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

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.

• Authors: Jaqueline Soares da Silva, Sharlene Lopes Pereira, Rodolfo do Couto Maia, Sharon Schilling Landgraf, Celso Caruso-Neves, Arthur Eugen Kümmerle, Carlos Alberto Manssour Fraga, Eliezer Jesus Barreiro, Roberto Takashi Sudo, Gisele Zapata-Sudo
• Journal: Life sciences (Life Sci) Vol. 94 Issue 1 Pg. 30-6 (Jan 14 2014) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 24269214 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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