Circulation, Vol 80, 1049-1062, Copyright © 1989 by American Heart Association
LH Opie
Reperfusion injury includes a spectrum of events, such as reperfusion
arrhythmias, vascular damage and no-reflow, and myocardial functional
stunning. The concept of reperfusion injury remains controversial with many
proposed mechanisms when applied to humans, whereas in animal models, there
are two main proposed mechanisms: calcium over-load and formation of oxygen
free radicals. To prove that reperfusion injury is specifically caused by
reperfusion would require evidence that an intervention given at the time
of reperfusion can diminish or abolish the injury as in the case of
arrhythmias, which are thought to be mediated by excess recycling of
cytosolic calcium with delayed afterdepolarizations and ventricular
automaticity. In the case of myocardial stunning, the phenomenon may be
mediated, at least in part, by a burst of free radicals formed within the
first minute of reperfusion and improved by free radical scavengers given
at the time of reperfusion. The alternate hypothesis is that cytosolic
calcium overload damages mechanisms for normal intracellular calcium
regulation so that the stunned myocardium responds to agents that are
thought to increase intracellular cytosolic calcium, such as beta-receptor
agonists. A further component of reperfusion injury, under active
investigation, is microvascular damage with alterations at the level of
platelets, leukocytes, and endothelial integrity. From the therapeutic
point of view, the divergent results of experimental interventions and the
possibility that the abrupt onset of reperfusion in animals differs from
the situation in humans with thrombolysis means that the best way currently
available to limit reperfusion injury is by minimizing the ischemic period
by early reperfusion and by optimizing the metabolic status of the ischemic
myocardium at the end of the ischemic period.
ARTICLES
Reperfusion injury and its pharmacologic modification
Heart Research Unit, University of Cape Town, Medical School, South Africa.
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