Acute pre- or -post, ischaemic treatment with elevated extracellular glucose imparts a cardioprotection to isolated cardiomyocytes

37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCB015

Poster Communications: Acute pre- or -post, ischaemic treatment with elevated extracellular glucose imparts a cardioprotection to isolated cardiomyocytes

C. E. Poile1, I. B. Squire1, R. D. Rainbow1

1. Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.

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Reperfusion of the myocardium after an ischaemic insult can cause marked and irreversible damage. Minimizing infarct size is important for improving prognosis after a prolonged ischaemia. A number of cardioprotective interventions have been demonstrated to improve the outcome after myocardial infarction, including ischaemic pre-and post-conditioning and pharmacological pre-treatment (1, 2, and 3). Here we present data demonstrating that perfusing isolated cardiomyocytes for a short period of time with elevated extracellular glucose prior to, or following, the ischaemic insult, gives a marked cardioprotection. Adult male Wistar rats were culled humanely in accordance with Home Office guidelines and cardiomyocytes were enzymatically isolated. Contractile function of the isolated cardiomyocytes was assessed using a simulated ischaemia/reperfusion injury protocol, where cardiomyocytes were stimulated to contract at 1Hz by electrical field stimulation and perfused with Normal Tyrode (NT) solution at 32±2°C. Ischaemia was simulated using a metabolic inhibition (MI) solution of Substrate-Free Tyrode solution containing cyanide (2mM) and iodoacetic acid (1mM) for 7 minutes, followed by 10 minutes of ‘reperfusion’ with NT. Our data shows that supplying cardiomyocytes with a 5 minute pre-treatment of an elevated extracellular glucose concentration (20mM) prior to simulated ischaemia significantly increases the percentage of cardiomyocytes able to regain contractile function from 29.5±2.4% (control) to 61.8±2.4%*** (Results presented as mean ±S.E.M; N= 6 experiments, ≥116 cardiomyocytes for each experiment, ***P<0.001 Bonferroni’s post-hoc test). Additionally, supplying 20mM glucose for only the first 5 minutes of the 10 minute reperfusion stage significantly increases contractile recovery to 62.8±4.8%*** (Results presented as mean ±S.E.M; N= 6 experiments, ≥115 cardiomyocytes for each experiment, ***P<0.001 Bonferroni’s post-hoc test). These data show that both pre- and post-treatment of isolated cardiomyocytes with an acute elevated glucose concentration imparts a degree of cardioprotection. We hypothesise that there is increased glycolytic substrate availability during ischaemia after pre-treatment with 20mM glucose. For cardiomyocytes treated with elevated glucose on reperfusion it is hypothesised to give a more gradual ATP delivery therefore reducing reperfusion injury.



Where applicable, experiments conform with Society ethical requirements.

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