Catheter ablation of paroxysmal atrial fibrillation using a 3D mapping system.

BACKGROUND: We treated paroxysmal recurrent atrial fibrillation (AF) with radiofrequency (RF) catheter ablation by creating long linear lesions in the atria. To achieve line continuity, a 3D electroanatomic nonfluoroscopic mapping system was used. METHODS AND RESULTS: In 27 patients with recurrent AF, a catheter incorporating a passive magnetic field sensor was navigated in both atria to construct a 3D activation map. RF energy was delivered to create continuous linear lesions: 3 lines (intercaval, isthmic, and anteroseptal) in the right atrium and a long line encircling the pulmonary veins in the left atrium. After RF application, the atria were remapped to validate completeness of the block lines, demonstrated by late activation of the areas circumscribed by the lines. The mean procedure duration was 312+/-103 minutes (range, 187 to 495), with mean fluoroscopy time of 107+/-44 minutes (range, 32 to 185 minutes). No acute complications occurred, but 1 patient experienced early prolonged sinus pauses and received a pacemaker. During the first day, 17 patients (63%) had AF episodes, but at discharge, 25 patients were in sinus rhythm. After a follow-up of 6. 0 to 15.3 months (average, 10.5+/-3.0 months), 16 patients are asymptomatic, 3 have an almost complete disappearance of symptoms, 1 patient is improved, and 7 patients have their AF attacks unchanged. CONCLUSIONS: Paroxysmal recurrent drug-refractory AF can be treated by RF catheter ablation. Creation of long continuous linear lesions necessary to compartmentalize the atria is facilitated by a nonfluoroscopic electroanatomic mapping system.

Atrial linear ablations in pigs. Chronic effects on atrial electrophysiology and pathology.

BACKGROUND: Generation of long and continuous linear ablations is required in a growing number of atrial arrhythmias. However, deployment and assessment of these lesions may be difficult, and there are few data regarding their short- and long-term effects on atrial electrophysiology and pathology. METHODS AND RESULTS: A nonfluoroscopic mapping and navigation technique was used to generate 3-dimensional (3D) electroanatomic maps of the right atrium in 8 pigs. The catheter was then used to deliver sequential radiofrequency (RF) applications (power output gradually increased until 80% reduction in the amplitude of the unipolar electrogram) to generate a continuous lesion between the superior and inferior venae cavae. The animals were remapped 4 weeks after ablation during septal pacing. Lesion continuity was confirmed in all cases by the following criteria: (1) activation maps indicating conduction block [significant disparities in activation times (52.0+/-16.0 ms) and opposite orientation of the activation wave front on opposing sides of the lesion], (2) evidence of double potentials (interspike time difference of 52.3+/-17.1 ms), and (3) low peak-to-peak amplitude of the bipolar electrograms (0.7+/-0.6 mV) along the lesion. At autopsy, all lesions were continuous and transmural, averaged 50.5+/-6.7 mm, and were characterized histologically by transmural fibrosis throughout the length of the lesion. CONCLUSIONS: Long linear atrial ablation, created by sequential RF applications (using unipolar amplitude attenuation as the end point for energy delivery), results in long-term continuous and transmural lesions. Lesion continuity is associated with evidence of conduction block in the 3D activation maps and the presence of double potentials and low electrogram amplitude along the lesion.

Renal response of euryhaline toad (Bufo viridis) to acute immersion in tap water, NaCl, or urea solutions.

Green toads (Bufo viridis) were acclimated to either tap water, 230 mOsmol NaCl kg-1 H2O (saline), 500 mOsmol NaCl kg-1 H2O (high saline), or 500 mmol L-1 urea. Renal functions for each acclimation group were studied on conscious animals that had one ureter chronically catheterized. Reciprocal immersion of tap-water- and saline-acclimated toads in the opposite solution did not stress the animals osmotically, and plasma osmolality increased or decreased by no more than 15%. However, urine osmolality and ionic composition changed immediately and profoundly on exposure to the other solution. Exposure of tap-water-acclimated toads to saline decreased urine flow by 30%, whereas the reciprocal immersion led to an increase of 30%. Immersion of tap-water-acclimated toads in high saline led to immediate cessation of urine flow, whereas immersion of 500 NaCl- or urea-acclimated toads in tap water led to a large increase in urine flow, with an overshoot that lasted 10 h (as a result of either salt or urea diuresis). Urine flow then stabilized at a level 5-6 times higher than the value attained at high-salt environment. On immersion of 500 urea-acclimated toads in 500 NaCl, urine flow doubled, accompanied by a change in ion composition, without change in the osmolality. In all experimental conditions, plasma potassium concentration was maintained within a narrow range. The results show that the toad's kidneys contributed efficiently both to osmo- and ionoregulation in a wide range of ambient solutions.

