糖尿病对心肌预/后处理效应的影响及机制

背景 大量研究已经证实预处理和后处理对正常心脏有保护作用.糖尿病是缺血性心脏病独立的高危因素,对长期预后不利.同时现有研究大多表明糖尿病能干扰心肌保护机制,进而减弱心肌保护效应.目的 综述糖尿病对心肌预/后处理效应的影响及机制的研究进展,使人们能系统了解糖尿病对心肌预/后处理效应的影响及可能的机制.内容 主要从糖尿病对心血管病的影响;糖尿病对心肌缺血/再灌注的影响;糖尿病对心肌预/后处理效应的影响及机制等方面展开阐述.趋向 目前糖尿病对心肌预/后处理效应的影响还存在争议,且具体机制也尚未明确,还需进一步研究来证实,通过前驱大量研究积极寻找糖尿病患者心肌保护的理想药物,提高患者预后和生存率.     

心肌缺血预适应延迟相研究进展

心肌缺血预处理是指一次或几次短暂重复的缺血/再灌注，能够增强心肌对以后较长时间心肌缺血缺氧的耐受能力，减轻心肌缺血，再灌注损伤。根据对心肌保护作用出现的时间，可将其分为预处理的快速相和延迟相。近几年来人们对心肌缺血预处理延迟相做了大量研究，现综述如下。     

糖尿病大鼠心肌缺血再灌注时Rev-erbα与NLRP3炎症小体的关系

目的评价糖尿病大鼠心肌缺血再灌注时Nr1D1核受体亚家族1, 组D, 成员1(Rev-erbα)与NOD样受体热蛋白结构域相关蛋白3 (NLRP3)炎症小体的关系。方法 SPF级健康成年雄性SD大鼠, 体重210～240 g, 采用腹腔注射1%链脲佐菌素60 mg/kg制备1型糖尿病模型。取非糖尿病大鼠18只, 采用随机数字表法分为2组:非糖尿病假手术组(NS组, n=6)和非糖尿病心肌缺血再灌注组(NIR组, n=12)。取糖尿病大鼠30只, 采用随机数字表法分为3组:糖尿病假手术组(DS组, n=6)、糖尿病心肌缺血再灌注组(DIR组, n=12)和糖尿病心肌缺血再灌注+ Rev-erbα抑制剂SR8278组(DIR+SR组, n=12)。采用结扎左冠脉前降支30 min后再灌注120 min的方法建立心肌缺血再灌注损伤模型。DIR+SR组于缺血前1 h时经股静脉注射SR8278 2 mg/kg。再灌注结束时经采用ELISA法检测血清CK-MB、LDH和cTnI浓度, TTC法测心肌梗死面积百分比, HE染色法观察心肌组织病理学结果, Western blot法检测心肌组织Rev-...     

艾司洛尔对大鼠离体心脏缺血-再灌注时心肌C-fos基因表达的影响

心肌缺血．再灌注损伤机制的研究表明：兔、鼠和人类的心肌细胞在经过一定时间的缺血一再灌注后可出现明显的细胞凋亡，缺血时间越长c-fos表达越多，c-fos参与了心肌缺血．再灌注损伤。艾司洛尔是选择性8受体阻断剂，可降低心肌氧和能量的消耗，临床研究证明冠状动脉含艾司洛尔温血液灌注可避免心肌缺血，减少心肌水肿，产生心肌保     

