Biomedical subjects

Jérôme Kalifa

Publications and source records attributed to Jérôme Kalifa.

5 recordsLinked to original sources

PubMed2006

Activation of inward rectifier potassium channels accelerates atrial fibrillation in humans: evidence for a reentrant mechanism.

BACKGROUND: It is unclear whether atrial fibrillation (AF) drivers in humans are focal or reentrant. To test the hypothesis that functional reentry is involved in human AF maintenance, we determined the effects of adenosine infusion on local dominant frequency (DF) at different atrial sites. By increasing inward rectifier potassium channel conductance, adenosine would increase DF of reentrant drivers but decrease it in the case of a focal mechanism. METHODS AND RESULTS: Thirty-three patients were studied during AF (21 paroxysmal, 12 persistent) using recordings from each pulmonary vein-left atrial junction (PV-LAJ), high right atrium, and coronary sinus. DFs were determined during baseline and peak adenosine effect. In paroxysmal AF, adenosine increased maximal DF at each region compared with baseline (PV-LAJ, 8.03+/-2.2 versus 5.7+/-0.8; high right atrium, 7+/-2.2 versus 5.4+/-0.7; coronary sinus, 6.6+/-1.1 versus 5.3+/-0.7 Hz; P=0.001) and increased the left-to-right DF gradient (P=0.007). In contrast, in persistent AF, adenosine increased DF only in the high right atrium (8.33+/-1.1 versus 6.8+/-1.2 Hz; P=0.004). In 4 paroxysmal AF patients, real-time DF mapping of the left atrium identified the highest DF sites near the PV-LAJ, where adenosine induced an increase in DF (6.7+/-0.29 versus 4.96+/-0.26 Hz; P=0.008). Finally, simulations demonstrate that the frequency of reentrant drivers accelerates proportionally to the adenosine-modulated inward rectifier potassium current. CONCLUSIONS: Adenosine accelerates drivers and increases frequency differently in paroxysmal compared with persistent human AF. The results strongly suggest that AF is maintained by reentrant sources, most likely located at the PV-LAJ in paroxysmal AF, whereas non-PV locations are more likely in persistent AF.

Adenosine↗

PubMed2006

Mechanisms of wave fractionation at boundaries of high-frequency excitation in the posterior left atrium of the isolated sheep heart during atrial fibrillation.

BACKGROUND: High-frequency fractionated electrograms recorded during atrial fibrillation (AF) in the posterior left atrium (PLA) and elsewhere are being used as target sites for catheter ablation. We tested the hypothesis that highly periodic electric waves emerging from AF sources at or near the PLA give rise to the most fractionated activity in adjacent locations. METHODS AND RESULTS: Sustained AF was induced in 8 isolated sheep hearts (0.5 micromol/L acetylcholine). Endocardial videoimaging (DI-4-ANEPPS) and electric mapping of the PLA enabled spatial characterization of dominant frequencies (DFs) and a regularity index (ratio of DF to total power). Regularity index showed that fractionation was lowest within the area with the maximal DF (DFmax domain; 0.19+/-0.02) and highest within a band of &3 mm (0.16+/-0.02; P=0.047) at boundaries with lower-frequency domains. The numbers of spatiotemporal periodic episodes (25.9+/-2.3) and rotors per experiment (1.9+/-0.7) were also highest within the DFmax domain. Most commonly, breakthrough waves at the PLA traveled toward the rest of the atria (76.8+/-8.1% outward versus 23.2+/-8.1% inward; P<0.01). In both experiments and simulations with an atrial ionic model, fractionation at DFmax boundaries was associated with increased beat-to-beat variability of conduction velocity and directionality with wavebreak formation. CONCLUSIONS: During stable AF, the PLA harbors regular, fast, and highly organized activity; the outer limit of the DFmax domain is the area where the most propagation pattern variability and fractionated activity occur. These new concepts introduce a new perspective in the clinical use of high-frequency fractionated electrograms to localize sources of AF precisely at the PLA and elsewhere.

Animals↗

PubMed2005

Mechanisms of atrial fibrillation termination by pure sodium channel blockade in an ionically-realistic mathematical model.

