愈风宁心滴丸抗异丙肾上腺素致心肌缺血的研究

目的:观察愈风宁心滴丸抗异丙肾上腺素致心肌缺血的效果。方法:采用心肌缺血实验中的增加心肌氧耗法。结果:愈风宁心滴丸高、中剂量组均可显著降低异丙肾上腺素引起大鼠ST段偏移总和值及ST偏移段均值,与异丙肾上腺素心肌缺血模型比较有统计学意义(P<0.05)。结论:愈风宁心滴丸具有一定抗异丙肾上腺素引起大鼠心肌缺血模型的作用。

大鼠心肌缺血心肌酶学、心肌超微结构的变化及淫羊藿苷的影响

淫羊藿苷（icariin,ICA）是从小檗科植物淫羊藿（Epimedium grandiflorum）茎叶中提取出来的一种8-异戊烯基黄酮醇苷类化合物。淫羊藿具有温阳补肾、强筋键骨、祛风除湿等功效。现代药理学研究证明,淫羊藿苷能有效对抗异丙肾上腺素致大鼠急性心肌缺血,可以降低大鼠血清中炎症因子IL-1β及心肌组织TNF-α的生成和释放,降低心肌组织MPO活性和NF-κB表达,改善心肌组织的病理变化。

心宁胶囊对大鼠急性心肌缺血的保护作用

目的:研究心宁胶囊对大鼠急性心肌缺血的保护作用。方法:用垂体后叶素、异丙肾上腺素造成大鼠急性心肌缺血模型,观察药物对心电图、心肌酶及栓死程度的影响。结果:心宁胶囊(420、210、105mg/kg)对垂体后叶素致大鼠心电图急性缺血性改变有明显的预防作用。在异丙肾上腺素引起的心肌损伤大鼠,可对抗T波升高,显著抑制心肌组织中CPK和LDH的释放;在结扎冠脉的心肌梗死大鼠,明显抑制血清CPK和LDH,缩小心肌梗死范围。结论:心宁胶囊对实验性心肌缺血有明显的保护作用。

Effect of Fish Oil on Left Ventricular Function in Anes-thetized Rats

The effect of fish oil on the basal left ventricular function and changes of left ventricular function induced by isoproterenol(ISO)were demonstrated in our study. The detennina-tion of cardiac perfonnance in vivo showed that supplementation with fish oil(EPA and DHA,70%,1.4 ml / kg) had no significant effect on basal cardiac perfonnance,while it could significantly inhibit changes of+ dp / dt_(max),V_(pm) and HR induced by ISO(0.4μg/ kg,4.0μg/ kg,40μg/ kg)intrave-nously.The results suggested that supplementation with fish oil perhaps affected the function of β-adrenoceptors on rat myocardial membrane.

Ion mechanism of isoproterenol on delayed afterdepolarization and triggered activity in the infarcted ventricle

Objectives This study aimed at investigating the cellular mechanism of isoproterenol （ISO） on delayed afterdepolarizations （DADs） and triggered activity （TA） of the noninfarcted myocardium in the myocardial infarcted rabbit model.Methods Rabbits with the left anterior descending coronary artery occlusion were prepared and recovered for 8 wk （healed myocardial infarction, HMI）. Myocytes were isolated from regions of the noninfarcted left ventricular free wall. ISO was added to cellular surface by perfusion way. Action potentials and ion currents were recorded with whole-cell patch clamp. Results The results showed that treatment with ISO induced more DADs and TA events in HMI myocytes. Iti and IC,_L of myocytes treated with ISO were increased significantly compared with HMI cells, which contributed to DADs-related triggered arrhythmia. Conclusions The results suggested that more arrhythmia events of DADs and TA developed in myocytes with ISO treatment. The underlying mechanism was associated with the augment of I6 and calcium influxing

Assessment of mitral valve reserve capacity before and after percutaneous balloon valvuloplasty with isoproterenol stress echocardiography

Objective: To explore whether successful valvuloplasty increases mitral valve reserve capacity in patients with mitral stenosis. Methods: Thirty-eight patients with pure rheumatic mitral stenosis underwent isoproterenol stress echocardiography before and after successful percutaneous balloon valvuloplasty. The mitral valve area (by direct planimetry of two-dimensional echocardiography), mean transmitral pressure gradient (by continuous-wave Doppler echocardiography), and cardiac output (by M-mode echocardiography) were measured at rest and under isoproterenol infusion to achieve heart rate of different stages. Results:Between the measurements before and after valvuloplasty, significant differences were observed in the mitral valve area (0. 91±0. 28 vs 1. 87±0. 23 cm2, P<0. 01), mean transmitral pressure gradient (12. 5±6. 3 vs 3. 9±1. 9 mmHg, P<0. 01) and cardiac output (3. 93±1. 44 vs 4. 73±1. 01 L/min, P<0. 05) at rest. Before valvuloplasty, the mean transmitral pressure gradient increased significantly (P<0. 01) as heart rate increased, but there were no significant differences in the measurements of mitral valve area and cardiac output (both P>0. 05). In contrast, there was a significant increase after valvuloplasty in the mean transmitral pressure gradient (P<0. 01), but both mitral valve area and cardiac output further increased (both P< 0. 01) as heart rate increased. Moreover, valvuloplasty decreased the mean transmitral pressure gradient at peak heart rate from 23. 0±4. 5 to 7. 75±2. 30 mmHg (F<0. 01) under submaximal stress. Conclusion: Successful percutaneous balloon valvuloplasty soon causes a significant increase of mitral valve reserve capacity in patients with mitral stenosis, which is conspicuously manifested under condition of hemodynamic stress. Stress echocardiography provides a safe, feasible and non-invasive means of assessing the reserve capacity.

