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January 1, 1995Circulation Research

External heart work of immunized guinea pigs was reduced by 54% (P < .005) compared with controls, and delta G(cyt-mit) declined from 4.9 to 2.3 kJ/mol ATP (P < .005), with a strong correlation between the two (r = .87).

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Why the study?

Does immunization with ADP-ATP carrier protein impair cardiac function and myocardial energy metabolism in guinea pigs?

Population

Guinea pigs immunized with the isolated ADP-ATP carrier protein

Comparison

Immunization with isolated ADP-ATP carrier protein vs Nonimmunized control guinea pigs

Design

Preclinical

Authors

HSHeinz‐Peter SchultheißKSKarsten SchulzeRSRolf Schauer

Discussion

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Overview

Supports immunopathic HF mechanisms in myocarditis models; leaves open translation to human dilated cardiomyopathy.

Key Points

  • This study aims to investigate how autoantibodies affect myocardial energy metabolism and cardiac function in guinea pigs.
  • Guinea pigs were immunized with the ADP-ATP carrier protein.
  • Cardiac function was assessed by measuring the external heart work of isolated perfused hearts and estimating the cytosolic-mitochondrial phosphorylation potential.
  • Aortic ligature and calcium stimulation were used for functional assessments.
  • External heart work of immunized guinea pigs decreased by 54% compared to controls (P < .005).
  • Phosphorylation potential (delta G(cyt-mit)) dropped from 4.9 kJ/mol ATP in controls to 2.3 kJ/mol ATP in immunized guinea pigs (P < .005).
  • A strong correlation (r = .87) was found between the decrease in delta G(cyt-mit) and reduced external heart work.

Structured PICO

Does immunization with ADP-ATP carrier protein impair cardiac function and myocardial energy metabolism in guinea pigs?

P
Population
Guinea pigs immunized with the isolated ADP-ATP carrier protein
I
Intervention
Immunization with isolated ADP-ATP carrier protein
C
Comparator
Nonimmunized control guinea pigs
O
Outcome
Cardiac function measured by external heart work (EHW) and electrogenic transport activity of the ADP-ATP carrier (cytosolic-mitochondrial difference of the phosphorylation potential of ATP [delta G(cyt-mit)])surrogate

Antibody-mediated ADP-ATP carrier dysfunction creates an imbalance in myocardial energy metabolism that correlates with impaired cardiac function, supporting an immunopathic mechanism for heart failure in myocarditis and dilated cardiomyopathy.

Cite This Study

Schultheiß et al. (1995) studied this question.

synapsesocial.com/papers/6a1c72c5107ed6dc7cc3d485https://doi.org/10.1161/01.res.76.1.64
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