Endogenous adenosine reduces depression of cardiac function induced by beta-adrenergic stimulation during low flow perfusion.
Endogenous adenosine reduces depression of cardiac function induced by beta-adrenergic stimulation during low flow perfusion.
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内源性腺苷可减少低流量灌注期间β-肾上腺素能刺激引起的心脏功能抑制。
DOI：
10.1016/s0022-2828(95)92055-2
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发表时间：
1995
影响因子：
5
通讯作者：
DobsonJr,JG
中科院分区：
文献类型：
--
作者：
Fenton,RA;Galeckas,KJ;DobsonJr,JG
心脏中高水平的去甲肾上腺素具有心脏毒性，通过 β-肾上腺素受体介导的机制导致收缩功能障碍和心律失常。使用含有葡萄糖的生理盐水灌注并用氧气混合物鼓泡的低流量心脏模型来确定腺苷（一种具有抗肾上腺素能特性的核苷）是否可以减轻儿茶酚胺心脏毒性的功能表现。用二丙基环戊基黄嘌呤（DPCPX；0.1 μm；A1 受体拮抗剂）处理离体大鼠心脏以阻断内源性腺苷。在低流量 (0.5 ml/min) 预灌注 45 分钟期间用异丙肾上腺素 (ISO: 1 μm) 刺激的 DPCPX 处理的心脏中，恢复正常流量后 15 分钟时收缩功能 (ConF) 的恢复为对照（低流量之前）值的 64%，而在没有 ISO 的情况下 ConF 恢复为 110%。当用 DPCPX 阻断内源性腺苷的作用时，控制流恢复后观察到的心律失常的发生率会因 ISO 增加。在缺乏 DPCPX 的情况下，由 ISO 引起的功能性抑制和心律失常在苯基异丙基腺苷（PIA；1 μm；A1 受体激动剂）的存在下均得到预防。 15分钟后恢复正常流量。使用 PIA 进行 ISO 处理的心脏中的 ConF 比不存在 PIA 且存在 DPCPX 的心脏高 83%。 DPCPX 显着降低了 PIA 对 ConF 的增强作用。血流恢复后 30 分钟，这些显着差异消失了。 DPCPX 逆转了在恢复正常血流后观察到的 PIA 诱导的心律失常减少。在不存在 ISO 的情况下单独使用 PIA 和 DPCPX，以及在不存在 PIA 和 DPCPX 的情况下使用 ISO，在恢复正常血流后不会导致 ConF 改变。这些发现表明，在缺乏腺苷 A1 受体活性的情况下，低流量灌注期间对心脏的强烈 β-肾上腺素能刺激会在恢复控制灌注后诱导收缩抑制和心律失常。结论是内源性腺苷通过刺激腺苷 A1 受体来保护心脏免受儿茶酚胺毒性。
High levels of norepinephrine in the heart are cardiotoxic resulting in contractile dysfunction and arrhythmic activity via β-adrenoceptor mediated mechanisms. A low flow heart model perfused with physiological saline containing glucose and bubbled with an O2gas mixture was used to dtermine whether adenosine, a nucleoside with antiadreneregic properties, could reduce te functional manifestations of catecholamine cardiotoxicity. Isolated rat hearts were treated with dipropylcyclopentylxanthine (DPCPX; 0.1 μm; A1receptor antagonist) to block endogenous adenosine. In DPCPX-treated hearts stimulated with isoproterenol (ISO: 1 μm) during 45 min of low flow (0.5 ml/min) prefusion, the recover of contractile function (ConF) at 15 min after the restoration of normal flow was 64% of control (before low flow) values as compared to 110% recovery of ConF in the absence of ISO. The incidence of arrhythmias observed upon restoration of control flow was increased by ISO when the action of endogenous adenosine was blocked with DPCPX. In the absence fo DPCPX both the functional depression and arrhythmias induced by ISO were prevented in the presence of phenylisopropyladenosine (PIA; 1 μm; A1receptor agonist). At 15 min after normal flow was restored. ConF in ISO-treated hearts with PIA was 83% greater than in the absence of PIA and presence of DPCPX. This enhancement of ConF by PIA was significantly reduced by DPCPX. By 30 min after flow restoration, these significant differences were absent. DPCPX reversed the PIA-induced reduction in arrhythmias observed upon restoration of normal flow. PIA and DPCPX alone in the absence of ISO, and ISO in the absence of PIA and DPCPX, did not result in altered ConF upon restoration of normal flow. These fidnings indicate that intense β-adrenergic stimulation of the heart during low-flow perfusion in the absence of adenosine A1receptor activity induces contractile depression and arrhythmicity subsequent to restoration of control perfusion. It is concluded that enndogenous adenosine protects the heart against catecholamine toxicity via stimulation of adenosine A1receptors.