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1、Ischemia-reperfusion Injury (缺血再灌注损伤）,,Xiao Qian Chen (陈晓钎), Ph.D.,Department of Pathophysiology Tongji Medical College Huazhong University of Science and Technology,Case Presentation,A 50-year-old man was admitted to the hospital with severe chest pain of 5 hours duration. Mental confusion and in a
2、cute dyspnea （呼吸困难）.,HR: 110 beats/min, sinus rhythm; BP: 75/50 mmHg; ECG: ST segment elevation, V1-V6 LVEF: 31% X-ray: gross pulmonary edema,Improvement in breath BP: 100/70 mmHg LVEF: 38% Temporary ventricular tachycardia （心律不齐）,diuretic, tissue plasminogen activator,Balloon angioplasty,Question:
3、why tachycardia occurred after operation?,Ischemic Injury is enhanced during reperfusion,Reperfusion Injury,Oxygen paradox, calcium paradox, pH paradox,Ischemia Components,0 hr,Reperfusion,Ischemic Injury of Neurons,1 hr,2 hr,Ischemia,Time,Injury,Death,Injury Windows,Reperfusion,Reperfusion injury,R
4、ecover,Early reperfusion,Delayed reperfusion,Persistent perfusion deficit, 6 hr,24 hr,Causes and Conditions of Reperfusion Injury,Causes,Conditions,Recover from cardiac arrest Organ transplantation Lysing thrombi,Ischemia time Branch circulation Oxygen consumption Temperature, Na+, pH, Ca2+,Mechanis
5、ms of Reperfusion Injury,Free radicals Ca2+i Others,Free radical Any atom or molecule possessing unpaired electrons,Superoxide anion (O2.-) Hydroxyl radical (OH.) Nitric oxide (NO.) Peroxynitrite （ONOO- )( 过氧亚硝酸盐） Lipid peroxide radical (LOO.),Oxygen free radicals,Reactive oxygen species (ROS),Oxyge
6、n free radicals Hydrogen peroxide Others,1. Mitochondria,2. Activated inflammatory cells,3. Nitric oxide,4. Ionizing radiation,Formation of ROS,Reperfusion, Ca2+i,ROS,Mechanism 1, Xanthine oxidese,Reperfusion,Ischemia,ATP,Ca2+i,Xanthine dehydrogenase,Hypoxanthine,xanthine,O2,Uric acid, AMP,O2,O2.- H
7、2O2,Endothelial cell,Mechanism 2,Ischemia,Reperfusion,O2,Pro-inflammatory mediators (e.g. cytokines),NO,ONOO-,O2.-,(Respiration burst),Mechanism 3,Biochemical Impacts of ROS,Calcium Overload,The abnormal increase of intracellular calcium which causes cell injury,Mechanism 1,Reperfusion,Ischemia, ATP
8、 Membrane depolarization,Ca2+,Na+,Na/Ca exchanger, Ca2+,Na+,Reperfusion,H+,H+, Na+,Ischemia,Ca2+,Na+,Mechanism 2,H+,Na/H exchanger,Reperfusion,Ca2+,Na+,H+,Na+,a1,NA,PLC,PI,DG,PKC,IP3,SR,Ca2+,Mechanism 3,Mechanism 4,Reperfusion,Mitochondria,ER SR,Ca2+,Na+i Gene activation Neutrophil activation,Others
9、,Neutrophil activation,ROS,Inflammatory mediators,Injury of Micro-vessels,No-reflow phenomenon,Cell injury,Role of Neutrophil,Reperfusion,Structural and Functional Changes,Reperfusion arrhythmia Myocardial stunning Edema,Heart:,Brain:,Cell death,Electrocardiographic Alterations Associated with the T
10、hree Zones of Myocardial Infarction,Heart Injury,Ischemia-reperfusion injury,Calcium overload Free radical,Destroy of contractile protein,Myocardial dysfunction,Ca+ K+ Na+,Arrhythmia,Cell death,Brain Injury,Principles of Prevention and Treatment,Control of reperfusion conditions Removal of free radi
11、cals Use of calcium antagonists Use of cell protection reagents Treatment of edema,O2.-,OH.,SOD,GSH,ONOO-,LOO.,TOH,LOOH,H2O,Removal of ROS,Case Presentation,A 50-year-old man was admitted to the hospital with severe chest pain of 5 hours duration. Mental confusion and in acute dyspnea.,HR: 110 beats
12、/min, sinus rhythm; BP: 75/50 mmHg; ECG: ST segment elevation, V1-V6 LVEF: 31% X-ray: gross pulmonary edema,Improvement in breath BP: 100/70 mmHg LVEF: 38% Temporary ventricular tachycardia,diuretic, tissue plasminogen activator,Balloon angioplasty,Question: why tachycardia occurred after operation?
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