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Related Experiment Videos

Inotropic responses change during postnatal maturation in rabbit.

M Artman1, P A Kithas, J S Wike

  • 1Department of Pediatrics, University of South Alabama College of Medicine, Mobile 36688.

The American Journal of Physiology
|August 1, 1988
PubMed
Summary

Newborn rabbit hearts show limited response to beta-adrenergic stimulation due to underdeveloped receptor-adenylate cyclase coupling, despite normal phosphodiesterase activity. This impacts inotropic drug effectiveness in early life.

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Area of Science:

  • Cardiovascular Physiology
  • Developmental Biology
  • Pharmacology

Background:

  • Neonatal cardiac function differs significantly from adult function.
  • Understanding age-related changes in myocardial contractility is crucial for pediatric pharmacology.
  • Beta-adrenergic signaling plays a key role in regulating heart muscle contraction.

Purpose of the Study:

  • To compare the inotropic responses of newborn, immature, and adult rabbit ventricular papillary muscles to various pharmacological stimuli.
  • To investigate the developmental changes in myocardial beta-adrenergic receptor function and cyclic adenosine monophosphate (cAMP) signaling pathways.
  • To assess the role of cAMP phosphodiesterase activity in age-dependent inotropic responses.

Main Methods:

  • Isolated right ventricular papillary muscles from rabbits of different age groups (newborn, immature, adult) were used.

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  • Muscles were exposed to pharmacological agents including forskolin, isoproterenol, milrinone, and sulmazole.
  • Adenylate cyclase activity and cAMP phosphodiesterase kinetics were analyzed.
  • Maximal rate of tension development was measured to assess inotropic response.

    • Main Results:

    • Forskolin, an adenylate cyclase activator, significantly increased tension development in newborns.
    • Isoproterenol's maximum response was only 45% of forskolin's in newborns, indicating impaired beta-adrenergic receptor coupling.
    • Milrinone, a cAMP hydrolysis inhibitor, was less effective in newborns compared to other age groups.
    • Sulmazole showed its maximal inotropic effect in immature myocardium, suggesting developmental changes in calcium sensitivity.

    Conclusions:

    • Neonatal rabbit myocardium exhibits incomplete physiological coupling of beta-adrenergic receptors to adenylate cyclase.
    • Age-related differences in inotropic responsiveness are not explained by changes in myocardial cytosolic cAMP phosphodiesterase activity.
    • Pharmacological interventions targeting cAMP pathways may have varying efficacy depending on the developmental stage of the heart.