方长太---重症感染心肌损伤课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,*,重症感染心肌损伤：受体阻滞剂的评价,安庆市立医院 重症医学科,方长太,主要内容,一、基本概念；,二、SIC流行病学；,三、SIC的临床表现；,四、SIC的发病机制；,五、受体阻滞剂在SIC运用中的效果评价；,六、小结,一、基本慨念,脓毒症,：,感染+全身炎症反应综合征,严重脓毒症,：,脓毒症+组织低灌注/脏器功能不全,脓毒症休克,：,脓毒症+容量复苏不能纠正的休克,脓毒性心肌病 Sepsis-induced cardiomyopathy(SIC)：,脓毒症,+,心肌损伤伴或不伴有心输出量减少,主要内容,一、基本概念；,二、SIC流行病学；,三、SIC的临床表现；,四、SIC的发病机制；,五、受体阻滞剂在SIC运用中的效果评价；,六、小结,二、SIC流行病学,The heart is one of the most frequently affected organs in,sepsis.Approximately 50%of the patients who are diagnosed,with sepsis exhibit signs of myocardial dysfunction.Several,reports have suggested that patients with sepsis who develop,myocardial dysfunction are more likely to die compared with,those without evidence of myocardial dysfunction,.,心脏是脓毒血症患者最常受,累,的器官之一，大约有50%的脓毒症患者有心功能障碍,，且患有心功能障碍的患者其病死率明显高于无心功能障碍的患者。,Charpentier J,Luyt CE,Fulla Y,:Brain natriuretic peptide:a marker of myocardial dysfunction and prognosis during severe sepsis.Crit Care Med32(3):660Y665,2004.,Blanco J:Incidence,organ dysfunction and mortality in severe sepsis:a Spanish,multicentre study.Crit Care12(6):R158,2008,主要内容,一、基本概念；,二、SIC流行病学；,三、SIC的临床表现；,四、SIC的发病机制；,五、受体阻滞剂在SIC运用中的效果评价；,六、小结,三、SIC的临床表现,1.,急性发生的可逆性心肌抑制,Bouhemad,*,等指出，左心射血分数（LVEF）可以在几天内恢复正常；,2.,左心收缩,、舒张,功能的障碍,左心室顺应性下降引起左心收缩功能,降低18-60%，舒张功能降低约20%,；,3.,右室射血分数减少,当合并ARDS时引起的肺动脉阻力增加，导致了右心室后负荷增加，进一步造成右室射血分数减少。,*,Bouhemad B,Nicolas-Robin A,Arbelot C,et al.Acute left ventricular dilatation and shock-induced myocardial dysfunction.Crit Care Med,2009,37:441-447.,三、SIC的临床表现,脓毒血症伴有cTnl增高和射血分数50 ms from the preceding NN interval;,LF,low-frequency power domain;,HF,high-frequency domain;,VLF,very low frequency domain;,LF/HF=LFdivided by HF.Not only HRV but also baroreflex sensitivity(BRS)and chemoreflex sensitivity(CRS)are significantly,compromised.,这些指标，在一定程度上，反应了脓毒症患者心率变异性降低，自率性紊乱,。,-Data from Schmidt et al.2005,四、SIC的发病机制,-自律性紊乱,Prospective observational study in 89 patients,with MODS,defined as an APACHE-II scoreC,20.,前瞻性，观察性研究；,研究对象：89名诊断为MODS患者，且,APACHE-II,评分20分。,四、SIC的发病机制-,免疫炎症失调,脓毒血症激活单核、白细胞释放各种炎性因子,（包括,IL-1,IL-6,TNF,IL-12,IL-15 and IL-18,）,和后期调节介质，如巨噬细胞移动抑制因子等,Activated,mononuclear cells release a broad variety of,proinflammatory,cytokines,including IL-1,IL-6,TNF,IL-12,IL-15 and IL-18,as well as the so-called late mediators,high mobility groupbox 1 and macrophage,migration inhibitory factor,四、SIC的发病机制,-,免疫炎症失调,单核细胞在心脏不同部位分布频率（Fig 2）；,心脏坏死带在不同部位的分布（Fig 1）。,Shock2013 Apr;39(4):329-35,四、SIC的发病机制,-免疫炎症失调,同时，脓毒血症诱导,内皮系统,（如ICAM,E-selectin,von,willebrand factor,VCAM-1等）活化，增加如IL,TNF等炎性细胞因子的表达。