Heterogeneous sympathetic innervation in German shepherd dogs with inherited ventricular arrhythmia and sudden cardiac death.

BACKGROUND: Recently, a colony of German shepherd dogs with inherited spontaneous cardiac arrhythmias and associated sudden death has been developed and characterized. Due to the median age of onset of the arrhythmia (4.5 months), the tendency for the arrhythmia to occur during REM sleep or after exercise, and the absence of structural heart disease, we hypothesized a developmental abnormality of the sympathetic innervation to the heart. METHODS AND RESULTS: We studied 11 dogs from this colony, ranging in age from 6 months to 6 years, and four 7-month-old German shepherd dogs unrelated to the colony as controls. We imaged the distribution of functional myocardial sympathetic innervation and perfusion with [123I]metaiodobenzylguanidine (MIBG) and 201Tl, respectively. Sympathetic nerve distribution was evaluated morphologically by immunocytochemical localization of tyrosine hydroxylase. All of the hearts showed evidence of a regional decrease in MIBG uptake, ranging from 5.3% to 53.4% of the myocardium, whereas control dogs showed homogeneous MIBG uptake. Immunocytochemical studies on sections from regions with decreased MIBG uptake showed a striking paucity of nerves compared with regions with normal MIBG uptake, confirming denervation. When the dogs were grouped into those with (n=6) and without (n=5) evidence of ventricular tachycardia on ambulatory ECG, the group with ventricular tachycardia showed 35+/-16.5% denervation, whereas the group without ventricular tachycardia showed 12+/-5.6% denervation (P<.02). CONCLUSIONS: Abnormal heterogeneous sympathetic innervation exists in these dogs with inherited ventricular arrhythmia and sudden cardiac death. Mechanisms relating the presence and extent of regional denervation to the incidence of ventricular arrhythmia remain to be defined.

Biophysical characteristics of radiofrequency lesion formation in vivo: dynamics of catheter tip-tissue contact evaluated by intracardiac echocardiography.

During clinical radiofrequency catheter ablation a wide range of delivered power may be necessary to achieve success despite an apparently stable catheter position on fluoroscopy. The purpose of this study was to use intracardiac echocardiography to characterize the relation between catheter tip-tissue contact and the efficiency of heating during applications of radiofrequency energy in vivo and to determine whether intracardiac echocardiography could be used prospectively to improve tissue contact. A closed-loop temperature feedback control system was used during radio-frequency applications at five anatomic regions in the right atrium of 15 anesthetized dogs to ensure achievement of a predetermined temperature (70 degrees C) at the catheter tip thermistor by automatic adjustment of delivered power (maximum 100 W). The efficiency-of-heating index was defined as the ratio of steady-state temperature (degrees Celsius) to power (watts). Two-dimensional intracardiac echocardiography was used to evaluate movement of the catheter tip relative to the endocardium. Perpendicular contact was scored as good, average, or poor and lateral catheter sliding as < 2, 2 to 5, or > 5 mm. Two groups of animals were included: group 1, in which tissue contact was guided by fluoroscopic and electrographic criteria for stability of contact, with intracardiac echocardiography used simply to observe the application; and group 2, in which tissue contact was guided by intracardiac echocardiography. Of 66 applications, 18 (27.3%) had poor perpendicular contact on echocardiography, and 12 (18.2%) demonstrated lateral sliding of > 5 mm even though they had been considered to have good tissue contact by fluoroscopic and electrographic criteria. Perpendicular catheter contact and anatomic location were shown to be independently related to the efficiency-of-heating index. Applications with good perpendicular contact had a significantly higher efficiency-of-heating index and a significantly greater lesion size than those with average or poor contact. The percentage of applications having good perpendicular tissue contact and the lesion size were significantly greater when tissue contact was guided by intracardiac echocardiography compared with fluoroscopic and electrographic guidance. This study demonstrates that variations in catheter tip-tissue contact account for differences in the efficiency of tissue heating, independently of the anatomic site of the application. Poor tissue contact was observed by intracardiac echocardiography and confirmed by indexes of tissue heating in approximately one third of radiofrequency applications despite a fluoroscopic appearance and electrographic morphologic appearance suggestive of good tissue contact. There was a significant correlation between echocardiographic evaluation of tissue contact, parameters of tissue heating (efficiency-of-heating index), and lesion size. In addition, intracardiac echocardiography could be used prospectively to improve the percentage of good contact applications and increase the lesion size.

Radiofrequency catheter modification of sinus pacemaker function guided by intracardiac echocardiography.

