Abstract
Although blunted cardiac response to sympathetic stimulation in patients with heart failure is usually attributed to myocardial beta1-adrenoceptor downregulation secondary to elevated circulating catecholamines, cardiomegaly per se may also play a role through presynaptic mechanisms such as reduction in cardiac norepinephrine (NE) concentration. To evaluate effects of cardiac dilatation on cardiac response to sympathetic stimulation, we studied left ventricular contractile and heart rate responses to plasma NE levels increased by exercise in 10 asymptomatic patients with a dilated left ventricle due to aotric regurgitation (AR), but with normal resting plasma NE levels, using 10 normal subjects and 10 patients with heart failure due to dilated cardiomyopathy (DCM) as controls. Plasma NE levels, systemic blood pressure, echocardiograph left ventricular dimensions, and heart rate were measured at rest, and at 3 submaximal levels of supine bicycle exercise. The ratio of peak systolic blood pressure to end-systolic dimension (P/D ratio), heart rate, and plasma NE increased with the intensity of exercise. In each subject, both P/D ratio and heart rate increased in a logarithmic manner against plasma NE levels. The solpe of the regression line for log (plasma NE)-P/D ratio relation, and that for log (plasma NE)-heart rate relation, were significantly less in patients with AR than in normal subjects (p<0.001 and p<0.05, respectively), and were less in patients with DCM than in patients with AR (p<0.005 and p=0.051, respectively). Thus, the left ventricular contractile and heart rate responses to sympathetic stimulation are blunted in patients with dilated hearts due to AR, even in the absence of overt heart failure and elevated plasma NE levels. These responses were further de-creased in patients with heart failure due to DCM. Cardiac responses to sym-
