针刺正常骼肌及力竭肌对胞浆自由钙离子浓度的影响机制

利用荧光指示剂Fura2测定离体青蛙半腱肌胞浆自由钙离子浓度（[Ca2+]i），已发现肌肉经长时间电刺激至力竭后，[Ca2+]i上升。对针刺影响力竭肌[Ca2+]i的机制进行了进一步探讨。研究发现，针刺正常肌使[Ca2+]i上升，其上升可被钙通道阻滞剂异博定大部分阻断；针刺电刺激后半腱肌则使[Ca2+]i下降，其下降可被Na－Ca交换阻断剂奎尼丁阻断。如在针刺前予先加入奎尼丁，可抑制针刺对电刺激肌的降钙作用。上述结果证实：1）针刺正常肌的升钙作用主要由于细胞膜慢钙通道开放：2）针刺电刺激肌的降钙作用则是通过提高细胞膜对Na+通透性，促进Na－Ca交换而完成。研究亦发现，在针刺入肌肉的留针期内，细胞内Ca2+有上升和下降两类反应。其意义与机制尚待探讨。

用荧光指示剂Fura－2测定正常和电刺激后蛙肌胞浆自由Ca^（2＋）浓度

蛙半腱肌肌束负载Ｆｕｒａ－２／ＡＭ后，可用荧光信号Ｆ３４０、３８０ｎｍ波长比值（Ｒ３４０／３８０）反映胞浆内游离Ｃａ２＋浓度（〔Ｃａ２＋〕）。利用这一技术，我们发现长时间电刺激后的骨骼肌〔Ｃａ２＋〕，高于未刺激肌，Ｒ３４０／３８０分别为１．４９±０．５４（ｎ＝１０）和１．０２±０．２６（ｎ＝１０）。加入Ｃａ２＋载体伊屋诺霉素（ｉｏｎｏｍｙｃｉｎ，１μｍｏｌ／Ｌ）后，正常肌与电刺激肌〔Ｃａ２＋〕，均上升，但刺激肌上升幅度低，持续时间短。说明电刺激至力竭后，细胞内有较多的Ｃａ２＋负载。增加细胞外Ｃａ２＋浓度至１５ｍｍｏｌ／Ｌ，〔Ｃａ２＋〕ｉ下降。而给予Ｎａ＋－Ｃａ２＋交换阻断剂奎尼丁（１０４ｍｏｌ／Ｌ）后，正常肌〔Ｃａ２＋〕ｉ上升，刺激肌〔Ｃａ２＋〕ｉ下降。结果提示：Ｎａ＋－Ｃａ２＋交换是正常骨胳肌外排Ｃａ２＋的途径之一；而长时间肌肉活动则可能使细胞膜Ｎａ＋－Ｃａ２＋交换方式改变，从而导致力竭肌〔Ｃａ２＋〕ｉ上升。

Valsartan prevents the development of rabbit＇s heart failure by restoring calcium uptake of sarcoplasmic reticulum

Objective Clinical evidence has suggested that AT1 receptor blocker （ARB） could prevent the development of heart failure. Decreased sarcoplasmic reticulum（SR） Ca2＋ content, which is due to reduced SR calcium reuptake by SERCA2a, is responsible for defective systolic function in failing heart. To better understand how ARB could improve cardiac systolic dysfunction, we studied the effects of Valsartan on calcium reuptake of SR and its regulatory proteins in heart failure rabbits. Methods Thirty rabbits were divided into three groups： sham rabbits（controls, n=11）, rabbits with heart failure treated with Valsartan （n=11） and rabbits with heart failure but without Valsartan treatment （n=8）.Rabbit heart failure model was established by volume plus pressure overload. Cardiac function was measured by echocardiography, SR calcium uptake was determined by measuring extra vesicular free [Ca2＋] changes in a fluorescence spectrophotometer. SERCA2a, Ser 16-phosphorylated phospholamban （p-PLB）, PKA and PP 1 a protein abundance were determined by use of Western blot analysis. Results Compared to control rabbits, the ejection fractions in the HF rabbits were significantly decreased （P〈0.05）, these changes could be significantly attenuated by Valsartan treatment （P〈0.05）.Calcium reuptake of SR, activity of SERCA2a and PKA decreased in heart failing myocytes （P〈0.05）, with down regulations of p-PLB, SERCA2a and PKA, but up regulation ofPP la in ventricular samples from the failing rabbits （P〈0.05）. All of these changes were attenuated by Valsartan treatment （all P〈0.05）. Conclusion Valsartan improved cardiac function in volume plus pressure overload induced heart failure of rabbits possibly by restoring the SR calcium uptake resulted from attenuating the activities and expressions of SERCA2a and its regulatory proteins （J Geriatr Cardio12009; 6：173-177）.

