ligation-left-anterior-descending-coronary-artery-rats-for-developing

Ligation of Left Anterior Descending Coronary Artery in Rats for Developing Occlusive Myocardial Infarction Model

Cardiovascular disease (CVD), including ischemic heart disease and stroke, is a major cause of mortality and morbidity throughout the world. Myocardial ...

Khalsa College of Pharmacy

Reperfusion of ischaemic myocardium results in reduced nitric oxide (NO) biosynthesis by endothelial nitric oxide synthase (eNOS) leading to endothelial dysfunction and subsequent tissue damage. Impaired NO biosynthesis may be partly due to increased levels of asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of eNOS. As dimethylarginine dimethylaminohydrolase (DDAH) is a key enzyme responsible for degradation of ADMA, the present study was designed to explore the role of DDAH/ADMA/NO pathway in cardio-protective mechanism of ischaemic postconditioning.

Exploring the role of dimethylarginine dimethylaminohydrolase-mediated reduction in tissue asymmetrical dimethylarginine levels in cardio-protective mechanism of ischaemic postconditioning in rats.

EphA2 receptor has emerged as a novel cardioprotective target against myocardial infarction by preserving cardiac function, limiting infarct size and inflammation and enhancing cell survival via elevating phosphorylated Akt protein levels. However, the role of Eph receptors in postconditioning remains to be elucidated. Thus, the present study was designed to explore the role of EphA2 receptors in cardioprotective mechanism of postconditioning by employing Doxazosin as EphA2 receptor agonist, Lithocholic acid as antagonist and Wortmannin as specific phosphoinositide 3-kinase (PI3K) inhibitor. In Langendorff perfused isolated rat hearts, exposure of ischemia for 30 min succeeded by reperfusion for 2 h produced cardiac damage as determined by increase in size of infarct, LVDP, liberation of LDH and CK in effluent from coronary arteries. The reperfused hearts were homogenized and tissue concentrations of TBARs, reduced GSH and Catalase were determined. A marked rise in infarct size, liberation of LDH and CK in effluent and TBARs in myocardial tissue was observed in ischemic and reperfused hearts. Ischemic postconditioning comprising of 6 alternate episodes of 10 s ischemia and 10 s reperfusion and pharmacological post-conditioning by Doxazosin infusion for 5 min Before reperfusion confers significant protection against myocardial injury as manifested by remarkably decreased infarct size, levels of LDH, CK and tissue TBARs along with increase in GSH and Catalase activity. Pre-treatment of EphA2 antagonist, Lithocholic acid and PI3K inhibitor, Wortmannin attenuated the cardioprotective effect of postconditioning. Our results suggest that EphA2 receptors may be involved in postconditioning mediated cardioprotection probably through PI3K/Akt pathway.

Article	Year
Exploring the role of dimethylarginine dimethylaminohydrolase-mediated reduction in tissue asymmetrical dimethylarginine levels in cardio-protective mechanism of ischaemic postconditioning i... Iranian journal of basic medical sciences\| PubMed ID: 32133059	2019
Potential role of EphrinA2 receptors in postconditioning induced cardioprotection in rats. European journal of pharmacology\| PubMed ID: 32589885	2020

Kamaldeep Kaur

Biography

JoVE Journal Publications

Other Publications