Isopotential Maps Research Articles

Three-dimensional mapping of right atrial activation during sinus rhythm and its relationship to endocardial architecture.

Previous mapping studies of right atrial (RA) activation during sinus rhythm have been limited by the use of epicardial electrode plaques in open chest subjects or microelectrodes in the excised heart. This study describes global RA endocardial activation patterns using high-density mapping and compares the results with underlying endocardial architecture. Noncontact mapping of the RA was performed in 21 anesthetized swine. Isopotential and isochronal maps were superimposed upon three-dimensional reconstructions of RA geometry. Hearts were excised and endocardial dissection performed. Two patterns of RA activation were recorded. The site of earliest endocardial activation occurred either laterally at a position consistent with the terminal crest or superiorly at the junction between the superior caval vein and RA appendage. The subsequent spread of depolarization followed the longitudinal orientation of muscle fibers. Areas of conduction delay and block were seen at the junction between the terminal crest and posterior wall, the cavotricuspid isthmus, and around the margins of the triangle of Koch. Endocardial dissection at these sites demonstrated complex fiber orientation. A lateral site of earliest activation demonstrated a more prominent display of conduction delay or block. The spread of the sinus impulse follows endocardial myofiber orientation and is dictated by the site of earliest activation. Even during sinus rhythm, anisotropic conduction results in areas of conduction block or delay. These findings have implications in the development of reentrant arrhythmias and may influence surgical or electrophysiologic procedures.

Identification of Ventricular Tachycardia of Epicardial Origin from Unipolar Potentials Obtained at the Endocardial Surface: Is It Feasible?

VT late after myocardial infarction usually originates from the endocardial surface; subepicardial substrates are also possible. The identification of these atypical locations with endocardial mapping remains unresolved even with new mapping technologies. This study compared isopotential maps, signal morphology, and activation patterns around left endocardial breakthroughs recorded in VTs originating from the subepicardium or subendocardium after remote myocardial infarction. These results were extracted from a database of 111 tachycardias obtained at surgery in 34 patients. Mapping was performed with a 128-unipolar electrode system using an epicardial mesh and a left ventricular endocardial balloon. Subepicardial (n = 7) and subendocardial VTs (n = 10) were defined as complete superficial reentry and/or as tachycardias with a > or = 25-ms delay between the earliest activity and the breakthrough of activation on the opposite surface. A positive potential distribution covering the area of initial endocardial activity was observed in a single subepicardial VT but in none of the subendocardial ones (P = NS). R waves were observed on the earliest endocardial unipolar signals in two subepicardial VTs and five subendocardial VTs (P = NS). The area covered by the first 5-ms or 10-ms isochrone at the endocardial level was larger in subepicardial VTs than in subendocardial VTs but the difference was not significant. In conclusion, despite a wider endocardial area of early activity in VTs of subepicardial origin, no reliable criteria can be proposed to identify these tachycardias from mapping data restricted to the endocardial surface. This is probably due to highly nonuniform anisotropic propagation around the scarred tissue.

Non-contact mapping to guide catheter ablation of untolerated ventricular tachycardia

