DIFFERENTIAL-EFFECTS OF NOREPINEPHRINE ON CONTRACTILE RECOVERY OF RATTRABECULAE FOLLOWING METABOLIC INHIBITION

We have recently shown that norepinephrine (NE) pretreatment attenuate s Ca2+ overloading in cardiac rat trabeculae during metabolic inhibiti on (MI) with NaCN (2 mmol/l), and improves contractile recovery during a subsequent recovery period (RP). In the present study, we investiga ted the effects of the continuous presence of NE (1 mu mol/l), i.e. be fore, during and after MI, on Ca2+ homeostasis maintenance and contrac tile recovery in the same model at 24 degrees C. In addition, we teste d the effects of NE when only present in the rigor period during MI. T he continuous presence of NE both before (30 min) and during MI (120 m in) + RP (60 min) (group NE-I) significantly increased the proportion of trabeculae that resumed to contract during RP from 46 +/- 4% (mean +/- S.E.M.) in controls to 82 +/- 8%. The Ca2+ rise at the end of MI i n failing control trabeculae (1.85 +/- 0.04 mu mol/l) was more than do ubled compared to recovering control preparations (0.78 +/- 0.02 mu mo l/l). However, the time-course of the Ca2+ rise during MI in recoverin g and failing NE-I preparations was similar, and eventually of the sam e magnitude as observed in failing control preparations (1.6 +/- 0.02 and 1.85 +/- 0.07 mu mol/l, respectively). In contrast, when NE was pr esent only in the rigor period during MI (group NE-II) the proportion of recovering preparations decreased significantly to 27 +/- 9%. Simil ar 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 d uring MI + RP, (i) recovery probability following MI is still improved , in spite of the deleterious effect on contractile recovery of the pr esence of NE in the rigor during MI, and (ii) there is no relationship between the magnitude of Ca2+ overload during MI and recovery probabi lity during RP. (C) 1998 Academic Press Limited.