The cellular and molecular origin of reactive oxygen species generation during myocardial ischemia and reperfusion

Raedschelders, Koen; Ansley, David M.; Chen, David D. Y.

doi:10.1016/j.pharmthera.2011.11.004

Cited by 322 publications

(277 citation statements)

References 427 publications

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“…6). 12,13,21 During ischemia, the mitochondrial electron transport chain (ETC) is damaged. B-cell lymphoma 2, a mitochondrial protein, is depleted.…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative phosphorylation becomes uncoupled, increasing ROS production and release of cell death activators that induce mitochondrial rupture. 12 While the effects of ROS are largely compartmentalized within cells, they trigger generation of stable diffusible lipid peroxidation products like 15-F 2t -isoprostane, a coronary artery vasoconstrictor implicated in the development of postoperative ventricular dysfunction. 19,26 We attribute our findings to patient characteristics, surgical conditions, and study interventions that differ from prior studies.…”

Section: Discussionmentioning

confidence: 99%

“…35,36 Detoxification of ROS by phenolic antioxidants involves conversion to peroxide and a phenoxyl radical that stimulates DNA fragmentation. 12 Furthermore, propofol induced transcriptional changes in fatty acid metabolism and DNA damage signalling, correlating with release of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of cardiac dysfunction. 37 Propofol concentrations were not measured and were likely suboptimal.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8][9][10][11] As oxidative stress is a major factor in the pathophysiology of IRI, propofol, an anesthetic and phenolic antioxidant, could be a therapeutic alternative. 12,13 Nevertheless, metaanalyses of clinical trials show reduced indices of myocardial injury and dysfunction with inhalational agents compared with propofol anesthesia (2-4 lgÁmL…”

Section: Résumémentioning

confidence: 99%

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Propofol cardioprotection for on-pump aortocoronary bypass surgery in patients with type 2 diabetes mellitus (PRO-TECT II): a phase 2 randomized-controlled trial

Ansley

Raedschelders

Choi

et al. 2015

Can J Anesth/J Can Anesth

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Purpose The efficacy of myocardial conditioning strategies is compromised in patients with advanced age, diabetes, or low ejection fraction. We conducted a singlecentre parallel-arm blinded randomized-controlled trial to determine whether propofol provides perioperative myocardial protection. Methods Patients enrolled in this study were scheduled for primary aortocoronary bypass surgery utilizing normothermic cardiopulmonary bypass (CPB) with blood cardioplegia. The participants were stratified by diabetic status and left ventricular ejection fraction and randomly assigned to receive either an elevated dose of propofolpreviously associated with experimental cardioprotectionor an isoflurane preconditioning regime. The primary endpoint was the coronary sinus (CS) concentration of 15-F 2t -isoprostane (isoP). Secondary endpoints included inhospital low cardiac output syndrome (LCOS) and major adverse cardiac events, 12-and 24-hr CS cardiac troponin I (cTnI) release, and myocardial B-cell lymphoma 2 (Bcl-2) protein expression. Results Data were analyzed from 125 of 137 randomized participants. Participants receiving propofol experienced a greater mean (SD) increase from baseline in CS 15-F 2t -isoP levels compared with those receiving isoflurane [26.9 (10.9) pgÁmL -1 vs 12.1 (10.4) pgÁmL -1 , respectively; mean difference, 14.8; 95% confidence interval (CI), 11.0 to 18.6; P \ 0.001] but a decreased incidence of LCOS (20.9% vs 57.1%, respectively; relative risk [RR],0.37; 95% CI, 0.22 to 0.62; P \ 0.001). The incidence of LCOS was similar between groups in participants without type 2 diabetes mellitus (DM2) (P = 0.382) but significantly decreased in the propofol DM2 subgroup compared with the isoflurane DM2 subgroup (17.9% vs 70.3%, respectively; RR, 0.26; 95% CI, 0.13 to 0.52; P \ 0.001). Propofol was associated with an increase in myocardial Bcl-2 protein expression (P = 0.005), a lower incidence of a CS cTnI threshold for myocardial infarction (P = 0.014), and fewer heart failure events (P \ 0.001). Conclusion Propofol may be a preemptive intraoperative cardioprotectant for patients with DM2 under conditions of normothermic CPB and blood cardioplegic arrest. The study is registered at www.clinicaltrials.gov (NCT00734383) and www.controlled-trials.com (ISRCTN70879185). RésuméObjectif L'efficacité des stratégies de conditionnement myocardique est compromise chez les patients âgés ainsi que chez ceux atteints de diabète ou présentant une fraction d'éjection faible. Nous avons réalisé une étude randomisée contrô lée unicentrique à bras parallèles et en aveugle afin de déterminer si le propofol procurait une protection myocardique en période périopératoire. Méthode Les patients enrô lés dans cette étude devaient subir une chirurgie de pontage aorto-coronarien primaire avec circulation extracorporelle (CEC) normothermique et cardioplégie sanguine. Les participants ont été stratifiés par statut diabétique et fraction d'éjection ventriculaire gauche, puis aléatoirement répartis en deux groupes, dont l'un recevrait...

