Biomedical subjects

Imad Libbus

Publications and source records attributed to Imad Libbus.

3 recordsLinked to original sources

PubMed2004

Electrotonic load triggers remodeling of repolarizing current Ito in ventricle.

A change in activation sequence electrically remodels ventricular myocardium, causing persistent changes in repolarizing currents (T-wave memory). However, the underlying mechanism for triggering activation sequence-dependent remodeling is unknown. Optical action potentials were mapped with high resolution from the epicardial surface of the arterially perfused canine wedge preparation (n = 23) during 30 min of baseline endocardial stimulation, followed by 40 min of epicardial stimulation, and, finally, restoration of endocardial stimulation. Immediately after the change from endocardial to epicardial stimulation, phase 1 notch amplitude of epicardial cells was attenuated by 74 +/- 8% (P < 0.001) compared with baseline and continued to diminish during the period of epicardial pacing, suggesting progressive remodeling of the transient outward current (Ito). When endocardial pacing was restored, notch amplitude did not immediately recover but remained attenuated by 23 +/- 10% (P < 0.001), also consistent with a remodeling effect. Peak Ito current measured from isolated epicardial myocytes changed by 12 +/- 4% (P < 0.025), providing direct evidence for Ito remodeling occurring on a surprisingly short time scale. The mechanism for triggering remodeling of Ito was a significant reduction (by 14 +/- 4%, P < 0.001) of upstroke amplitude in epicardial cells during epicardial stimulation. Reduction in upstroke amplitude during epicardial pacing was explained by electrotonic load on epicardial cells by fully repolarized downstream endocardial cells. These data suggest a novel mechanism for triggering electrical remodeling in the ventricle. Electrotonic load imposed by a change in activation sequence reduces upstroke amplitude, which, in turn, attenuates Ito according to its known voltage-dependent properties, triggering downregulation of current.

Action Potentials↗

PubMed2003

Transmural action potential changes underlying ventricular electrical remodeling.

INTRODUCTION: Although it is well established that alterations in heart rate or activation sequence induce electrical remodeling in the atria, electrical remodeling in the ventricle is poorly understood. METHODS AND RESULTS: To determine the changes in cellular repolarization that underlie ventricular electrical remodeling caused separately by altered heart rate and activation sequence, optical action potentials were recorded simultaneously from 256 sites spanning the transmural wall of the arterially perfused canine wedge preparation (n = 15). Action potentials were compared from the same sites under identical conditions [endocardial pacing, cycle length (CL) = 1,000 msec], before and after an intervening 20- to 60-minute period of remodeling induced by (1) rapid pacing (CL = 300 msec) with no change in activation sequence; (2) altered activation sequence (epicardial pacing) with no change in rate; or (3) no change in rate or activation sequence (control). Action potential duration (APD) shortened by 24.8 +/- 4.8 msec following a period of rapid heart rate (P < 0.05) but prolonged (by 12.7 +/- 1.8 msec) following a period of altered activation sequence (P < 0.05). Hence, even after restoration of baseline heart rate and activation sequence, there were persistent changes in APD from baseline, indicative of electrical remodeling. Moreover, the orientation of the maximum APD gradient across the transmural wall changed more significantly following heart rate remodeling (by 27.7 degrees +/- 4.9 degrees, P < 0.05) than following activation sequence remodeling (by 12.3 degrees +/- 2.4 degrees, P < 0.05). CONCLUSION: Persistent changes in ventricular repolarization can be induced by surprisingly short periods of altered rate or activation sequence. In contrast to atrial remodeling, electrical remodeling in the ventricle can result in prolonged APD (with altered activation sequence) or reversal of APD gradient orientation (with rapid rate), suggesting that the nature of ventricular electrical remodeling induced by these two perturbations is different.

Action Potentials↗

PubMed2002

Remodeling of cardiac repolarization: mechanisms and implications of memory.

Memory is a well established property of biological organisms, allowing them to adapt to their environment and respond to novel stimuli. Sensitization occurs in response to a noxious stimulus, and increases the behavioral response to subsequent stimuli. In contrast, habituation occurs in response to an innocuous stimulus, and decreases the behavioral response to subsequent stimuli. Therefore, the response of an organism to a stimulus does not simply depend on the stimulus, but also on previous stimuli that the organism has received. Similarly, the response of the heart to a stimulus does not simply depend on the stimulus, but also on previous patterns of depolarization and repolarization, due to electrical remodeling. Electrical remodeling, the persistent change in electrophysiological properties of myocardium in response to a change in rate or activation sequence, has been well described in atria. It can be induced by rapid pacing or atrial fibrillation (AF), and results in shortened atrial refractory period and increased susceptibility to atrial arrhythmias. These changes have been associated with alterations of potassium and calcium currents. However, the fundamental mechanisms responsible for triggering changes in channel expression in response to alterations in rate and activation sequence in AF are poorly understood. Even less is known about electrical remodeling in ventricle. Rapid ventricular pacing or an alteration of ventricular activation sequence produces persistent changes in heterogeneity of repolarization and, in contrast to atria, a prolongation of action potential duration. Ventricular electrical remodeling is responsible for "T-wave memory," which is observed commonly in patients after periods of altered activation sequence (e.g., chronic pacing). These changes have been associated with alterations of potassium currents, specifically I(to), implying that electrical remodeling is heterogeneously expressed in the different cell types across the transmural wall. Finally, remodeling of gap junctions may also play a prominent role in action potential changes during remodeling. The signal transduction pathways through which a change in rate or activation sequence triggers changes in the expression of ionic currents are being actively investigated.

Action Potentials↗