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, such as anoxia, acidosis, and hyperkalemia, on exocytotic noradrenaline release 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 noradrenaline release (S2) was intraindividually compared with the release induced by a control stimulation (S1). In perfused hearts, 10 minutes of global ischemia caused a reduction of noradrenaline overflow in rat hearts (mean S2/S1,0.31), whereas the overflow was increased in guinea pig hearts (S2/S1, 1.89). This species-dependent effect may be caused by quantitatively different responses to facilitating and suppressing factors of noradrenaline release in both species. Anoxia and substrate-free perfusion increased noradrenaline overflow in guinea pig hearts (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 release in rat hearts (S2/S1, 0.16), whereas it had only a minor inhibiting effect in guinea pig hearts (S2/S1, 0.67). Hyperkalemia had a comparable effect in both species (S2/S1 at 15 mmol/L K⁺, 1.17 in rat and 1.14 in guinea pig; and S2/S1 at 20 mmol/L K⁺, 0.64 in rat and 0.41 in guinea pig). To obtain results regarding the modulation of noradrenaline release in human myocardium, human atrial tissue was incubated, and the effect of anoxia, acidosis, and hyperkalemia on stimulation-evoked noradrenaline release was investigated. Anoxia had a moderate facilitating effect on stimulation-evoked noradrenaline release (S2/S1, 1.20), whereas acidosis (S2/S1, 0.35) and hyperkalemia resulted in a suppression (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 pig atrial tissue, stimulation-evoked noradrenaline release was modulated by the same metabolic factors as in perfused hearts. In conclusion, stimulation-evoked noradrenaline release in ischemic myocardium is determined by facilitating and suppressing factors in guinea pig, rat, and human cardiac tissue. In human hearts, the suppressing factors dominate even more than in rat hearts, whereas in guinea pig hearts, the facilitating factors outweigh the suppressing factors during early myocardial ischemia.