The role of a novel non-contact mapping system (ESI 3000, Endocardial Solutions) to guide radiofrequency catheter ablation of untolerated ventricular tachycardia was investigated in 17 patients; 11 with prior myocardial infarction, three with arrhythmogenic right ventricular dysplasia, and three with idiopathic dilated cardiomyopathy. Twenty-seven monomorphic ventricular tachycardias were induced (mean cycle 320+/-60 ms, range 230-450 ms), mapped for 15-20 s, and terminated by overdrive pacing or DC shock. Off-line analysis of isopotential activation mapping was performed to identify the diastolic pathway and/or the exit point of the ventricular tachycardia reentry circuit. Radiofrequency current was applied to create a line of block across the diastolic pathway or around the exit point. All 27 ventricular tachycardias were mapped with the non-contact system. The endocardial exit point (-7+/-15 ms before QRS onset) was defined in 21/21 postinfarction ventricular tachycardias, in 3/3 arrhythmogenic right ventricular dysplasia and in 1/3 idiopathic dilated cardiomyopathy ventricular tachycardias, respectively. The diastolic pathway (earliest endocardial diastolic activity: -65+/-49 ms before QRS onset) was identified in 17/21 postinfarction ventricular tachycardias, in 1/3 arrhythmogenic right ventricular dysplasia and in 1/3 idiopathic dilated cardiomyopathy ventricular tachycardias, respectively. Catheter ablation was performed in 25/27 ventricular tachycardias (93%) in 15/17 patients (88%): 16/25 ventricular tachycardias (64%) were successfully ablated in 10/17 patients (59%). Catheter ablation was not performed in two patients or proved unsuccessful in five patients. At a follow-up of 15+/-5 months, there was no recurrence of documented ventricular tachycardia in all 10 patients with successful catheter ablation; in two of them a previously non-documented ventricular tachycardia occurred. A high recurrence of ventricular tachycardia was observed in patients with a failed procedure (5/7: 71%). No major complication or death occurred. Non-contact mapping can be effectively used to map and guide radiofrequency catheter ablation of untolerated ventricular tachycardias. Given the favourable acute and clinical long-term results, this approach proves to be more effective in patients with postinfarction ventricular tachycardias, in comparison to patients with arrhythmogenic right ventricular dysplasia and idiopathic dilated cardiomyopathy.

Simultaneous noncontact mapping of left atrium in patients with paroxysmal atrial fibrillation

Background Catheter ablation of pulmonary vein ectopic foci is a potentially curative treatment strategy for patients with atrial fibrillation. However, identification of arrhythmogenic pulmonary veins with conventional mapping is difficult, especially in patients with rare focal activity, multiple active foci, or extrapulmonary foci. The present study was designed to investigate use of simultaneous noncontact mapping in this setting. Methods and Results In 17 consecutive patients with paroxysmal atrial fibrillation, a catheter-mounted noncontact multielectrode array positioned in the left atrium was used to reconstruct 3300 electrograms simultaneously from a single beat. Isopotential maps were generated during sinus rhythm and focal activity. After ectopic foci were identified, radiofrequency catheter ablation was performed in patients with 1 or 2 foci. However, in patients who had multiple foci, intraoperative ablation of atrial fibrillation was advised. A total of 28 ectopic foci (25 pulmonary vein foc...

Feasibility of a left atrial electrical disconnection procedure for atrial fibrillation using transcatheter radiofrequency ablation.

An effective, catheter-based treatment for persistent atrial fibrillation (AF) remains elusive. This study assessed the feasibility of transcatheter left atrial (LA) electrical disconnection and its effect on AF inducibility. Thirteen anesthetized swine underwent noncontact mapping of the right atrium (RA) during coronary sinus (CS) pacing. Sites of earliest RA activation were identified using isopotential maps. An ablation catheter was navigated to these sites and a cluster of radiofrequency (RF) lesions applied until earliest activation shifted to a new site. The procedure was repeated until the atria were electrically disconnected. AF induction was attempted before and after ablation. Earliest RA activation was the CS os during proximal CS pacing and Bachmann's bundle during distal CS pacing. These two sites were successfully ablated in all 13 animals. Earliest activation then shifted to the fossa ovalis. RF energy was applied at a median of 2.5 sites (range 1 to 5) around the fossa, then at sites in the triangle of Koch, septum, cavotricuspid isthmus, and posterior wall. Atrial electrical disconnection was achieved in 10 of 13 animals (5 LA electrical disconnection, 3 RA electrical disconnection, 2 biatrial electrical disconnection with complete heart block). After atrial electrical disconnection, the LA became electrically silent. Before ablation, AF was inducible in every animal. After atrial electrical disconnection, AF was inducible in 3 of 10 animals. Atrial electrical disconnection is feasible using noncontact mapping and RF ablation. Successful electrical disconnection of the atria reduces AF inducibility. This approach is worthy of further evaluation as a management strategy for persistent AF, combined with device therapies.

