Effects of pulmonary ischemia-reperfusion on platelet adhesion in subpleural arterioles in rabbits.
Reperfusion of the ischemic lung is associated with increased pulmonary vascular resistance and reduced alveolar perfusion in conjunction with an inflammatory response. To determine the contribution of platelet-endothelial interactions, we examined effects of pulmonary ischemia-reperfusion (IR) on platelet adhesion and diameter of arterioles and investigated the hypothesis that this process is P-selectin mediated. In anesthetized rabbits with open-chest and ventilated lungs, we examined subpleural arterioles by fluorescence microscopy. Ischemia was caused by reversibly occluding the right pulmonary artery for 2 h. Fluorescently labeled platelets were injected into the right atrium and the right lung was observed after 0.5, 1.0, and 2.0 h of reperfusion. Platelets rolling and adherence along arterioles occurred with a decrease in diameter that was significant during IR, but not after 3- to 5-min occlusion (control). Systemic pretreatment with Fucoidan (a ligand to P- and L-selectin) inhibited platelet rolling, adherence, and the decrease in diameter. Pretreatment of only exogenously labeled platelets with monoclonal antibody (MoAb) to P-selectin prevented platelet rolling and adherence, but not the decrease in diameter. These results indicate that in the intact lung, pulmonary IR causes platelet rolling and adhesion along arteriolar walls, and suggest that this process, which is mediated by P-selectin, contributes to vasoconstriction and hypoperfusion. Thus, it appears that platelet-endothelial interactions may contribute to the development of pulmonary IR injury.
Roberts
Andrew M
AM
Department of Physiology & Biophysics, School of Medicine, University of Louisville, Louisville, KY 40292, USA. amrobe01@gwise.louisville.edu
Ovechkin
Alexander V
AV
Mowbray
John G
JG
Robinson
Tonya W
TW
Lominadze
David
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001160:Arterioles / Q000473:pathology*; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D001794:Blood Pressure; D002448:Cell Adhesion; D004730:Endothelium, Vascular; D006325:Heart Atria / Q000166:cytology; D008024:Ligands; D008168:Lung / Q000473:pathology*; D008297:Male; D008833:Microcirculation; D019007:P-Selectin / Q000378:metabolism; D010477:Perfusion; D010973:Platelet Adhesiveness; D011134:Polysaccharides / Q000494:pharmacology; D011817:Rabbits; D015424:Reperfusion; D015427:Reperfusion Injury; D019087:Selectins; D013997:Time Factors
D000911:Antibodies, Monoclonal; D008024:Ligands; D019007:P-Selectin; D011134:Polysaccharides; D019087:Selectins; C007789:fucoidan