Antioxidant Solution in Combination with Angiotensin-(1-7) Provides Myocardial Protection in Langendorff-Perfused Rat Hearts

Abstract

As progressive organ shortage in cardiac transplantation demands extension of donor criteria, effort is needed to optimize graft survival. Reactive oxygen and nitrogen species, generated during organ procurement, transplantation, and reperfusion, contribute to acute and late graft dysfunction. The combined application of diverse substances acting via different molecular pathways appears to be a reasonable approach to face the complex mechanism of ischemia reperfusion injury. Thus, an antioxidant solution containing α-ketoglutaric acid, 5-hydroxymethylfurfural, N-acetyl-L-methionine, and N-acetyl-selenium-L-methionine was combined with endogenous angiotensin-(1-7). Its capacity of myocardial protection was investigated in isolated Langendorff-perfused rat hearts subjected to warm and cold ischemia. The physiological cardiac parameters were assessed throughout the experiments. Effects were evaluated via determination of the oxidative stress parameters malondialdehyde and carbonyl proteins as well as immunohistochemical and ultrastructural tissue analyses. It was shown that a combination of 20% (v/v) antioxidant solution and 220 pM angiotensin-(1-7) led to the best results with a preservation of heart tissue against oxidative stress and morphological alteration. Additionally, immediate cardiac recovery (after warm ischemia) and normal physiological performance (after cold ischemia) were recorded. Overall, the results of this study indicate substantial cardioprotection of the novel combination with promising prospective for future clinical use.

Alpha-Ketoglutarate: A Potential Inner Mitochondrial and Cytosolic Protector against Peroxynitrite and Peroxynitrite-Induced Nitration?

“…Those findings were verified by another research group [ 27 ]. Furthermore, nitro-tyrosine residue levels on rat myocytes pretreated with an antioxidative solution containing αKG were significantly lower than those for control rats without pre-treatment [ 2 ].…”

“…Any loss of αKG, e.g., by peroxynitrite or hydrogen peroxide, might result in multiple dysfunctions due to αKG’s several functions as an energy donor, a precursor in amino acid biosynthesis, a signalling molecule, and a regulator of epigenetic processes and cellular signalling via protein binding. In vitro and in vivo antioxidative activities, protection against oxidative stress, and increased energy levels in αKG-supplemented humans were obtained in multiple studies [ 1 , 2 , 23 ].…”

“…αKG is known to react with H 2 O 2 non-enzymically to form succinate and carbon dioxide in several biological systems, including cell cultures [ 2 ] in vitro and in vivo [ 3 ] and even in cell culture media alone [ 4 ]. We recently reported that αKG reduced oxidatively modified proteins in the presence of cigarette smoke radicals, estimated from the content of carbonyl proteins [ 5 ].…”