INDIVIDUAL RESEARCHERDonald R. Bell , Ph.D.
Education1976 - Ph.D. from University of Maryland, Dept. of Physiology
Acute ischemia followed by reperfusion is associated with edema formation in skeletal muscle of the extremities. If severe, the edema can lead to compressive decreases in tissue perfusion and loss of the limb. Investigations in this laboratory are directed towards studying the neutrophil mediated inflammatory response which appears to be the initial cause of edema formation. Recent studies on anesthetized rabbits following tourniquet ischemia indicate that a decrease in the amount and the size of hyaluronan may cause chronic edema formation following the acute changes in microvascular protein permeability. Hyaluronan is the major polysaccharide in the extracellular matrix of most tissues and provides hydrated areas through which cells, proteins and other molecules can move. Oxygen radicals released during an inflammatory response can easily cause hyaluronan depolymerization and disruption of the extracellular matrix. The time dependent changes in hyaluronan depolymerization and synthesis are studied in vivo following ischemia-reperfusion to test the hypothesis that ischemia disrupts synthesis while activated neutrophils cause depolymerization, leading to chronic edema. Oxygen radical scavengers and iron chelators are used to inhibit hyaluronan depolymerization. Additional studies are focused on identifying the cytokines that control hyaluronan synthesis and cellular uptake by cultured endothelial cells or fibroblasts.
- Armstrong SE, Bell DR: Ischemia-reperfusion does not cause significant hyaluronan depolymerization in skeletal muscle. Microvasc Res (in press), 2002.
- Armstrong SE, Bell DR: Measurement of high molecular weight hyaluronan in solid tissue using agarose gel electrophoresis. Anal Biochem (in press), 2002.
- Kupinski A M, Bock DE, Bell DR: Skeletal muscle ischemia-reperfusion causes transitory increase in microvascular protein permeability. Am. J. Physiol. 273:303-H309, 1997.
- Kreienberg PB, Vincent PA, Bell DR, Saba TM, Minnear FL: Isoproterenol decreases protein permeability in edematous, isolated rabbit lungs: estimation of PS and sigma. J. Appl. Physiol. 77:325-331, 1994.
- Kupinski AM, Shah DM, Bell DR: Transvascular albumin flux in the rabbit hindlimb following tourniquet ischemia. Am. J. Physiol. 264:H901-H908, 1993.