Serial changes of the plasma prostanoids during myocardial ischemia-reperfusion in swine. Effects of magnesium, diltiazem, and a novel Mac-1 inhibitor.
The key role of prostanoids has been recognized in patients with ischemic heart disease. However, serial changes of thromboxane and prostacyclin during both brief and prolonged ischemia-reperfusion are poorly known. These plasma prostanoids were measured during myocardial stunning (MS) and acute myocardial infarction (AMI). The effects of magnesium (Mg), diltiazem, and a Mac-1 inhibitor on the level of the stable metabolites of thromboxane (TXB2) and prostacyclin (6-keto-PGF1 alpha) were elucidated. Forty-nine swine underwent brief (8 min) or prolonged (50 min) coronary artery occlusion followed by reperfusion. The occlusion phase was associated with a decline of plasma prostanoids, followed by a significant increase during reperfusion. Mg and diltiazem similarly affected plasma prostanoids by reducing TXB2 release at 1 h of reperfusion. There was, however, no effect on plasma 6-keto-PGF1 alpha. The Mac-1 inhibition was associated with stabilization of both antagonistic prostanoids as well. Ability of Mg, diltiazem, and leumedins to favorably modulate plasma prostanoid levels have direct clinical implications for the use of these agents in patients with coronary artery disease.
Serebruany
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Heart Associates Research & Education Foundation, Union Memorial Hospital, Baltimore, MD 21218, USA. Heartdrug@aol.com
Herzog
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Gurbel
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D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000097:blood / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000097:blood; D017202:Myocardial Ischemia / Q000097:blood*; D015428:Myocardial Reperfusion Injury / Q000097:blood*; D017682:Myocardial Stunning / Q000097:blood; D011453:Prostaglandins / Q000097:blood*; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016177:Macrophage-1 Antigen; D011453:Prostaglandins; C071244:N-(9H-(2,7-dimethylfluoren-9-ylmethoxy)carbonyl)leucine; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D004110:Diltiazem; D007930:Leucine; D008274:Magnesium