title: Spatial and temporal correlation between leukocyte behavior and cell injury in postischemic rat skeletal muscle microcirculation.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla.
authors.forename: M
authors.initials: M
authors.lastname: Suematsu
authors.forename: F A
authors.initials: FA
authors.lastname: DeLano
authors.forename: D
authors.initials: D
authors.lastname: Poole
authors.forename: R L
authors.initials: RL
authors.lastname: Engler
authors.forename: M
authors.initials: M
authors.lastname: Miyasaka
authors.forename: B W
authors.initials: BW
authors.lastname: Zweifach
authors.forename: G W
authors.initials: GW
authors.lastname: Schmid-Schönbein
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure; D018821:CD18 Antigens; D002196:Capillaries / Q000473:pathology / Q000503:physiopathology; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000473:pathology / Q000503:physiopathology*; D008856:Microscopy, Fluorescence; D009132:Muscles / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology; D014699:Venules / Q000473:pathology / Q000503:physiopathology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D014227:Triazines; C072977:BOF 4272; D014969:Xanthine Oxidase