects of U50 488H were abolished by 1 mumol/L nor-BNI. Cytosolic cAMP production was augmented by 1 mumol/L NA and this was significantly attenuated by 1 mumol/L U50 488H. 5. At 1 mumol/L, U50 488H also reduced [Ca2+]i oscillations induced by 0.5 mumol/L NA and 0.5 mumol/L forskolin, an activator of adenylate cyclase (AC). 6. In conclusion, U50 488H exerted pro- and anti-arrhythmic actions at high and lower concentrations, respectively. The former effect was mediated via the PLC/IP3 pathway, while the latter was mediated via the AC/cAMP pathway.