title: Levosimendan reduces myocardial damage and improves cardiodynamics in streptozotocin induced diabetic cardiomyopathy via SERCA2a/NCX1 pathway.
abstract: OBJECTIVE
  Diabetic cardiomyopathy (DCM) is one of the most common causes of mortality. Its pathophysiology is not fully understood and involve number of factors including, cardiovascular and metabolic disorders. The present study was designed to study the pathogenesis of DCM and to explore the effects of levosimendan along with either ramipril or insulin in the long term management of DCM.
  
  
  METHODS
  Streptozotocin (STZ) was used to develop DCM in Wistar rats at the dose of 25mg/kg body weight for three consecutive days. Rats were randomly divided into 9 groups and treatments were started after 2weeks of STZ administration.
  
  
  RESULTS
  Persistent hyperglycemia was observed in STZ treated rats, leading to significant contractile dysfunction as evidenced by decreased left ventricular pressure (LVP), +LV (dp/dt), -LV (dp/dt) as well as elevated Tau and LVEDP. Marked myocardial damage such as fibrosis, increased wall tension, depletion of contractile proteins were observed as evidenced by increased levels of TGF-β, BNP, cTroponin-I, as well as decreased expression of SERCA2a and NCX1 proteins in diabetic rats. The levosimendan alone and also in combination with either ramipril or insulin significantly normalized the myocardial dysfunctions developed during the course of persistent hyperglycemia.
  
  
  CONCLUSIONS
  The study suggests that levosimendan treatment improves cardiac dysfunction significantly. Its combined use with ramipril proves better than with insulin in correcting myocardial performance as well as reduction in myocardial damage.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi -62, India.
authors.forename: Md Sayeed
authors.initials: MS
authors.lastname: Akhtar
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi -62, India.
authors.forename: Krishna Kolappa
authors.initials: KK
authors.lastname: Pillai
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi -62, India.
authors.forename: Md Quamrul
authors.initials: MQ
authors.lastname: Hassan
authors.affiliation: School of Sciences, Disciplines of Life Sciences, IGNOU, New Delhi 110068, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Dhyani
authors.affiliation: Department of Community Medicine, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard, New Delhi -62, India.
authors.forename: Md Vasim
authors.initials: MV
authors.lastname: Ismail
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi -62, India. Electronic address: aknajmi@jamiahamdard.ac.in.
authors.forename: Abul Kalam
authors.initials: AK
authors.lastname: Najmi
mesh_terms: D000818:Animals; D001835:Body Weight; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics; D006835:Hydrazones / Q000627:therapeutic use*; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011724:Pyridazines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D000077464:Simendan; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D013311:Streptozocin; D016212:Transforming Growth Factor beta / Q000378:metabolism; D019210:Troponin I / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D019831:Sodium-Calcium Exchanger; D016212:Transforming Growth Factor beta; D019210:Troponin I; C110374:sodium-calcium exchanger 1; D020097:Natriuretic Peptide, Brain; D009569:Nitric Oxide; D000077464:Simendan; D013311:Streptozocin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
keywords: Cardiomyopathy; Diabetes; Levosimendan; Mitochondrial damage; Myocardial contractility; Streptozotocin