BACKGROUND: The sinus P wave arises from a pacemaker complex distributed along the crista terminalis. We investigated the feasibility of modification of sinus pacemaker function using graded applications of radiofrequency energy along the crista terminalis in dogs to achieve sinus rate control. METHODS AND RESULTS: Modification of sinus pacemaker function (30 +/- 5% reduction in intrinsic heart rate with retention of a normal P-wave axis) was performed in 11 dogs (group 1). Total sinus pacemaker ablation (> 50% reduction in intrinsic heart rate with development of a low ectopic atrial or a junctional rhythm) was performed in 4 dogs (group 2). Intracardiac echocardiography was used to identify the crista terminalis as an anatomic marker of sinus node location. Sinus pacemaker modification caused a significant decrease in intrinsic heart rate (31% reduction, P < .001), heart rate responsiveness to isoproterenol (30% reduction, P < .0001), and average (20% reduction, P = .0002) and maximal (22% reduction, P = .0007) heart rates during 24-hour Holter monitoring. In 6 of the 11 animals, the targeted rate reduction of 30 +/- 5% was accurately achieved (mean, 31.6 +/- 4.3%; P < .001), and in the other 5, significant reduction of intrinsic heart rate was achieved but with greater variation (28.0 +/- 17.3%, P < .005). Corrected sinus node recovery time was not prolonged. After modification, earliest activation was mapped to the crista terminalis inferior to the lesion in all animals. In long-term follow-up (3.7 +/- 1.0 months), effects were maintained. After total sinus pacemaker ablation, junctional and low atrial escape pacemakers were unstable. CONCLUSIONS: This study demonstrates the feasibility of modification of sinus pacemaker function for sinus rate control using catheter-based radiofrequency ablation guided by intracardiac echocardiography. This can be done while pacemaker stability and attenuated responsiveness to autonomic influences are preserved. Intracardiac echocardiography accurately defined the crista terminalis and provided a reliable means to anatomically localize catheter position in relation to the sinus node.

Acute and chronic effects of transient myocardial ischemia on sympathetic nerve activity, density, and norepinephrine content.

OBJECTIVES: The sympathetic nervous system has profound influences on myocardial function, particularly during ischemia. There is controversy, however, as to whether myocardial ischemia results in damage to myocardial sympathetic nerves coursing through the ischemic territory. To further evaluate these issues, we assessed the acute and chronic effects of transient myocardial ischemia on sympathetic nerve function and morphology. METHODS: A total of 20 dogs were studied. For acute studies (n = 9), we performed serial dynamic imaging of I-123 metaiodobenzylguanidine (MIBG) washout during coronary occlusion and reperfusion, and assessed residual myocardial perfusion with thallium-201. For chronic studies (n = 11), we assessed sympathetic innervation and perfusion 11 days following a transient intracoronary balloon occlusion. Imaging results were correlated with electrocardiographic responses, histology, and tissue norepinephrine (NE). RESULTS: In the acute studies, regional MIBG washout increased more than 2-fold in the ischemic territory compared to the control region during coronary occlusion (14.2 +/- 2.3 vs. 5.9 +/- 1.2%, P < 0.01). Tissue NE was reduced in the ischemic territory compared to the non-ischemic territory (335 +/- 162 vs. 751 +/- 190 ng/g, P < 0.01). Myocardial perfusion was normal. In the chronic studies, 9/11 dogs showed ischemic ECG changes during balloon occlusion, and developed ventricular arrhythmias. On follow-up imaging, 5/11 dogs showed reduced MIBG uptake relative to thallium, in viable myocardium overlying necrotic subendocardium, reduced NE (226 +/- 77 vs. 733 +/- 82 ng/g in control regions, P < 0.01), decreased nerve density, and a larger extent of denervation than scar (25.5 +/- 3.7 vs. 8.2 +/- 2.7%, P < 0.02). Six of 11 dogs showed normal innervation patterns. CONCLUSIONS: These studies suggest that the sympathetic nerves are acutely affected in regions of myocardial ischemia as detected by enhanced regional washout of MIBG. In addition, chronic sympathetic nerve denervation can occur in the absence of transmural myocardial necrosis; however, the occurrence of transient ischemia does not predict the development of chronic denervation. The severity of ischemia, as evidenced by the extent of the related necrosis, does appear to predict chronic denervation. The severity of ischemia, as evidenced by the extent of the related necrosis, does appear to predict chronic denervation. The mechanisms leading to chronic denervation of sympathetic nerves in the absence of transmural infarction remain to be defined.

Effects of long-term right ventricular apical pacing on left ventricular perfusion, innervation, function and histology.

