EFFECT OF MYOCARDIAL-ISCHEMIA ON STIMULATION-EVOKED NORADRENALINE RELEASE - MODULATED NEUROTRANSMISSION IN RAT, GUINEA-PIG, AND HUMAN CARDIAC TISSUE

The effect of myocardial ischemia and its major metabolic changes, suc h as anoxia, acidosis, and hyperkalemia, on exocytotic noradrenaline r elease was investigated in rat, guinea pig, and human cardiac tissue. Noradrenaline release was evoked by electrical field stimulation, and the effect of each experimental intervention on stimulation-evoked nor adrenaline release (S2) was intraindividually compared with the releas e induced by a control stimulation (S1). In perfused hearts, 10 minute s of global ischemia caused a reduction of noradrenaline overflow in r at hearts (mean S2/S1, 0.31), whereas the overflow was increased in gu inea pig hearts (S2/S1, 1.89). This species-dependent effect may be ca used by quantitatively different responses to facilitating and suppres sing factors of noradrenaline release in both species. Anoxia and subs trate-free perfusion increased noradrenaline overflow in guinea pig he arts (S2/S1, 2.40) but had no significant effect in rat hearts (S2/S1, 0.75). Acidosis (pH 6.0) resulted in a suppression of noradrenaline r elease in rat hearts (S2/S1, 0.16), whereas it had only a minor inhibi ting effect in guinea pig hearts (S2/S1, 0.67). Hyperkalemia had a com parable effect in both species (S2/S1 at 15 mmol/L K+, 1.17 in rat and 1.14 in guinea pig; and S2/Sl at 20 mmol/L K+, 0.64 in rat and 0.41 i n guinea pig). To obtain results regarding the modulation of noradrena line release in human myocardium, human atrial tissue was incubated, a nd the effect of anoxia, acidosis, and hyperkalemia on stimulation-evo ked noradrenaline release was investigated. Anoxia had a moderate faci litating effect on stimulation-evoked noradrenaline release (S2/S1, 1. 20), whereas acidosis (S2/S1, 0.35) and hyperkalemia resulted in a sup pression (S2/S1 at 15 mmol/L K+, 0.63; and S2/S1 at 20 mmol/L K+, 0.03 ). When the same studies were performed in incubated rat and guinea pi g atrial tissue, stimulation-evoked noradrenaline release was modulate d by the same metabolic factors as in perfused hearts. In conclusion, stimulation-evoked noradrenaline release in ischemic myocardium is det ermined by facilitating and suppressing factors in guinea pig, rat, an d human cardiac tissue. In human hearts, the suppressing factors domin ate even more than in rat hearts, whereas in guinea pig hearts, the fa cilitating factors outweigh the suppressing factors during early myoca rdial ischemia.