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Khazraei H, Akmali M, Mirkhani H. Mechanical effects of ranolazine on normal and diabetic-isolated rat heart. Res Pharm Sci. 2021;16(3):269-277doi: 10.4103/1735-5362.314825.
Khazraei, H., Akmali, M., & Mirkhani, H. (2021). Mechanical effects of ranolazine on normal and diabetic-isolated rat heart. Research in pharmaceutical sciences, 16(3), 269-277. https://doi.org/10.4103/1735-5362.314825
Khazraei, Hajar, et al. "Mechanical effects of ranolazine on normal and diabetic-isolated rat heart." Research in pharmaceutical sciences vol. 16,3 (2021): 269-277. doi: https://doi.org/10.4103/1735-5362.314825
Khazraei H, Akmali M, Mirkhani H. Mechanical effects of ranolazine on normal and diabetic-isolated rat heart. Res Pharm Sci. 2021 May 12;16(3):269-277. doi: 10.4103/1735-5362.314825. eCollection 2021 Jun. PMID: 34221060; PMCID: PMC8216165.
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Res Pharm Sci. 2021 May 12;16(3):269-277. doi: 10.4103/1735-5362.314825. eCollection 2021 Jun.

Mechanical effects of ranolazine on normal and diabetic-isolated rat heart.

Research in pharmaceutical sciences

Hajar Khazraei, Masoumeh Akmali, Hossein Mirkhani

Affiliations

  1. Colorectal Research Center, Shiraz University of Medical Sciences, Shiraz, I.R. Iran.
  2. Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz, I.R. Iran.
  3. Department of Pharmacology, Shiraz University of Medical Sciences, Shiraz, I.R. Iran.
  4. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, I.R. Iran.

PMID: 34221060 PMCID: PMC8216165 DOI: 10.4103/1735-5362.314825

Abstract

BACKGROUND AND PURPOSE: Diabetic cardiomyopathy is a complication of diabetes defined as cardiac dysfunction without the involvement of pericardial vessels, hypertension, or cardiac valve disorders. Ranolazine, an antianginal drug, acts through blocking of cardiac late sodium channels and/or inhibiting beta-oxidation of fatty acids. With regard to its mechanism of action, the present work has been carried out to investigate the potential useful effects of ranolazine on the systolic and diastolic dysfunctions in an experimental rat model of diabetic cardiomyopathy. Lidocaine, as a sodium channel blocker, was used to have a clearer image of the involved mechanisms.

EXPERIMENTAL APPROACH: Diabetes was induced by streptozocin. After 8 weeks, the effects of cumulative concentrations of ranolazine and lidocaine were evaluated on diabetic and normal hearts by the Langendorff method. Finally, the hearts were isolated from the Langendorff system and adenosine three phosphates (ATP) and adenosine diphosphate (ADP) concentrations were measured to assay the metabolic effect of ranolazine.

FINDINGS/RESULTS: Ranolazine significantly decreased the velocity of systolic contraction (+dP/dt) and the velocity of diastolic relaxation (-dP/dt) and developed pressure in normal and diabetic rat hearts. However, this negative effect was greater in normal hearts compared to diabetics. Ranolazine (100 μM) decreased the ATP level only in normal hearts and the ATP/ADP ratio decreased significantly (

CONCLUSION AND IMPLICATIONS: It is concluded that in the isolated rat heart preparation, ranolazine has no benefit on diabetic cardiomyopathy and may even worsen it. It seems that these effects are related to the metabolic effects of ranolazine.

Copyright: © 2021 Research in Pharmaceutical Sciences.

Keywords: Diabetes; Langendorff isolated heart system; Lidocaine; Ranolazine

Conflict of interest statement

The authors declared no conflict of interest in this study.

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