Catheter ablation of ventricular tachycardia related to coronary artery disease: the role of noncontact mapping.

There are a number of limitations associated with conventional mapping for ablation of ventricular tachycardia (VT) in ischemic heart disease, such as the high recurrence rates after initially successful ablation. The development of a noncontact mapping system capable of producing high-resolution isopotential maps of the entire left ventricle has enabled rapid identification of diastolic activity that maintains VT for ablation. With this system it is possible to map nonsustained and fast unstable as well as stable VTs. In this article we review the historic background and concepts of noncontact mapping, its clinical application, and the results of ablations for human VT guided by this mapping system.

Radiofrequency ablation of idiopathic left ventricular tachycardia at the site of earliest activation as determined by noncontact mapping.

The most effective method for guiding radiofrequency (RF) ablation of idiopathic left ventricular tachycardia (ILVT) has yet to be determined. We investigated the use of noncontact mapping in five patients with this condition. The multielectrode array was positioned in the left ventricular apex via the retrograde approach. Isopotential color maps of ILVT were examined to determine the site of earliest endocardial activation. The ablation catheter was steered to the target site using the locator signal. Pace mapping was performed and contact electrograms examined for diastolic potentials. RF energy was applied to the target site. Sustained ventricular tachycardia was induced in 2 patients and nonsustained ventricular tachycardia in 3. The site of earliest activation was at the apical septum in 3, the inferior apex in 1, and the base of the inferior wall in 1. Mean timing was 21 +/- 10 msec before onset of the surface QRS. Diastolic activity was visualized with noncontact mapping at the base of the septum in 1 patient. A Purkinje potential was seen at the ablation site in only 1 patient. No diastolic activity was seen in the remaining 3 patients. Tachycardia was successfully terminated in all 5 patients with a median of four RF applications. No patient suffered a recurrence after 9.6 +/- 4.7 months of follow-up. By identifying the precise site of earliest activation during ILVT, noncontact mapping has been shown to be an effective and safe method for guiding RF ablation.

Endocardial mapping of atrial fibrillation in the human right atrium using a non-contact catheter.

Endocardial mapping of atrial fibrillation in humans is limited by its low resolution and by complexities in the arrhythmia and atrial anatomy. A catheter mounted non-contact multielectrode was deployed in the right atrium of 11 patients with atrial fibrillation and used to reconstruct 3360 electrograms, superimposed onto a computer-simulated model of the endocardium, using inverse solution mathematics. This allows construction of isopotential maps of the right atrium. Patients had either sustained atrial fibrillation (n=3) for >6 months or developed atrial fibrillation during the study (n=8). Spontaneous initiation of atrial fibrillation was recorded in one patient and was demonstrated by the non-contact system to arise from two successive atrial ectopic beats from the site of a roving contact catheter. Reconstruction of electrograms recorded during atrial fibrillation was validated by comparison with contact electrograms with cross-correlation. During established atrial fibrillation, four patients predominantly had a single right atrial wave front, two had two wave fronts and five patients had three to five wave fronts for most of the time. Periods of electrical silence were seen in the right atrium in eight patients, after which, activity emerged from consistent septal sites alone, suggesting a left atrial origin. During intravenous administration of flecainide, atrial fibrillation in two patients terminated spontaneously or following pacing manoeuvres, while in the remaining patient sinus rhythm was restored via atrial tachycardia. Non-contact mapping of the right atrium has demonstrated modes of initiation and termination of atrial fibrillation, characterized different patterns of right atrial activation in atrial fibrillation and suggests that the left atrium may sustain atrial fibrillation in some patients. Simultaneous mapping of the right and left atrium is required to further elucidate the mechanisms of human atrial fibrillation.

