Spatial and temporal correlation between leukocyte behavior and cell injury in postischemic rat skeletal muscle microcirculation

M. Suematsu, F. A. DeLano, D. Poole, R. L. Engler, M. Miyasaka, B. W. Zweifach, G. W. Schmid-Schonbein

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124 Citations (Scopus)

Abstract

BACKGROUND: Although leukocyte adhesion and capillary plugging are postulated to play a role in postischemic tissue injury, there is only limited evidence demonstrating the relationship between tissue leukocyte accumulation and cell injury in terms of their temporal sequence and spatial distribution. EXPERIMENTAL DESIGN: This study was designed to study in vivo neutrophil behavior and its correlation with cell injury in postischemic skeletal muscle microcirculation. The microcirculation of the rat spinotrapezius muscle was observed in vivo using dual-color digital microfluorography to simultaneously visualize leukocyte traffic and cell death (irreversible nuclear damage) on the basis of carboxyfluorescein diacetate succinimidyl ester and propidium iodide, respectively. A 1-hour period of hemorrhagic hypotension (40 mm Hg) followed by reperfusion was carried out to induce muscle injury. RESULTS: Hypotension was followed by an increase in leukocyte recruitment in two different ways: capillary obstruction and venular adhesion. Upon reperfusion, a majority of the leukocytes were initially dispersed from the muscle capillaries and venules, but then the number of leukocytes plugging capillaries and adherent to venules increased again in a time-dependent manner. The number of leukocytes obstructing capillaries was closely correlated with the postischemic systemic blood pressure. The cell injury became detectable initially at the end of the hypotensive period and then increased explosively after reperfusion before a significant leukocyte accumulation. Reperfusion-induced early nuclear injury was seen predominantly in reperfused capillaries without plugging leukocytes. A majority of the initially damaged nuclei were those of myocytes in the pericapillary space, but no nuclei of capillary endothelium was involved. Sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo [1,5-a]-1,3,5- triazine-4-olate monohydrate, a novel inhibitor of xanthine oxidase, significantly attenuated the early increase in muscle injury and subsequent venular leukocyte adhesion after reperfusion. CONCLUSIONS: These results suggest the involvement of an endothelium-dependent mechanism involving xanthine oxidase in postischemic irreversible myocyte injury. It is conceivable that leukocytes adherent to venules as well as those plugging capillaries play only minor roles in the initial mechanism of reperfusion injury.

Original languageEnglish
Pages (from-to)684-695
Number of pages12
JournalLaboratory Investigation
Volume70
Issue number5
Publication statusPublished - 1994 Jan 1
Externally publishedYes

Keywords

  • Capillary plugging
  • Endothelial cells
  • Glycolytic fiber
  • Ischemia-reperfusion
  • Leukocyte adhesion
  • Oxygen radicals
  • Xanthine oxidase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Suematsu, M., DeLano, F. A., Poole, D., Engler, R. L., Miyasaka, M., Zweifach, B. W., & Schmid-Schonbein, G. W. (1994). Spatial and temporal correlation between leukocyte behavior and cell injury in postischemic rat skeletal muscle microcirculation. Laboratory Investigation, 70(5), 684-695.