Leukocyte adhesion, edema, and development of postischemic capillary no-reflow.
The aim of this study was to determine whether the formation of edema that occurs secondary to the neutrophil-dependent increase in microvascular permeability contributes to the genesis of no-reflow in postischemic skeletal muscle. To address this issue, four experimental approaches were used. In the first group, capillary perfusion was assessed in nonischemic canine gracilis muscles in which interstitial fluid volume was increased to a level similar to that in postischemic muscle. In the second and third groups, edema formation was prevented in postischemic skeletal muscles by administration of phalloidin or a hypertonic hyperosmotic saline-dextran solution (HSD; 7.5% saline-6% Dextran 70), and the extent of capillary no-reflow was assessed. In the final group of experiments, a monoclonal antibody (MAb) that binds to the common beta-subunit of the leukocyte integrin CD11/CD18 (MAb IB4) was administered after the development of postischemic edema, and capillary perfusion was determined. Formation of edema in nonischemic preparations and ischemia-reperfusion (I-R) were associated with marked reduction in the number of patent capillaries per fiber (1.2 +/- 0.1 and 0.4 +/- 0.1, respectively) compared with nonedematous nonischemic controls (2.5 +/- 0.3). Treatment with phalloidin or HSD prevented edema formation and attenuated the reduction in the number of patent capillaries per fiber (1.62 +/- 0.2 and 1.71 +/- 0.2, respectively) induced by I-R, whereas administration of MAb IB4 after the formation of edema in reperfused muscles failed to limit capillary no-reflow (0.5 +/- 0.1 patent capillaries/fiber).(ABSTRACT TRUNCATED AT 250 WORDS)
Jerome
S N
SN
Department of Physiology, Louisiana State University Medical Center, School of Medicine in Shreveport 71130-3932.
Akimitsu
T
T
Korthuis
R J
RJ
D000704:Analysis of Variance; D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D002448:Cell Adhesion; D004285:Dogs; D004487:Edema / Q000503:physiopathology* / Q000517:prevention & control; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D006982:Hypertonic Solutions; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D009132:Muscles / Q000098:blood supply* / Q000473:pathology; D009504:Neutrophils / Q000502:physiology*; D010590:Phalloidine / Q000494:pharmacology; D012016:Reference Values; D012039:Regional Blood Flow
D006982:Hypertonic Solutions; D010590:Phalloidine