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Levosimendan reduces myocardial damage and improves cardiodynamics in streptozotocin induced diabetic cardiomyopathy via SERCA2a/NCX1 pathway.
Akhtar, Md Sayeed; Pillai, Krishna Kolappa; Hassan, Md Quamrul; Dhyani, Neha; Ismail, Md Vasim; Najmi, Abul Kalam.
Afiliación
  • Akhtar MS; Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi -62, India.
  • Pillai KK; Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi -62, India.
  • Hassan MQ; Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi -62, India.
  • Dhyani N; School of Sciences, Disciplines of Life Sciences, IGNOU, New Delhi 110068, India.
  • Ismail MV; Department of Community Medicine, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard, New Delhi -62, India.
  • Najmi AK; Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, New Delhi -62, India. Electronic address: aknajmi@jamiahamdard.ac.in.
Life Sci ; 153: 55-65, 2016 May 15.
Article en En | MEDLINE | ID: mdl-27058979
AIMS: 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. MATERIALS AND 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. KEY FINDINGS: 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-ß, 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. SIGNIFICANCE: 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piridazinas / Cardiotónicos / Intercambiador de Sodio-Calcio / Diabetes Mellitus Experimental / ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico / Corazón / Hidrazonas / Cardiomiopatías Límite: Animals Idioma: En Revista: Life Sci Año: 2016 Tipo del documento: Article País de afiliación: India Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piridazinas / Cardiotónicos / Intercambiador de Sodio-Calcio / Diabetes Mellitus Experimental / ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico / Corazón / Hidrazonas / Cardiomiopatías Límite: Animals Idioma: En Revista: Life Sci Año: 2016 Tipo del documento: Article País de afiliación: India Pais de publicación: Países Bajos