The influence of arachidonic acid metabolites on leukocyte activation and skeletal muscle injury after ischemia and reperfusion.
Derivatives of arachidonic acid have been found to play a role in the reperfusion injury of various tissues. These compounds have a broad spectrum of activity, including modulation of white blood cell response to injured tissue. This study was designed to determine the effect of thromboxane and lipoxygenase derivatives on the local and systemic response to ischemia and reperfusion of skeletal muscle. Fifteen dogs were separated into three groups and subjected to gracilis muscle ischemia followed by 2 hours of reperfusion. One group served as controls, one group was treated with OKY-046 (a thromboxane synthetase inhibitor), and one group was treated with diethylcarbamazine (a lipoxygenase inhibitor). White blood cell activation as measured by superoxide anion production, and eicosanoid levels were measured both in the gracilis venous effluent and central venous circulation. These results were compared to infarct size in the gracilis muscle. OKY-046 significantly reduced thromboxane production in both the central venous (102 +/- 30 to 31 +/- 9 pg/ml, p less than 0.05) and gracilis samples (107 +/- 22 to 25 +/- 6 pg/ml, p less than 0.005). This was accompanied by a reduced white cell activation in the central venous blood (15 +/- 1 to 10 +/- 1 nmol O2-, p less than 0.05), but did not affect infarct size or white cell activation in the gracilis. Conversely, diethylcarbamazine significantly reduced both white cell activation (16 +/- 1 to 10 +/- 1 nmol O2-, p less than 0.005) and infarct size in the gracilis muscles (61.6% +/- 4.5% to 28.5% +/- 8.6%, p less than 0.01), as well as reduced systemic white blood cell activation.(ABSTRACT TRUNCATED AT 250 WORDS)
Cambria
R A
RA
Section of Vascular Surgery, University of Medicine and Dentistry of New Jersey, Newark 07103.
Anderson
R J
RJ
Dikdan
G
G
Lysz
T W
TW
Hobson
R W
RW
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004049:Diethylcarbamazine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D007511:Ischemia / Q000473:pathology* / Q000503:physiopathology; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009132:Muscles / Q000098:blood supply* / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015427:Reperfusion Injury / Q000473:pathology* / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors / Q000494:pharmacology
D001095:Arachidonic Acids; D008689:Methacrylates; D013481:Superoxides; D007975:Leukotriene B4; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013930:Thromboxane-A Synthase; C034364:ozagrel; D004049:Diethylcarbamazine