Walker J D, Crawford F A, Spinale F G
Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425, USA.
J Thorac Cardiovasc Surg. 1995 Aug;110(2):315-27. doi: 10.1016/s0022-5223(95)70227-x.
Circulating levels of 3,5,3'triiodo-L-thyronine are depressed after cardiopulmonary bypass and have been implicated to play a contributory role in the alterations in left ventricular function after hypothermic cardioplegic arrest and rewarming. The central hypothesis of the present study was that pretreatment of isolated myocytes with triiodothyronine will have a direct and beneficial effect on contractile performance after hypothermic cardioplegic arrest and rewarming. Contractile function in isolated pig left ventricular myocytes was examined by video microscopy after the following treatment protocols: (1) 37 degrees C incubation in medium (normothermia) for 2 hours with triiodothyronine followed by a 2-hour normothermic incubation with no triiodothyronine, (2) 4 hours of normothermic incubation with no triiodothyronine, (3) normothermic incubation for 2 hours with triiodothyronine followed by 2 hours of hyperkalemic, hypothermic cardioplegic arrest ([K+]:24 mmol/L; 4 degrees C) and subsequent rewarming, and (4) normothermic incubation for 2 hours with no triiodothyronine followed by 2 hours of hyperkalemic, hypothermic cardioplegic arrest and rewarming. Two hours of normothermia with triiodothyronine increased myocyte contractile function by 30% compared with values in untreated control myocytes, and this increase persisted after a subsequent 2-hour incubation under normothermic conditions with no triiodothyronine. For example, myocyte velocity of shortening in triiodothyronine-pretreated myocytes was 84 +/- 4.9 microns/sec compared with 62 +/- 2.8 microns/sec in control myocytes (p < 0.05). Cardioplegic arrest and subsequent rewarming caused a significant reduction in myocyte velocity of shortening from normothermic values (37 +/- 3.4 microns/sec, p < 0.05). However, in myocytes pretreated with triiodothyronine, myocyte contractile function was significantly higher after hypothermic cardioplegic arrest and rewarming (54 +/- 2.5 microns/sec, p < 0.05). In a second series of experiments, beta-adrenergic responsiveness was examined after pretreatment with triiodothyronine. In the presence of the beta-adrenergic agonist isoproterenol (25 nmol/L), myocyte contractile function was increased by 26% in the triiodothyronine-treated myocytes compared with that in untreated control myocytes. This enhanced beta-adrenergic responsiveness with triiodothyronine pretreatment persisted with subsequent exposure to hypothermic cardioplegic arrest and rewarming. In summary, triiodothyronine pretreatment caused an increase in myocyte contractile function and beta-adrenergic responsiveness under normothermic conditions and after hypothermic cardioplegic arrest and rewarming. Thus the present study provides direct evidence to suggest that preemptive treatment with triiodothyronine may improve left ventricular contractile performance after hypothermic cardioplegic arrest and rewarming.
心肺转流术后，循环中的3,5,3'-三碘-L-甲状腺原氨酸水平降低，且被认为在低温心脏停搏及复温后左心室功能改变中起一定作用。本研究的核心假设是，用甲状腺原氨酸预处理分离的心肌细胞，对低温心脏停搏及复温后的收缩性能会有直接且有益的影响。采用以下处理方案后，通过视频显微镜检查分离的猪左心室心肌细胞的收缩功能：(1) 在含甲状腺原氨酸的培养基中于37℃孵育2小时（正常体温），随后在不含甲状腺原氨酸的情况下进行2小时正常体温孵育；(2) 4小时不含甲状腺原氨酸的正常体温孵育；(3) 含甲状腺原氨酸的正常体温孵育2小时，随后进行2小时高钾、低温心脏停搏（[K⁺]：24 mmol/L；4℃）及随后的复温；(4) 不含甲状腺原氨酸的正常体温孵育2小时，随后进行2小时高钾、低温心脏停搏及复温。与未处理的对照心肌细胞相比，含甲状腺原氨酸的2小时正常体温孵育使心肌细胞收缩功能提高了30%，且在随后不含甲状腺原氨酸的2小时正常体温孵育后，这种增加仍持续存在。例如，经甲状腺原氨酸预处理的心肌细胞的缩短速度为84±4.9微米/秒，而对照心肌细胞为62±2.8微米/秒（p<0.05）。心脏停搏及随后的复温导致心肌细胞缩短速度从正常体温值显著降低（37±3.4微米/秒，p<0.05）。然而，在经甲状腺原氨酸预处理的心肌细胞中，低温心脏停搏及复温后的心肌细胞收缩功能显著更高（54±2.5微米/秒，p<0.05）。在第二系列实验中，检查了甲状腺原氨酸预处理后的β-肾上腺素能反应性。在存在β-肾上腺素能激动剂异丙肾上腺素（25 nmol/L）的情况下，经甲状腺原氨酸处理的心肌细胞的收缩功能比未处理的对照心肌细胞提高了26%。甲状腺原氨酸预处理增强的β-肾上腺素能反应性在随后暴露于低温心脏停搏及复温后仍然存在。总之，甲状腺原氨酸预处理在正常体温条件下以及低温心脏停搏及复温后均导致心肌细胞收缩功能和β-肾上腺素能反应性增加。因此，本研究提供了直接证据表明，甲状腺原氨酸的预防性治疗可能改善低温心脏停搏及复温后的左心室收缩性能。
