title: Age-related responses of the microcirculation to ischemia-reperfusion and inflammation.
abstract: Aging is a major risk factor for a variety of ischemic disorders including ischemic heart disease and stroke. Intense research over the past decade into ischemia-reperfusion (I/R) injury has implicated a general mechanism whereby reactive oxygen species produced at the onset of reperfusion overwhelm endogenous antioxidants, resulting in a cascade of events including mast cell degranulation, recruitment of neutrophils to the endothelial wall, arteriolar constriction that limits tissue perfusion, and increased vascular permeability that leads to inflammation and edema. Much of our knowledge regarding I/R injury comes from animal models; however, despite the fact that I/R disproportionately affects older individuals, young animals are usually chosen in models of I/R injury due to their greater availability, lower cost, and fewer health problems. Results obtained from young animals demonstrate a central role for both neutrophils and mast cells in I/R-induced increases in microvascular permeability and arteriolar constriction; however, it is not clear that a role for neutrophils is extended to older animals. A growing body of evidence indicates that neutrophils isolated from elderly individuals exhibit attenuated chemotaxis, oxidant release, and phagocytosis, and it has been suggested that these deficiencies are related to an age-associated increase in glucocorticoid production and oxidative stress. Therefore, neutrophils may have a limited capacity to influence microcirculatory tissue in the elderly compared to in the young. In support of this hypothesis, I/R-induced increases in microvascular permeability and decreases in vascular perfusion have been found to occur in older rats despite the absence of a significant increase in leukocyte-endothelial cell adhesion. Furthermore, elimination of circulating neutrophils attenuates I/R-induced mesenteric permeability only in young rats. Therefore, it appears that neutrophil-independent mechanisms of inflammation may be responsible for much of the microvascular dysfunction initiated by I/R in older animals.
authors.affiliation: Department of Bioengineering, Pennsylvania State University, 205 Hallowell Building, 16802-6804, University Park, PA, USA
authors.forename: N R.
authors.initials: NR
authors.lastname: Harris
authors.forename: R E.
authors.initials: RE
authors.lastname: Rumbaut