Shock: ischemia, reperfusion, and inflammation.
The pathophysiology of shock after trauma and hemorrhage has traditionally been viewed as a result of ischemic cellular damage. However, it is now clear that ischemia alone does not result in all cellular damage after shock. Rather, much of the cellular injury follows reperfusion and subsequent inflammation. Sublethal ischemia alters (primes) cells. This priming is mediated by second messengers, such as intracellular calcium, cyclic adenosine monophosphate, phosphatidic acids, and reactive oxygen species (ROS). Cells so primed by ischemia are both more susceptible to injury by subsequent reperfusion and inflammation, and may be primed to participate as effectors in the subsequent inflammatory response. Reperfusion of ischemic cells results in an oxygen radical burst. The resulting ROS are both directly cytotoxic and activate transcription factors for new protein synthesis. This activation of transcription factors results in activation of leukocytes, macrophages, and endothelial cells, initiating an inflammatory state which may result in organ failure and death. Monitoring to detect evidence of reperfusion and inflammation will be of value as new therapeutic approaches are developed. Antioxidant therapy has the potential to limit cellular and organ damage from reperfusion and inflammation after shock.
Waxman
K
K
Department of Surgical Education, Santa Barbara Cottage Hospital, CA 93102, USA.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015687:Cell Hypoxia; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000503:physiopathology; D007962:Leukocytes / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D015290:Second Messenger Systems / Q000502:physiology; D012769:Shock / Q000150:complications / Q000503:physiopathology* / Q000628:therapy
D000975:Antioxidants; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate