Mechanical unloading versus neurohumoral stimulation on myocardial structure and endocrine function in vivo

Ondrej Lisy, Margaret M. Redfield, Sofija Jovanovic, Michihisa Jougasaki, Aleksandar Jovanovic, Hanna Leskinen, Andre Terzic, John C. Burnett

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Background - Mechanical load and humoral stimuli such as endothelin (ET) and angiotensin II (Ang 11) are potent modulators of cardiac structure and endocrine function, specifically gene expression and production and release of atrial natriuretic peptide (ANP). We define the contribution of mechanical load compared with neurohumoral stimulation in vivo with specific focus on myocardial and circulating ANP during chronic myocardial unloading produced by thoracic inferior vena caval constriction (TIVCC). Methods and Results - TIVCC was produced by banding the IVC for 10 days in 7 dogs, whereas in the 6 control dogs, the band was not constricted. TIVCC was characterized by a decrease in cardiac output, right atrial pressure, and left ventricular (LV) end-diastolic diameter and marked activation of ET and Ang II in plasma and atrial and ventricular myocardium. Despite neurohumoral stimulation, LV mass index and myocyte diameters in unloaded hearts decreased, reflecting myocyte atrophy. The total number of myocytes in the LV remained unchanged. Atrial stores of ANP increased, but plasma ANP did not change, in association with a trend toward ANP gene expression to decrease in unloaded hearts. Conclusions - Chronic mechanical unloading of the heart results in myocardial atrophy and lack of activation of ANP synthesis despite marked neurohumoral stimulation by the growth promoters ET and Ang 11.

Original languageEnglish (US)
Pages (from-to)338-343
Number of pages6
Issue number3
StatePublished - Jul 18 2000


  • Angiotensin
  • Atrial natriuretic peptide
  • Endothelin
  • Heart-assist device
  • Myocardium

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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