title: Captopril and its time of administration in myocardial ischaemic-reperfusion injury.
abstract: The present study was designed to investigate the role of captopril in an in vivo model of myocardial ischaemic-reperfusion injury with respect to its time of administration. In open-chest pentobarbitone anaesthetized cats, the left anterior descending coronary artery was occluded for 15 min followed 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, ischaemic-reperfusion injury (IRI) was evidenced by enhanced plasma renin activity, depression of global haemodynamic function (mean arterial pressure, left ventricular-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 antioxidants (glutathione, superoxide dismutase and catalase). Pre-treatment with captopril prevented (i) loss of myocardial haemodynamic function, (ii) rise in TBARS 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 TBARS, was observed. Glutathione, superoxide dismutase and catalase were unaffected by either treatment schedules. The results of the present study suggest that captopril is more effective in attenuating ischaemic-reperfusion injury when administered before ischaemia rather than before reperfusion.
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India. subirmaulik@hotmail.com
authors.forename: S K
authors.initials: SK
authors.lastname: Maulik
authors.forename: R
authors.initials: R
authors.lastname: Kumari
authors.forename: M
authors.initials: M
authors.lastname: Maulik
authors.forename: S C
authors.initials: SC
authors.lastname: Manchanda
authors.forename: S K
authors.initials: SK
authors.lastname: Gupta
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use*; D002374:Catalase / Q000378:metabolism; D002415:Cats; D003402:Creatine Kinase / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010725:Phosphocreatine / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007773:Lactates; D017392:Thiobarbituric Acid Reactive Substances; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D002216:Captopril; D002374:Catalase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D005978:Glutathione