Ischemia and reperfusion induced formation of eicosanoids in isolated rat hearts.
Isolated, ejecting rat hearts, perfused with Krebs-Henseleit buffer, were exposed to various periods of global ischemia. Arachidonic acid (AA) accumulated significantly in the ischemic heart when the duration of ischemia exceeded 45 min. During 30 min of reperfusion, tissue levels of AA raised steadily to values of 10.5, 17.7, and 63.1 nmol/g, after 30, 45, and 60 min of ischemia, respectively. During reperfusion, significant amounts of AA metabolite prostacyclin (determined as stable metabolite 6-ketoprostaglandin F1 alpha, by radioimmunoassay and high-performance liquid chromatography) were released after 30, 45, and 60 min of ischemia. Beside prostacyclin, only small amounts of thromboxane B2 could be found during reperfusion. In contrast to increasing amounts of AA in reperfused tissue, prostacyclin release was maximal during the first 5 min of reperfusion and declined rapidly thereafter. Relatively small proportions of the accumulated AA are converted into prostacyclin, i.e., less than 1%. When hearts were treated with mepacrine, AA accumulation was almost completely abolished during 60 min of ischemia. The cumulative release of prostacyclin was found to be reduced to 134 pmol/g during 30 min of subsequent reperfusion. A close, rectilinear correlation could be established between AA accumulation and cumulative prostacyclin release during reperfusion. It is likely, however, that the site of bulk AA accumulation and that of conversion of AA into eicosanoids does not coincide in the ischemic and reperfused heart because of the low conversion rates of AA into prostacyclin and the different time courses of AA accumulation and prostacyclin production after reinstallation of flow.
Engels
W
W
Department of Physiology, University of Limburg, Maastricht, The Netherlands.
Van Bilsen
M
M
De Groot
M J
MJ
Lemmens
P J
PJ
Willemsen
P H
PH
Reneman
R S
RS
Van der Vusse
G J
GJ
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism*; D015777:Eicosanoids / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006439:Hemodynamics; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000201:enzymology; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew
D001095:Arachidonic Acids; D015777:Eicosanoids; D005227:Fatty Acids; D016718:Arachidonic Acid; D007770:L-Lactate Dehydrogenase; D011796:Quinacrine