Comparison of the effect of left ventricular volume and pressure overload on β-adrenoceptor density in left heart valvular disease

Abstract

The sympathetic responses in left heart valvular disease may depend on the ventricular load conditions. We proposed to evaluate this possibility by comparing the effects of left ventricular pressure (LVP) and volume (LVV) overload on β-adrenoceptor density and ligand binding affinity in lymphocytes and in the four myocardial chambers in rheumatic heart valvular patients. Receptor activity was determined by radioligand binding using [ 125I]iodocyanopindolol. In the lymphocytes ( n = 45), the β-adrenoceptor density was reduced by 88% ( P < 0.001) in LVP patients ( n = 15) and 79% ( P < 0.001) in LVV patients ( n = 30) compared with 23 controls. In the myocardium, the receptor density of the LVP ( n = 12) was attenuated by 55% ( P < 0.05) in the left ventricle, 42% in the right ventricle, 13% in the left atrium, and 37% in the right atrium, while in LVV patients ( n = 22) it decreased by 73% ( P < 0.01) in the left ventricle, 62% ( P < 0.05) in the right ventricle, 30% in the left atrium, and 34% in the right atrium compared with 15 controls. Thus, the reduction in density was greatest in lymphocytes and least in the atria in both groups. The decrease in ventricular density of the LVV group was similar to the reduction in the lymphocytes and two-fold higher than in the atrial density. These alterations were significantly greater for the LVV than for the LVP group. The K d for the myocardial receptor binding to [ 125I]iodocyanopindolol was not significantly influenced in either group, but was lower in the lymphocytes. These findings suggest that in patients with left heart valvular disease, there is a significant attenuation in both peripheral and myocardial β-adrenoceptor density. The decrease in receptor density is significantly greater in the left ventricular volume overload than in the left ventricular pressure overload patients.