Influence of intracellular Ca2+-overload in eicosanoid synthesis of the myocardium.

Intracellular Ca2+-overload in the myocardium can be induced not only after readmission of Ca2+-containing fluid to rat hearts previously perfused with a Ca2+-free buffer, a phenomenon called “the calcium paradox”, but also during administration of a Ca2+-ionophore to cardiac tissue. In rat hearts, the myocardial damage induced by the Ca2+ paradox was more pronounced than that after administration of the Ca2+-ionophore A23187, as indicated by the amount of lactate dehydrogenase released. The accumulation of NEFA, and especially arachidonic acid, was greater during the Ca2+ paradox than after the administration of the Ca2+-ionophore. Administration of the Ca2+-ionophore resulted in a considerable release of 6-keto-F1α , (the stable breakdown product of prostacyclin), and LTD4 and LTE4 (breakdown products of LTC4). In contrast, the formation of eicosanoids was absent during the Ca2+ paradox. It is concluded that the relation between Ca2+-overload and accumulation of arachidonic acid is ambiguous and that there is no close relation between the amount of arachidonic acid accumulated and the formation of eicosanoids in Ca2+-overloaded tissue. The absence of eicosanoid formation during the Ca2+ paradox might be explained by compartmentation of the arachidonic acid accumulation and its converting enzymes or impairment of the enzymatic machinery required for eicosanoid synthesis.