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“…6). 12,13,21 During ischemia, the mitochondrial electron transport chain (ETC) is damaged. B-cell lymphoma 2, a mitochondrial protein, is depleted.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Résumémentioning

confidence: 99%

See 2 more Smart Citations

Propofol cardioprotection for on-pump aortocoronary bypass surgery in patients with type 2 diabetes mellitus (PRO-TECT II): a phase 2 randomized-controlled trial

Ansley

Raedschelders

Choi

et al. 2015

Can J Anesth/J Can Anesth

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“…Oxidative stress and reactive oxygen species have been implicated in endothelial damage, progression to atherosclerosis, injury in sustained myocardial infarction and ischaemia reperfusion (76,(90)(91)(92) . Monocytes and macrophages are critical cells that are involved in atherosclerosis.…”

Section: Role Of Phenolic Compounds On Endothelium Protectionmentioning

confidence: 99%

New perspectives on bioactivity of olive oil: evidence from animal models, human interventions and the use of urinary proteomic biomarkers

et al. 2015

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Olive oil (OO) is the primary source of fat in the Mediterranean diet and has been associated with longevity and a lower incidence of chronic diseases, particularly CHD. Cardioprotective effects of OO consumption have been widely related with improved lipoprotein profile, endothelial function and inflammation, linked to health claims of oleic acid and phenolic content of OO. With CVD being a leading cause of death worldwide, a review of the potential mechanisms underpinning the impact of OO in the prevention of disease is warranted. The current body of evidence relies on mechanistic studies involving animal and cell-based models, epidemiological studies of OO intake and risk factor, small-and large-scale human interventions, and the emerging use of novel biomarker techniques associated with disease risk. Although model systems are important for mechanistic research nutrition, methodologies and experimental designs with strong translational value are still lacking. The present review critically appraises the available evidence to date, with particular focus on emerging novel biomarkers for disease risk assessment. New perspectives on OO research are outlined, especially those with scope to clarify key mechanisms by which OO consumption exerts health benefits. The use of urinary proteomic biomarkers, as highly specific disease biomarkers, is highlighted towards a higher translational approach involving OO in nutritional recommendations.

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Polymer Conjugation of Docosahexaenoic Acid Potentiates Cardioprotective Therapy in Preclinical Models of Myocardial Ischemia/Reperfusion Injury

Tejedor

Dolz-Pérez

Decker

et al. 2021

Adv Healthcare Materials

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While coronary angioplasty represents an effective treatment option following acute myocardial infarction, the reperfusion of the occluded coronary artery can prompt ischemia–reperfusion (I/R) injury that significantly impacts patient outcomes. As ω‐3 polyunsaturated fatty acids (PUFAs) have proven, yet limited cardioprotective abilities, an optimized polymer‐conjugation approach is reported that improves PUFAs bioavailability to enhance cardioprotection and recovery in animal models of I/R‐induced injury. Poly‐l‐glutamic acid (PGA) conjugation improves the solubility and stability of di‐docosahexaenoic acid (diDHA) under physiological conditions and protects rat neonatal ventricular myocytes from I/R injury by reducing apoptosis, attenuating autophagy, inhibiting reactive oxygen species generation, and restoring mitochondrial membrane potential. Enhanced protective abilities are associated with optimized diDHA loading and evidence is provided for the inherent cardioprotective potential of PGA itself. Pretreatment with PGA–diDHA before reperfusion in a small animal I/R model provides for cardioprotection and limits area at risk (AAR). Furthermore, the preliminary findings suggest that PGA–diDHA administration in a swine I/R model may provide cardioprotection, limit edema and decrease AAR. Overall, the evaluation of PGA–diDHA in relevant preclinical models provides evidence for the potential of polymer‐conjugated PUFAs in the mitigation of I/R injury associated with coronary angioplasty.

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The cellular and molecular origin of reactive oxygen species generation during myocardial ischemia and reperfusion

Cited by 322 publications

References 427 publications

Propofol cardioprotection for on-pump aortocoronary bypass surgery in patients with type 2 diabetes mellitus (PRO-TECT II): a phase 2 randomized-controlled trial

Propofol cardioprotection for on-pump aortocoronary bypass surgery in patients with type 2 diabetes mellitus (PRO-TECT II): a phase 2 randomized-controlled trial

New perspectives on bioactivity of olive oil: evidence from animal models, human interventions and the use of urinary proteomic biomarkers

Polymer Conjugation of Docosahexaenoic Acid Potentiates Cardioprotective Therapy in Preclinical Models of Myocardial Ischemia/Reperfusion Injury

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