Inhibition of semicarbazide-sensitive amine oxidase attenuates myocardial ischemia-reperfusion injury in an in vivo rat model.

Abstract

AIMS:

This study tested the hypothesis that the inhibition of semicarbazide-sensitive amine oxidase (SSAO) after ischemia could attenuate myocardial ischemia-reperfusion (I/R) injury.

MAIN METHODS:

Anesthetized male Sprague-Dawley rats underwent myocardial I/R injury. Saline, semicarbazide (SCZ, 30 mg/kg), hydralazine (HYD, 10mg/kg), or LJP 1207 (30 mg/kg) was administered intraperitoneally 3 min before reperfusion. After 30 min of ischemia and 180 min of reperfusion, the myocardial infarct size was determined using nitroblue tetrazolium staining. Myocardial myeloperoxidase activity was determined through biochemical assay. HE staining was used for histopathological evaluation. Myocardial SSAO activity was assayed with high performance liquid chromatography analysis. Additionally, the endothelial expression of P-selectin was evaluated using immunohistochemistry after 30 min of ischemia and 20 min of reperfusion.

KEY FINDINGS:

Myocardial SSAO activity was increased in myocardial I/R injury. Administration of SCZ, HYD, or LJP 1207 reduced the myocardial infarct size and decreased leukocyte infiltration and endothelial P-selectin expression in myocardial I/R injury in vivo.

SIGNIFICANCE:

These data suggest that myocardial I/R injury up-regulates myocardial SSAO activity, and the inhibition of SSAO prior to reperfusion is able to attenuate acute myocardial I/R injury.

• Authors: Wei Yang, Hui Li, Hongjun Luo, Wenhong Luo
• Journal: Life sciences (Life Sci) Vol. 88 Issue 7-8 Pg. 302-6 (Feb 14 2011) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 21146547 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Hydrazines
• N'-(2-phenylallyl)hydrazine
• P-Selectin
• Semicarbazides
• Hydralazine
• carbamylhydrazine
• Peroxidase
• Amine Oxidase (Copper-Containing)

Topics

• Amine Oxidase (Copper-Containing) (analysis, antagonists & inhibitors, physiology)
• Animals
• Blood Pressure (drug effects)
• Chromatography, High Pressure Liquid
• Disease Models, Animal
• Heart Rate (drug effects)
• Hydralazine (pharmacology)
• Hydrazines (pharmacology)
• Male
• Myocardial Infarction (metabolism, physiopathology)
• Myocardial Reperfusion Injury (drug therapy, metabolism, physiopathology)
• Myocardium (enzymology)
• P-Selectin (analysis, biosynthesis)
• Peroxidase (analysis)
• Rats
• Rats, Sprague-Dawley
• Semicarbazides (pharmacology, therapeutic use)