E第十三章缺血再灌注损伤.ppt

Principles of Prevention and Treatment Control of reperfusion conditions Removal of free radicals Use of calcium antagonists Use of cell protection reagents Treatment of edema * Ischemia-reperfusion Injury (缺血再灌注损伤） chenxq@mails.tjmu.edu.cn 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 acute 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: 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 Recover 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+ Mechanisms 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）ˉ Lipid peroxide radical (LOO.)ˉ Oxygen free radicals Reactive oxygen species (ROS) Oxygen 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 Xanthin