Cardiovascular Drugs and Therapy

, Volume 26, Issue 3, pp 205–216 | Cite as

Effect of Chronic CPT-1 Inhibition on Myocardial Ischemia-Reperfusion Injury (I/R) in a Model of Diet-Induced Obesity

  • Gerald Maarman
  • Erna Marais
  • Amanda Lochner
  • Eugene F du Toit
Article

Abstract

Purpose

By increasing circulating free fatty acids and the rate of fatty acid oxidation, obesity decreases glucose oxidation and myocardial tolerance to ischemia. Partial inhibition of fatty acid oxidation may improve myocardial tolerance to ischemia/reperfusion (I/R) in obesity. We assessed the effects of oxfenicine treatment on post ischemic cardiac function and myocardial infarct size in obese rats.

Methods

Male Wistar rats were fed a control diet or a high calorie diet which resulted in diet induced obesity (DIO) for 16 weeks. Oxfenicine (200 mg/kg/day) was administered to control and DIO rats for the last 8 weeks. Isolated hearts were perfused and infarct size and post ischemic cardiac function was assessed after regional or global ischemia and reperfusion. Cardiac mitochondrial function was assessed and myocardial expression and activity of CPT-1 (carnitine palmitoyl transferase-1) and IRS-1 (insulin receptor substrate-1) was assessed using Western blot analysis.

Results

In the DIO rats, chronic oxfenicine treatment improved post ischemic cardiac function and reduced myocardial infarct size after I/R but had no effect on the cardiac mitochondrial respiration. Chronic oxfenicine treatment worsened post ischemic cardiac function, myocardial infarct size and basal mitochondrial respiration in control rat hearts. Basal respiratory control index (RCI) values, state 2 and state 4 respiration rates and ADP phosphorylation rates were compromised by oxfenicine treatment.

Conclusion

Chronic oxfenicine treatment improved myocardial tolerance to I/R in the obese rat hearts but decreased myocardial tolerance to I/R in control rat hearts. This decreased tolerance to ischemia of oxfenicine treated controls was associated with adverse changes in basal and reoxygenation mitochondrial function. These changes were absent in oxfenicine treated hearts from obese rats.

Key words

Oxfenicine Cardiac metabolism CPT-1 inhibition Obesity Ischemia/reperfusion 

Notes

Acknowledgments

This study was financially supported by the South African National Research Foundation (Prof. E.F. Du Toit and Dr. E. Marais). We would also like to thank Prof. A. Lochner and Prof. B. Huisamen for expert advice and guidance.

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Gerald Maarman
    • 1
    • 3
  • Erna Marais
    • 1
  • Amanda Lochner
    • 1
  • Eugene F du Toit
    • 2
  1. 1.Departments of Biomedical Sciences, Faculty of Health SciencesUniversity of StellenboschTygerbergSouth Africa
  2. 2.Heart Foundation Research Center, School of Medical Science, Gold Coast CampusGriffith UniversityQueenslandAustralia
  3. 3.Hatter Institute for Cardiovascular Research in AfricaUniversity of Cape TownCape TownSouth Africa

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