Home LiteratureArticle Details
PMID: 2723059 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Effects of exogenous free radicals on electromechanical function and metabolism in isolated rabbit and guinea pig ventricle. Implications for ischemia and reperfusion injury.

The Journal of clinical investigation ·Vol. 83 ·No. 6 ·1989-06-00 ·Pages 1800-9

Goldhaber JI, Ji S, Lamp ST, Weiss JN

Abstract

Oxygen-derived free radicals have been implicated in the pathogenesis of cardiac dysfunction during ischemia, postischemic myocardial "stunning," and reperfusion injury. We investigated the effects of oxygen-derived free radicals on cardiac function in intact isolated rabbit hearts and single guinea pig ventricular myocytes. In the intact rabbit ventricle, exposure to free radical-generating systems caused increased cellular K+ efflux, shortening of the action potential duration, changes in tension, and depletion of high energy phosphates similar to ischemia and metabolic inhibition. In patch-clamped single ventricular myocytes, free radical-generating systems activated ATP-sensitive K+ channels, decreased the calcium current, and caused cell shortening by irreversibly inhibiting glycolytic and oxidative metabolism. The results suggest that free radicals generated during ischemia and reperfusion may contribute to electrophysiologic abnormalities and contractile dysfunction by inhibiting glycolysis and oxidative phosphorylation. Inhibition of metabolism by free radicals may be an important factor limiting functional recovery from an ischemic insult after reestablishment of effective blood flow.

