Platelet-activating factor (PAF) receptor antagonism by WEB 2170 improves the survival of ischaemic skeletal muscle.
The platelet-activating factor (PAF) receptor antagonist, WEB 2170, significantly improved the survival of ischaemic rabbit skeletal muscle from 42% in saline-infused muscle to 65% in WEB 2170-infused muscle at 24 hours post reperfusion. Evidence is presented which suggests that WEB 2170 inhibits neutrophil infiltration during reperfusion. In addition, tissue lipid peroxide levels and the release into blood of the enzyme creatine kinase were inhibited by local infusion of WEB 2170. In contrast, the level of oedema in muscles receiving an infusion of WEB 2170 was not different from that in saline controls. It is concluded that infusion of a PAF antagonist into ischaemic skeletal muscle at the time of reperfusion inhibits neutrophil recruitment and activation. These results provide an impetus for PAF receptor antagonism as a means of reducing reperfusion injury in limb replantation surgery.
Lepore
D A
DA
Bernard O'Brien Institute of Microsurgery, St Vincent's Hospital, Fitzroy Vic, Australia.
Knight
K R
KR
Stewart
A G
AG
Riccio
M
M
Morrison
W A
WA
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D003402:Creatine Kinase / Q000037:antagonists & inhibitors; D007511:Ischemia / Q000503:physiopathology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D011817:Rabbits; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control; D012092:Replantation; D014021:Tissue Preservation; D014022:Tissue Survival / Q000187:drug effects* / Q000502:physiology; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C063964:bepafant; D003402:Creatine Kinase