1,6-二磷酸果糖对普萘洛尔和维拉帕米中毒啮齿动物模型血流动力学参数和存活的影响。

The effects of fructose-1,6-diphosphate on haemodynamic parameters and survival in a rodent model of propranolol and verapamil poisoning.

机构信息

Southern Health Emergency Medicine and Clinical Toxicology Research Group, Southern Clinical School, Monash University, Monash Medical Centre, Clayton, VIC, Australia.

出版信息

Clin Toxicol (Phila). 2012 Aug;50(7):546-54. doi: 10.3109/15563650.2012.705847.

DOI:10.3109/15563650.2012.705847

PMID:22871053

Abstract

BACKGROUND

Fructose-1,6-diphosphate (FDP) is a metabolite in the glycolytic pathway created from glucose. Exogenously administered FDP increases the yield of ATP from anaerobic glycolysis. FDP reduces ischaemic tissue area in experimentally-induced cerebral and myocardial infarction and improves haemodynamics post-cardiac bypass. We hypothesised that FDP improves haemodynamics in propranolol and verapamil poisoning.

METHOD

Anesthetized Wistar rats were instrumented to record BP, heart rate (HR), cardiac output (CO) and QRS-duration. Propranolol or verapamil were infused continually. When BP dropped by 50%, propranolol-poisoned rats received one of 10% FDP125 mg/kg or 10% FDP250 mg/kg loading dose over 20 minutes followed by infusion 20 mg/kg/h. Verapamil-poisoned rats received the higher dosing regimen of FDP250. Controls received comparable volumes of 10% glucose. Haemodynamic time-points were compared for FDP to control by unpaired t-test or Mann-Whitney test as appropriate (p < 0.05). Survival was assessed using Kaplan-Meier survival analysis.

RESULTS

FDP-treated animals survived significantly longer than glucose-treated controls at both doses in propranolol poisoning and in verapamil-poisoning. In propranolol poisoning, FDP250-treated animals showed a statistically significant increase in BP. However, there was no significant difference in cardiac output at this dose. There were also no significant differences in any haemodynamic parameters compared to control at the lower FDP dose in propranolol poisoning or in verapamil poisoning.

CONCLUSION

FDP improved survival for both toxicants with an improvement in haemodynamics at the higher dose in propranolol poisoning. Future research could examine the efficacy of FDP in other beta-blocker and calcium channel-blocker poisoning as well as in concert with established inotropic therapies in drug-induced cardiovascular collapse.

摘要

背景

1,6-二磷酸果糖（FDP）是糖酵解途径中的一种代谢产物，由葡萄糖生成。外源性给予 FDP 可增加无氧糖酵解产生 ATP 的产量。FDP 可减少实验性脑梗死和心肌梗死的缺血组织面积，并改善体外循环后的血液动力学。我们假设 FDP 可改善心得安和维拉帕米中毒的血液动力学。

方法

麻醉 Wistar 大鼠，记录血压（BP）、心率（HR）、心输出量（CO）和 QRS 持续时间。持续输注心得安或维拉帕米。当血压下降 50%时，心得安中毒的大鼠接受 10% FDP125mg/kg 或 10% FDP250mg/kg 的负荷剂量，持续 20 分钟，然后以 20mg/kg/h 的速度输注。维拉帕米中毒的大鼠给予更高剂量的 FDP250。对照组给予等量的 10%葡萄糖。使用配对 t 检验或 Mann-Whitney 检验比较 FDP 与对照组的血液动力学时间点（p<0.05）。使用 Kaplan-Meier 生存分析评估生存率。