Objectives: In heart failure cardiac sympathetic neuronal function and activity appear to be altered. Although these changes are widely accepted, controversy exists concerning the neurohormonal changes occurring in pressure and volume overloaded hearts. The present study in rabbits was performed to assess the effects of mechanical overload on cardiac sympathetic neuronal function and beta-adrenoceptor density, in relation to left ventricular function.
Methods: In nine rabbits the aortic valve was perforated to induce left ventricular volume overload. Pressure overload was induced by suprarenal banding of the aorta abdominalis (group 1). Five animals were sham operated (group 2). Subanalysis of group 1 was performed for non-failing (n = 5) and failing (n = 4) hearts. Heart failure was defined as any reduction in left ventricular fractional shortening 2 weeks after the second operation compared to baseline.
Results: In animals with cardiac overload, left ventricular weight was higher compared with the control animals, 7.99 +/- 1.13 vs. 6.16 +/- 0.86 g (P < 0.02). Left ventricular end diastolic diameter increased from 1.35 +/- 0.16 to 1.57 +/- 0.15 cm (P < 0.005) after surgically induced overload. Left ventricular end systolic diameter and fractional shortening did not change significantly. Myocardial noradrenaline (NA) concentration and beta-adrenoceptor density were significantly lower in group 1 than in group 2, 1005 +/- 393 vs. 1643 +/- 109 ng/g (P < 0.02) and 167 +/- 36 vs. 224 +/- 36 fmol/mg protein (P < 0.03), respectively. Myocardial [123I]-MIBG uptake did not significantly differ between group 1 and 2, 2.1 +/- 0.58 vs. 1.8 +/- 0.44 (%ID/g x kg). A significant positive correlation between myocardial NA concentration and beta-adrenoceptor density was found (r = 0.66, P < 0.02). Myocardial NA concentration was inversely related to left ventricular weight (r =-0.75, P < 0.003).
Conclusion: The present data indicate that in a condition of cardiac volume and pressure overload, sympathetic activity is enhanced as shown by myocardial noradrenaline depletion and beta-adrenoceptor downregulation. In contrast, no cardiac neuronal dysfunction is observed, even in the stage of early heart failure.