Early association of electrocardiogram alteration with infarct size and cardiac function after myocardial infarction

Objective: Myocardial infarction (MI) is the main cause of heart failure, but the relationship between the extent of MI and cardiac function has not been clearly determined. The present study was undertaken to investigate early changes in the electrocardiogram associated with infarct size and cardiac function after MI. Methods: MI was induced by ligating the left anterior descending coronary artery in rats. Electrocardiograms, echocardiographs and hemodynamic parameters were assessed and myocardial infarct size was measured from mid-transverse sections stained with Masson抯 trichrome. Results: The sum of pathological Q wave amplitudes was strongly correlated with myocardial infarct size (r = 0.920, P < 0.0001), left ventricular ejection fraction (r = -0.868, P < 0.0001) and left ventricular end diastolic pressure (r = 0.835, P < 0.0004). Furthermore, there was close relationship between MI size and cardiac function as assessed by left ventricular ejection fraction (r = -0.913, P < 0.0001) and left ventricular end diastolic pressure (r = 0.893, P < 0.0001). Conclusion: The sum of pathological Q wave amplitudes after MI can be used to estimate the extent of MI as well as cardiac function.

Review:Cell therapy in congestive heart failure

Congestive heart failure （CHF） has emerged as a major worldwide epidemic and its main causes seem to be the aging of the population and the survival of patients with post-myocardial infarction. Cardiomyocyte dropout （necrosis and apoptosis） plays a critical role in the progress of CHF; thus treatment of CHF by exogenous cell implantation will be a promising medical approach. In the acute phase of cardiac damage cardiac stem cells （CSCs） within the heart divide symmetrically and/or asymmetrically in response to the change of heart homeostasis, and at the same time homing of bone marrow stem cells （BMCs） to injured area is thought to occur, which not only reconstitutes CSC population to normal levels but also repairs the heart by differentiation into cardiac tissue. So far, basic studies by using potential sources such as BMCs and CSCs to treat animat CHF have shown improved ventricular remodelling and heart function. Recently, however, a few of randomized, double-blind, placebo-controlled clinical trials demonstrated mixed results in heart failure with BMC therapy during acute myocardial infarction.

Development and course of heart failure after a myocardial infarction in younger and older people

Background Acute myocardial infarction （AMI） is a common cause of heart failure （HF）, which can develop soon after AMI and may persist or resolve or develop late. HF after an MI is a major source of mortality. The cumulative incidence, prevalence and resolution of HF after MI in different age groups are poorly described. This study describes the natural history of HF after AMI according to age. Methods Patients with AMI during 1998 were identified from hospital records. HF was defined as treatment of symptoms and signs of HF with loop diuretics and was considered to have resolved if loop diuretic therapy could be stopped without recurrence of symptoms. Patients were cate- gorised into those aged 〈 65 years, 65-75 years, and 〉 75 years. Results Of 896 patients, 311,297 and 288 were aged 〈 65, 65-75 and 〉75 years and of whom 24%, 57% and 82% had died respectively by December 2005. Of these deaths, 24 （8%）, 68 （23%） and 107 （37%） oc- curred during the index admission, many associated with acute HF. A further 37 （12%）, 63 （21%） and 82 （29%） developed HF that persisted until discharge, of whom 15, 44 and 62 subsequently died. After discharge, 53 （24%）, 55 （40%） and 37 （47%） patients developed I-IF for the first time, of whom 26%, 62% and 76% subsequently died. Death was preceded by the development of HF in 35 （70%）, 93 （91%） and 107 （85%） in aged 〈 65 years, 65-75 years and 〉75 years, respectively. Conclusions The risk of developing HF and of dying after an MI in- creases progressively with age. Regardless of age, most deaths after a MI are preceded by the development of HF.

PERIPARTUM CARDIOMYOPATHY——REPORT OF 16 CASES

Objective.To analyze the clinical characteris tics of peripartum cardiomyopathy a nd to evaluate the different factors that influence the prognosis of the peripartum cardiomyopathy.Method.A retrospective review was undertak en on records of women who were diagnosed with peripartum cardiomyopathy at Peking Union Medi cal College Hospital between Jan.1983and May 1999.Results.During the research period,only 16p regnant women were documented as peripartum cardiomyopa-thy.Some of the women undertook ultr asonic cardiographic(UCG)examination that showed decreased s ystolic function.Seven women were complica ted with pregnancy induced hyperten sion.Three died of disseminated intravascular coagulation,embolism and cardiogenic shock respectively.Conclusion.Early diagnosis of the peripartum ca rdiomyopathy is extremely important.The UCG can pro-vide helpful information on disease progression or regression.