Electromechanical characterization of chronic myocardial infarction in the canine coronary occlusion model.

BACKGROUND: Defining the presence, extent, and nature of the dysfunctional myocardial tissue remains a cornerstone in diagnostic cardiology. A nonfluoroscopic, catheter-based mapping technique that can spatially associate endocardial mechanical and electrical data was used to quantify electromechanical changes in the canine chronic infarction model. METHODS AND RESULTS: We mapped the left ventricular (LV) electromechanical regional properties in 11 dogs with chronic infarction (4 weeks after LAD ligation) and 6 controls. By sampling the location of a special catheter throughout the cardiac cycle at multiple endocardial sites and simultaneously recording local electrograms from the catheter tip, the dynamic 3-dimensional electromechanical map of the LV was reconstructed. Average endocardial local shortening (LS, measured at end systole and normalized to end diastole) and intracardiac bipolar electrogram amplitude were quantified at 13 LV regions. Endocardial LS was significantly lower at the infarcted area (1.2+/-0.9% [mean+/-SEM], P<0.01) compared with the noninfarcted regions (7.2+/-1.1% to 13. 5+/-1.5%) and with the same area in controls (15.5+/-1.2%, P<0.01). Average bipolar amplitude was also significantly lower at the infarcted zone (2.3+/-0.2 mV, P<0.01) compared with the same region in controls (10.3+/-1.3 mV) and with the noninfarcted regions (4. 0+/-0.7 to 10.2+/-1.5 mV, P<0.01) in the infarcted group. In addition, the electrical maps could accurately delineate both the location and extent of the infarct, as demonstrated by the high correlation with pathology (Pearson's correlation coefficient=0.90) and by the precise identification of the infarct border. CONCLUSIONS: Chronic myocardial infarcted tissue can be characterized and quantified by abnormal regional mechanical and electrical functions. The unique ability to assess the regional ventricular electromechanical properties in various myocardial disease states may become a powerful tool in both clinical and research cardiology.

Effect of alpha-ketoglutarate on organic anion transport in single rabbit renal proximal tubules.

The effect of exogenous alpha-ketoglutarate (alpha KG) and the peritubular Na(+)-dicarboxylate (Na-DC) cotransporter on organic anion/dicarboxylate (OA/DC) exchange in S2 segments of single, nonperfused rabbit proximal tubules was measured using 1 microM fluorescein (FL), a model OA, and epifluorescence microscopy. The effect of different transmembrane distributions of 10 microM alpha KG on peritubular FL uptake was measured at 37 degrees C using bicarbonate-buffered, nutrient-containing buffers, which are conditions similar to those found in vivo. Compared with FL uptake in the absence of exogenous alpha KG, preloading tubules with alpha KG (trans-configuration) or acute exposure to alpha KG (cis-configuration) increased FL uptake 62% and 54%, respectively, whereas a cis-trans-configuration of alpha KG increased FL uptake by 76%. The cis-stimulation of FL uptake by alpha KG was rapid, within 5-7 s. This stimulation was blocked 96% by simultaneous exposure to 2 mM Li+, indicating that stimulation of transport was secondary to the uptake of exogenous alpha KG. In the absence of exogenous alpha KG, selective inhibition of Na-DC cotransport using 2 mM Li+ or 1 mM methylsuccinate decreased FL uptake by 25% (effects that were reversible but not additive), suggesting that the Na-DC cotransporter recycles endogenous alpha KG that has left the cell in exchange for FL and that this activity supports approximately 25% of baseline activity of the OA/DC exchanger. With recycling of alpha KG accounting for approximately 25% of FL uptake and with accumulation of exogenous alpha KG accounting for another approximately 75% increase in FL uptake, Na-DC cotransport appears to directly support (25% + 75%)/175%, or approximately 57%, of total FL transport.

Hemodynamic evaluation of the heart with a nonfluoroscopic electromechanical mapping technique.

