Marked difference in the sensitivity to endogenous vs exogenous norepinephrine in isolated heart

Infusion or Superinfusion of catecholamine in isolated preparations are widely used to study the effect of sympatheticactivation on the heart. However, the difference in myocardial effects of norephinephrine (NE) released by nerve terminals vs NE exogenously applied needs to be quantified, in order to meaningfully extrapolateto to the intact heart data obtained in isolated preparations.Langendorff perfused rats hearts were used. In the first group of experiments, NE vas infused to obtain stady-state NE concentrationranging from 1 to 1000 nMand the increase of heart rate (HR)at each concentration recorded (n=24). In the second group (n=12)Tyramine (1-10 microM)was infused, the increase in HR recorded and the effluent collected every 30 sec. for measuring (with HPLC) NE release by Tyramine.Increase in HR was plotted against both exogenous (group 1) and endogenous (group 2) NE concentration. The slope uf the curve by linear regression analysis was much higher for endogenous vs exogenous NE (99 vs 13 b/min-1 log[NE]-1. Also, the maximal increase in HR was significantly higer (142 +- 19 vs 68 +-16 b/min -1. This marked difference implies that (1)similar effect on pacemaker automaticity is obtained with NE concentration that are one-two order or magnitude higher for exogenous vs endogenous NE; (2) the maximal effect of exogenous NE is only a fraction of the chronotropic effect of NE released from nerve endings.