Determination of isoproterenol in pharmaceutical and biological samples using a pyrogallol red multiwalled carbon nanotube paste electrode as a sensor

Isoproterenol （ISPR） is an important catecholamine‐based drug that is widely used in the treatment of heart disease. However, overdose of this drug is very dangerous to the human body. In this study, a new sensor based on a pyrogallol red modified‐multiwalled carbon nanotube paste electrode （PGRMMWCNTPE） was prepared and used for high sensitivity determination of ISPR in aqueous solution. Electrocatalytic oxidation of ISPR at the PGRMMWCNTPE was investigated by chronoam‐perometry, cyclic voltammetry, and square‐wave voltammetry. The values of the catalytic rate con‐stant, electron transfer coefficient, and diffusion coefficient for ISPR oxidation were then calculated using voltammetric data. A linear calibration curve was constructed for ISPR concentration in the range 0.8–570μmol/L with a detection limit of 0.47μmol/L ISPR. The sensor was then applied to the determination of ISPR in urine and drug samples with satisfactory results.

Distinct actions of intermittent and sustained β-adrenoceptor stimulation on cardiac remodeling

Heart disease is associated with increased sympathetic nerve activity and elevated levels of circulating catecholamines,resulting in chronic stimulation of the β-adrenergic receptors (β-AR) and consequent pathological cardiac remodeling.Experimentally,chronic administration of the β-AR agonist isoproterenol (ISO) has been most commonly used to model β-AR-induced cardiac remodeling.However,it remains unclear whether β-AR-mediated cardiac remodeling and dysfunction differs between sustained versus pulsatile (intermittent) exposure to a β-agonist.Here,we compare the effects of intermittent versus sustained administration of ISO on cardiac remodeling and function in mice.Animals were administered 5 mg (kg d)-1 ISO for 2 weeks either by daily subcutaneous injection,or continuous infusion via an implanted osmotic minipump.Cardiac function and remodeling were determined by echocardiography,micromanometry and histology.Moreover,Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were utilized to define the proteins and genes involved.Both sustained and intermittent administration of ISO resulted in a similar degree of cardiac hypertrophy (16% and 19%,respectively).However,mice receiving ISO by daily injection developed more severe ventricular systolic and diastolic dysfunction and myocardial fibrosis compared with mice receiving ISO via the osmotic minipump.The disparity in results between the delivery methods is suggested to be due,at least in part,to increased expression of fibrogenic factors,including connective tissue growth factor (CTGF) and NADPH oxidase (NOX4),in mice receiving intermittent application of ISO.In summary,compared with sustained exposure to a β-AR agonist,intermittent β-AR stimulation leads to more severe cardiac dysfunction and fibrosis.These findings not only further our understanding of β-AR function in the setting of cardiac pathophysiology,but also highlight that significant differences can result dependent upon the mode of experimental β-AR stimulation in inducing cardiomyopathy.

Protein and RNA expression of acid-sensing ion channels 2 and 3 in myocardial ischemia rats induced by isoproterenol

OBJECTIVE:To investigate the impact of electro-acupuncture at the Neiguan(PC 6) acupoint on protein and RNA expression of acid-sensing ion channel 2(ASIC2) and ASIC3 in myocardial ischemia rats.METHODS:Fifty male Sprague-Dawley rats were used,weighing(230 ± 50) g.The rats were randomized into a normal group A,model group B,Neiguan(PC 6) group C,Lieque(LU 7) group D,and A-shi points group E.There were 10 rats in each group.Rats were continuously administered 85 mg/kg intravenous isoproterenol daily to establish the model.Successfully modeled rats in groups C,D,and E were given electro-acupuncture treatment.Each group of rats was sacrificed with chloral hydrate(1 mL/100 g) intraperitoneal injection.The left ventricular myocardium was extracted and placed at- 70 ℃ until use.Western blot analysis and real-time PCR were performed to assay protein and RNA expressions of ASIC2 and ASIC3,respectively.Fold changes in RNA expression were quantified with the 2~^(-△△Ct) method.Blood samples were drawn from the aorta abdominalis and tested for creatine kinase-MB(CK-MB) and lactate dehydrogenase(LDH) levels using enzyme-linked immunosorbent assay.RESULTS:Myocardial ischemia rats given electro-acupuncture at the Neiguan(PC 6) acupoint had significantly lower protein and RNA expression of ASIC2 and ASIC3,and CK-MB and LDH levels,compared with model rats(P < 0.01).CONCLUSION:Electro-acupuncture at the Neiguan(PC 6) acupoint can not only decrease the protein and RNA expression of ASIC2 and ASIC3,but also inhibit the opening of ASICs and reduce the cardiomyocyte damage in myocardial ischemia rats.