Rat liver blood flow after ischemia and reperfusion. The effects of the platelet-activating factor antagonist WEB-2170 and of removing circulating leukocytes.
The inflammatory response to trauma induces release of platelet activating factor (PAF), which promotes leukocyte adherence to the vascular endothelium. Ischemia and reperfusion induces inflammatory reactions that play a role in reperfusion injury, and here we investigate the role of both PAF and of leukocytes in damage to reperfused rat liver. The experimental procedure consisted of the temporary interruption of blood flow to the left lateral and medial lobes of the rat liver in vivo, and subsequent reperfusion after defined periods. Rats were pretreated either with the PAF-antagonist WEB-2170 or with vinblastine to induce leukopenia, and compared with controls. The postischemic liver blood flow and liver oxyhemoglobin saturation were recorded using an He-Ne Laser doppler flowmeter and photometer. Reperfusion after 30 and 45 min of ischemia was associated with partial recovery to normal values and was inversely proportional to the duration of ischemia. In the WEB-2170-treated group, liver flow and hemoglobin saturation upon reperfusion did not show significant differences when compared with the untreated control groups, suggesting that inhibition of PAF activity did not protect against the microcirculatory disturbance induced by ischemia and reperfusion in the liver. In contrast, rats made leukopenic by treatment with vinblastine showed significantly better recovery of blood flow and hemoglobin saturation than the control group after 45 min of ischemia. Thus, we found that although PAF alone did not appear to have a pivotal role in the cascade of reperfusion injury, the effect of leukocytes is critical.
Chávez-Cartaya
R E
RE
University of Cambridge Clinical School, Addenbrooke's Hospital, United Kingdom.
Metcalfe
S
S
Ramirez-Romero
P
P
Calne
R
R
Jamieson
N V
NV
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply*; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010108:Oxyhemoglobins / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D014230:Triazoles / Q000494:pharmacology*; D014747:Vinblastine / Q000494:pharmacology
D001381:Azepines; D010108:Oxyhemoglobins; D010972:Platelet Activating Factor; D014230:Triazoles; D014747:Vinblastine; C063964:bepafant