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May 3, 2005CirculationOpen Access

Forced Expression of α-Myosin Heavy Chain in the Rabbit Ventricle Results in Cardioprotection Under Cardiomyopathic Conditions

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Key result

Transgenic expression of alpha-MHC in rabbits subjected to rapid ventricular pacing improved shortening fraction, septal thinning, and +/-dP/dt compared to nontransgenic controls.

Why the study?

Does transgenic expression of alpha-MHC improve cardiac function in a rabbit model of tachycardia-induced cardiomyopathy?

Population

Transgenic rabbits and nontransgenic littermates subjected to rapid ventricular pacing to induce dilated…

Comparison

Transgenic expression of rabbit alpha-MHC cDNA… vs Nontransgenic (NTG) littermates

Design

Preclinical

Authors

JJJeanne JamesChildren's Hospital of WisconsinLMLisa MartinCincinnati Children's Hospital Medical CenterMKMaike KrenzUniversity of Missouri

Discussion

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Overview

Alpha-MHC re-expression may confer cardioprotection; leaves open whether isoform switching is a viable human therapeutic target.

Key Points

  • Investigate the physiological effects of alpha-MHC expression in the rabbit heart under cardiomyopathic conditions.
  • Developed transgenic rabbits expressing alpha-MHC cDNA in the ventricle to replace endogenous myosin.
  • Compared transgenic (TG) rabbits with nontransgenic (NTG) littermates under baseline and stress conditions.
  • Assessed molecular, histological, and functional parameters post rapid ventricular pacing.
  • Both TG and NTG rabbits developed dilated cardiomyopathy after pacing; however, TG rabbits showed a higher shortening fraction (p<0.05).
  • TG rabbits exhibited less septal thinning than NTG rabbits (p<0.05).
  • Normal +/-dP/dt was improved in TG rabbits compared to NTG rabbits under stress.

Structured PICO

Does transgenic expression of alpha-MHC improve cardiac function in a rabbit model of tachycardia-induced cardiomyopathy?

P
Population
Transgenic and nontransgenic rabbits subjected to rapid ventricular pacing to induce dilated cardiomyopathy.
I
Intervention
Transgenic expression of rabbit alpha-MHC cDNA in the ventricle
C
Comparator
Nontransgenic (NTG) littermates
O
Outcome
Cardiac function and remodeling (shortening fraction, septal thinning, +/-dP/dt)surrogate

Forced expression of alpha-MHC in the rabbit ventricle provides cardioprotection against tachycardia-induced cardiomyopathy, suggesting a potential functional advantage of this isoform in failing hearts.

Cite This Study

James et al. (2005) studied Tachycardia-induced cardiomyopathy. Transgenic expression of alpha-MHC vs. Nontransgenic (NTG) littermates was evaluated on Shortening fraction, septal thinning, and +/-dP/dt. Transgenic expression of alpha-MHC in rabbits subjected to rapid ventricular pacing improved shortening fraction, septal thinning, and +/-dP/dt compared to nontransgenic controls.

synapsesocial.com/papers/6a63f3ea94d8bae735b37bb4https://doi.org/10.1161/01.cir.0000164233.09448.b1
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Also Consider

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

  1. 1Functional consequences of altered cardiac myosin isoenzymes1986 · 34 citations
  2. 2Differential expression of cardiac ANP and BNP in a rabbit model of progressive left ventricular dysfunction2001 · 58 citations
  3. 3The economy of isometric force development, myosin isoenzyme pattern and myofibrillar ATPase activity in normal and hypothyroid rat myocardium.1985 · 209 citations
  4. 4Changes in Titin Isoform Expression in Pacing-Induced Cardiac Failure Give Rise to Increased Passive Muscle Stiffness2002 · 184 citations
  5. 5Transgenic Rabbit Model for Human Troponin I–Based Hypertrophic Cardiomyopathy2005 · 74 citations