OBJECTIVES: The purpose of this study was to better understand the effects of long-term right ventricular pacing on left ventricular perfusion, innervation, function and histology. BACKGROUND: Long-term right ventricular apical pacing is associated with increased congestive heart failure and mortality compared with atrial pacing. The exact mechanism for these changes is unknown. In this study, left ventricular perfusion, sympathetic innervation, function and histologic appearance after long-term pacing were studied in dogs in an attempt to see whether basic changes might be present that might ultimately be associated with the adverse clinical outcome. METHODS: A total of 24 dogs were studied. Sixteen underwent radiofrequency ablation of the atrioventricular (AV) junction to produce complete AV block. Seven of these underwent long-term pacing from the right ventricular apex (ventricular paced group), and nine had atrial and right ventricular apical pacing with AV synchrony (dual-chamber paced group). A control group of eight dogs had sham ablations with normal AV conduction. These dogs had atrial pacing only. Regional perfusion and sympathetic innervation were studied in all dogs by imaging with thallium-201 and [I123]metaiodobenzylguanidine, respectively. The degree of innervation was also determined by assay of tissue norepinephrine levels. Left ventricular function was assessed by radionuclide ventriculography. Cardiac histology was studied with both light and electron microscopy. RESULTS: Mismatching of perfusion and innervation in the ventricular paced group was noted, with perfusion abnormalities of both the septum and free wall. Regional [I123]metaiodobenzylguanidine distribution was homogeneous. Tissue norepinephrine levels were elevated in both the ventricular and dual-chamber paced groups compared with the control group. No light or electron microscopic findings were noted in any groups. In the dual-chamber paced group, diastolic dysfunction was noted, with normal systolic function. CONCLUSIONS: Ventricular pacing resulted in regional changes in tissue perfusion and heterogeneity between perfusion and sympathetic innervation. Both ventricular and dual-chamber pacing were associated with an increase in tissue catecholamine activity. The abnormal activation of the ventricles via right ventricular apical pacing may result in multiple abnormalities of cardiac function, which may ultimately affect clinical outcome.

Radiofrequency catheter ablation guided by intracardiac echocardiography.

BACKGROUND: Radiofrequency catheter ablation requires precise positioning of the ablation electrode. Fluoroscopically guided catheter manipulation has limitations, and there are risks of radiation exposure. The purpose of this study was to examine the feasibility of guiding catheter ablation within the right atrium with catheter-based intracardiac echocardiography. METHODS AND RESULTS: A 10F, 10-MHz intracardiac imaging catheter was used to direct an ablation electrode at four or five anatomic landmarks in the right atrium. Thirty-eight radiofrequency energy applications were performed in nine anesthetized dogs, and 38 lesions were identified on pathological examination. Lesions were created a mean of 1.9 +/- 2.1 mm from the ultrasound-guided site. Twenty-six of 38 lesions (68%) were less than 2.2 mm from the imaged site. Intracardiac echocardiography also was used to confirm stable electrode-endocardial contact in 37 energy applications (97%) and identified catheter movement in 9 energy applications (24%). Discrete lesions, microcavitations, and thrombi were observed in 13 (34%), 23 (61%), and 19 (50%) of 38 energy applications, respectively. Microcavitations predicted the appearance of thrombus. Fluoroscopy time required to create four or five lesions decreased from 23 minutes in the first study to less than 2 minutes in the last five studies. CONCLUSIONS: Catheter-based intracardiac echocardiography can accurately guide catheter ablation directed at anatomic landmarks and potentially reduced ionizing radiation exposure. Intracardiac imaging can be used to confirm endocardial contact, identify electrode movement, and directly visualize lesions. Intracardiac echocardiography also can be used to identify microcavitations, which predict thrombus formation during radiofrequency energy applications.

Transesophageal defibrillation: animal studies and preliminary clinical observations.

Ventricular fibrillation (VF) that fails to respond to transthoracic defibrillation leaves the clinician with few alternatives. The purpose of this study was to develop a technique of rescue defibrillation by use of transesophageal electrodes. Fourteen anesthetized dogs (20-30 kg) were investigated in this study. Two electrodes (300 mm2) were mounted 8 cm apart on an esophageal probe and inserted approximately 40 cm from the mouth. VF was induced using AC current delivered to the myocardium. Defibrillation was then performed between the distal electrode (anode) and anterior skin patch (cathode). After 15 seconds of induced VF, transesophageal and transthoracic defibrillation thresholds (DFTs) were determined in random order. The esophageal DFT (90 +/- 15 joules) tended to be lower than the transthoracic DFT (115 +/- 35 joules), though this difference was not statistically significant. One dog could not be defibrillated by transthoracic defibrillation but responded to transesophageal defibrillation. Esophageal electrodes were also useful for arrhythmia discrimination and ventricular pacing (pacing threshold of 38 +/- 5 mA at a pulse duration of 2.5 msec). Following transesophageal DFT determination, in ten dogs (total energy of 600 +/- 150 joules), acute esophageal histopathology demonstrated mild to severe focal injury to the mucosa and/or muscular layers. However, esophagi in four chronic dogs (total energy of 470 +/- 110 joules) showed no gross evidence of mucosal damage, perforation, or stricture 4 weeks following defibrillation. Histopathology showed only focal myocyte atrophy and repair. As a last resort, transesophageal defibrillation was performed in the emergency room on four patients with out-of-hospital refractory VF who failed > 6 high energy transthoracic shocks.(ABSTRACT TRUNCATED AT 250 WORDS)

