Related Experiment Videos
Are oxygen radicals implicated in the calcium paradox of the rat heart?
1Zoology Department, School of Life Sciences, Liverpool University, England.
Insights
This study found that oxygen radicals do not cause creatine kinase (CK) release during calcium paradox in rat hearts. Various antioxidants and radical scavengers failed to protect against CK release, refuting the oxygen radical hypothesis.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
- Cellular Biology
Background:
- The calcium paradox is a phenomenon where heart cells experience damage upon reperfusion with calcium after a period of calcium deprivation.
- Creatine kinase (CK) release is a marker of cellular damage in cardiac tissue.
- The role of oxygen radicals in mediating this damage has been hypothesized but not definitively proven.
Purpose of the Study:
- To investigate the potential involvement of oxygen radicals in creatine kinase (CK) release during the calcium paradox in isolated rat hearts.
- To assess the efficacy of various antioxidant and radical scavenging agents in preventing CK release under calcium paradox conditions.
Main Methods:
- Langendorff-perfused rat heart model was used to induce calcium paradox.
- Hearts were perfused with various agents including anoxic perfusion, superoxide dismutase, catalase, mannitol, dimethylthiourea (DMTU), vitamin E, and desferrioxamine.
- CK release was measured as an indicator of cellular damage.
- Mild calcium paradox conditions were also tested.
Main Results:
- Anoxic perfusion did not reduce CK release.
- Radical scavengers (superoxide dismutase, catalase, mannitol, DMTU), antioxidant (vitamin E), and iron chelator (desferrioxamine) did not prevent CK release.
- No protective effect was observed even under modified, milder calcium paradox conditions.
- Nitrogen perfusion did not reduce CK release caused by other agents.
Conclusions:
- The study provides no evidence to support the hypothesis that oxygen radicals are involved in creatine kinase release during the calcium paradox.
- The findings suggest that mechanisms other than oxygen radical generation are responsible for CK release in this model.
Abstract:
No reduction in creatine kinase (CK) release during standard Ca2+ paradox in the Langendorff-perfused rat heart was afforded by anoxic perfusion, nor by addition of the radical scavengers superoxide dismutase (150,000 U/L), catalase (150,000 U/L), mannitol (15 or 50 mM), dimethylthiourea (DMTU, 10 mM), the antioxidant vitamin E (0.25 or 0.75 mM), or the iron chelator desferrioxamine (0.8 mM). Even under mild Ca(2+)-paradox conditions, achieved by (a) reducing the duration of the Ca(2+)-free period, (b) increasing [Ca2+]0 during the "Ca(2+)-free" period, or (c) reperfusing with 0.1 mM Ca2+, no protection was achieved by mannitol, DMTU, or desferrioxamine. Perfusion with N2 did not cause a reduction in CK release caused by caffeine or dinitrophenol or Ca2+ paradox. We conclude that no evidence supports the hypothesis that oxygen radicals are implicated in release of CK in Ca2+ paradox.