MeSH Terms
Adenosine Triphosphate/physiology Animals Electrophysiology Free Radicals Glycolysis/drug effects Guinea Pigs Heart Ventricles/drug effects,metabolism,pathology Hydrogen Peroxide/toxicity Male Myocardial Reperfusion Injury/metabolism,pathology,physiopathology Myocardium/metabolism,pathology Oxygen Consumption/drug effects Potassium Channels/drug effects,physiology Rabbits
Chemicals
Free Radicals Potassium Channels Adenosine Triphosphate Hydrogen Peroxide
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Goldhaber J I
Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90024.
Ji S
Lamp S T
Weiss J N
References (49)
49 references, click to expand
  1. Inhibitory effect of superoxide radicals on cardiac myofibrillar ATPase activity.
    Ital J Biochem. 1985 Jul-Aug;34(4):267-74 PMID: 2997080
  2. Damage to proteins, enzymes, and amino acids by peroxidizing lipids.
    Arch Biochem Biophys. 1966 Jan;113(1):5-8 PMID: 4161330
  3. A uniform enzymatic method for dissociation of myocytes from hearts and stomachs of vertebrates.
    Am J Physiol. 1985 Nov;249(5 Pt 2):H1056-60 PMID: 2998207
  4. The oxygen free radical system: a fundamental mechanism in the production of myocardial necrosis.
    Prog Cardiovasc Dis. 1986 May-Jun;28(6):449-62 PMID: 3010377
  5. Reperfusion-induced arrhythmias and oxygen-derived free radicals. Studies with "anti-free radical" interventions and a free radical-generating system in the isolated perfused rat heart.
    Circ Res. 1986 Mar;58(3):331-40 PMID: 3087653
  6. Myocardial ischemia revisited. The osmolar load, membrane damage, and reperfusion.
    J Mol Cell Cardiol. 1986 Aug;18(8):769-80 PMID: 3746924
  7. Mechanism of calcium potentiation of oxygen free radical injury to renal mitochondria. A model for post-ischemic and toxic mitochondrial damage.
    J Biol Chem. 1986 Oct 25;261(30):14201-8 PMID: 2876985
  8. O2 free radical-mediated myocardial and vascular dysfunction.
    Am J Physiol. 1986 Dec;251(6 Pt 2):H1225-31 PMID: 3789177
  9. Evidence for a reversible oxygen radical-mediated component of reperfusion injury: reduction by recombinant human superoxide dismutase administered at the time of reflow.
    Circulation. 1987 Jan;75(1):282-91 PMID: 3791610
  10. O2 free radicals: cause of ischemia-reperfusion injury to cardiac Na+-K+-ATPase.
    Am J Physiol. 1987 Feb;252(2 Pt 2):H252-7 PMID: 3028176
  11. Pathophysiology and pathogenesis of stunned myocardium. Depressed Ca2+ activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts.
    J Clin Invest. 1987 Mar;79(3):950-61 PMID: 3818956
  12. Direct measurement of free radical generation following reperfusion of ischemic myocardium.
    Proc Natl Acad Sci U S A. 1987 Mar;84(5):1404-7 PMID: 3029779
  13. Free radicals and reperfusion-induced arrhythmias: protection by spin trap agent PBN in the rat heart.
    Circ Res. 1987 Mar;60(3):375-83 PMID: 3581446
  14. Neutrophil-mediated vascular injury.
    Acta Med Scand Suppl. 1987;715:123-9 PMID: 3296674
  15. Proarrhythmic effects of an oxygen-derived free radical generating system on action potentials recorded from guinea pig ventricular myocardium: a possible cause of reperfusion-induced arrhythmias.
    Circ Res. 1987 Jul;61(1):50-4 PMID: 3038367
  16. Oxypurinol limits myocardial stunning but does not reduce infarct size after reperfusion.
    Circulation. 1987 Sep;76(3):678-86 PMID: 3621527
  17. Glycolysis preferentially inhibits ATP-sensitive K+ channels in isolated guinea pig cardiac myocytes.
    Science. 1987 Oct 2;238(4823):67-9 PMID: 2443972
  18. Effects of oxygen radicals on substrate oxidation by cardiac myocytes.
    Biochim Biophys Acta. 1987 Nov 6;926(2):127-31 PMID: 2822138
  19. Role of changes in [Ca2+]i in energy deprivation contracture.
    Circ Res. 1987 Nov;61(5):726-34 PMID: 3664978
  20. Rate-tension staircase in rabbit ventricular muscle: relation to ionic exchange.
    Am J Physiol. 1967 Nov;213(5):1115-24 PMID: 6054857
  21. Quantitative aspects of the production of superoxide anion radical by milk xanthine oxidase.
    J Biol Chem. 1970 Aug 25;245(16):4053-7 PMID: 5496991
  22. Effects of strophanthidin upon contraction and ionic exchange in rabbit ventricular myocardium: relation to control of active state.
    J Mol Cell Cardiol. 1970 Mar;1(1):65-90 PMID: 4106468
  23. Mitochondrial production of superoxide radical and hydrogen peroxide.
    Adv Exp Med Biol. 1977;78:67-82 PMID: 197811
  24. The biology of oxygen radicals.
