| الوصف: |
There is substantial evidence to suggest that the sympathetic nervous system is intimately involved in the development of ventricular arrhythmias during acute myocardial ischaemia. Nevertheless factors controlling myocardial noradrenaline (NA) release during ischaemia are only partly understood. Therefore, the effect or duration and severity of ischaemia on neuronal NA release (left stellate ganglion stimulation, 5Hz) was studied using a perfused, innervated rat heart model. The effect of ischaemia on presynaptic inhibition by α-adrenergic, muscarinic and purinergic receptors was also examined. There is higher density of α-adrenoceptors in female tissues but it is not clear whether there is a gender difference in presynaptic inhibitory mechanisms. NA overflow progressively declined during 10 min stop-flow ischaemia, but was maintained for up to 60 min during less severe ischaemia (95% flow reduction). α-Adrenergic or purinergic antagonists increased NA overflow during low-flow but not stop-flow ischaemia. In normoxic hearts, neuronal NA overflow was inhibited by vagal nerve stimulation (VS, 15 Hz) but not after 10 min low-flow or 1-5 min stop-flow ischaemia. The loss of VS-induced inhibition of NA overflow during ischaemia may be due to enhanced α-adrenergic presynaptic inhibition of acetylcholine release, since an α-adrenoceptor antagonist could restore this effect. The inhibitory effect of the muscarinic agonist methacholine on NA overflow was also attenuated by low-flow or stop-flow ischaemia, indicating a dysfunction of muscarinic presynaptic receptors. The effect of gender on α-adrenergic presynaptic inhibition of neuronal NA release was also studied. In normoxic hearts, NA overflow by control nerve stimulation was similar. The α-adrenergic inhibitor rauwolscine potentiated NA overflow more in female (F) than in male (M) hearts, both during normoxia and ischaemia. Ovariectomy attenuated α-adrenergic presynaptic inhibition of NA overflow. During normoxia, presynaptic inhibition of neuronal NA overflow by VS was greater in F than in M hearts but methacholine reduced NA overflow equally in F and M hearts. In conclusion, sympathetic nerve stimulation leads to ischaemic-reperfusion arrhythmias. The antiarrhythmic effect of VS and of dietary polyunsaturated fatty acids cannot be explained by presynaptic modulation of NA release. Cardiac neuronal function, especially sympathetic neurotransmitter release and presynaptic modulation, is affected by the severity of ischaemia, parasympathetic nervous activity and gender. |
