Release of 6-KET0-PGFlα and thromboxane B2 in late appearing cardioprotection induced by the stable PGI analogue: 7-OXO-PGI
We have shown earlier that prostacyclin (PGI2) and its stable analogue: 7-oxo-prostacyclin(7-OXO) may induce a prolonged, late appearing (24–48 h after drug administration), dose dependent protection of the heart from harmful consequences of a subsequent severe ischaemic stress, such as myocardial ischaemia, life-threatening ventricular arrhythmias and early ischaemic morphological changes. In an other study we observed that a similar but shortlived (less than 1 h) cardioprotection, induced by ‘preconditioning’ brief coronary artery occlusions, is greatly reduced by blockade of the cyclooxygenase pathway, suggesting that prostanoids might play a role in this shortlasting protection.
Objective of our present study was to elucidate the importance of some arachidonic acid (AA) metabolites, such as PGI2 and thromboxane A2 (TXA2) in the mechanism of the late appearing, prolonged cardioprotection. Estimation of the metabolites: 6-keto-PGFlα (6-KETO) and thromboxane B2 (TXB2) was made from the perfusate of isolated Langendorff hearts of guinea-pigs pretreated with 50μg/kg 7-OXO, 24 and 48 h before preparation. Pretreatment alone produced a slight, but significant elevation of 6-KETO (from 206 ± 11 to 284 ± 19 pg/ml/min after 24 h, and to 261 ± 18 pg/ml/min after 48 h). No change was seen in TXB2 production. Global ischaemia for 25 min (followed by 25 min reperfusion) markedly increased the release of both A A metabolites; maximal values were observed in the third min of reperfusion (6-KETO from 206 ± 11 to 1275 ± 55 pg/ml/min and TXB2 from 29 ± 4 to 172 ± 12pg/ml/min). All values returned to the preischaemic level by the 25th min of reperfusion. Ischaemic increase in 6-KETO level was significantly higher in the perfusate of hearts from pretreated animals (1507 ± 73 pg/ml/min after 24 h, and 1398 ± 54 pg/ml/min after 48 h) that in those of untreated controls. There was no difference in TXB2 values. Thus both basal and ischaemic release of PGI2 increased 24 and 48 h after pretreatment with 7-OXO but not TXA2 production. Results suggest that endogenous prostanoids might play a role in late appearing cardioprotection. (Mol Cell Biochem 119: 129–132, 1993)
Key wordslate appearing cardioprotection PGI2 TXA2 ischaemia reperfusion
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