缺血再灌注损伤ischemia-reperfusioninjury.ppt

Ischemia-Reperfusion injury Ischemia ? Anesthesiologist: MI, peripheral vascular insufficiency, stroke, and hypovolemic shock ? Restoration of blood flow to an ischemic organ is essential to prevent irreversible cellular injury ? Reperfusion may augment tissue injury Ischemia-Reperfusion ? Thrombolytic therapy, organ transplantation, coronary angioplasty, aortic cross-clamping, or cardiopulmonary bypass ? Severe: systemic inflammatory response syndrome (SISS) or multiple organ dysfunction syndrome (MODS) ? Account for 30 – 40% of the mortality in tertiary referral ICU Cellular change during Ischemia ? Altered membrane potential ? Altered ion distribution (++ intracellular Ca/Na) ? Cellular swelling ? Cytoskeletal disorgnization ? Increased hypoxanthine ? Decreased ATP ? Decreased phosphocreatinine ? Cellular acidosis Cellular Effects of Ischemia ? Decreased ATP ? Intracellular accumulation of hypoxanthine ? Toxic reactive oxygen species (ROS) during reperfusion Ischemia at Endothelium ? Express certain proinflammatory gene products(leukocyte adhesion molecules, cytokines) bioactive agents (endothelin, thromboxane A 2 ) ? Repressing other “ protective ” gene products (constitutive nitric oxide synthase, thrombomodulin) and bioactive agents ( prostacyclin, nitric oxide). Role of Reactive Oxygen Species ? Including (O 2 – ), (OH – ), (HOCl), (H 2 O 2 ), and nitric oxide – derived peroxynitrite ? Directly damage cellular membranes by lipid peroxidation. ? Stimulate leukocyte activation and chemotaxis by activating plasma membrane phospholipase A 2 to form arachidonic acid (thromboxane A 2 and leukotriene B 4 ) ? Increase leukocyte activation, chemotaxis, and leukocyte – endothelial adherence after I-R Role of Complement ? I/R results in complement activation and the formation of several proinflammatory mediators that alter vascular homeostasis ? C3a, C5a, iC3b, C5b9 ? Most potent is C5a ? complement m