Center for Neuroscience and Cell Biology, Largo Marquês de Pombal, University of Coimbra, 3004-517 Coimbra, Portugal.
J Cardiovasc Pharmacol. 2012 Aug;60(2):227-33. 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 males and females 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 males consumed glucose mostly between 240 and 360 minutes, whereas HBS-preserved hearts from females 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 males presented a higher redox state than those from females preserved in Cs after 300 minutes. Both Cs and HBS were capable of preventing acidification in hearts from females but not in hearts from males, which decreased the extracellular pH. HBS-preserved hearts from males and females produced 0.1 ± 0.01 and 0.15 ± 0.03 μmol·min·gdw 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 females, 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的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性别特异性的代谢适应。我们在 Cs 和 HBS 中保存 6 小时的雄性和雌性心脏中研究了能量代谢。心脏在 Cs 或 HBS 中进行冷缺血（4°C），并在整个保存过程中收集心脏停搏液的等分试样进行核磁共振分析。在 HBS 中保存的雄性心脏在 240 至 360 分钟之间主要消耗葡萄糖，而 HBS 中保存的雌性心脏在整个 6 小时的缺血过程中消耗葡萄糖。在 HBS 中保存的心脏中，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（一种氧化还原状态的指标）增加。与 Cs 保存的雌性心脏相比，Cs 保存的雄性心脏在 300 分钟后具有更高的氧化还原状态。Cs 和 HBS 都能够防止女性心脏酸化，但不能防止男性心脏酸化，从而降低细胞外 pH 值。在 HBS 中保存的雄性和雌性心脏分别产生 0.1±0.01 和 0.15±0.03 μmol·min·gdw 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。我们得出结论，在 HBS 保存的心脏中，糖酵解和乳酸的产生被刺激。HBS 显示出更好的整体效果，特别是在女性心脏中，其细胞外酸化程度较低，并且更有效地回收代谢副产物。