BACKGROUND: Clinical cardiac volumetric measurement techniques are essential for assessing cardiac performance but produce significant inaccuracies in extrapolation of the volume of a three-dimensional (3D) object from two-dimensional images and lack the ability to associate cardiac electrical and mechanical activities. In this study, we tested the accuracy of cardiac volumetric measurements using a new catheter-based system. METHODS AND RESULTS: The system uses magnetic technology to accurately locate a special catheter at a frequency of 125 Hz and is currently used in the field of electrophysiology, in which activation maps are superimposed on the 3D geometry of the cardiac chamber. The mapping procedure is based on sequentially acquiring the location of the tip and local electrogram while in contact with the endocardium. The 3D geometry of the chamber is reconstructed in real time, and its volume could be calculated at every time step (8 ms). The volumetric measurements of the system were found to be highly accurate for simple phantoms (mean+/-SEM deviation, 2.3+/-1.1%), left ventricular casts (9.6+/-1.3%), and a dynamic test jig. In addition, left ventricular volumes of 12 swine were measured. Intraobserver and interobserver variabilities were found to be minimal (ejection fraction, 6.5+/-1.9% and 7.1+/-2.0%; stroke volume, 4.5+/-1.0% and 11.3+/-2.4%). Comparison with the thermodilution method for measuring stroke volume showed an average deviation of 8.1+/-2.2%. Typical pressure-volume loops were also obtained. CONCLUSIONS: The new mapping image provides, for the first time, simultaneous information regarding cardiac mechanics, hemodynamics, and electrical properties. Furthermore, all this information is achieved without the use of fluoroscopy, contrast medium, or complicated image processing.

Guidance of radiofrequency endocardial ablation with real-time three-dimensional magnetic navigation system.

BACKGROUND: Ablation therapy for certain arrhythmias requires the formation of complex lesions based on electrical and anatomic mapping. We tested the accuracy and reproducibility of a nonfluoroscopic mapping and navigation (NFM) system to guide delivery of radiofrequency (RF) energy in the right atrium (RA) of swine. METHODS AND RESULTS: The NFM system uses an ultralow magnetic field to measure the real-time three-dimensional (3D) location of the tip of the locatable catheter. While in stable contact with the endocardium, between 30 and 40 consecutive tip locations were sampled and used for the 3D reconstruction of the RA geometry. The location of the catheter tip was presented in real time, superimposed over the RA geometry. We selected a point on the 3D reconstruction and delivered RF energy to that site via the tip of the locatable catheter. The catheter was then completely withdrawn and renavigated twice to the same point, at which RF energy was delivered again. At autopsy, the distance between the centers of the three ablation points (mean+/-SEM) was 2.3+/-0.5 mm (n=27). Similarly, we used the NFM system to guide the generation of linear lesions. The measured length of the linear lesions on the NFM 3D view was close to the actual lesion length measured at autopsy (correlation coefficient, .96; P=.002; n=6). Furthermore, the location, shape, and continuity of the linear lesions corresponded to the autopsy findings. CONCLUSIONS: We conclude that the NFM system can guide the application of RF energy without the use of fluoroscopy in a highly accurate and reproducible manner.

Interaction of alpha-KG with basolateral organic anion transporter in isolated rabbit renal S3 proximal tubules.

To understand the basolateral p-aminohippurate (PAH) transporter in the S3 segment of rabbit proximal tubules and its relationship to the transporter in the S2 segment, we measured the 30-s uptake and efflux of PAH across the basolateral membrane of single isolated S3 segments at 37 degrees C in bicarbonate-buffered media. Kinetic analysis of uptake data revealed a concentration of PAH at one-half Jmax of approximately 107 microM (same as in the S2 segment) but a Jmax of 600 fmol.min-1.nl-1 (one-tenth that of S2 segment). The coefficient for efflux across the basolateral membrane was also only one-sixth to one-tenth of that in the S2 segment. These data suggest that the basolateral PAH transporter is the same in both segments but that there are fewer transporters in the S3 than in the S2 segment. However, the apparent inhibitor constant values for cis-inhibition by probenecid (approximately 29 microM in S3, approximately 15 microM in S2) and by alpha-ketoglutarate (alpha-KG) in the presence of LiCl (approximately 40 microM in S3, approximately 160 microM in S2) suggest that the transporters may not be identical in the two segments. In bicarbonate-buffered medium, preloading the tubules with 100 microM alpha-KG did not trans-stimulate PAH uptake across the basolateral membrane, whereas preloading with 1.0 microM alpha-KG caused a significant stimulation of 43%. However, in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered medium, preloading the tubules with 100 microM alpha-KG caused a twofold increase in PAH uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal function at steady state in a toad (Bufo viridis) acclimated in hyperosmotic NaCl and urea solutions.

