Attenuation of neutrophil function by inhibitors of arachidonate metabolism reduces the extent of canine myocardial infarction.
To assess the role of neutrophils and arachidonate metabolites in evolving myocardial infarction, the effect of inhibitors of arachidonate metabolism on the extent of myocardial damage and neutrophil function was examined in a 90-minute occlusion/5-hour reperfusion model of canine myocardial infarction. A thromboxane A2 synthetase inhibitor, CV-4151, and a lipoxygenase inhibitor, AA-861, greatly reduced the infarct size. They also attenuated the production of chemoattractant leukotriene B4 and chemotactic activity of neutrophils isolated from peripheral circulation. Under these conditions, both the increases in peripheral leukocyte count and neutrophil infiltration in ischemic myocardium were inhibited. These results indicate that the inhibition of 2 pathways of arachidonate metabolism may decrease infiltration of activated neutrophils in ischemic myocardium by attenuating chemotactic function of neutrophils, resulting in reduction of the extent of myocardial infarction.
Hoshida
S
S
First Department of Medicine, Osaka University School of Medicine, Japan.
Kuzuya
T
T
Nishida
M
M
Kim
Y
Y
Kitabatake
A
A
Kamada
T
T
Tada
M
M
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D016227:Benzoquinones; D003097:Collateral Circulation / Q000187:drug effects; D004285:Dogs; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D016859:Lipoxygenase Inhibitors; D009203:Myocardial Infarction / Q000503:physiopathology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology*; D011809:Quinones / Q000494:pharmacology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D001095:Arachidonic Acids; D016227:Benzoquinones; D005229:Fatty Acids, Monounsaturated; D016859:Lipoxygenase Inhibitors; D011725:Pyridines; D011809:Quinones; D016718:Arachidonic Acid; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D013930:Thromboxane-A Synthase; C045446:isbogrel