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.