Active compression-decompression resuscitation: a novel method of cardiopulmonary resuscitation.

Chest compression is an important part of cardiopulmonary resuscitation (CPR), but it only aids circulation during a portion of the compression cycle and has been shown to only minimally increase blood flow to vital organs. The purpose of this study was to quantitate the short-term hemodynamic effects of CPR with a hand-held suction device that incorporates both active compression and decompression of the chest. The suction device was applied to the middle of the sternum and compared with standard manual CPR in eight nonventilated anesthetized dogs. Coronary perfusion pressure, systolic and diastolic aortic pressures, right atrial diastolic pressure, and the velocity time integral (an analog of cardiac output), which were obtained by means of transesophageal pulsed wave Doppler echocardiography from the main pulmonary artery, were measured every 30 seconds during CPR. Minute ventilation was measured over the last minute of each CPR technique. Both active compression-decompression CPR and standard CPR were sequentially performed for 2 minutes in random order 30 seconds after induced ventricular fibrillation. The CPR techniques consisted of 100 compressions per minute, with a compression depth of 1.5 to 2 inches and a 50% duty cycle. Coronary perfusion pressure, velocity time integral (cardiac output analog), minute ventilation, and systolic arterial pressure were all significantly improved by active compression-decompression CPR when compared with standard CPR. We conclude that active compression-decompression CPR is a simple technique that appears to improve coronary perfusion pressure, systolic arterial pressure, cardiac output, and minute ventilation in nonventilated animals when compared with standard CPR.(ABSTRACT TRUNCATED AT 250 WORDS)

Ablation of ventricular tachycardia using multiple sequential transcatheter application of radiofrequency energy.

Multiple sequential radiofrequency energy was applied in the left and right ventricles of 24 dogs to produce large ablated areas limited to endocardial and subendocardial regions. Endocardial ablation was performed in nine dogs with normal ventricles and 15 that had survived remote myocardial infarcts, three with inducible sustained monomorphic ventricular tachycardia. A quadripolar catheter was positioned either at the site of earliest ventricular activation during induced monomorphic ventricular tachycardia or at circumscribed areas of the left ventricle. Radiofrequency energy was delivered between two adjacent poles of the catheter, successively applying radiofrequency energy to the distal, middle, and proximal electrode pairs; this was repeated 9 to 11 times with the catheter in a slightly different position. A cumulative energy of 9,688 +/- 4,191 joules resulted in an ablated endocardial/subendocardial surface area of 4.7 +/- 2.2 cm2 (range 2.4-10 cm2, maximum depth 4 mm). Sustained tachycardia was not inducible by aggressive programmed ventricular stimulation in the dogs with previously inducible tachycardia, indicating successful ablation of the tachycardia foci. Only seven normal dogs were available for electrophysiological studies; three were used in acute and four in chronic studies. Ventricular tachycardia was not induced in the remaining dogs either before or after radiofrequency ablation, indicating the lack of an arrhythmogenic effect of this method. Histologic examination was performed in all nine normal dogs (five were sacrificed for acute pathological examination) as well as in the 15 with myocardial infarction. The late pathological examination of the radiofrequency lesion in these 19 animals showed homogeneous areas of coagulation necrosis and endocardial proliferation. Thus, this modified technique of radiofrequency ablation produced large homogeneous endocardial/subendocardial scars suitable for treating ventricular tachycardia and showed no evidence of an arrhythmogenic influence.

Active compression-decompression. A new method of cardiopulmonary resuscitation. Cardiopulmonary Resuscitation Working Group.

