N-acylhydrazone improves exercise intolerance in rats submitted to myocardial infarction by the recovery of calcium homeostasis in skeletal muscle

Life Sci. 2014 Jan 14;94(1):30-6. doi: 10.1016/j.lfs.2013.11.012. Epub 2013 Nov 21.

Abstract

Aims: This work investigated the effects of 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294) treatment on the contractile response of soleus (SOL) muscle from rats submitted to myocardial infarction (MI).

Main methods: Following coronary artery ligation, LASSBio-294 (2mg/kg, i.p.) or vehicle was administrated once daily for 4 weeks.

Key findings: The run time to fatigue for sham rats was 17.9 ±2.6 min, and it was reduced to 3.3 ± 0.8 min (P<0.05) in MI rats. In MI rats treated with LASSBio-294, the time to fatigue was 15.1 ± 3.6 min. During the contractile test, SOL muscles from sham rats showed a response of 7.12 ± 0.54N/cm(2) at 60 Hz, which was decreased to 5.45 ± 0.49 N/cm(2) (P<0.05) in MI rats. The contractility of SOL muscles from the MI-LASSBio-294 group was increased to 9.01 ± 0.65N/cm(2). At 16 mM caffeine, the contractility was reduced from 2.31 ± 0.33 to 1.60 ± 0.21 N/cm(2) (P<0.05) in the MI group. In SOL muscles from MI-LASSBio-294 rats, the caffeine response was increased to 2.62 ± 0.33 N/cm(2). Moreover, SERCA2a expression in SOL muscles was decreased by 0.31-fold (31%) in the MI group compared to the Sham group (P<0.05). In the MI-LASSBio-294 group, it was increased by 1.53-fold (153%) compared to the MI group (P<0.05). Meanwhile, the nuclear density in SOL muscles was increased in the MI group compared to the Sham group. Treatment with LASSBio-294 prevented this enhancement of cellular infiltrate.

Significance: LASSBio-294 treatment prevented the development of muscular fatigue and improved exercise intolerance in rats submitted to MI.

Keywords: Exercise intolerance; LASSBio-294; Myocardial infarction; SERCA2a expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Disease Models, Animal
  • Exercise Tolerance / drug effects*
  • Exercise Tolerance / physiology
  • Homeostasis
  • Hydrazones / pharmacology*
  • Male
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle Fatigue / drug effects*
  • Muscle Fatigue / physiology
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiology
  • Myocardial Infarction / physiopathology*
  • Physical Conditioning, Animal / physiology
  • Rats
  • Rats, Wistar
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
  • Thiophenes / pharmacology*
  • Time Factors

Substances

  • Hydrazones
  • LASSBio 294
  • Thiophenes
  • Caffeine
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium