Proclivity of activated neutrophils to cause postischemic cardiac dysfunction: participation in stunning?
Myocardial stunning is a reversible defect in contractile function provoked by brief episodes of ischemia followed by reperfusion. Many studies have demonstrated the potential involvement of free radicals in the etiology of myocardial stunning. While activated neutrophils have the capacity to release free radicals and evoke contractile dysfunction, it is not clear that this potential is realized in the absence of myocellular damage. Attempts to define the contribution of activated neutrophils to myocardial stunning by removing the cells from the bloodstream are contradictory, and the apparent simplicity of this seemingly logical approach is an illusion. For example, it is not known how many neutrophils are required to induce contractile failure, the site of action within the heart, the mechanisms that may be responsible, or even the time course or process of neutrophil activation. The production of free radicals and endothelial dysfunction may create conditions propitious for neutrophil recruitment. However, because activated neutrophils synthesize and release various mediators that are potentially toxic to myocardium, once the stage is reached for leukocyte accumulation, it may herald the progression from reversible to irreversible cardiac injury.
Mullane
K
K
Gensia Pharmaceuticals, Inc., San Diego, CA 92121.
Engler
R
R
D000818:Animals; D003327:Coronary Disease / Q000209:etiology* / Q000503:physiopathology; D008833:Microcirculation; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009504:Neutrophils; D014655:Vascular Resistance