Background. We have shown previously that norepinephrine (NE) uptake activity is reduced in the failing right ventricle of animals with right heart failure (RHF) produced by tricuspid avulsion and progressive pulmonary constriction. However, it is unknown whether this defect in neuronal NE uptake is related to reduction of noradrenergic nerve terminals or whether these changes also occur in animals with left heart failure (LHIF). It is also unknown whether increased NE release in heart failure contributes to the noradrenergic nerve abnormalities.Methods and Results. We measured myocardial NE content, NE uptake function, and noradrenergic nerve profiles in dogs with either RHF or LHF induced by rapid ventricular pacing. NE uptake activity was
Left ventriculography with simultaneous pressure micromanometry was performed in 11 normal control subjects and 17 patients with dilated cardiomyopathy (DCM). Left ventricular silhouettes in the right anterior oblique projection were divided into eight areas, and regional wall stress was computed by Janz's method in each area excluding the two most basal areas. Wall stress was higher in DCM patients than in control subjects (p<0.01). The percent area changes from end diastole to end systole in each area were lower in DCM patients than in control subjects (mean for six areas, 22+14% versus 54±9%o, respectively, p <0.01), but the coefficient of variation for the percent area changes in the six areas of the left ventricle in DCM patients was greater than that in control subjects (32±17% versus 15±4%, respectively, p<0.01), indicating regional differences in hypokinesis. There was a significant negative correlation between end-systolic regional wall stress and percent area change (r=-0.60 to -0.86, p<0.05) in each area. Thus, excessive regional afterload may play an important role in causing regional hypokinesis in DCM. (Circulation 1990;82:2075-2083 iffuse hypokinesis of the left ventricular wall D motion has been reported in patients with dilated cardiomyopathy (DCM).' However, recent studies on DCM with the use of left ventricular cineangiography2-5or radionuclide ventriculography6,7 suggest that left ventricular wall motion is not always diffusely hypokinetic and that regional differences in the degree of hypokinesis are frequently present. In clinical settings, patients with segmental wall motion abnormality may have better global left ventricular function and better prognosis than patients with diffuse wall motion abnormality.6 Thus, the importance of estimating left ventricular regional wall dynamics in patients with DCM has been emphasized.3-7
The reduction of myocardial Na,K-ATPase in CHF is limited to the alpha 3 isoform. Furthermore, because similar changes in myocardial ouabain-binding sites and Na,K-ATPase alpha 3 isoform were produced by chronic norepinephrine infusion, the decrease in the Na,K-ATPase in CHF is most likely mediated via excess sympathetic stimulation.
We used the rapid ventricular pacing model to examine myocardial norepinephrine (NE) uptake kinetics in congestive heart failure. Dogs subjected to pacing at 225 beats/min for 8 wk developed heart failure as evidenced by elevated left atrial pressure, depressed first derivative of left ventricular pressure with respect to time, and depressed cardiac output compared with dogs paced at 100 beats/min for 8 wk. Fast-paced dogs also exhibited an elevated plasma NE and reduced myocardial NE content. Myocardial NE uptake kinetics and interstitial NE concentration were measured in vivo using a triple-isotope intracoronary tracer technique. The rate constant of neuronal uptake of NE was significantly depressed in the fast-paced animals (0.224 +/- 0.027 vs. 0.725 +/- 0.097 s-1, P < 0.001), while the interstitial NE concentration was significantly increased in the heart (1.12 +/- 0.15 vs. 0.17 +/- 0.07 ng/ml, P < 0.001). Myocardial beta-adrenoceptor density was significantly reduced in the fast-paced animals (49 +/- 7 vs. 86 +/- 6 fmol/mg, P < 0.001), and there was a significant inverse correlation between beta-adrenoceptor density and interstitial NE concentration. Thus we conclude that excess myocardial interstitial NE content contributes to the abnormalities in the beta-adrenoceptor system.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.