November 15, 1996Circulation
Selective Effects of Oxygen Free Radicals on Excitation-Contraction Coupling in Ventricular Muscle
Population
Trabeculae from the right ventricles of rat hearts loaded iontophoretically with fura-2
Design
Preclinical
Follow-up
10 to 20 minutes
Authors
Discussion
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Implication
Findings in isolated muscle do not yet inform clinical management of stunning; extends mechanistic understanding of radical-specific effects on Ca2+ handling.
Key Points
- Determine how direct exposure to distinct oxygen free radical-generating systems causes contractile dysfunction in cardiac muscle and evaluate whether these changes mimic myocardial stunning.
- Measured intracellular calcium ([Ca2+]i) using fura-2 in rat right ventricular trabeculae alongside steady-state force-[Ca2+]i relationships.
- Exposed muscle strips to either H2O2 + Fe3+ to produce hydroxyl radicals for 10 minutes or xanthine oxidase plus purine (XO + P) to produce superoxide for 20 minutes.
- Hydroxyl radical exposure decreased twitch force from 41 ± 7 to 23 ± 4 mN/mm2 (P < .05) and Ca2+ transient amplitude from 0.96 ± 0.09 to 0.70 ± 0.05 µmol/L (P < .05), with no change in Ca50.
- Superoxide exposure decreased twitch force from 50 ± 9 to 39 ± 8 mN/mm2 (P < .05) without altering Ca2+ transients, while increasing Ca50 from 0.71 ± 0.06 to 1.07 ± 0.07 µmol/L (P < .05).
Structured PICO
P
Population
Trabeculae from the right ventricles of rat hearts loaded iontophoretically with fura-2
I
Intervention
Exposure to exogenous oxygen free radical-generating systems: H2O2 + Fe(3+)-nitrilotriacetic acid (H2O2 + Fe3+) for 10 minutes, or xanthine oxidase+purine (XO + P) for 20 minutes
O
Outcome
Twitch force, Ca2+ transients, maximal Ca(2+)-activated force (Fmax), Ca50, and Hill coefficientsurrogate
Exogenously generated oxygen free radicals, particularly those produced by xanthine oxidase and purine, mimic the effects of myocardial stunning on cardiac excitation-contraction coupling by decreasing myofilament Ca2+ sensitivity.
Cite This Study
Gao et al. (1996) studied this question.