DISCUSSION
The objective of the present study was evaluation of arrhythmogenesis in the diabetic animals in respect to two factors that can “quantify” the progress of untreated DM, i.e. the time lapsed from DM induction and the plasma glucose concentration. It was found that reperfusion VT/VF development was associated with DM duration. Electrophysiological property associated with DM duration and reperfusion arrhythmogenesis and possibly linking the former with the latter appeared to be prolonged ARIs. Glucose concentration did not demonstrate independent association with reperfusion VT/VF inducibility, and VT/VFs arising during occlusion period were not associated with neither DM duration, nor glucose concentration.
In general, the diabetic state in our study was associated with prolongation of activation and repolarization processes. Specifically, it concerned the duration of total and epicardial activation and average duration of ARI. These findings correspond to our previous observations in rabbits and mice18, 19 and may be related to down-regulation of sodium20 and potassium21-25 currents. Both delay in activation (implying decrease of conduction velocity) and prolongation of ARIs (implying increase of action potential duration) might have been arrhythmogenic. However, only the prolonged ARIs were associated with VT/VF development and only in the reperfusion state.
The relationship between reperfusion VT/VF inducibility and prolonged duration of repolarization seen in the present study was also demonstrated in the previous reports from our group concerning reperfusion arrhythmogenesis in nondiabetic rats26 and cats27. It is noteworthy, that in these cited studies as well as in the present work, it is repolarization of the perfused myocardium that plays a crucial role in development of reperfusion VT/VFs. Here, we evaluated the electrophysiological parameters only in the baseline state preceding ischemia, and previously26, 27 we tested ARIs both in ischemic and nonischemic regions, and only nonischemic ARIs demonstrated associations with VT/VF inducibility. Mechanisms of the arrhythmogenic role of long action potential duration in the nonischemic myocardium may concern increase of DOR (considering repolarization shortening in the affected myocardium) and facilitation of early afterdepolarizations serving as triggers for reentrant arrhythmias. Since DOR was directly tested as a VT/VF predictor and did not show association with reperfusion arrhythmias in the present study and previously 26, 27, we believe that the afterdepolarization-related mechanism is more probable. The plausible explanation for the absence of association between DM and ischemic arrhythmias is that the latter had several electrophysiological predictors, namely ARI duration, DOR and time of epicardial breakthrough (an estimate for duration of conduction via His-Purkinje system), and only ARIs were associated with DM conditions, specifically DM duration.
The present study demonstrated that the increase in duration augments arrhythmogenic potential of DM via influences on action potential duration assessed here as ARI. Also, the longer DM duration was associated with the longer total ventricular activation time, which however was not related to VT/VF inducibility. Previous works demonstrated the role of DM duration in alterations of cardiac autonomic innervation16, 28 and ischemic preconditioning14. Both effects may be related to the changes of the electrophysiological properties, but our study was the first, to our knowledge, to report direct electrophysiological myocardial parameters in respect to DM duration and arrhythmogenesis.
It was an unexpected finding that VT/VF development was not related to the glucose concentration, which can be considered as the extent of severity of DM. Probably, this result is due to that glucose concentration might not be stable during the time-course of DM development. However, it was observed that duration of epicardial activation (an indirect measure of intramyocardial conduction) was associated with the plasma glucose concentration. These data taken together with the association between DM duration and total ventricular activation supports the notion that DM is associated with conduction disturbances19, 20, 29. These disturbances observed in baseline can underlie DM-induced reduction of conduction reserve in ischemic conditions29, which however may not necessarily be arrhythmogenic.