Mechanisms of postischemic contractile dysfunction.
Prolonged reversible postischemic contractile dysfunction that follows single or multiple brief periods of regional or global ischemia has been termed "stunned myocardium," and is thought to be the result of a decreased responsiveness of the cardiac myofilaments to calcium. A number of hypotheses have been proposed to explain the pathogenesis of stunned myocardium; however, the two major theories that are supported by the most experimental evidence suggest that the generation of oxygen-derived free radicals and a disturbance in calcium homeostasis are responsible for the postischemic contractile dysfunction observed. These mechanisms are not mutually exclusive, and data are available that support both theories. Evidence exists that indicates that one may pharmacologically enhance the recovery of stunned myocardium by use of oxygen radical scavengers, adenosine agonists, calcium channel blockers, and openers of the ATP-sensitive potassium channel, including the volatile anesthetic isoflurane. Ischemic preconditioning (IPC) has also been shown to produce delayed protection against myocardial stunning, and a novel pharmacological agent, monophosphoryl lipid A, has been shown to mimic the effect of IPC. Because stunning appears to occur in a number of clinical settings, it is important to understand the mechanisms involved and to develop pharmacological therapy that will result in an improved clinical outcome.
Gross
G J
GJ
Department of Pharmacology, Medical College of Wisconsin, Milwaukee 53226, USA. ggross@post.its.mcw.edu
Kersten
J R
JR
Warltier
D C
DC
D000818:Animals; D002118:Calcium / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial; D009200:Myocardial Contraction / Q000502:physiology*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D017682:Myocardial Stunning / Q000503:physiopathology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D007473:Ion Channels; D017382:Reactive Oxygen Species; D002118:Calcium