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Masahiro Yasutake, Metin Avkiran, Exacerbation of reperfusion arrhythmias by α1 adrenergic stimulation: a potential role for receptor mediated activation of sarcolemmal sodium-hydrogen exchange, Cardiovascular Research, Volume 29, Issue 2, February 1995, Pages 222–230, https://doi.org/10.1016/S0008-6363(96)88574-9
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Abstract
Objective: Stimulation of myocardial α1 adrenoceptors causes (1) exacerbation of reperfusion induced arrhythmias, and (2) stimulation of sarcolemmal Na+/H+ exchange. The aims of this study were to identify the α1 adrenoceptor subtype involved in the former effect and to determine whether stimulation of the Na+/H+ exchanger may play a role in this phenomenon. Methods: Isolated rat hearts were subjected to independent perfusion of the left and right coronary beds. After 15 min of aerobic perfusion of both beds, the α1 adrenoceptor agonist phenylephrine (0.1, 1, or 10 μM) was infused selectively into the left coronary bed for 2 min. The left coronary bed was then subjected to 7 min of zero flow ischaemia and 5 min of reperfusion. Results: The incidence of reperfusion induced ventricular fibrillation was increased from 0% in controls to 8%, 42%*, and 75%* with 0.1, 1, and 10 μM phenylephrine (* P < 0.05); this dose dependent effect occurred in the absence of significant intergroup differences in vascular resistance or heart rate. Similar infusion of methoxamine at 10 μM also increased the incidence of reperfusion induced ventricular fibrillation from 13% to 88%*. Infusion of 10 μM phenylephrine during reperfusion alone did not affect the incidence of reperfusion induced ventricular fibrillation. Infusion of the selective α1A adrenoceptor antagonist WB4101 at 0.1, 1, or 10 μM for 2 min immediately before ischaemia (concomitantly with 10 μM phenylephrine) reduced the incidence of reperfusion induced ventricular fibrillation from 83% to 75%, 25%*, and 0%*. Similar infusion of the selective α1B adrenoceptor antagonist chloroethylclonidine (0.1 or 1 μM) or the selective β1 adrenoceptor antagonist atenolol (0.1 or 1 μM) did not reduce the incidence of reperfusion induced ventricular fibrillation. The novel NHE-1 selective Na+/H+ exchange inhibitor HOE694 (10 μM), when infused into the left coronary bed before ischaemia (concomitantly with 10 μM phenylephrine) and throughout reperfusion, reduced the incidence of reperfusion induced ventricular fibrillation from 83% to 25%*. In hearts that received 10 μM phenylephrine before ischaemia. HOE694 (10 μM) was partially effective when infused during reperfusion alone (ventricular fibrillation incidence reduced from 83% to 42%). Conclusions: (1) the exacerbation of reperfusion induced arrhythmias by α1 adrenergic stimulation during ischaemia is mediated by the α1A adrenoceptor subtype, and (2) increased Na+/H+ exchanger activity during ischaemia and reperfusion may play a causal role in this phenomenon.
