Magnesium orotate elicits acute cardioprotection at reperfusion in isolated and in vivo rat hearts

Author:

Mirica Silvia N.1,Duicu Oana M.1,Trancota Simona L.1,Fira-Mladinescu Ovidiu1,Angoulvant Denis2,Muntean Danina M.1

Affiliation:

1. Department of Pathophysiology, University of Medicine and Pharmacy, Timisoara, Romania.

2. Intensive Cardiac-Care Unit and Interventional Cardiology, CHRU de Tours, Hôpital Trousseau, F-37044 Tours, France; EA4245 Université François-Rabelais de Tours, PRES Centre-Val de Loire Université, Tours, France.

Abstract

Orotic acid and its salts chronically administered have been shown to significantly improve cardiac function in pathological settings associated with ischemia–reperfusion (I/R) injury. The aim of our study was to investigate the effect of magnesium orotate (Mg-Or) administration at the onset of post-ischemic reperfusion on myocardial function and infarct size (IS). Ex-vivo experiments performed on isolated perfused rat hearts were used to compare Mg-Or administration with a control group (buffer treated), ischemic post-conditioning, orotic acid treatment, and MgCl2treatment. Mg-Or administration was also investigated in an in-vivo model of regional I/R performed in rats undergoing reversible coronary ligation. The effect of Mg-Or on mitochondrial permeability transition pore (mPTP) opening after I/R was investigated in vitro to gain mechanistic insights. Both ex-vivo and in-vivo experiments showed a beneficial effect from Mg-Or administration at the onset of reperfusion on myocardial function and IS. In-vitro assays showed that Mg-Or significantly delayed mPTP opening after I/R. Our data suggest that Mg-Or administered at the very onset of reperfusion may preserve myocardial function and reduce IS. This beneficial effect may be related to a significant reduction of mPTP opening, a usual trigger of cardiac cell death following I/R.

Publisher

Canadian Science Publishing

Subject

Physiology (medical),Pharmacology,General Medicine,Physiology

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