Oxygen Radicals Can Induce Preconditioning in Rabbit Hearts
Abstract
Abstract Indirect evidence suggests that oxygen radicals may contribute to ischemic preconditioning. We directly investigated whether exposure to oxygen radicals per se, in the absence of ischemia, could reproduce the beneficial effects of ischemic preconditioning on infarct size and on postischemic contractile dysfunction. In one branch of the study, isolated rabbit hearts underwent 30 minutes of total global ischemia and 45 minutes of reperfusion (n=6, control group). A second group, before ischemia/reperfusion, was exposed for 5 minutes to a low flux of oxygen radicals generated by purine/xanthine oxidase (P/XO), followed by a 15-minute washout (n=6). Oxygen radical pretreatment significantly improved postischemic recovery of contractile function. We then investigated in another branch of the study whether this preconditioning effect would also reduce infarct size and whether it was mediated by protein kinase C activation. Control hearts were subjected to coronary artery occlusion for 30 minutes, followed by 2.5 hours of reperfusion (n=6). A second group, before coronary occlusion, was exposed to oxygen radicals and washout as described (n=8). A third group was subjected to oxygen radical infusion, but an inhibitor of protein kinase C (polymyxin B, 50 μmol/L) was administered throughout subsequent ischemia (n=7). A fourth group was exposed to oxygen radicals in the presence of scavengers (superoxide dismutase, 250 U/mL; catalase 500, U/mL; n=8). Pretreatment with oxygen radicals markedly reduced infarct size, from 65±19% of risk region in controls to 12±4% ( P <.05). Protein kinase C inhibition significantly attenuated this effect (infarct size, 37±9% of risk region; P <.05 versus P/XO; P =NS versus controls). Oxygen radical–induced preconditioning was prevented by scavengers (infarct size, 55±14% of risk region; P <.05 versus P/XO; P =NS versus P/XO+polymyxin B). Our data show that in the absence of ischemia, exposure to low concentrations of oxygen radicals can reproduce the beneficial effects of ischemic preconditioning on infarct size and postischemic recovery of left ventricular function. Thus, oxygen radicals might be potential contributors to ischemic preconditioning.
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UCPs 1-4 are believed to induce an inward proton leak in charged mitochondria.
“A small class of “uncoupling” proteins, called UCPs 1–4, are believed to induce an inward proton “leak” in charged mitochondria (49, 55, 176, 300).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [300]
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MODIFICATION OF OXIDATIVE STRESS IN RESPONSE TO INTESTINAL PRECONDITIONING1
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- Authors
- Tritto, I., D’Andrea, D., Eramo, N., Scognamiglio, A., De Simone, C., Violante, A., Esposito, A., Chiariello, M., & Ambrosio, G.
- Affiliations
- University of Perugia (IT)
- From the Divisions of Cardiology (D.D’A., N.E., A.S., C. De S., A.V., A.E., M.C.), “Federico II” School of Medicine, Naples, Italy, and the University of Perugia School of Medicine (I.T., G.A.), Perugia, Italy.
- Venue
- Circulation Research
- Published
- 1997-05
- Volume
- 80
- Issue
- 5
- Pages
- 743-748
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2144640999
- Cited by
- 288
- References
- 33
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 8 · 2015: 7 · 2014: 8 · 2013: 12 · 2012: 8
- FWCI
- 7.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- oxygen free radicals, ischemic preconditioning, myocardial infarct size, protein kinase C, superoxide dismutase, catalase, radical scavengers, polymyxin B, coronary artery occlusion, ischemia-reperfusion injury, left ventricular function
- MeSH terms
- Analysis of Variance, Animals, Anti-Bacterial Agents, Catalase, Coronary Circulation, Enzyme Activation, Female, Free Radicals, Hemodynamics, Myocardial Infarction, Polymyxin B, Protein Kinase C, Rabbits, Superoxide Dismutase, Time Factors, Myocardial Reperfusion, Free Radical Scavengers, Myocardial Ischemia, Reactive Oxygen Species, Ischemic Preconditioning, Myocardial, In Vitro Techniques
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