Gál J, Riedel B J, Róth E, Bogár L, Tekeres M, Royston D
Pécsi Tudományegyetem, Altalános Orvostudományi Kar, Aneszteziológiai és Intenzív Terápiás Intézet.
Orv Hetil. 2000 Sep 10;141(37):2021-5.
During ischaemia, the glycolytic pathway (Embden-Meyerhof) is up regulated in an attempt to produce ATP anaerobically. However, this is short-lived due to negative feedback on the key glycolytic enzyme phosphofructokinase by accumulating lactate. Fructose-1,6-diphosphate (FDP), a high energy intermediary metabolite of this pathway, is unique in that is enters glycolysis distal to this inhibitory site. Exogenously administered FDP should therefore theoretically yield ATP independent of lactate accumulation and thereby ameliorate ischaemic injury. Clinical benefit has been shown in coronary artery bypass grafting (CABG) surgery, congestive cardiac failure and adult respiratory distress syndrome. Ischaemia-reperfusion injury induced by cardiopulmonary bypass (CPB) presents clinically as an impairment of myocardial function in the postoperative period. At a cellular level this reflects myocardial metabolic changes and nucleotide degradation (directly linked to high energy phosphate turnover). Quantification of myocardial nucleotide catabolite release therefore provides useful information regarding intermediary metabolism and cytoprotection conferred to myocardial (inosine, uridine) and endothelial (hypoxanthine) tissue. The authors investigated the myocardial cytoprotective effects of FDP in 16 patients scheduled for elective CABG surgery. Aortic and coronary sinus blood were collected directly into liquid nitrogen and analysed by high performance liquid chromatography prior to CPB and at different time points after reperfusion. FDP was administered intravenously in 8 patients and 5% dextrose was administered in 8 other patients. Analysis of transmyocardial (coronary sinus-aortic) nucleotide metabolite levels showed increased release of inosine, hypoxanthine and uridine in both the FDP and the control groups following reperfusion. However, compared to baseline (pre-aortic clamping) values, hypoxanthine and inosine concentrations were significantly elevated at 0, 1, 5 and 10 minutes following reperfusion in the control group. This was in contrast to earlier recovery to baseline levels (after 5 minutes of reperfusion) in the FDP group. Furthermore, when compared to control group, the hypoxanthine and inosine concentrations were significantly decreased by FDP treatment. Uridine concentrations were significantly elevated at 1 and 5 minutes in the control group and no significant change was observed in the FDP group. In conclusion, these data suggest that FDP, through an intermediary metabolic effect, may contribute to myocardial and endothelial cytoprotection during the ischaemic insult of cardiac surgery.
在缺血期间，糖酵解途径（Embden-Meyerhof途径）被上调，试图通过无氧方式产生三磷酸腺苷（ATP）。然而，由于累积的乳酸对关键糖酵解酶磷酸果糖激酶产生负反馈，这种情况是短暂的。果糖-1,6-二磷酸（FDP）是该途径的一种高能中间代谢产物，其独特之处在于它在这个抑制位点的下游进入糖酵解过程。因此，理论上外源性给予FDP应该能够产生ATP而不依赖乳酸的累积，从而减轻缺血性损伤。在冠状动脉旁路移植术（CABG）、充血性心力衰竭和成人呼吸窘迫综合征中已显示出临床益处。体外循环（CPB）引起的缺血-再灌注损伤在临床上表现为术后心肌功能受损。在细胞水平上，这反映了心肌代谢变化和核苷酸降解（直接与高能磷酸周转相关）。因此，心肌核苷酸分解代谢产物释放的定量分析提供了有关中间代谢以及给予心肌（肌苷、尿苷）和内皮（次黄嘌呤）组织的细胞保护作用的有用信息。作者研究了FDP对16例计划进行择期CABG手术患者的心肌细胞保护作用。在CPB前以及再灌注后的不同时间点，直接将主动脉和冠状窦血收集到液氮中，并通过高效液相色谱法进行分析。8例患者静脉注射FDP，另外8例患者静脉注射5%葡萄糖。跨心肌（冠状窦-主动脉）核苷酸代谢产物水平分析显示，再灌注后FDP组和对照组的肌苷、次黄嘌呤和尿苷释放均增加。然而，与基线（主动脉阻断前）值相比，对照组在再灌注后0、1、5和10分钟时次黄嘌呤和肌苷浓度显著升高。这与FDP组在再灌注5分钟后较早恢复到基线水平形成对比。此外，与对照组相比，FDP治疗使次黄嘌呤和肌苷浓度显著降低。对照组在1和5分钟时尿苷浓度显著升高，而FDP组未观察到显著变化。总之，这些数据表明，FDP可能通过中间代谢作用，在心脏手术的缺血性损伤期间对心肌和内皮起到细胞保护作用。
