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June 1, 1993Journal of Clinical InvestigationOpen Access

Enhanced expression of superoxide dismutase messenger RNA in viral myocarditis. An SH-dependent reduction of its expression and myocardial injury.

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Why the study?

Does treatment with sulfhydryl-containing agents (captopril or MPG) improve survival and reduce myocardial injury in a murine model of viral myocarditis?

Population

4-week-old BALB/c mice inoculated with encephalomyocarditis virus.

Comparison

Captopril or N,2-mercapto-propionyl glycine once… vs Infected control mice given 0.1 ml of a glucose…

Design

Preclinical, Randomized on day 4, Histological examination performed by two…

Follow-up

14 days

Authors

HSHarukazu SuzukiRIKEN Center for Integrative Medical SciencesAMAkira MatsumoriKanazawa UniversityYMYoshiki MatobaBrigham and Women's Hospital

Discussion

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Implication

Hypothesis-generating for sulfhydryl agents in viral myocarditis; prospective human trials needed before clinical adoption.

Key Points

  • To investigate the role of oxygen free radicals in viral myocarditis pathogenesis and evaluate the therapeutic effects of sulfhydryl-containing antioxidant agents.
  • Inoculated 4-week-old BALB/c mice with encephalomyocarditis virus.
  • Administered captopril or N,2-mercaptopropionyl glycine (MPG), a sulfhydryl-containing agent lacking ACE inhibitor activity, from days 4 to 14 post-infection.
  • Assessed survival, histopathological myocardial injury (necrosis, cellular infiltration, calcification), and cardiac Mn-SOD and Cu/Zn-SOD mRNA expression levels on day 14.
  • Captopril and MPG significantly improved mouse survival and reduced myocardial necrosis, cellular infiltration, and calcification in a dose-dependent manner.
  • Viral infection caused an 8- to 13-fold induction of Mn-SOD mRNA and a 4- to 11-fold induction of Cu/Zn-SOD mRNA in infected hearts compared with uninfected controls.
  • MPG administration completely suppressed the upregulation of both Mn-SOD and Cu/Zn-SOD mRNAs even when treatment was delayed until day 4.

Structured PICO

Does treatment with sulfhydryl-containing agents (captopril or MPG) improve survival and reduce myocardial injury in a murine model of viral myocarditis?

P
Population
4-week-old BALB/c mice inoculated with encephalomyocarditis virus (n=238 total, including uninfected controls).
I
Intervention
Captopril (10, 30, or 100 mg/kg orally) or N,2-mercapto-propionyl glycine (MPG) (8, 25, or 75 mg/kg intraperitoneally) once daily from days 4 to 14.
C
Comparator
Infected control mice (placebo group) given 0.1 ml of a glucose solution orally or intraperitoneally.
O
Outcome
Survival and myocardial injury (necrosis, cellular infiltration, and calcification) on day 14.hard clinical

Sulfhydryl-containing compounds like captopril and MPG significantly improve survival and reduce myocardial injury in a murine model of viral myocarditis, likely by scavenging oxygen free radicals.

Cite This Study

Suzuki et al. (1993) studied this question.

synapsesocial.com/papers/6a7a22d414b028facf0e2e34https://doi.org/10.1172/jci116513

Topics

Myocarditis
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1An experimental model for congestive heart failure after encephalomyocarditis virus myocarditis in mice.1982 · 127 citations
  2. 2INHIBITION OF CELL FUNCTIONS BY RNA-VIRUS INFECTIONS1984 · 83 citations
  3. 3Relationships between structure and effects of ACE inhibitors: comparative effects in myocardial ischaemic/reperfusion injury.1989 · 48 citations
  4. 4MYOCARDITIS AND DILATED CARDIOMYOPATHY1987 · 83 citations
  5. 5Cardiac persistence of cardioviral RNA detected by polymerase chain reaction in a murine model of dilated cardiomyopathy.1992 · 76 citations