The mechanisms by which Na+-channel blocking antiarrhythmic drugs terminate atrial fibrillation (AF) remain unclear. Classical "leading-circle" theory suggests that Na+-channel blockade should, if anything, promote re-entry. We used an ionically-based mathematical model of vagotonic AF to evaluate the effects of applying pure Na+-current (I(Na)) inhibition during sustained arrhythmia. Under control conditions, AF was maintained by 1 or 2 dominant spiral waves, with fibrillatory propagation at critical levels of action potential duration (APD) dispersion. I(Na) inhibition terminated AF increasingly with increasing block, terminating all AF at 65% block. During 1:1 conduction, I(Na) inhibition reduced APD (by 13% at 4 Hz and 60% block), conduction velocity (by 37%), and re-entry wavelength (by 24%). During AF, I(Na) inhibition increased the size of primary rotors and reduced re-entry rate (eg, dominant frequency decreased by 33% at 60% I(Na) inhibition) while decreasing generation of secondary wavelets by wavebreak. Three mechanisms contributed to I(Na) block-induced AF termination in the model: (1) enlargement of the center of rotation beyond the capacity of the computational substrate; (2) decreased anchoring to functional obstacles, increasing meander and extinction at boundaries; and (3) reduction in the number of secondary wavelets that could provide new primary rotors. Optical mapping in isolated sheep hearts confirmed that tetrodotoxin dose-dependently terminates AF while producing effects qualitatively like those of I(Na) inhibition in the mathematical model. We conclude that pure INa inhibition terminates AF, producing activation changes consistent with previous clinical and experimental observations. These results provide insights into previously enigmatic mechanisms of class I antiarrhythmic drug-induced AF termination. The full text of this article is available online at http://circres.ahajournals.org

Algorithms↗

PubMed2003

Intra-atrial pressure increases rate and organization of waves emanating from the superior pulmonary veins during atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) commonly associates with atrial dilatation by poorly understood mechanisms. We hypothesized that elevation of intra-atrial pressure elicits high-frequency and spatio-temporally organized left atrial (LA) sources emanating from the superior pulmonary veins. METHODS AND RESULTS: We used a stretch-related AF model in the sheep heart to induce stable episodes of AF (>40 minutes) in 9 animals. Video movies of the LA free wall (LAFW) and LA superior pulmonary vein junction (JPV) were obtained by using di-4-ANEPPS. Electrograms from the right atrium were recorded. At intra-atrial pressures >10 cm H2O, the maximum dominant frequency (DFMax) was significantly higher in the JPV than in the LAFW (12.0+/-0.2 and 10.5+/-0.2 Hz, respectively [mean+/-SEM]; P<0.001). Below 10 cm H2O, DFMax was similar in the JPV and LAFW (10.8+/-0.3 versus 10.2+/-0.3 Hz; P=0.6); DFMax in both JPV and LAFW was significantly higher than in the right atrium (7.8+/-0.3 Hz; P<0.001). Analysis of excitation direction in JPV showed positive correlation between intra-atrial pressure and the number of waves emanating from the left superior pulmonary vein (r=0.79, P=0.02) but not from the LAFW (r=0.54, P=0.09). The number of spatio-temporally periodic waves in the JPV correlated with pressure (r=0.92, P=0.002). In 3 cases, JPV rotors were identified with a cycle length equal to 1/DFMax. CONCLUSIONS: We demonstrate for the first time that an increase in intra-atrial pressure increases the rate and organization of waves emanating from the superior pulmonary veins underlying stretch-related AF.

Animals↗

PubMed2003

Regularization in tomographic reconstruction using thresholding estimators.

In tomographic medical devices such as single photon emission computed tomography or positron emission tomography cameras, image reconstruction is an unstable inverse problem, due to the presence of additive noise. A new family of regularization methods for reconstruction, based on a thresholding procedure in wavelet and wavelet packet (WP) decompositions, is studied. This approach is based on the fact that the decompositions provide a near-diagonalization of the inverse Radon transform and of prior information in medical images. A WP decomposition is adaptively chosen for the specific image to be restored. Corresponding algorithms have been developed for both two-dimensional and full three-dimensional reconstruction. These procedures are fast, noniterative, and flexible. Numerical results suggest that they outperform filtered back-projection and iterative procedures such as ordered-subset-expectation-maximization.

Algorithms↗