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

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.