Molecular and Cellular Biochemistry

, Volume 370, Issue 1–2, pp 59–67 | Cite as

The effects of homocysteine-related compounds on cardiac contractility, coronary flow, and oxidative stress markers in isolated rat heart

  • Vladimir Zivkovic
  • Vladimir Jakovljevic
  • Dusica Djordjevic
  • Milena Vuletic
  • Nevena Barudzic
  • Dragan Djuric


Research on the effects of homocysteine on the vascular wall, especially in endothelial and smooth muscle cells, has indicated that increased homocysteine levels lead to cellular stress and cell damage. Considering the adverse effects of homocysteine on vascular function and the role of oxidative stress in these mechanisms, the aim of this study was to estimate the influence of different homocysteine isoforms on cardiac contractility, coronary flow, and oxidative stress markers in isolated rat heart. The hearts of male Wistar albino rats (n = 36, age 8 weeks, body mass 180–200 g), were excised and retrogradely perfused according to the Langendorff technique at a constant perfusion pressure (70 cmH2O) and administered with three isoforms of 10 μM homocysteine [dl-Hcy, dl-Hcy thiolactone-hydrochloride (TLHC) and l-Hcy TLHC). After the insertion and placement of the sensor in the left ventricle, the parameters of heart function: maximum rate of pressure development in the left ventricle (dP/dt max), minimum rate of pressure development in the left ventricle (dP/dt min), systolic left ventricular pressure (SLVP), diastolic left ventricular pressure (DLVP), mean blood pressure (MBP) and heart rate (HR)] were continuously registered. Flowmetry was used to evaluate the coronary flow. Markers of oxidative stress: index of lipid peroxidation measured as TBARS, nitric oxide measured through nitrites (NO2 ), superoxide anion radical (O2 ), and hydrogen peroxide (H2O2) in the coronary venous effluent were assessed spectrophotometrically. Our results showed that administration of Hcy compounds in concentration of 10 μM induced depression of cardiac contractility, manifested by a decrease in dp/dt max after administration of any Hcy compound, decrease in dp/dt min after administration of l-Hcy TLHC, decrease in SLVP after administration of dl-Hcy TLHC and dl-Hcy, and the drop in CF after administration of any Hcy compound. Regarding the effects of Hcy on oxidative stress parameters, only l-Hcy TLHC significantly affected O2 release. l-Hcy TLHC showed a cardiotoxic effect by affecting heart contractility, but surprisingly, it decreased the release of O2 .


Cardiac contractility Coronary flow Homocysteine Isolated rat heart Oxidative stress 





Coronary artery disease


Cystathionine β-synthase


Coronary flow


Constant perfusion pressure


Cardiovascular disease


Endothelial nitric oxide synthase






Peroxidase from horse radish




Methionine synthase


Methylene-tetrahydrofolate reductase


Nitro blue tetrazolium


Nitric oxide


Phenol red solution


Thiobarbituric acid reactive substances


Thiobarbituric acid




Tumor necrosis factor alpha



This work is supported by the Grant No. 175043 from the Ministry of Science and Technical Development of the Republic of Serbia and Junior project 04/2011 Faculty of Medicine, University of Kragujevac.

Conflict of interests

All authors of the present paper disclose no actual or potential conflict of interests including any financial, personal or other relationships with other people or organizations.


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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Vladimir Zivkovic
    • 1
  • Vladimir Jakovljevic
    • 1
  • Dusica Djordjevic
    • 1
  • Milena Vuletic
    • 1
  • Nevena Barudzic
    • 1
  • Dragan Djuric
    • 2
  1. 1.Department of Physiology, Faculty of MedicineUniversity of KragujevacKragujevacSerbia
  2. 2.Institute of Medical Physiology “Richard Burian”, Faculty of MedicineUniversity of BelgradeBelgradeSerbia

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