title: Possible role of thromboxane A2 in remote hind limb preconditioning-induced cardioprotection.
abstract: Remote hind limb preconditioning (RIPC) is a protective strategy in which short episodes of ischemia and reperfusion in a remote organ (hind limb) protects the target organ (heart) against sustained ischemic reperfusion injury. The present study was designed to investigate the possible role of thromboxane A2 in RIPC-induced cardioprotection in rats. Remote hind limb preconditioning was performed by four episodes of 5 min of inflation and 5 min of deflation of pressure cuff. Occlusion of the hind limb with blood pressure cuff is most feasible, non-invasive, clinically relevant, and safe method for inducing RIPC. Isolated rat hearts were perfused on Langendorff apparatus and were subjected to global ischemia for 30 min followed by 120-min reperfusion. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were measured in coronary effluent to assess the degree of myocardial injury. The extent of myocardial infarct size along with the functional parameters including left ventricular developed pressure (LVDP), dp/dtmax, and dp/dtmin were also measured. Ozagrel (thromboxane synthase inhibitor) and seratrodast (thromboxane A2 receptor antagonist) were employed as pharmacological modulators of thromboxane A2. Remote hind limb preconditioning significantly attenuated ischemia/reperfusion-induced myocardial injury and produced cardioprotective effects. However, administration of ozagrel and seratrodast completely abolished the cardioprotective effects of RIPC suggesting the key role of thromboxane A2 in RIPC-induced cardioprotection. It may be concluded that brief episodes of preconditioning ischemia and reperfusion activates the thromboxane synthase enzyme that produces thromboxane A2, which may elicit cardioprotection either involving humoral or neurogenic pathway.
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, Patiala, 147002, India.
authors.forename: Roohani
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, Patiala, 147002, India.
authors.forename: Puneet Kaur
authors.initials: PK
authors.lastname: Randhawa
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, Patiala, 147002, India.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University Patiala, Patiala, 147002, India. amteshwarjaggi@yahoo.co.in.
authors.forename: Amteshwar Singh
authors.initials: AS
authors.lastname: Jaggi
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D003402:Creatine Kinase / Q000378:metabolism; D005260:Female; D006321:Heart; D006538:Heptanoic Acids / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply*; D019194:Ischemic Preconditioning; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
chemical_list: D016227:Benzoquinones; D006538:Heptanoic Acids; D008689:Methacrylates; C060230:seratrodast; D013928:Thromboxane A2; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D013930:Thromboxane-A Synthase; C034364:ozagrel
keywords: Cardioprotection; Humoral; Neurogenic; Remote hind limb preconditioning; Thromboxane A2