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首页> 外文期刊>Clinical toxicology: the official journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists >The effects of fructose-1,6-diphosphate on haemodynamic parameters and survival in a rodent model of propranolol and verapamil poisoning
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The effects of fructose-1,6-diphosphate on haemodynamic parameters and survival in a rodent model of propranolol and verapamil poisoning

机译：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

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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 MannWhitney test as appropriate (p <0.05). Survival was assessed using KaplanMeier 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.
机译：背景。 1,6-二磷酸果糖（FDP）是葡萄糖产生的糖酵解途径中的代谢产物。外用FDP可提高厌氧糖酵解过程中ATP的产量。 FDP减少了实验性诱发的脑梗塞和心肌梗塞的缺血组织面积，并改善了心脏搭桥术后的血流动力学。我们假设FDP可以改善心得安和维拉帕米中毒的血流动力学。方法。用麻醉的Wistar大鼠记录血压，心率（HR），心输出量（CO）和QRS持续时间。普萘洛尔或维拉帕米不断注入。当BP下降50％时，在20分钟内，普萘洛尔中毒大鼠接受10％FDP125 mg / kg或10％FDP250 mg / kg负荷剂量之一，然后输注20 mg / kg / h。维拉帕米中毒的大鼠接受更高剂量的FDP250给药方案。对照组接受相当量的10％葡萄糖。酌情通过不配对t检验或MannWhitney检验比较FDP的血流动力学时间点与对照之间的差异（p <0.05）。使用KaplanMeier生存分析评估生存。结果。在普萘洛尔中毒和维拉帕米中毒的两种剂量下，用FDP处理的动物的存活时间均明显长于用葡萄糖处理的对照组。在心得安中毒中，经FDP250处理的动物的BP有统计学上的显着增加。但是，在此剂量下，心输出量无明显差异。在普萘洛尔中毒或维拉帕米中毒中，在较低FDP剂量下，与对照组相比，在任何血流动力学参数上也没有显着差异。结论。在心得安中较高剂量下，FDP可以提高两种毒物的存活率，并改善血流动力学。未来的研究可能会检查FDP在其他β受体阻滞剂和钙通道阻滞剂中毒的疗效，以及与已确立的正性肌力疗法在药物诱发的心血管衰竭中的疗效。

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