Cardioprotection with esmolol cardioplegia: efficacy as a blood-based solution.
OBJECTIVE
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.


METHODS
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.


RESULTS
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%).


CONCLUSIONS
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.
Cardiac Surgical Research/Cardiothoracic Surgery,  The Rayne Institute (King's College London), St Thomas' Hospital, London,  UK.
Masahiro
M
Fujii
David J
DJ
Chambers
D000818:Animals; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006324:Heart Arrest, Induced / Q000379:methods*; D008297:Male; D017202:Myocardial Ischemia / Q000517:prevention & control; D015425:Myocardial Reperfusion / Q000379:methods*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D011412:Propanolamines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects
D002314:Cardioplegic Solutions; D002316:Cardiotonic Agents; D011412:Propanolamines; C036604:esmolol