Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
J Cardiovasc Pharmacol. 2012 Feb;59(2):151-7. doi: 10.1097/FJC.0b013e3182391d17.
Understanding heart metabolism during preservation is crucial to develop new effective cardioplegic solutions. We aim to investigate metabolic alterations during heart preservation in the clinically used Celsior (Cs) and histidine buffer solution (HBS). We also focused in gender-specific metabolic adaptations during ischemia. We followed energy metabolism in hearts from men and women preserved during 6 hours in Cs and HBS. Hearts were subjected to cold ischemia (4°C) in Cs or HBS, and aliquots of the cardioplegic solution were collected throughout preservation for nuclear magnetic resonance analysis. HBS-preserved hearts from men consumed glucose mostly between 240 and 360 minutes, whereas HBS-preserved hearts from women consumed glucose throughout the 6 hours of ischemia. Lactate production rates followed approximately the glucose consumption rates in HBS-preserved hearts. The lactate to alanine ratio, an indicator of the redox state, was increased in HBS-preserved hearts when compared with Cs-preserved hearts. Hearts from men presented a higher redox state than those from women preserved in Cs after 300 minutes. Both Cs and HBS were capable of preventing acidification in hearts from women but not in hearts from men, which decreased the extracellular pH. HBS-preserved hearts from men and women produced 0.1 ± 0.01 and 0.15 ± 0.03 μmol·min(-1)·gdw(-1) of lactate, respectively. Those rates were significantly higher than in Cs-preserved hearts. Thus, Cs was more effective in preventing lactate production. We conclude that glycolysis and lactate production are stimulated in HBS-preserved hearts. HBS shows better overall results particularly in hearts from women, which presented less extracellular acidification and were more effective in recycling the metabolic subproducts.
了解心脏保存过程中的代谢对于开发新的有效心脏停搏液解决方案至关重要。我们旨在研究临床使用的 Celsior(Cs)和组氨酸缓冲液(HBS)在心脏保存过程中的代谢变化。我们还关注了缺血过程中的性别特异性代谢适应。我们研究了 Cs 和 HBS 保存 6 小时的男性和女性心脏的能量代谢。心脏在 Cs 或 HBS 中进行冷缺血(4°C),并在整个保存过程中采集部分心脏停搏液进行核磁共振分析。HBS 保存的男性心脏在 240 至 360 分钟之间主要消耗葡萄糖,而 HBS 保存的女性心脏在 6 小时的缺血过程中消耗葡萄糖。HBS 保存的心脏中,乳酸的产生速率大致与葡萄糖的消耗速率相匹配。与 Cs 保存的心脏相比,HBS 保存的心脏中的乳酸/丙氨酸比值(指示氧化还原状态)增加。Cs 保存的男性心脏的氧化还原状态高于 Cs 保存的女性心脏。Cs 和 HBS 均能防止女性心脏的酸化,但不能防止男性心脏的酸化,从而降低了细胞外 pH 值。HBS 保存的男性和女性心脏分别产生 0.1±0.01 和 0.15±0.03 μmol·min(-1)·gdw(-1)的乳酸,这两个速率明显高于 Cs 保存的心脏。因此,Cs 更有效地防止乳酸的产生。我们的结论是,HBS 保存的心脏中糖酵解和乳酸的产生受到刺激。HBS 的总体效果更好,特别是在女性心脏中,细胞外酸化较少,代谢副产物的再循环更有效。