New Body Surface Isopotential Map Evaluation Method to Detect Minor Potential Losses in Non–Q-Wave Myocardial Infarction

Potential losses caused by stable non-Q-wave myocardial infarction (MI) are too small to diagnose with the use of standard ECG. The aim of the present study was to obtain accurate diagnostic criteria for this prognostically important disease with the help of body surface mapping. Body surface potentials were recorded with the use of 63 unipolar leads in 45 patients with a non-Q-wave MI (41 to 75 years old); 24 healthy adults, 42 patients with unstable angina, and 70 patients with Q-wave MI served as reference groups. Qualitative pathological features of the isopotential maps, such as onset time and site and magnitude of the first right-anterior/anterior minimum, as well as pathological negativities at that time, were defined in non-Q-wave MI cases. These features, which account for the activation sequence and the body surface projections of specific cardiac regions (Selvester classification), showed a 91% sensitivity and an 88% specificity for the detection of non-Q-wave MI. In comparison, the different departure maps (first third QRS, QRS, and QRST isoarea) resulted in less favorable specificities (50% to 58%). Concordance between the isopotential maps and the acute-phase ECG (90%), hypokinesis (64%), fixed perfusion defects (59%), and significant stenosis of the infarct-related coronary artery (87%) supported the concept that these isopotential map changes correspond to the supposed sites of MI. There were pathological features in 69% of patients with unstable angina, with similar concordances as in non-Q-wave MI. Isopotential maps revealed characteristic features that were suitable for the detection and localization of non-Q-wave MI in the clinical setting of unstable coronary artery disease.

Mapping and ablation of ventricular tachycardia guided by virtual electrograms using a noncontact, computerized mapping system

OBJECTIVESThe purpose of this study was to describe a computerized mapping system that utilizes a noncontact, 64 electrode balloon catheter to compute virtual electrograms simultaneously at 3,360 left ventricular (LV) sites and to assess the clinical utility of this system for mapping and ablating ventricular tachycardia (VT).BACKGROUNDMapping VT in the electrophysiology laboratory conventionally is achieved by sequentially positioning an electrode catheter at multiple endocardial sites.METHODSFifteen patients with VT underwent 18 electrophysiology procedures using the noncontact, computerized mapping system. A 9F 64 electrode balloon catheter and a conventional 7F electrode catheter for mapping and ablation were positioned in the LV using a retrograde aortic approach. Using a boundary element inverse solution, 3,360 virtual endocardial electrograms were computed and used to derive isopotential maps. An incorporated locator system was used in conjunction with or instead of fluoroscopy to position the conventional electrode catheter.RESULTSA total of 21 VTs, 12 of which were hemodynamically-tolerated and 9 of which were not, were mapped. Isolated diastolic potentials, presystolic areas, zones of slow conduction and exit sites during VT were identified using virtual electrograms and isopotential maps. Among 19 targeted VTs, radiofrequency ablation guided by the computerized mapping system and the locator signal was successful in 15.CONCLUSIONSThe computerized mapping system described in this study computes accurate isopotential maps that are a useful guide for ablation of hemodynamically stable or unstable VT.

Augmentation of QRS wave amplitudes in the precordial leads during narrow QRS tachycardia.

QRS morphology during narrow QRS supraventricular tachycardia in patients without ventricular preexcitation generally is considered the same as that seen during sinus rhythm. This study presents a new ECG observation that the QRS amplitude increased significantly in leads V2 through V5 during tachycardia. Using the same ECG machine and the same electrode patches applied to the same electrode positions, 12-lead ECGs during sinus rhythm and narrow QRS tachycardia were analyzed comparatively in 23 patients without ventricular preexcitation. Precordial QRS amplitudes were measured as the vertical distance from the peak of the R to the nadir of the S wave. The amplitudes also were measured during atrial rapid pacing and extrastimulation. Furthermore, ventricular excitation during sinus rhythm and tachycardia was studied using body surface mapping. Body surface distributions of QRS potentials and ventricular activation time (VAT) were displayed as maps. Gross area of QRS (AQRS, equivalent to the QRS amplitude) was compared during sinus rhythm versus tachycardia. During tachycardia, QRS amplitude significantly increased in leads V2 through V5, without any noticeable change in the transitional zone or QRS wave duration. Increase of QRS amplitude also was noted during atrial rapid pacing and extrastimulation. Gross AQRS values during tachycardia significantly increased in the left parasternal area, whereas QRS isopotential and VAT isochronal maps were similar during sinus rhythm and tachycardia, suggesting a minimal role of conduction delay in the increase of QRS amplitude. QRS wave amplitude significantly increased in leads V2 through V5 during narrow QRS tachycardia compared with QRS waves in sinus rhythm. Increase of QRS amplitude seemed unlikely due to a conduction delay within the ventricular myocardium.

