Mechanical Unloading Versus Neurohumoral Stimulation on Myocardial Structure and Endocrine Function In Vivo

O. Lisy, M. M. Redfield, S. Jovanovic, M. Jougasaki, A. Jovanovic, H. Leskinen, A. Terzic, J. C. Burnett
2000 Circulation  
Background-Mechanical load and humoral stimuli such as endothelin (ET) and angiotensin II (Ang II) 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
more » ... al 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 II. (Circulation. 2000;102:338-343.) Key Words: myocardium Ⅲ heart-assist device Ⅲ atrial natriuretic peptide Ⅲ endothelin Ⅲ angiotensin
doi:10.1161/01.cir.102.3.338 pmid:10899099 fatcat:iqmykwu7endh7o4oyoskg6zvwq