Effect of Acute Hyperglycemia on Cardiac Conduction

Abstract

Diabetes is associated with a relatively high prevalence of sudden cardiac death but the underlying mechanism is not well understood. In experimental diabetes, cardiac expression of connexin43 is reduced. Downregulation of connexin43 is linked to a slowing of cardiac conduction which increases the risk of cardiac arrhythmias and thereby sudden cardiac death. It is known that hyperglycemia causes downregulation of connexin43 but it is unknown to which extend this occurs in whole hearts. Here, we test the hypothesis that acute hyperglycemia leads to slowing of cardiac conduction through downregulation of connexin43 in whole hearts. We measured ventricular conduction velocity in Langendorff perfused guinea pig hearts using a multi-electrode array under normo- and hyperglycemic conditions (5.5 and 30mM glucose respectively) for up to 4 hrs. In addition, one group of hearts was perfused with a mannitol solution as a control for changes in osmolarity. Expression of connexin43 was quantified by western blotting. In the control group, longitudinal conduction velocity remained stable over 4 hrs (63 cm/s) while transverse conduction decreased slightly (from 27 to 25 cm/s). Similar results were obtained from both the hyperglycemia and mannitol groups suggesting that conduction was unaffected by changes in glucose concentration and osmolarity. Accordingly, no differences were observed in the protein levels of connexin43 between the groups supporting the functional results. In conclusion, acute exposure to hyperglycemia does not appear to have any significant effects on cardiac conduction and does not modulate the expression of connexin43 in guinea pig hearts.