Calculating the electrostatic properties of RNA provides new insights into molecular interactions and function.

Solutions to the nonlinear Poisson-Boltzmann equation were used to obtain the electrostatic potentials of RNA molecules that have known three-dimensional structures. The results are described in terms of isopotential contours and surface electrostatic potential maps. Both representations have unexpected features: 'cavities' within isopotential contours and areas of enhanced negative potential on molecular surfaces. Intriguingly, the sites of unusual electrostatic features correspond to functionally important regions, suggesting that electrostatic properties play a key role in RNA recognition and stabilization. These calculations reveal that the electrostatic potentials generated by RNA molecules have a variety of functionally important characteristics that cannot be discerned by simple visual inspection of the molecular structure.

Recent advances in cardiac mapping techniques.

Recently several new mapping modalities have been introduced into clinical electrophysiologic laboratories, including basket catheter mapping, electromagnetic mapping, and noncontact mapping. In addition, intracardiac echocardiography is being used increasingly to visualize important intracardiac structures for catheter ablation. Basket catheter mapping and noncontact mapping are simultaneous mapping devices, whereas electromagnetic mapping is a sequential mapping tool. The new basket-shaped catheters provide up to 64 electrodes mounted on a variable number of splines that encircle the cardiac contour. Animation programs help in identifying the earliest activation and analyzing the activation sequence. Electromagnetic mapping uses low density magnetic fields to navigate the catheter position and to allow nonfluoroscopic mapping and ablation. Sequential recording of intracardiac potentials produces a real-time, color-coded, three-dimensional activation map. Noncontact mapping does not require direct contact with the endocardium and permits the reconstruction of more than 3000 simultaneous computed electrograms via mathematical algorithms. Three-dimensional isopotential maps are generated to visualize the impulse propagation and guide catheter ablation.

A novel interpolation method for electric potential fields in the heart during excitation.

In mapping the electrical activity of the heart, interpolation of electric potentials plays two important roles. First, it permits the estimation of potentials in regions that could not be sampled or where signal quality was poor, and second, it supports the construction of isopotential lines and surfaces for visualization. The difficulty in developing robust interpolation techniques for cardiac applications lies in the abrupt change in potential in the vicinity of the activation wave front. Despite the resulting nonlinearities in spatial potential distributions, simple linear interpolation methods are the current standard and the resulting errors due to aliasing can be large if electrode spacing does not lie on the order of 0.5-2 mm--the thickness of the activation wave front. We have developed a novel interpolation method that is based on two observations specific to the spread of excitation in the heart: (1) that propagation velocity changes smoothly within a region large enough to contain several measurement electrodes and (2) that electrogram morphology varies very little in the neighborhood of each sample point except for a time shift in the potential wave forms. The resulting interpolation scheme breaks the interpolation of one highly nonlinear variable--extracellular potential--into two separate interpolations of variables with much less drastic spatial variation--activation time and electrogram morphology. We have applied this method to potentials originally recorded at 1.5 mm spacing and then subsampled at a range of densities for testing of the interpolation. The results based both on reconstruction of isopotential contour maps and statistical comparison showed significant improvement of this novel approach over standard linear techniques. The applications of the new method include improved determination of electrophysiological parameters such as spatial gradients of potential and the path of cardiac activation and recovery, estimation of electrograms at desired locations, and visualization of electric potential distributions.

