ABC | Volume 114, Nº1, January 2019

Original Article Alegre et al. Açaí and myocardial ischemia-reperfusion in rats Arq Bras Cardiol. 2020; 114(1):78-86 adenine dinucleotide produced during fatty acid oxidation are used in mitochondrial ATP synthesis via oxidative phosphorylation. 43 This is critically dependent on the maintenance of an electrochemical proton gradient across the inner mitochondrial membrane generated by the extrusion of protons from the matrix to the intermembrane space by complexes I, III and IV, which form the ETC. 44 In our study, açaí supplementation led to higher activity of β -hydroxyacyl CoA-dehydrogenase and citrate synthase enzymes, which can characterize higher fatty acid oxidation. Moreover, there was lower activity of phosphofructokinase, the enzyme for glycolysis. This shows that açai supplementation altered the substrate selection for mitochondrial oxidation in reperfusion from glucose to fatty acids, maintaining energy metabolism closer to a physiological situation, as showed previously in an experimental model of renal ischemia‑reperfusion. 45 Additionally,  açaí supplementation increased the activity of complexes I, II and ATP synthase by protecting the damage to mitochondrial complexes. However, fatty acid oxidation decreases the metabolic efficiency of injured hearts. Interestingly, açaí pulp is composed predominantly by lipids that correspond to 48%. 46 Offering more lipids could contribute to increased β -hydroxyacyl CoA-dehydrogenase activity in the treated açaí group. This pattern was observed in the experimental myocardial infarction model that administered a chow rich in lipids. 47 Regarding the infarcted area, as expected for the 30-minute periodof ischemia,weobserveda large infarctedarea inour study, approximately 50% in both groups. Previously, supplementation of a diet rich in anthocyanins in an experimental model of ischemia-reperfusion decreased the myocardial infarcted area. 48 However, in the present study, açaí supplementation did not reduce infarct size. Large infarctions usually present with important left ventricular dysfunction resulting from the impairment of cellular processes and changes in cardiac morphology. Increased oxidative stress compromises the plasma membrane permeability of myocytes, the activity of ionic pumps in the plasma membrane and in the sarcoplasmic reticulum, and intracellular calcium transit, compromising both systole and diastole. 7 It would be expected that the attenuation of oxidative stress would be followed by an improvement in left ventricular function, as showed in different myocardial damage models. 25,49,50 However, this study evidenced that the administration of açaí worsened the diastolic function after cardiac ischemia-reperfusion. This leads us to infer that the ventricular dysfunction observed in this model depends on mechanisms other than oxidative damage. Curiously, a study performed to investigate the effect of anthocyanin extract in global rat heart ischemia-reperfusion suggests that anthocyanin was cardioprotective in low doses and could be cardiotoxic in high ones. 51 Additionally, the change in energetic metabolism that occurs in stress situations has a protective role in the myocardium. 42 The fact that açai supplementation prevents the use of glucose and favors the maintenance of myocardial metabolism close to normal may have negatively interfered with this adaptive protective mechanism. Whereas ischemia induces morphological and functional alterations and reperfusion injury canexacerbate these features, the discovery of newdrugs, substances or strategies that canminimize cardiac damage is essential. The quantity of açaí that rats took was equivalent to 600 mg for a 60 kg human, 52 which is feasible human açaí ingestion. Therefore, açaí could be a potential strategy to attenuate ischemia-reperfusion injury in clinical scenario. However, there are some limitations that difficult the translational impact of these results. First, rats share several metabolic pathways with humans, but the organisms are quite different. Second, in this study we evaluated a global myocardial ischemia that is not the routine in clinical practice. The ischemic process in humans is the result of a long inflammatory process that can modulate completely different metabolic pathways from our model. 53 Conclusion Açaí supplementation did not decrease the infarcted area nor improve the left ventricular function in the global ischemia-reperfusion model despite improving cardiac energy metabolism and attenuating myocardial oxidative stress, suggesting that these mechanisms may not be the main determinants of the worsened diastolic left ventricular function observed after ischemia and reperfusion with açaí  supplementation. Author contributions Conception and design of the research: Zornoff L, Paiva SAR, Polegato BF; Acquisition of data: Alegre P, Mathias L, Lourenço MA, Gonçalves A, Fernandes AA; Analysis and interpretation of the data: Alegre P, Santos PP, Gaiolla PSA, Minicucci MF, Zornoff L, Paiva SAR, Polegato BF; Statistical analysis: Minicucci MF, Paiva SAR, Polegato BF; Writing of the manuscript: Alegre P, Santos PP, Polegato BF; Critical revision of the manuscript for intellectual content: Alegre P, Mathias L, Lourenço MA, Santos PP, Gonçalves A, Fernandes AA, Gaiolla PSA, Minicucci MF, Zornoff L, Paiva SAR, Polegato BF. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding There were no external funding sources for this study. Study Association This article is part of the thesis of master submitted by Patricia Alegre, from pela Universidade Estadual Paulista, Faculdade de Medicina de Botucatu. Ethics approval and consent to participate This study was approved by the Animal Ethics Committee of the Faculdade de Medicina de Botucatu under the protocol number 1111/2014. All the procedures in this study were in accordancewith the 1975Helsinki Declaration, updated in 2013. 84