Captopril and its time of administration in myocardial ischaemic-reperfusion injury

The present study was designed to investigate the role of captopril in an i n vivo model of myocardial ischaemic-reperfusion injury with respect to its time of administration. In open-chest pentobarbitone anaesthetized cats, t he left anterior descending coronary artery was occluded for 15 min followe d by 60 min of reperfusion. Vehicle (saline) or captopril (4 mg kg(-1)) was administered 10 min before instituting ischaemia (pre-treatment) or 5 min before reperfusion (post-treatment). In the vehicle-treated group, ischaemi c-reperfusion injury (IRI) was evidenced by enhanced plasma renin activity, depression of global haemodynamic function (mean arterial pressure, left v entricular-end-diastolic-pressure, peak positive and negative dP/dt) along with depletion of myocardial high energy phosphate (HEP) compounds. Oxidant stress in IRI was evidenced by raised levels of myocardial thiobarbituric acid reactive substances (TBARS) and depletion of endogenous myocardial ant ioxidants (glutathione, superoxide dismutase and catalase). Pre-treatment w ith captopril prevented (i) loss of myocardial haemodynamic function, (ii) rise in TEARS and (iii) depletion of myocardial HEP compounds. However, in the post-treatment group, only partial recovery of myocardial haemodynamic function, with no significant reduction in TEARS, was observed. Glutathione , superoxide dismutase and catalase were unaffected by either treatment sch edules. The results of the present study suggest that captopril is more eff ective in attenuating ischaemic-reperfusion injury when administered before ischaemia rather than before reperfusion. (C) 2001 Academic Press.