Ning X H, Xu C S, Song Y C, Childs K F, Xiao Y, Bolling S F, Lupinetti F M, Portman M A
Department of Pediatrics, University of Washington, Seattle 98195, USA.
Cryobiology. 1998 Feb;36(1):2-11. doi: 10.1006/cryo.1997.2054.
Hypothermia protects ischemic tissues by reducing ATP utilization and accumulation of harmful metabolites. However, it also reduces ATP production, which might cause deterioration in the energy supply/demand ratio. Modulation of energy supply/demand according to temperature has not been previously studied in detail. In this study, isolated, perfused rabbit hearts (n = 60) were used to determine the effects of various temperatures on myocardial energy metabolism and function during cardioplegic arrest. Ischemia was induced by crystalloid cardioplegic solution at 4, 18, 30, and 34 degrees C for 120 min, respectively. At each temperature, the hearts were divided into a glucose-treated group which contained 22 mM glucose in cardioplegic solution as the only substrate and a control group which contained 22 mM mannitol to keep same osmolarity. Following 15 min reperfusion, recovery of left ventricular developed pressure (DP), +/- dP/dtmax, and the product of heart rate and DP were significantly higher in 30, 18, and 4 degrees C groups than those in 34 degrees C control group. The functional recovery was also significantly higher in the 34 degrees C glucose-treated group than that in the 34 degrees C control group, but there was no difference between those groups at 30 degrees C and the temperature below 30 degrees C. Myocardial ATP concentration was significantly lower in 34 degrees C control group than those in other groups. There is a close relationship between myocardial ATP concentration and functional recovery (R2 = 0.90). The accumulations of lactate and CO2 were significantly higher at 34 degrees C in glucose-treated group than those in the control group. However, there was no significant difference between these two groups at 30 degrees C and the temperature below 30 degrees C. These results indicate that under these study conditions: (1) a marked decrease in energy supply/demand occurs above 30 degrees C, implying that a temperature threshold exists; and (2) this can be ameliorated by provision of glucose as substrate in cardioplegia solution.
低温通过减少ATP利用和有害代谢产物的积累来保护缺血组织。然而,它也会减少ATP生成,这可能导致能量供需比恶化。此前尚未对根据温度调节能量供需进行详细研究。在本研究中,使用离体灌注兔心脏(n = 60)来确定不同温度对心脏停搏期间心肌能量代谢和功能的影响。分别用4℃、18℃、30℃和34℃的晶体心脏停搏液诱导缺血120分钟。在每个温度下,心脏被分为葡萄糖处理组(心脏停搏液中含有22 mM葡萄糖作为唯一底物)和对照组(含有22 mM甘露醇以保持相同渗透压)。再灌注15分钟后,30℃、18℃和4℃组的左心室舒张末压(DP)、±dP/dtmax以及心率与DP的乘积的恢复明显高于34℃对照组。34℃葡萄糖处理组的功能恢复也明显高于34℃对照组,但在30℃及低于30℃的温度下,这些组之间没有差异。34℃对照组的心肌ATP浓度明显低于其他组。心肌ATP浓度与功能恢复之间存在密切关系(R2 = 0.90)。葡萄糖处理组在34℃时乳酸和CO2的积累明显高于对照组。然而,在30℃及低于30℃的温度下,这两组之间没有显著差异。这些结果表明,在这些研究条件下:(1)在30℃以上能量供需显著下降,这意味着存在一个温度阈值;(2)在心脏停搏液中提供葡萄糖作为底物可改善这种情况。