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Protective efficacy of dinitrosyl iron complexes with reduced glutathione in cardioplegia and reperfusion.
- Source :
-
Pflugers Archiv : European journal of physiology [Pflugers Arch] 2019 Apr; Vol. 471 (4), pp. 583-593. Date of Electronic Publication: 2019 Jan 06. - Publication Year :
- 2019
-
Abstract
- Disturbed homeostasis of nitric oxide (NO) is one of the causes of myocardial ischemia/reperfusion (I/R) injury during open-heart surgery. This study was designed to explore mechanisms of action of dinitrosyl iron complexes with reduced glutathione ({(GS <superscript>-</superscript> ) <subscript>2</subscript> Fe <superscript>+</superscript> (NO <superscript>+</superscript> ) <subscript>2</subscript> } <superscript>+</superscript> , DNIC-GS) added to crystalloid cardioplegia or reperfusion solution in isolated working rat hearts. Hearts of male Wistar rats were subjected to cardioplegic arrest by St. Thomas' Hospital cardioplegic solution (STH) and normothermic global ischemia followed by reperfusion. DNIC-GS were used with STH or during early reperfusion. Lactate dehydrogenase (LDH) activity in the coronary effluent and myocardial contents of adenine nucleotides, phosphocreatine, and lactate were determined spectrophotometrically. Reactive oxygen species (ROS) formation in the coronary effluent and myocardial DNIC content was assessed by EPR technique. Cardioplegia or reperfusion with DNIC-GS significantly improved recovery of coronary flow and cardiac function compared with control. Carboxy-[2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidozoline-1-oxy-3-oxide] (C-PTIO), a selective NO scavenger, reduced/abolished protective action of DNIC-GS. Enhanced recovery of cardiac function with DNIC-GS reduced LDH release in the coronary effluent, augmented recovery of myocardial energy state, and decreased formation of ROS-generating systems at reperfusion. Beneficial effects of DNIC-GS were related to the transfer of [Fe(NO) <subscript>2</subscript> ] cores to thiol groups of myocardial proteins to form intracellular DNIC pools. The study concluded that DNIC-GS is a promising adjunct agent for metabolic and antioxidant protection of the heart during cardioplegic arrest and reperfusion.
- Subjects :
- Animals
Antioxidants metabolism
Heart Arrest, Induced methods
Isotonic Solutions metabolism
Male
Myocardial Reperfusion Injury metabolism
Myocardium metabolism
Nitric Oxide metabolism
Rats
Rats, Wistar
Reactive Oxygen Species metabolism
Glutathione pharmacology
Heart drug effects
Iron pharmacology
Myocardial Reperfusion Injury drug therapy
Nitrogen Oxides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-2013
- Volume :
- 471
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Pflugers Archiv : European journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 30613864
- Full Text :
- https://doi.org/10.1007/s00424-018-02251-2