Mechanisms of postischemic contractile dysfunction

Prolonged reversible postischemic contractile dysfunction that follows sing le or multiple brief periods of regional or global ischemia has been termed "stunned myocardium," and is thought to be the result of a decreased respo nsiveness of the cardiac myofilaments to calcium. A number of hypotheses ha ve been proposed to explain the pathogenesis of stunned myocardium; however , the two major theories that are supported by the most experimental eviden ce suggest that the generation of oxygen-derived free radicals and a distur bance in calcium homeostasis are responsible for the postischemic contracti le dysfunction observed. These mechanisms are not mutually exclusive, and d ata are available that support both theories. Evidence exists that indicate s that one may pharmacologically enhance the recovery of stunned myocardium by use of oxygen radical scavengers, adenosine agonists, calcium channel b lockers, and openers of the ATP-sensitive potassium channel, including the volatile anesthetic isoflurane. Ischemic preconditioning (IPC) has also bee n shown to produce delayed protection against myocardial stunning, and a no vel pharmacological agent, monophosphoryl lipid A, has been shown to mimic the effect of IPC. Because stunning appears to occur in a number of clinica l settings, it is important to understand the mechanisms involved and to de velop pharmacological therapy that will result in an improved clinical outc ome. (C) 1999 by The Society of Thoracic Surgeons.