异丙酚预先给药对糖尿病大鼠心肌缺血再灌注损伤的影响

目的 探讨异丙酚预先给药对糖尿病大鼠心肌缺血再灌注损伤的影响.方法 健康雄性SD大鼠84只,体重230～280 g,随机分为7组(n=12),假手术组(Ⅰ组);Ⅱ组采用结扎左冠状动脉前降支30 min,再灌注120 min制备心肌缺血再灌注模型;糖尿病大鼠假手术组(Ⅲ组)采用腹腔注射链脲左菌素(STZ)55 mg/kg制备糖尿病模型;糖尿病大鼠心肌缺血再灌注组(Ⅳ组)腹腔注射STZ 3周后制备心肌缺血再灌注模型;Ⅴ组、Ⅵ组和Ⅶ组糖尿病大鼠分别于缺血前10 min至再灌注120 min时静脉输注异丙酚3、6、12 mg·kg-1·h-1.记录再灌注120 min时心率(HR)、左心室收缩峰压、左心室舒张末压(LVDEP)及左心室内压上升,下降最大速率(±dp/dtmax),计算左心室发展压(LVDP);测定血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)活性、心肌组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量、心肌线粒体肿胀度、总ATP酶和谷胱苷肽过氧化物酶(GSH-Px)活性;透射电镜观察心肌组织超微结构.结果 与Ⅲ组比较,Ⅳ组HR、LVDP和±dp/dtmax、心肌组织SOD活性、线粒体总ATP酶及GSH-Px活性降低,LVEDP、血清LDH、CK-MB活性、心肌组织MDA含量及线粒体肿胀度升高(P<0.05或0.01);与Ⅳ组比较,Ⅵ组和Ⅶ组HR、LVDP和±dp/dtmax、心肌组织SOD活性、线粒体总ATP酶及GSH-Px活性升高,LVEDP、血清LDH、CK-MB活性、心肌组织MDA含量和线粒体肿胀度降低,Ⅴ组+dp/dtmax及线粒体总ATP酶活性升高,血清CK-MB活性降低(P<0.05).Ⅵ组和Ⅷ组心肌组织超微结构损伤减轻.结论 异丙酚6、12 mg·kg-1·h-1预先给药可减轻糖尿病大鼠心肌缺血再灌注损伤,可能与其抑制心肌组织脂质过氧化反应,改善心肌细胞线粒体膜通透性有关.     

丙泊酚对2型糖尿病大鼠心肌缺血-再灌注损伤的影响

目的观察丙泊酚对2型糖尿病大鼠心肌缺血-再灌注损伤的影响。方法雄性Wister2型糖尿病模型大鼠21只,随机均分为三组:心肌缺血-再灌注组(DI组)、心肌缺血-再灌注+丙泊酚组(DP组)、假手术组(D组)。另取21只健康大鼠作为对照,随机均分为三组:心肌缺血-再灌注组(CI组)、心肌缺血-再灌注+丙泊酚组(CP组)、假手术组(C组)。DI组和CI组结扎冠状动脉左前降支30min后再灌注2h建立心肌缺血-再灌注模型;D组和C组只穿线不结扎;DP组和CP组在缺血前10min静脉泵注丙泊酚6mg·kg-1·h-1至再灌注结束。测定基础状态及再灌注2h末大鼠血清乳酸脱氢酶(LDH)、肌酸激酶(CK)、血清及心肌丙二醛(MDA)和超氧化物歧化酶(SOD)含量。结果与基础状态相比,再灌注2h末DI、DP、CI、CP组血清LDH和CK含量升高(P<0.05);与CI组相比,CP组血清LDH、CK、MDA含量降低(P<0.05),且血清和心肌SOD含量升高(P<0.05);与DI组相比,DP组心肌SOD含量升高(P<0.05)。结论丙泊酚减轻正常大鼠心肌缺血-再灌注损伤,但对2型糖尿病大鼠心肌缺血-再灌注损伤无明显保护作用。     

纳络酮对缺血再灌注心肌儿茶酚胺释放的影响

利用犬心肌缺血再灌注模型，观察了纳络酮对缺血再灌注心肌内源性儿茶酚胺释放和心肌ｃＡＭＰ、钙含量的影响。其结果表明：心肌缺血４０分钟，去甲肾上腺素大量释放，并伴有ｃＡＭＰ和钙含量增加；再灌注３０分钟后，这些指际变化更趋明显；纳络酮可以明显减少再灌注心肌去甲肾上腺素释放，同时降低心肌ｃＡＭＰ和钙含量，这可能是纳络团抗心肌缺血再灌注损伤的重要因素之一。     