,在脓毒性犬实验中，TNF-能使左心射血分数降低，而使用TNF-阻滞剂时，能明显提高脓毒性休克患者的LV功能。,-,Am J Physio1992,l263(3 Pt 2):H668-H675.,-Ches1992,t101(3):810-815.,四、SIC的发病机制,-,免疫炎症失调,C3、IL-6、TNF-、多巴胺、多巴酚丁胺与心脏循环系统,（MAPCISVRILVSWI/PAOP）密切相关。,Immunol Invest2010;39(8):849-62,其次，免疫效应细胞引起的,促炎性信号和抗炎的信号之间,失,平衡。,过度的全身炎症反应可能有利于器官衰竭，过量抗炎介质的发展，,也,会危及,各脏器功能。,*,Pinsky MR:Dysregulation of the immune response in severe,sepsis.Am J Med Sci 2004,328:220-229.,四、SIC的发病机制-,免疫炎症失调,四、SIC的发病机制-,循环代谢系统,Sepsis-induced cardiac dysfunction.Cardiac performance during sepsis is impaired due to,changes in the macro-and microcirculation,autonomic dysfunction,and inflammation-induced,intrinsic myocardial depression.The mechanisms of myocardial depression include down-regulation,of adrenergic pathways,disturbed intracellular calcium(Ca,2)trafficking,and impaired electromechanical coupling at the myofibrillar level.Mitochondrial dysfunction seems to plays a central role in,this sepsis-induced organ dysfunction.,大、微循环改变，自主神经功能紊乱，炎性介导的内源性心肌抑制共同作用诱导肾上腺素下调，干扰Ca输送，肌原纤维受损。线粒体功能障碍起到核心作用，其抑制ATP的产生，引起心肌细胞凋亡。,-Crit Care Med 2007 Vol.35,No.6,四、SIC的发病机制,-,循环代谢系统,-,-,Effects of esmolol on systemic and pulmonary hemodynamics and on oxygenation in pigs with hypodynamic endotoxin shock.,四、SIC的发病机制,-,儿茶酚胺系统,Short-term,-adrenergic stimulation with catecholamines increases cardiac contractility and heart rate.However,prolonged,and excess stimulation can lead to myocardial damage by calcium overload and,consequent cell necrosis,。,短期的肾上腺素能刺激儿茶酚胺增加心肌收缩力和心脏速率。然而，长期和过量的刺激可通过钙超载和随之而来的细胞坏死,引起,心肌损伤,。,-Opie LH:Receptors and signal transduction.In:Heart Physiology:From Cell to,Circulation.Fourth Edition.Opie LH(Ed).London,Lippincott Williams&Wilkins,2004,pp 186 220,四、SIC的发病机制,-,儿茶酚胺系统,-,AM J RESPIR CRIT CARE MED 1999;160:458465.,四、SIC的发病机制,-,儿茶酚胺系统,在皮下注射20mmol/kg儿茶酚胺类药药物后，心肌凋亡（浅灰色）和坏死（深灰色）矩形图（左）；,运用异丙肾上腺素不同剂量后，心肌心肌凋亡（浅灰色）和坏死（深灰色）矩形图（右）。,-J Intensive Care Med2009 Sep-Oct;24(5):293-316,主要内容,一、基本概念；,二、SIC流行病学；,三、SIC的临床表现；,四、SIC的发病机制；,五、受体阻滞剂在SIC运用中的效果评价；,六、小结,五、受体阻滞剂在SIC运用中的效果评价,随机、双盲性小鼠试验；,通过不同试验方法检测脓毒性小鼠的存活率，血流动力学，细胞因子，,炎性介质等。,-Crit Care Med 2010 Vol.38,No.2,A.注射LPS(30mg/kg)前48小时开始腹腔内注射美托洛尔（100mg/kg）或阿替洛尔,(6mg/kg),能明显提高存活率（,P,0.01/,P,=0.03）.B.在注射LPS后6小时注射美托洛尔或,阿替洛尔不能提高存活率（,P,=0.28）.C.美托洛尔不能提高注射CLP小鼠的存活率,（,P,=0.56）.,五、受体阻滞剂在SIC运用中的效果评价,五、受体阻滞剂在SIC运用中的效果评价,在脓毒性小鼠侧脑室内注射美托洛尔，其心率和短期内心率变异性有意义*,P,0.05，但对于MAP下降50%，存活率、TNF、IL-6无统计学意义。,五、受体阻滞剂在SIC运用中的效果评价,大鼠试验；,静脉注射LPS用或不用兰地洛尔,，监测大鼠血清炎性介质和肺HMGB-1(High-