Synthesis and anticonvulsant properties of triazolo- and imidazopyridazinyl carboxamides and carboxylic acids

Analogues of 3-amino-7-(2,6-dichlorobenzyl)-6-methyltriazolo[4,3-b]pyridazine PC25 containing amide or carboxylic acid function were synthesized and tested for anticonvulsant activity. The compounds having the imidazole ring substituted with an amide group have been found to be generally more active against maximal electroshock-induced seizures in mice (15.2≤ ED50 ≤ 37.5mgkg−1 orally). Furthermore, maximum activity was generally associated with a 2,6-dichlorobenzyl substitution pattern. 3-Amido-7-(2,6-dichlorobenzyl)-6-methyltriazolo[4,3-b]pyridazine 4b was also protective in the pentylenetetrazole-induced seizures test (ED50=91.1mgkg−1 orally) and blocked strychnine-induced tonic extensor seizures (ED50=62.9mgkg−1 orally). Moreover, calculated electrostatic isopotential maps of the whole active compounds were quite similar and, consequently, could be associated to optimum anticonvulsant activity.

Human Left Ventricular Endocardial Activation Mapping Using a Novel Noncontact Catheter

The patient was a 39-year-old male who had recurrent sustained monomorphic ventricular tachycardia, satisfying the electrocardiographic criteria for fascicular tachycardia, in a structurally normal heart. These isopotential maps were acquired from the patient’s left ventricle during an otherwise routine electrophysiology study by deploying a catheter-mounted multielectrode array consisting of a wire braid on the surface of an 8-mL balloon (Endocardial Solutions Inc). Without endocardial contact, this system uses inverse solution mathematics (boundary-element method) to reconstruct 3360 “virtual” electrograms onto a shell model of the endocardium. A manually selected line of virtual electrograms shows a …

Body surface mapping criteria for diagnosis of left ventricular hypertrophy associated with complete right bundle branch block

The standard electrocardiographic (ECG) criteria for left ventricular hypertrophy are unreliable in patients with complete right bundle branch block. This study was undertaken to formulate criteria for diagnosing these patients by using body surface mapping. The echocardiographic left ventricular mass was calculated by the Penn method from M-mode measurements. Of 56 patients, 27 were defined as having left ventricular hypertrophy with a left ventricular mass of 215 g or more. Isopotential and isointegral maps of the QRS complex were observed. The QRS isointegral maps were separated into two parts at the end of the downstroke of the initial R wave of vector spatial magnitude. The body surface mapping criteria with the highest sensitivity were EPmax (maximum of early part of the QRS) 45 μV·s or greater (sensitivity 93%, specificity 90%), EPmax/d (EPmax averaged by EP duration) 0.8 mV or greater (sensitivity 93%, specificity 97%), and Max (initial maximum) 2.2 mV or greater (sensitivity 89%, specificity 90%). These results suggest that body surface mapping is a useful technique in diagnosing patients with left ventricular hypertrophy and right bundle branch block.

Evaluation of novel measurement methods for detecting heterogeneous repolarization

There exists a well-documented link between heterogeneity of cardiac recovery characteristics and vulnerability to arrhythmia; however, electrocardiographic detection of this heterogeneity remains problematic. The only modalities suitable for measuring variation of repolarization are electrophysiologic in nature, with action potential duration in single cells the most direct method and QT intervals from the body surface electrocardiogram the most common clinical approach. The authors have shown previously, however, that the QT interval is a poor measure of regional change in repolarization, especially when shortening occurs. Here, the authors discuss an experimental preparation based on an isolated canine heart suspended in a human-shaped, instrumented, electrolytic tank and describe a method of applying cold to create local, transient changes in recovery characteristics. The authors have simultaneously recorded epicardial and torso tank surface potentials before, during, and after intervention, and from them have generated isopotential and isointegral maps and computed activation-recovery intervals (ARIs). In all cases, epicardial potentials revealed changes in recovery associated with localized heating and cooling. The changes were visible from tank surface potential distributions in some, but not all, cases. The results also suggest that epicardial ARIs are sensitive to changes in recovery and that, at least for a subset of tank surface leads, ARIs can be used to create noninvasive indices of disparity of repolarization characteristics.