Primary percutaneous coronary intervention on older patients with acute ST-segment elevation myocardial infarction: analysis of its risk factors

Objective: The aim of the present study was to assess the early clinical outcome and risk factors in old patients with acute ST elevation myocardial infarction (STEMI) following primary percutaneous coronary intervention (PCI). Methods: A total of 136 patients older than 60 years with STEMI who received successful PCI were included in this study. The patients were classified in 2 age groups: patients ≥75 years and <75 years of age. The extent of coronary artery lesions was measured by quantitative coronary artery angiography (QCA). Subjects were tracked for subsequent cardiovascular events: cardiac death, myocardial infarction, heart failure, percutaneous coronary intervention, coronary artery bypass and stroke. Results: Though the older group had a higher prevalence of adverse baseline characteristics and lower final TIMI flow than patients<75y (P<0.05), the procedural success did not make difference between the two groups. In 12 months follow-up of 136 study participants, there occurred 39 CV events : cardiac death (five patients), heart failure (nineteen patients), and stroke (six patients). Three patients received coronary bypass grafts and six patients underwent PCI. Heart failure and overall cardiovascular event rates were higher in older patients compared with those in patients<75y. The main adverse clinical events (MACE) for the old group were a little higher comparing with the younger in 12-month follow-up (P=0.029 6 and P=0.043 4). Multivariate cox analysis identified that a diagnosis of diabetes (HR 2.495, 95%CI 1.224 to 5.083, P= 0.011 8) and time from symptom(HR 1.450, 95%CI 1.143 to 1.841, P= 0.008 2) to PCI as independent predictors of CV events after adjustment of all entered baseline variables. Conclusion: Our study suggests that drug-eluting stent implantation in older patients with acute ST elevation myocardial infarction has high initial procedural success rates despite having more severe baseline risk characteristics, and to shorten the time from symptom onset to PCI may decrease cardiovascular events in old patients following PCI.

Influence of Valsartan on myocardial apoptosis in spontaneously hypertensive rats

OBJECTIVE: To explore the pathogenic changes of myocardial apoptosis in heart hypertrophy during hypertension and evaluate the anti-apoptosis effect of Valsartan. METHODS: Thirty spontaneously hypertensive rats (SHRs) were divided into two groups: 15 treated with Valsartan (20 mg x kg(-1) x d(-1)) (SHR + Valsartan group), the others with placebo (SHR + placebo group), with 15 normal Wistar rats as control. Systolic blood pressure was measured by the tail-cuff method. The observation period was from 8 to 16 weeks of age. Cardiac apoptosis was evaluated by a Terminal Deoxynucleotidyl Transferase-Mediated dUTP-biotin Nick End Labeling (TUNEL) assay. RESULTS: Mean blood pressure values were 127 +/- 2 mm Hg in controls, 163 +/- 6 mm Hg in the SHR + Valsartan group and 193 +/- 7 mm Hg in the SHR + placebo group at 16 weeks of age, whereas the blood pressure in 8-week-old SHR and Wistar rats were 175 +/- 3 mm Hg and 125 +/- 5 mm Hg, respectively. The ratio of the heart weight over body weight declined in Wistar (3.07 +/- 0.03 mg/g) and SHR + Valsartan groups (3.22 +/- 0.19 mg/g) compared with the SHR + placebo group (4.02 +/- 0.31 mg/g) (P

Roles of SIRT3 in heart failure: from bench to bedside

Heart failure （HF） represents the most common endpoint of most cardiovascular diseases （CVDs） which are the leading causes of death around the world. Despite the advances in treating CVDs, the prevalence of HF con- tinues to increase. It is believed that better results of prognosis are obtained from prevention rather than additional treatment for HF. Therefore, it is reasonable to prevent the development of CVDs or other complications to HF. Most types of HF are attributed to contractile dysfunction, cardiac hypertrophy or remodeling, and ischemic injuries. SIRT3 is a mitochondrial nicotinamide adenine dinucleotide （NAD＊）-dependent deacetylase whose substrates vary from met- abolic biogenesis-associated proteins to stress-responsive proteins. In recent years, a number of studies have high- lighted the cardio-protective role of SIRT3 and, as such, efforts have been made to induce over-expression or in- creased activity of this protein. In this review, we provide an overview of the roles of SIRT3 in cardiac hypertrophy induced by pressure overload or agonists and cardiomyocytes ischemic injuries. Moreover, we will introduce the application of SIRT3 agonists in the prevention of cardiac hypertrophy and ischemia reperfusion injury.

RESPIRATORY FAILURE AS THE FIRST PRESENTATION OF PATIENTS WITH MYASTHENIA GRAVIS:ONE CASE REPORT

Although respiratory failure commonly occurs during the course of myasthenia gravis (MG),it is rarely described as the first presentation in patients with previously unrecognized MG.Here we reported one case of MG in a 76-year-old man with the isolated respiratory failure as the first symptom.As illustrated by this case,it is important to consider neuromuscular disorders in cases of unexplained respiratory failure.