Modi Paul, Suleiman M-Saadeh, Reeves Barnaby C, Pawade Ash, Parry Andrew J, Angelini Gianni D, Caputo Massimo
Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol, United Kingdom.
Ann Thorac Surg. 2006 Mar;81(3):943-9. doi: 10.1016/j.athoracsur.2005.08.071.
The immature heart has a much greater dependence than the adult heart on amino acid transamination in determining its ischemic tolerance. Compared with adult hearts, experimental models of the immature heart have quantified higher resting concentrations of free amino acids (AA) which are depleted by acute hypoxia. However, we have found no clinical studies that have looked at the free AA profile of the immature human heart or the effects of cyanosis, age, and pathology upon this.
One hundred eighty-one pediatric patients (37 cyanotic, 144 acyanotic) undergoing open-heart surgery were recruited. Myocardial biopsies were collected prior to ischemia and analyzed for free AAs (eg, glutamate, aspartate) using high-performance liquid chromatography. The effects of cyanosis, age, and pathology on amino acid concentrations were estimated by multiple regression modeling with and without controlling for diagnosis; the effects of age and pathology were estimated only in acyanotic children.
Alanine concentrations were about 20% higher in cyanotic than acyanotic patients (p = 0.04). Cyanosis was not associated with any other amino acid levels. In acyanotic patients, after controlling for diagnosis, concentrations of glutamate, aspartate, and alanine decreased from birth to about 8 to 10 years, then started to increase again (p < 0.05 for both linear and quadratic terms); concentrations of taurine and the branched chain AAs decreased steadily with increasing age (p < 0.05). There were significant effects of pathology on glutamate (p = 0.006), glutamine (p = 0.003), and branched chain AA (p = 0.004) levels.
There is no evidence that chronic hypoxia depletes endogenous AAs. Young age is associated with higher resting AA levels.
与成年心脏相比,未成熟心脏在决定其缺血耐受性方面对氨基酸转氨作用的依赖性要大得多。与成年心脏相比,未成熟心脏的实验模型已量化出更高的游离氨基酸(AA)静息浓度,这些氨基酸会因急性缺氧而耗尽。然而,我们尚未发现有临床研究关注未成熟人类心脏的游离氨基酸谱,或紫绀、年龄和病理状况对其的影响。
招募了181名接受心脏直视手术的儿科患者(37名紫绀患者,144名非紫绀患者)。在缺血前采集心肌活检样本,并使用高效液相色谱法分析游离氨基酸(如谷氨酸、天冬氨酸)。通过多元回归模型评估紫绀、年龄和病理状况对氨基酸浓度的影响,模型分为控制诊断和不控制诊断两种情况;仅在非紫绀儿童中评估年龄和病理状况的影响。
紫绀患者的丙氨酸浓度比非紫绀患者高约20%(p = 0.04)。紫绀与任何其他氨基酸水平均无关联。在非紫绀患者中,控制诊断后,谷氨酸、天冬氨酸和丙氨酸的浓度从出生到约8至10岁时下降,然后又开始上升(线性和二次项的p均<0.05);牛磺酸和支链氨基酸的浓度随年龄增长稳步下降(p < 0.05)。病理状况对谷氨酸(p = 0.006)、谷氨酰胺(p = 0.003)和支链氨基酸(p = 0.004)水平有显著影响。
没有证据表明慢性缺氧会耗尽内源性氨基酸。年轻与较高的静息氨基酸水平相关。