Numerical Modelling of the Hydrodynamically Trapped Milk River Gas Field, Western Canada

Abstract The Milk River Gas Field, located in southeastern Alberta, is the largest single gas accumulation in the Western. Canadian Sedimentary Basin, with recoverable reserves estimated at 140 000 X 106m3. This hydrodynamically trapped gas field, positioned over the-Sweetgrass Arch, covers an area greater than 200 townships and has no identifiable up-dip structural closure. A steady-state, finite difference, single-phase, numerical fluid flow model was constructed for a 24 X 24 township area (Townships 1 – 24, Ranges 25W3-19\V4M). The water migration from the Belly River to the Bow Island was modelled in three dimensions. The primary input data included aquifer structure thickness and permeability. The permeability of the aquitards was varied until a good match was obtained with observed water potentials. The structural top and the modelled potentiometric surface for the Milk River aquifer were combined using the method described by Hubbert in 1953 (UVZ). The resulting gas isopotential map illustrates 'the migration paths and accumulation sites of gas within a hydrodynamic system. Since the gas pool interferes with the water migration, the model was sensitized to account for the effective aquifer and aquitard permeabilities with the presence of the gas. This altered the position and gross pay distribution of the gas pool. The model was used to estimate the significance of cross formational flow. When the aquitards were made impermeable, the resulting water potentials showed no resemblance to field data. A minimum of three layers are required to represent flow within the aquifer. The middle layer represents the aquifer and the adjacent layers account for vertical, cross-formational flow into and out of the aquifer- The model demonstrates that aquitard permeability is a controlling factor, and that hydrocarbon pools will alter water migration in their vicinity and therefore need to be taken into account. Introduction This paper illustrates the utility of hydrogeological modelling in explaining the trapping of the Milk River Gas Field. An understanding of the nature of this hydrodynamic trap will greatly assist future exploration efforts in similar environments. The project area illustrated in Figure 1 extends from the U.S. border up to Township 24, and from Range 24W3M in Saskatchewan to Range 19W4M in Albena. The first well drilled to produce gas from the Milk River formation was spudded in 1904(1). The Medicine Hen #2, located at JO-31-012-05W-t-M the centre of the city of Medicine Hat supplied the city with natural gas. In 1911, three additional Milk River gas wells were put on production within the dry of Medicine Hat and ten more in 1913. It wasn't until 1914 that the first well was drilled outside of the city limits. Some of the wells drilled within the city limits were owned by local businesses (e.g., Alberta Clay and Maple Leaf). Development of the field around the Suffield Military Reserve was controlled by gas prices and drilling areas offsetting existing production. Today, the Milk River Gas Field has grown to cover over 200 townships, and has 30,000 gas wells and total proven recoverable reserves exceeding 140.000 × 106m3.

Synthesis and anticonvulsant activity of N-benzylpyrrolo[2,3-d]-, -pyrazolo[3,4-d]-, and -triazolo[4,5-d]pyrimidines: imidazole ring-modified analogues of 9-(2-fluorobenzyl)-6-(methylamino)-9H-purine.

Analogues of 9-(2-fluorobenzyl)-6-(methylamino)-9H-purine (1) containing isosteric replacements of the imidazole ring atoms were synthesized and tested for anticonvulsant activity. The pyrrolo[2,3-d]-, pyrazolo[3,4-d]-, and triazolo[4,5-d]pyrimidines were less active than 1 against maximal electroshock-induced seizures (MES) in rats when given po. The differences in anti-MES activity for these analogues was not explained by differences in pKa or lipophilicity. However, the four classes of heterocycles have distinctly different calculated electrostatic isopotential maps, which may be related to optimum anticonvulsant activity.