Tóm tắt
The effects of thromboxane (Tx) inhibition or arachidonic acid (AA) infusion were studied in anesthetized cats during acute myocardial ischemia (MI). AA (7.2 mg kg−1 h−1) or imidazole (25 mg kg−1 h−1) infusions were initiated 30 min after occlusion of the left anterior descending coronary artery. Assessment of the degree of protection of the ischemic myocardium was made by measurement of S-T segment elevation, plasma and myocardial creatine phosphokinase (CPK) activities, and myocardial amino-nitrogen content. Assessment of Tx inhibition was performed by radioimmunoassay. Administration of imidazole inhibited the sevenfold increase in plasma thromboxane B2 (TxB2) levels occurring in MI (p < 0.001 at 2–5 h), markedly decreased S-T segment elevations at 2–5 h (p < 0.025), significantly prevented the elevation in plasma CPK (p < 0.05, at 4 and 5 h), and significantly reduced the loss in myocardial CPK activity and myocardial amino-nitrogen content. AA infusion also reduced the increase in TxB2 post-MI, significantly decreased (p < 0.025) S-T segment elevations at 2 5 h, caused a decrease in plasma CPK levels (p < 0.05 at 5 h), but did not prevent loss of myocardial CPK or amino-nitrogen. In summary, the administration of imidazole resulted in significant protection of the myocardium in all indices of ischemic damage measured, while AA infusion resulted in only a partial protection. The mechanism of the imidazole protection of ischemic myocardial tissue appears to be via inhibition of Tx synthesis although we cannot exclude a hemodynamic or cytoprotective mechanism. These results suggest that specific inhibition of Tx formation is beneficial during acute MI.
