Differential Effects of Norepinephrine on Contractile Recovery of Rat Trabeculae Following Metabolic Inhibition

We have recently shown that norepinephrine (NE) pretreatment attenuates Ca2+overloading in cardiac rat trabeculae during metabolic inhibition (MI) with NaCN (2 mmol/l), and improves contractile recovery during a subsequent recovery period (RP). In the present study, we investigated the effects of the continuous presence of NE (1μmol/l), i.e. before, during and after MI, on Ca2+homeostasis maintenance and contractile recovery in the same model at 24°C. In addition, we tested the effects of NE when only present in the rigor period during MI. The continuous presence of NE both before (30 min) and during MI (120 min)+RP (60 min) (group NE-I) significantly increased the proportion of trabeculae that resumed to contract during RP from 46±4% (mean± ) in controls to 82±8%. The Ca2+rise at the end of MI in failing control trabeculae (1.85±0.04μmol/l) was more than doubled compared to recovering control preparations (0.78±0.02μmol/l). However, the time-course of the Ca2+rise during MI in recovering and failing NE-I preparations was similar, and eventually of the same magnitude as observed in failing control preparations (1.6±0.02 and 1.85±0.07μmol/l, respectively). In contrast, when NE was present only in the rigor period during MI (group NE-II) the proportion of recovering preparations decreased significantly to 27±9%. Similar to the control group, recovering and failing preparations in group NE-II could be distinguished by a differential course in the Ca2+rise during MI. The results show that when NE is present both before and during MI+RP, (i) recovery probability following MI is still improved, in spite of the deleterious effect on contractile recovery of the presence of NE in the rigor during MI, and (ii) there is no relationship between the magnitude of Ca2+overload during MI and recovery probability during RP.