    Science. 1978 Sep 8;201(4359):875-80 PMID: 210504
  25. Dissociation of energetic state and potassium loss from anoxic myocardium.
    Am J Physiol. 1978 Nov;235(5):H537-43 PMID: 727275
  26. Metabolic products and myocardial ischemia.
    Am J Pathol. 1981 Feb;102(2):282-91 PMID: 7008624
  27. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
    Pflugers Arch. 1981 Aug;391(2):85-100 PMID: 6270629
  28. [K+]o accumulation and electrophysiological alterations during early myocardial ischemia.
    Am J Physiol. 1982 Aug;243(2):H318-27 PMID: 7114241
  29. The effect of superoxide generation on the ability of mitochondria to take up and retain Ca2+.
    FEBS Lett. 1982 Sep 20;146(2):267-72 PMID: 6291991
  30. The role of lipid peroxidation in pathogenesis of ischemic damage and the antioxidant protection of the heart.
    Basic Res Cardiol. 1982 Sep-Oct;77(5):465-85 PMID: 7181828
  31. Mediation of sarcoplasmic reticulum disruption in the ischemic myocardium: proposed mechanism by the interaction of hydrogen ions and oxygen free radicals.
    Adv Exp Med Biol. 1983;161:377-89 PMID: 6307008
  32. Phosphorus-31 nuclear magnetic resonance studies of single muscle cells isolated from barnacle depressor muscle.
    Biochemistry. 1983 Jul 5;22(14):3531-6 PMID: 6615782
  33. Effect of superoxide generation on rat heart mitochondrial pyruvate utilization.
    J Mol Cell Cardiol. 1983 Dec;15(12):859-62 PMID: 6319722
  34. Canine myocardial reperfusion injury. Its reduction by the combined administration of superoxide dismutase and catalase.
    Circ Res. 1984 Mar;54(3):277-85 PMID: 6697450
  35. Free radical mediation of the effects of acidosis on calcium transport by cardiac sarcoplasmic reticulum in whole heart homogenates.
    Cardiovasc Res. 1984 Mar;18(3):149-57 PMID: 6322991
  36. Myocardial alterations due to free-radical generation.
    Am J Physiol. 1984 Jun;246(6 Pt 2):H776-83 PMID: 6331179
  37. Differential sensitivity of canine cardiac sarcolemmal and microsomal enzymes to inhibition by free radical-induced lipid peroxidation.
    Circ Res. 1984 Jul;55(1):120-4 PMID: 6086170
  38. Ischemia and reperfusion-induced arrhythmias in the rat. Effects of xanthine oxidase inhibition with allopurinol.
    Circ Res. 1984 Oct;55(4):545-8 PMID: 6548176
  39. Molecular oxygen: friend and foe. The role of the oxygen free radical system in the calcium paradox, the oxygen paradox and ischemia/reperfusion injury.
    J Mol Cell Cardiol. 1984 Nov;16(11):969-85 PMID: 6394765
  40. Functional compartmentation of glycolytic versus oxidative metabolism in isolated rabbit heart.
    J Clin Invest. 1985 Feb;75(2):436-47 PMID: 3973013
  41. Superoxide dismutase enhances recovery following myocardial ischemia.
    Am J Physiol. 1985 May;248(5 Pt 2):H637-43 PMID: 3993803
  42. Xanthine oxidase as a source of free radical damage in myocardial ischemia.
    J Mol Cell Cardiol. 1985 Feb;17(2):145-52 PMID: 3839024
  43. Alpha-adrenoceptor stimulation, lysophosphoglycerides, and lipid peroxidation in reoxygenation induced calcium uptake in rabbit myocardium.
    Cardiovasc Res. 1985 Apr;19(4):228-36 PMID: 2988776
  44. Properties of adenosine-triphosphate-regulated potassium channels in guinea-pig ventricular cells.
    J Physiol. 1985 Jun;363:441-62 PMID: 2410608
  45. Effect of some free radical scavengers on reperfusion induced arrhythmias in the isolated rat heart.
    J Mol Cell Cardiol. 1985 May;17(5):485-93 PMID: 3928898
  46. Therapeutic options to minimize free radical damage and thrombogenicity in ischemic/reperfused myocardium.
    Am Heart J. 1987 Nov;114(5):1206-15 PMID: 3314441
  47. Intracellular recording from moving tissues with a flexibly mounted ultramicroelectrode.
    Science. 1956 Jan 20;123(3186):100-1 PMID: 13281489
  48. Mitochondrial hydrogen peroxide generation and activities of glutathione peroxidase and superoxide dismutase following global ischemia.
    J Mol Cell Cardiol. 1987 Dec;19(12):1195-206 PMID: 3443986
  49. Myocardial reperfusion: a double-edged sword?
    J Clin Invest. 1985 Nov;76(5):1713-9 PMID: 4056048
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI114085
Published
1989-06-00
Pages
1800-9
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC303899
Subset
IM
Grants
NHLBI NIH HHS · 5T32 HL07412 · United States
NHLBI NIH HHS · KO4 HI-01890 · United States
NHLBI NIH HHS · R01 HL-36729 · United States
External Links
PubMed source DOI: 10.1172/JCI114085 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2