EFFECTS OF NEURONAL BLOCKADE OF NORADRENALINE REUPTAKE IN AN EXPERlMENTAL MODEL OF HEART FAILURE

We investigated neuronal uptake of noradrenaline (NA) at the level of larger vessels (thoracic aorta and vena cava left renal artery and left renal vein lateral saphenous artery and lateral saphenous vein and finally central ear artery and marginal ear vein) in a model devised to mimic heart failure. The model presented here is the rabbit coronary ligation model in which myocardial infarction was produced in male New Zealand white rabbits (2.6kg-3.0kg) by ligation of the marginal branch of the left descending coronary artery. The development of chronic heart failure was allowed to proceed over eight weeks. Animals were killed by overdose with pentobarbitone sodium (IV injection). Arteries and veins were carefully removed with as little connective tissue as possible and placed in cold physiological salt solution (PSS). The arterial and venous lings were mounted in 10mL isolated organ baths, bathed in Krebs maintained at 37°C and gassed with 95% O2 plus 5% CO2. The rings were then placed under different resting tensions. They were allowed to equilibrate for 1 hour before the experiments. Initially all tissues were exposed to cumulative concentrations of NA (lnM-300µM). Following complete washout, the preparations were left for 45 minutes to re-equilibrate. After preincubation with cocaine (10µM) for 10-15 minutes to inhibit neuronal uptake of NA, final NA cumulative concentration-response curves (CCRC) were conducted. Alierial plasma noradrenaline is 163% higher in patients with heart failure than in control patients. High plasma noradrenaline correlates directly with the hemodynamic severity of the disease and inversely with survival. Activation of the sympathetic nervous and renin-angiotensin systems may be important in the pathophysiology of heart failure associated with severity of the disease. Elevated levels of circulating noradrenaline in heart failure may result from impaired peripheral reuptake of this catecholamine. Cocaine has generally been used as the prototype drug for inhibition of neuronal uptake of catecholamines. The aim of our study was to investigate the possibility of changing reuptake of noradrenaline by using cocaine in this model of heart failure. In conclusion, effects of cocaine on noradrenaline responses were identical in sham operated compared with coronary ligated rabbits. These results suggest normal neuronal uptake of noradrenaline in this model of heart failure.