纳络酮对缺血再灌注心肌局部血流变化的影响

利用犬心肌缺血再灌注模型，观察了缺血和再灌注心肌局部血流改变及纳络酮对其的影 响。结果表明：结扎冠状动脉左前降支后，缺血区心肌血流量明显降低，靠结扎点越近血流量减少越明 显。再灌注５分钟左右缺血心肌明显充血，其后血流量逐渐减少。纳络酮明显增加正常、缺血和部份再灌 注心肌血流量。提示心肌缺血是一种不完全性缺血，缺血的程度亦不相同，“无再流”现象的发生有一定 的时间过程。纳络酮可以减轻心肌缺血程度，缩小“无再流”心肌的范围。     

辅酶Q10在换瓣术中对心肌缺血再灌注损伤的作用

目的：探讨换瓣术ＣＰＢ中ＣｏＱ１０对心肌缺血再灌注损伤的作用。方法：将２４例行体外循环心脏瓣膜置换术患者分为两组。对照组应用冷停跳液灌注，试验组于心肌冷停跳液中加入辅酶Ｑ１０（２ｍｇ／ｋｇ）。观察血浆丙二醛（ＭＤＡ），心肌三磷酸腺苷（ＡＴＰ），能量储备（ＥＣ），心肌超微结构（线粒体计分）。结果：（１）再次证实存在心肌缺血再灌注损伤；（２）试验组较对照组减轻了心肌缺血再灌注过程中血浆ＭＤＡ升高；心肌能量保存较多；超微结构改变较轻。结论：冷停跳液内加入辅酶Ｑ１０能减少氧自由基产生，抗脂质过氧化，稳定细胞膜，改善心肌能量代谢，从而对瓣膜置换术中心肌缺血再灌注损伤产生一定保护作用。为较有效的心肌保护方法，应用于临床是可行的。     

肿瘤坏死因子与心肌缺血再灌注损伤（文献综述）

肿瘤坏死因子（TNF）是一种自分泌的细胞因子，它在心肌缺血再灌注损伤中，可导致心肌机能障碍和心肌细胞死亡，作为一种具有负性肌力效应的细胞因子，TNF是通过NO依赖型和NO非依赖型两种机制来介导其心肌抑制作用的。心肌细胞死亡有凋亡和坏死两种形式，正确的适当的抗TNF治疗有望成为一种新的防止心肌缺血再灌注损伤的有效方法。     

WJD 5~(th) Anniversary Special Issues(2): Type 2 diabetes Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?

Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin.Compared with individuals without diabetes,patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality,and are disproportionately affected by cardiovascular disease.Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension,dyslipidaemia and obesity in these patients.However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors.Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus.Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events.Many of these risk factors could be common history for both di-abetes mellitus and cardiovascular disease,reinforcing the postulate that both disorders come independently from"common soil".The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients.     

Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?

Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin. Compared with individuals without diabetes, patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality, and are disproportionately affected by cardiovascular disease. Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension, dyslipidaemia and obesity in these patients. However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors. Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus. Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events. Many of these risk factors could be common history for both diabetes mellitus and cardiovascular disease, reinforcing the postulate that both disorders come independently from “common soil”. The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients.     

Diabetic patients with chronic kidney disease: Non-invasive assessment of cardiovascular risk

The prevalence and burden of diabetes mellitus and chronic kidney disease on global health and socioeconomic development is already heavy and still rising. Diabetes mellitus by itself is linked to adverse cardiovascular events, and the presence of concomitant chronic kidney disease further amplifies cardiovascular risk. The culmination of traditional (male gender, smoking, advanced age, obesity, arterial hypertension and dyslipidemia) and non-traditional risk factors (anemia, inflammation, proteinuria, volume overload, mineral metabolism abnormalities, oxidative stress, etc.) contributes to advanced atherosclerosis and increased cardiovascular risk. To decrease the morbidity and mortality of these patients due to cardiovascular causes, timely and efficient cardiovascular risk assessment is of huge importance. Cardiovascular risk assessment can be based on laboratory parameters, imaging techniques, arterial stiffness parameters, ankle-brachial index and 24 h blood pressure measurements. Newer methods include epigenetic markers, soluble adhesion molecules, cytokines and markers of oxidative stress. In this review, the authors present several non-invasive methods of cardiovascular risk assessment in patients with diabetes mellitus and chronic kidney disease.     

