Stunning: a radical re-view.
The recovery from trauma, whether ischemia or some other form of tissue injury, is never instantaneous; time is always required for repair and the return of normal metabolism and function. To what extent the delay in recovery of contractile activity (stunning) after a brief period of ischemia represents convalescence from ischemia-induced injury, as opposed to the expression of reperfusion-induced injury, is perhaps not as clear as the proponents of stunning would hope. Definitive evidence for a distinct reperfusion-induced pathology, which compromises the recovery of contractile function from the depressed state induced by ischemia, is elusive. If reperfusion-induced injury accounts for a significant proportion of stunning, then the molecular mechanisms responsible for initiating the event and those responsible for orchestrating the event at the level of the contractile protein are far from clear. Perturbations of calcium homeostasis are frequently cited as responsible for the depressed contractile state, however, some metabolic derangement must precede any pathologically induced ionic disturbance. In this connection, evidence indicates that free-radical-induced oxidant stress, during the early moments of reperfusion, may modify the activity of a number of thiol-regulated proteins that are directly, or indirectly, responsible for controlling the movement of calcium. Sarcolemmal sodium-calcium exchange and the calcium release channel of the sarcoplasmic reticulum may be activated, whereas the sarcolemmal calcium pump and sodium-potassium ATPase, together with the calcium pump of the sarcoplasmic reticulum, may be inhibited. Under the conditions prevailing during ischemia and reperfusion, this would be expected to promote an early intracellular calcium overload. It is difficult to reconcile such a change with the decreased inotropic state that characterizes stunning; however, it seems likely that the calcium overload is transient and that the stunned myocardium rapidly reestablishes normal levels of intracellular calcium. It is still difficult to explain adequately the reduced inotropic state; clearly, the mechanism of stunning is not quite as simple as its definition.
Hearse
D J
DJ
Cardiovascular Research, Rayne Institute, St Thomas' Hospital, London, UK.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*
D005609:Free Radicals; D002118:Calcium