Effect of pre- and posttreatment of losartan in feline model of myocardial ischemic-reperfusion injury.
This study investigated the differential effect of losartan, an AT1 receptor blocker, when administered in pre- and postischemic phases, on the biochemical, hemodynamic and oxidative stress associated with regional ischemic-reperfusion injury in cat. Losartan (5 microg/kg/min) or normal saline was administered intravenously in open chest barbiturate anesthetized cats, 15 min before and 10 min after the occlusion of the left anterior descending (LAD) coronary artery. The LAD was occluded for 15 min followed by 60 min reperfusion. In the saline treated group, there was significant depression of hemodynamic functions, i.e., mean arterial pressure (MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP) and left ventricular (LV) peak (+/-) dP/dt, along with depletion of adenosine triphosphate (ATP) of the affected myocardium. Oxidative stress during reperfusion injury was evidenced by significant increase in plasma thiobarbituric acid reactive substances (TBARS) accompanied by significant reduction in myocardial superoxide dismutase (SOD) activities. In both treatment groups, losartan caused recovery of all the hemodynamic parameters and repletion of ATP along with no significant change in plasma TBARS and myocardial SOD activity. There was no effect on catalase activity. Results from the study suggest that the effects of pre- and posttreatment of losartan are comparable in functional recovery of the heart from ischemic-reperfusion injury.
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India. Rashmikumari_s@hotmail.com
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R
Kumari
S C
SC
Manchanda
S K
SK
Maulik
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002374:Catalase / Q000378:metabolism; D002415:Cats; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000503:physiopathology; D019344:Lactic Acid / Q000378:metabolism; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D016019:Survival Analysis; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D002374:Catalase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D005978:Glutathione; D019808:Losartan