Cardiovascular Complications in Diabetic Kidney Disease

Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD). Due to an explosion in the incidence and the prevalence of Type 2 DM, the burden of CKD is expected to increase proportionately. Both DM and CKD are associated with a high incidence of cardiovascular (CV) morbidity and mortality, and it is important to understand the unique nature of CV disease in patients with the combination of these two conditions. In this report, we review the traditional and nontraditional risk factors that underlie the high risk of CV disease in this population, with a particular focus on vascular calcification, mineral metabolism, and therapeutic paradigms for the treatment of cardiovascular disease in this unique and high‐risk population.     

Diabetes mellitus in transplantation: 2002 consensus guidelines

Diabetes mellitus is a serious complication following organ transplantation that is underdiagnosed, possibly due to the inadequate definitions used in published literature and the lack of standardized screening. Diabetes in transplantation amplifies the already increased risk of cardiovascular disease among transplant patients, and increases the risk of graft loss and death. Patients at risk of developing diabetes in transplantation should therefore be prospectively identified and given individualized immunosuppressive therapy to minimize the risk of developing this disease. These guidelines are intended to: (1) help identify patients at risk for diabetes after transplantation; (2) set down a standard definition of posttransplant diabetes mellitus (PTDM); (3) create a standard monitoring protocol for the diagnosis of PTDM; and (4) optimize the management of patients at risk of developing or who develop diabetes after transplantation. With improved diagnosis, individualization of therapy, and proper early management, the incidence of diabetes in transplantation, and the accompanying additional burden of illness the disease carries, may be diminished. In turn, this will help achieve the therapeutic goals of reducing the risk of graft complications, improving quality of life, and reducing postoperative morbidity and mortality in transplant patients.     

Epicardial adipose tissue deposition in patients with diabetes and renal impairment: Analysis of the literature

Diabetes mellitus (DM) is defined as a chronic disease of disordered metabolism with an ongoing increase in prevalence and incidence rates. Renal disease in patients with diabetes is associated with increased morbidity and premature mortality, particularly attributed to their very high cardiovascular risk. Since this group of patients frequently lacks specific symptomatology prior to the adverse events, a screening tool for the identification of high-risk patients is necessary. The epicardial adipose tissue (EAT) is a biologically active organ having properties similar to visceral adipose tissue and has been associated with metabolic diseases and coronary artery disease. Superior to conventional cardiovascular risk factors and anthropometric measures, including body mass index and waist circumference, the EAT can early predict the development of coronary artery disease. Assessment of EAT can be performed by two-dimensional echocardiography, magnetic resonance imaging or computer tomography. However, its role and significance in patients with DM and nephropathy has not been thoroughly evaluated. The aim of the current editorial is to evaluate all available evidence regarding EAT in patients with DM and renal impairment. Systematic search of the literature revealed that patients with DM and nephropathy have increased EAT measurements, uncontrolled underlying disease, high body mass index and raised cardiovascular risk markers. Acknowledging the practical implications of this test, EAT assessment could serve as a novel and non-invasive biomarker to identify high-risk patients for cardiovascular adverse events.     

