Cardiac Surgical Research/Cardiothoracic Surgery, The Rayne Institute (King's College London), St Thomas' Hospital, London, UK.
Eur J Cardiothorac Surg. 2013 Mar;43(3):619-27. doi: 10.1093/ejcts/ezs365. Epub 2012 Jun 19.
Current cardiac surgery patients are older, sicker, with more diffuse disease and hence a reduced tolerance to ischaemia-reperfusion injury. We previously demonstrated that esmolol, an ultra-short-acting β-blocker, can be used as an arresting agent at high (millimolar) concentrations, and that a crystalloid-based esmolol cardioplegia afforded cardioprotection at least equivalent to hyperkalaemic (St Thomas' Hospital) cardioplegia. Esmolol is rapidly metabolized by blood esterases, so it was important to determine the feasibility of its use in blood-based solutions. This study compared the efficacy of blood-based esmolol cardioplegia with hyperkalaemic cardioplegia in a novel blood-perfused rat heart preparation.
Isolated rat hearts were Langendorff blood-perfused with a rat blood/buffer perfusate mixture (flow rate, 3.0 ml/min) and pre-ischaemic baseline function (left ventricular developed pressure) assessed. All values are expressed as mean ± SEM. Three studies were conducted: (i) the efficacy of blood-based vs crystalloid-based esmolol or hyperkalaemic cardioplegia (40 min ischaemia) was evaluated (five groups; six hearts/group); (ii) the effect of the mode of cardioplegia delivery (constant flow/pressure), esmolol concentration and extended delivery interval (45 min ischaemia) was evaluated (four groups; six hearts/group); (iii) the efficacy of blood-based esmolol compared with hyperkalaemic cardioplegia over extended (60 min) ischaemia duration was evaluated (two groups; six hearts/group). Hearts were reperfused (60 min) and recovery (percent of pre-ischaemic baseline function) measured at the end of reperfusion.
Hearts subjected to blood-based esmolol or hyperkalaemia cardioplegia recovered to 78 ± 4% and 68 ± 6%, whereas crystalloid-based esmolol or hyperkalaemic cardioplegia recovered to 84 ± 1% and 77 ± 2%, respectively [all P < 0.05 vs control (2 ± 2%)]; there were no differences between cardioplegia groups. When infusion duration was extended, a lower (2 mmol/l) esmolol concentration improved recovery compared with the higher (3 mmol/l) concentration (66 ± 4% vs 29 ± 12%, P < 0.05). Extending the ischaemic duration demonstrated enhanced efficacy for blood-based esmolol cardioplegia (70 ± 4%; P < 0.05) compared with hyperkalaemic cardioplegia (47 ± 10%).
Blood-based esmolol cardioplegia improved cardioprotective efficacy compared with hyperkalaemic cardioplegia; the metabolic effects of blood esterase did not appear to influence this efficacy. An esmolol-based cardioplegic solution may be a beneficial alternative to hyperkalaemic solutions.
目前的心脏外科患者年龄更大、病情更严重、疾病更广泛，因此对缺血再灌注损伤的耐受性降低。我们之前的研究表明，超短效β受体阻滞剂艾司洛尔可以在高（毫摩尔）浓度下用作阻断剂，并且基于晶体的艾司洛尔心脏停搏液可提供至少与高钾（圣托马斯医院）心脏停搏液等效的心脏保护。艾司洛尔被血液酯酶迅速代谢，因此确定其在基于血液的溶液中的使用可行性非常重要。本研究比较了新型血液灌注大鼠心脏模型中基于血液的艾司洛尔心脏停搏液与高钾心脏停搏液的疗效。
使用大鼠血液/缓冲液灌注混合物（流速为 3.0ml/min）对分离的大鼠心脏进行 Langendorff 血液灌注，并评估预缺血基础功能（左心室发展压）。所有值均表示为平均值±SEM。进行了三项研究：（i）评估基于血液的与基于晶体的艾司洛尔或高钾心脏停搏液（40 分钟缺血）的疗效（五组；每组六只心脏）；（ii）评估心脏停搏液输送方式（恒流/恒压）、艾司洛尔浓度和延长输送间隔（45 分钟缺血）的影响（四组；每组六只心脏）；（iii）评估基于血液的艾司洛尔与高钾心脏停搏液在延长（60 分钟）缺血持续时间方面的疗效（两组；每组六只心脏）。心脏在再灌注（60 分钟）后进行再灌注，并在再灌注结束时测量恢复（与预缺血基础功能的百分比）。
接受基于血液的艾司洛尔或高钾心脏停搏液的心脏恢复至 78±4%和 68±6%，而基于晶体的艾司洛尔或高钾心脏停搏液恢复至 84±1%和 77±2%，与对照组（2±2%）相比，所有组均有差异[均 P<0.05]；心脏停搏液组之间没有差异。当输注时间延长时，较低浓度（2mmol/L）的艾司洛尔与较高浓度（3mmol/L）相比，恢复情况更好（66±4%比 29±12%，P<0.05）。延长缺血时间可增强基于血液的艾司洛尔心脏停搏液（70±4%）的疗效，与高钾心脏停搏液（47±10%）相比，具有显著差异（P<0.05）。
基于血液的艾司洛尔心脏停搏液与高钾心脏停搏液相比，改善了心脏保护作用；血液酯酶的代谢作用似乎没有影响这种疗效。基于艾司洛尔的心脏停搏液可能是高钾溶液的有益替代。