Kidney function of the euryhaline toad Bufo viridis was studied in animals acclimated to tap water and solutions of NaCl (230 and 500 mosmol.kg-1 H2O) and urea (500 mmol.l-1) in steady-state conditions. An ureter was catheterized for continuous urine collection and blood was sampled from an iliac artery. A single injection of 3H-inulin served for estimation of glomerular filtration rate: this was in the range of 15-27 ml.kg-1.h-1 and did not differ significantly in any of the acclimation conditions. Urine flow, on the other hand, varied considerably and was highest in tap water (18.2 +/- 3.2 ml.kg-1.h-1; urine/plasma inulin ratio = 0.88), lower in 230 mosmol.kg-1 H2O NaCl solution (13.5 +/- 3.9 ml.kg-1.h-1; u/p inulin ratio = 1.73) and lowest in 500 mosmol.kg-1 H2O NaCl or urea acclimation solutions (5-7 ml.kg-1.h-1; u/p inulin = 3.7-4.2). Clearance of free water was high in the tap water group, lower in 230 mosmol.kg-1 H2O NaCl solution, and much lower in the hyperosmotic acclimation conditions. Clearances of both Na+ and Cl- were similar under our experimental conditions, but changed independently in accordance to the composition of the acclimation solution. Potassium clearance was similar in all acclimation conditions, and a constant plasma K+ concentration was maintained. Urea clearance was high in tap water and 500 mmol.l-1 urea acclimation groups and low in the NaCl acclimations.(ABSTRACT TRUNCATED AT 250 WORDS)

Anuran amphibia which are not acclimable to high salt, tolerate high plasma urea.

1. The capacity of five anuran Amphibians (Bufo viridis, B. regularis, Rana ridibunda, Hyla arborea and Pelobates syriacus) to acclimate to NaCl and urea solutions was investigated. 2. All species could be acclimated to relatively high concentrations of urea solutions, while only Bufo viridis and Hyla arborea could be acclimated to 500 mOsm/kg or higher NaCl solutions. 3. The plasma urea concentration in B. viridis and H. arborea was elevated to levels over 140 mmol/l. 4. The sum of plasma sodium and chloride concentrations did not increase over 400 mmol/l in any species. 5. Urine osmolality, which was normally low, increased, but never exceeded the plasma osmolality. 6. In the urea acclimation conditions, urine electrolytes diminished, similarly in all species in this study. 7. It is concluded that anuran Amphibians can tolerate high plasma urea concentrations, but only those species which can elevate it, either through retention or net synthesis, can be acclimated to high salt solutions.

Urea transport across urinary bladder and salt acclimation in toad (Bufo viridis).

The fluxes of urea across the urinary bladder of the toad Bufo viridis have been studied under conditions of acclimation to tap water or 500 mosM NaCl solution. The [14C]urea fluxes were measured simultaneously with [3H]inulin to test for nonspecific leakage. The fluxes are quite high (Ktrans = 75 x 10(-7) cm/s at 5 mmol/l urea) and are similar in either the mucosal-to-serosal or the opposite direction. "Summer" rates were five to six times higher than the "winter" rates. Antidiuretic hormone (ADH), theophylline, and forskolin increased the fluxes to variable degrees (two to five times), similar in the two acclimation conditions. Phloretin inhibited the urea fluxes by nearly 50%. 1,3-Dimethylurea and thiourea, but not acetamide, competed with the urea fluxes effectively. The fluxes of urea were not affected by the osmotic water flow, although both responded to ADH. It is concluded that urea transport across the urinary bladder of B. viridis is by facilitated diffusion through a specific pathway independent of water flux. The inhibitory effect of the structural analogues on the urea flux was affected by salt acclimation, whereas most other characteristics did not differ significantly at 5 mmol/l external urea under the two conditions of acclimation.

Saturable urea transport pathway across the urinary bladder of Bufo viridis and salt acclimation.

Urea fluxes across the urinary bladder of Bufo viridis were studied in vitro after modification of the mounting technique. The fluxes increased as a function of the bath urea concentration, saturating near 200 mmol/l. The apparent Km was 88 mmol/l in the bladders from tapwater-acclimated toads, and 107 mmol/l in toads acclimated to 500 mOsm NaCl. The Vmax which was 300 mumol.h-1.cm-2 at room temperature in bladders from tapwater acclimation, changed to more than 1500 mumol.h-1.cm-2 upon salt acclimation. It is suggested that urea movement across the urinary bladder of this species occurs by facilitated diffusion and that salt acclimation induces an increase in the density of this pathway, but not of its characteristics (Km).