Neutrophil-mediated microvascular dysfunction in postischemic canine skeletal muscle. Role of granulocyte adherence.
Recent studies implicate a role for granulocytes in the genesis of the microvascular and parenchymal cell dysfunction, which occurs upon reperfusion of ischemic tissues. Although the molecular mechanisms underlying this neutrophil-mediated injury are not completely understood, it is clear that an essential first step in granulocyte migration from the vascular lumen to the interstitial space is adherence to vascular endothelium. The purpose of this study was to determine whether prevention of neutrophil adherence with monoclonal antibody IB4 directed against the neutrophil CD11/CD18 glycoprotein adherence complex or neutrophil depletion with a specific polyclonal antineutrophil serum would attenuate the microvascular dysfunction seen in postischemic skeletal muscle. Changes in vascular permeability were assessed by measurement of the solvent drag reflection coefficient for total plasma proteins (sigma) in isolated canine gracilis muscle subjected to ischemia/reperfusion, ischemia/reperfusion plus antineutrophil serum, or ischemia/reperfusion plus IB4. Estimates of sigma averaged 0.83 +/- 0.04 in nonischemic, control gracilis muscles, while ischemia/reperfusion was associated with a marked increase in vascular permeability (decrease in sigma to 0.54 +/- 0.04) and vascular resistance (increased by 135 +/- 41% over the control value). Prevention of neutrophil adherence or neutrophil depletion prevented this increase in vascular permeability (sigma = 0.80 +/- 0.03 and 1.01 +/- 0.06, respectively) and resistance (decrease of 16.51 +/- 8.0% and increase of 2.4 +/- 4.6% over control values, respectively). The results of this study suggest that neutrophils play a critical role in the genesis of microvascular dysfunction in postischemic skeletal muscle. Furthermore, neutrophil adherence to vascular endothelium appears to be a prerequisite for the production of this injury.
Carden
D L
DL
Department of Physiology and Biophysics, Louisiana State University Medical Center, School of Medicine, Shreveport 71130.
Smith
J K
JK
Korthuis
R J
RJ
D000818:Animals; D001808:Blood Vessels / Q000503:physiopathology; D002199:Capillary Permeability; D002448:Cell Adhesion; D004285:Dogs; D005260:Female; D006098:Granulocytes / Q000502:physiology*; D007511:Ischemia / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation; D009132:Muscles / Q000098:blood supply* / Q000201:enzymology; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D015424:Reperfusion; D014655:Vascular Resistance
D009195:Peroxidase