Prevalence and treatment of cardiovascular disease and traditional risk factors in Australian adults with renal insufficiency

AIM: To evaluate the prevalence and treatment of cardiovascular disease and traditional cardiovascular disease risk factors in Australian adults with renal insufficiency. METHODS: The Australian Diabetes, Obesity and Lifestyle Study was a cross-sectional survey of Australian adults undertaken in 1999-2000. Participants were categorized based on the Cockcroft-Gault estimated glomerular filtration rate in terms of normal renal function (<60 mL/min per 1.73 m(2)) and renal insufficiency (<60 mL/min per 1.73 m(2)). Outcome measures were the prevalence of cardiovascular disease, estimated risk of cardiovascular disease (20% over 10 years) and traditional cardiovascular risk factors, and frequency of pharmacological treatment of traditional cardiovascular risk factors. RESULTS: Among adults with renal insufficiency, cardiovascular disease was present in 29.4 (95% CI: 25.1-33.6) per 100, with an additional 47.9 (95% CI: 44.9-50.9) per 100 having an estimated risk of cardiovascular disease (20% over 10 years). At least one cardiovascular risk factor was present in 90.1%. Hypertension and type 2 diabetes mellitus were three times more frequent, while hyperlipidaemia was nearly twice as frequent in those participants with renal insufficiency. Of those with renal insufficiency, 58.2% with hypertension were treated, with only 14.5% of this group being treated to current recommended target levels of blood pressure, while only 32.5% with hyperlipidaemia were treated, with 7.4% of this group being treated to target lipid levels. CONCLUSION: The present study demonstrates significant scope to reduce the high burden of cardiovascular risk factors in Australian adults with renal insufficiency in the general community, through treatment of traditional risk factors for cardiovascular disease.     

Guidelines for the treatment and management of new-onset diabetes after transplantation

Although graft and patient survival after solid organ transplantation have improved markedly in recent years, transplant recipients continue to experience an increased prevalence of cardiovascular disease (CVD) compared with the general population. A number of factors are known to impact on the increased risk of CVD in this population, including hypertension, dyslipidemia and diabetes mellitus. Of these factors, new-onset diabetes after transplantation has been identified as one of the most important, being associated with reduced graft function and patient survival, and increased risk of graft loss. In 2003, International Consensus Guidelines on New-onset Diabetes after Transplantation were published, which aimed to establish a precise definition and diagnosis of the condition and recommend management strategies to reduce its occurrence and impact. These updated 2004 guidelines, developed in consultation with the International Diabetes Federation (IDF), extend the recommendations of the previous guidelines and encompass new-onset diabetes after kidney, liver and heart transplantation. It is hoped that adoption of these management approaches pre- and post-transplant will reduce individuals' risk of developing new-onset diabetes after transplantation as well as ameliorating the long-term impact of this serious complication.     

Acute insulin resistance in myocardial ischemia: causes and consequences

Diabetes mellitus is associated with increased risk for cardiovascular mortality because of multiple pathophysiologic mechanisms. Acute stress-induced hyper-glycemia during acute myocardial infarction has gained much attention, as blood glucose levels seem to be an independent risk factor for acute myocardial infarction-related death. Clinical studies that identify stress-induced hyperglycemia as a risk factor are reviewed and its causes are discussed. They can be summarized as the consequence of acute insulin resistance, which in its turn is caused by stress hormones and by proinflammatory cytokines. Hyperglycemia causes the release of proinflammatory cytokines, the induction of reactive radicals, alterations in cardiovascular substrate metabolism, and propagation of coagulation and apoptosis. These all have harmful effects during and after acute myocardial infarction. Recommendations are for strict glycemic control in hyperglycemic patients with acute myocardial infarction, although the target glucose level is still a subject of debate.     

Which diabetics are at risk for lower-extremity problems and what preventive measures can be taken?

Diabetes mellitus is a well-known risk factor for development and progression of peripheral arterial disease. Prospective cardiovascular clinical trials have also clearly demonstrated that diabetics fare worse than their nondiabetic counterparts. Diabetics also differ from nondiabetics in that multiple revascularization procedures may be required in order for the clinical outcome to be equivalent to that of a nondiabetic patient. However, by advocating an aggressive approach to peripheral arterial disease, good results in survival and limb salvage can be achieved in diabetic patients despite the presence of increased medical comorbidities. Key to the management of such patients will be identifying which diabetic patients will be at most risk so that preventive measures can be undertaken.