School of Science and Technology, University of New England, McClymont Building, Armidale, NSW, 2351, Australia.
Pflugers Arch. 2012 Nov;464(5):513-22. doi: 10.1007/s00424-012-1152-5. Epub 2012 Sep 22.
The general anaesthetic propofol shows promise in protecting normal hearts against various cardiac insults, but little is known about its cardioprotective potential in hypertrophic hearts. This study tested the hypothesis that propofol at a clinically relevant dose would enhance functional recovery in hypertrophic hearts following ischaemia. Hypertrophic hearts from spontaneously hypertensive rats and hearts from their normotensive controls, Wistar Kyoto Rats, were equilibrated in the working mode prior to global normothermic ischaemia. Reperfusion commenced with 10 min in Langendorff mode, followed by 30-min working reperfusion. Functional performance was measured throughout the working mode, whilst reperfusion damage was assessed from myocardial troponin I release during Langendorff reperfusion. Where used, 4 μg/ml propofol was added 10 min before ischaemia and was washed out 10 min into working reperfusion. An additional protocol investigated recovery of hearts protected by normothermic hyperkalaemic cardioplegic arrest. Following 20-min ischaemia, reperfusion damage was significantly worse in hypertrophic hearts compared to normal hearts, whilst addition of propofol to hypertrophic hearts significantly improved the aortic flow (31 ± 5.8 vs. 11.6 ± 2.0 ml/min, n = 6-7 ± SE, p < 0.05). Propofol also conferred significant protection following 30-min ischaemia where the recovery of cardiac output and stroke volume was similar to that for cardioplegia alone. Incubation with propofol improved the NADH/NAD(+) ratio in freshly isolated cardiomyocytes from hypertrophic hearts, suggesting possible improvements in metabolic flux. These findings suggest that propofol at the clinically relevant dose of 4 μg/ml is as effective as cardioplegic arrest in protecting hypertrophic hearts against ischaemia-reperfusion.
全身麻醉药异丙酚有望保护正常心脏免受各种心脏损伤,但对于其在肥厚心脏中的保护作用知之甚少。本研究旨在验证异丙酚在临床相关剂量下是否能增强肥厚心脏缺血后的功能恢复。采用自发性高血压大鼠(SHR)肥厚心脏和其正常血压对照 Wistar Kyoto 大鼠(WKY)心脏,在整体常温缺血前于工作模式下平衡。复灌首先在 Langendorff 模式下进行 10min,然后在工作模式下进行 30min。在整个工作模式下测量功能性能,同时通过 Langendorff 复灌期间心肌肌钙蛋白 I 的释放来评估再灌注损伤。如果使用,在缺血前 10min 添加 4μg/ml 异丙酚,并在工作复灌开始 10min 内冲洗。附加方案研究了常温高钾心脏停搏保护的心脏恢复情况。与正常心脏相比,肥厚心脏缺血 20min 后再灌注损伤明显更严重,而异丙酚添加到肥厚心脏可显著改善主动脉流量(31±5.8 与 11.6±2.0ml/min,n=6-7±SE,p<0.05)。异丙酚在缺血 30min 后也具有显著的保护作用,此时心输出量和每搏量的恢复与单独心脏停搏相似。异丙酚孵育可改善肥厚心脏新鲜分离心肌细胞中的 NADH/NAD+ 比值,提示代谢通量可能得到改善。这些发现表明,在临床相关的 4μg/ml 剂量下,异丙酚与心脏停搏一样有效,可保护肥厚心脏免受缺血再灌注损伤。