Intravenous fructose-1,6-diphosphate improves survival and blood pressure in propranolol-poisoned rodents.

Abstract

Background: Fructose-1,6-diphosphate (FDP) is an intermediary metabolite in the glycolytic pathway created from glucose. Exogenously administered FDP potentially spares the consumption of 2ATP molecules required in its production from glucose, increasing net yield of ATP in anaerobic glycolysis. It reduces ischaemic tissue area in experimentally-induced cerebrovascular accident and myocardial infarction as well as improves haemodynamics post-cardiac bypass1. FDP also increases Na+/K+-ATPase activity and reduces toxicity in animal models of cardiac glycoside poisoning2. We hypothesised that exogenously administered FDP will improve survival in propranolol poisoning. Method(s): Anesthetized, ventilated Wistar rats (n = 10 per group) were instrumented to record BP, heart rate (HR), cardiac output (CO) and QRS-duration. Propranolol was infused continually. When BP dropped to 50% of baseline, rats received one of 10%FDP125mg/kg or 10%FDP250mg/ kg loading dose over 20 minutes followed by infusion 20 mg/kg/h. Controls received comparable volumes of 10% glucose for each treatment arm. Animals were observed until terminal bradycardia and hypotension resulted. Haemodynamics were compared at individual time points 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. Result(s): FDP-treated animals had significantly longer survival time than glucose-treated controls (median survival for both FDP doses was 140 mins v glucose 125 and 250 - 80 and 95 mins respectively, p < 0.0001). FDP250- treated animals showed a statistically significant increase in mean and systolic BP at t = 20, 35, 50, 65, 80 mins (P < 0.04). There was a trend to greater CO and HR and shorter QRS-duration with FDP250. FDP125 increased BP non-significantly with no difference in HR or QRSduration from Control. Conclusion(s): FDP improved survival with a moderate dose-dependent improvement in haemodynamics in propranolol poisoning. Future research could examine the efficacy of FDP in other betablocker and calcium channel-blocker poisoning as well as in concert with other established inotropic therapies in toxin-induced cardiovascular collapse.