CARDIAC SYMPATHETIC NEURONAL FUNCTION IN LEFT-VENTRICULAR VOLUME AND PRESSURE-OVERLOAD

Objectives: In heart failure cardiac sympathetic neuronal function and activity appear to be altered. Although these changes are widely acce pted, controversy exists concerning the neurohormonal changes occurrin g in pressure and volume overloaded hearts. The present study in rabbi ts was performed to assess the effects of mechanical overload on cardi ac sympathetic neuronal function and beta-adrenoceptor density, in rel ation to left ventricular function. Methods: In nine rabbits the aorti c valve was perforated to induce left ventricular volume overload. Pre ssure overload was induced by suprarenal banding of the aorta abdomina lis (group 1). Five animals were sham operated (group 2). Subanalysis of group 1 was performed for non-failing (n = 5) and failing (n = 4) h earts. Heart failure was defined as any reduction in left ventricular fractional shortening 2 weeks after the second operation compared to b aseline. Results: In animals with cardiac overload, left ventricular w eight 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 in creased from 1.35 +/- 0.16 to 1.57 +/- 0.15 cm (P < 0.005) after surgi cally induced overload. Left ventricular end systolic diameter and fra ctional shortening did not change significantly. Myocardial noradrenal ine (NA) concentration and beta-adrenoceptor density were significantl y 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 [I-123]-MIBG uptake did not significantly dif fer 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 concentratio n and beta-adrenoceptor density was found (r = 0.66, P < 0.02), Myocar dial 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 acti vity is enhanced as shown by myocardial noradrenaline depletion and be ta-adrenoceptor downregulation. In contrast, no cardiac neuronal dysfu nction is observed, even in the stage of early heart failure.