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Intravital Microscopy Demonstrates Hypoxia and Iron Chelation Share Microvascular Responses but not Generation of Free Radicals FREE TO VIEW

Sonja D. Bartolome, MD*; Amy R. O’Brien-Ladner, MD; A. J. Casillan; John G. Wood, PhD
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University of Kansas School of Medicine, Kansas City, KS


Chest. 2004;126(4_MeetingAbstracts):876S. doi:10.1378/chest.126.4_MeetingAbstracts.876S
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PURPOSE:  The program of genes induced by hypoxia appears, at least in part, to be shared by that induced by Deferoxamine (DFA), a chelator of iron. A number of these genes are integral to the regulation of the microvasculature and may have a protective role against continued hypoxia-related injury. In order to develop therapeutic targets for these advantageous effects, we sought to identify which physiologic responses are shared at the microvascular level.

METHODS:  To characterize the microvascular response to DFA exposure, 4 rat groups were utilized: saline control, DFA (7.1mg/hr/kg 6h), DFA/á-lipoic acid (an antioxidant), and hypoxia (10% FiO2 4h). Measurements of leukocyte adherence (# per 100mm venule), capillary leak by fluorescein isothiacyanate-labeled albumin (Fi/Fo), and generation of ROS (reactive oxygen species) by DHR fluorescence (an oxidant-sensitive probe [% control]), were performed during intravital microscopy of the rat mesenteric venular bed.

RESULTS:  Results: (+- SEM).

CONCLUSION:  DFA infusion and hypoxia regulate capillary leak and white blood cell adherence at similar levels. However, in contrast to hypoxia, the generation of ROS was not detectable above normoxia in the DFA groups. In addition, the microvascular responses in the DFA group were not inhibited by an antioxidant (á-lipoic acid). In conclusion, although DFA and hypoxia appear to regulate microvascular responses similarly, our experiments do not elucidate ROS-related mechanisms in common. Additional experiments are underway to fully characterize the unique aspects of iron chelation-related signaling.

CLINICAL IMPLICATIONS:  This may have particular importance in developing protective strategies during hypoxia. ROSCapillary LeakWBC AdherenceNormoxia100.14 +- .040.4 +- 0.1Hypoxia182 +- 16.82 +- .1414.5 +- 1.2DFA107 +- 3.1.71 +- .1012.7 +- 2.0DFA + alpha-lipoic acid106 +- 6.2.91 +- .078.7 +- 2.2

DISCLOSURE:  S.D. Bartolome, None.

Wednesday, October 27, 2004

12:30 PM- 2:00 PM




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