OBJECTIVE: To describe and compare with standard cardiopulmonary resuscitation (CPR) in humans a new form of CPR that involves both active compression and active decompression of the chest. DESIGN: Patients in cardiac arrest in whom standard advanced cardiac life support failed were randomized to receive 2 minutes of either standard or active compression-decompression (ACD) CPR using a custom, hand-held suction device, followed by 2 minutes of the alternate technique. The ACD device was applied midsternum and used to perform CPR according to the guidelines of the American Heart Association: 80 compressions per minute, compression depth of 3.8 to 5 cm, 50% duty cycle, and constant-volume ventilation. Mechanical Thumper CPR was also compared in five patients. End-tidal carbon dioxide (ETCO2) concentrations and hemodynamic variables were measured. Transesophageal Doppler echocardiography was used to assess contractility, the velocity time integral (an analogue of cardiac output), and diastolic myocardial filling times. RESULTS: Ten patients were enrolled. The mean +/- SD ETCO2 was 4.3 +/- 3.8 mm Hg with standard CPR and 9.0 +/- 3.9 mm Hg with ACD CPR (P less than .0001). Systolic arterial pressure with standard CPR was 52.5 +/- 14.0 mm Hg and with ACD CPR, 88.9 +/- 24.7 mm Hg (P less than .003). The velocity time integral increased from 7.3 +/- 2.6 cm with standard CPR to 17.5 +/- 5.6 cm with ACD CPR (P less than .0001), and diastolic filling times increased from 0.23 +/- .09 seconds with standard CPR to 0.37 +/- .12 seconds with ACD CPR (P less than .004). Mechanical Thumper CPR consistently underperformed both standard and ACD CPR. Minute ventilation obtained in four patients during ACD CPR without endotracheal ventilation was 6.6 +/- 0.9 L/min. After 1 hour of standard CPR failed, three of 10 patients randomized to ACD CPR rapidly converted to a hemodynamically stable rhythm following 2 minutes of ACD CPR. CONCLUSION: ACD CPR is a simple manual technique that improved cardiopulmonary circulation in 10 patients during cardiac arrest. Although ACD CPR may have produced a return of spontaneous circulation in three patients refractory to standard measures, its impact on survival when used early in cardiac arrest remains to be determined.

Catheter ablation of the atrioventricular junction using a helical microwave antenna: a novel means of coupling energy to the endocardium.

Catheter ablation with either direct current defibrillator discharges or radiofrequency energy produces tissue injury via current flow from an electrode into the adjacent myocardium. In order to affect tissue at a distance, excessive power density may be produced at the electrode-tissue interface with the possibility of explosive gas formation or coagulum formation. A novel microwave catheter was developed with a helical antenna distally. This coil, although not in direct contact with the endocardium, radiates an electromagnetic field into the tissue that, in turn, causes thermal injury. The utility of this system for ablation was assessed in six dogs. The antenna catheter was introduced percutaneously and positioned so as to record the largest His electrogram. Microwave power (50 watts at 2,450 MHz) was applied for 114 +/- 118 seconds. Complete AV block was produced in all six animals with 1.8 +/- 1.2 applications. There was no ventricular ectopy or change in blood pressure during microwave ablation. One dog died 6 days after ablation. The remaining five dogs had persistent, complete AV block during 6 weeks of follow-up. Pathological analysis at 6 weeks revealed a large (mean 2.8 x 4.7 mm) fibrovascular scar in the region of the AV junction. Percutaneous microwave ablation of the endocardium appears feasible. By radiating an electromagnetic field without direct contact, this system can produce large lesions without being limited by desiccation of tissue and impedance rise.

Histopathology of monopolar transcatheter radiofrequency ablation at the mitral valve annulus.

Although monopolar radiofrequency (RF) catheter ablation is being used to interrupt left-sided accessory pathways in patients with tachyarrhythmia, little is known of the histologic effects from this method of treatment. RF ablation at the mitral valve (MV) annulus was performed in ten dogs to examine the histology of the lesion area. A custom 6 French ablation catheter with a 4 mm distal electrode was positioned beneath the MV adjacent to the annulus. Mean preablation atrial to ventricular electrogram ratio (A/V ratio) was 0.26 +/- 0.17. Thirty +/- 1 watts of RF power were applied for 53 +/- 13 seconds between the distal electrode and a large skin electrode. Nine dogs were sacrificed 6 weeks and one dog 2 days following ablation. Annular lesions were seen in eight of the ten dogs. Lesion volume was 136 +/- 41 mm3 and correlated with the A/V ratio (r2 = 0.74, P = 0.006). Lesions consisted of necrosis of the left ventricle with extension into the atrioventricular groove and left atrium. No injury to the coronary sinus or circumflex artery was observed. A small area of injury was noticed on the mitral leaflet in one dog. Monopolar RF ablation creates lesions at the MV annulus without injury to adjacent vascular structures.

Catheter modification of the atrioventricular junction with radiofrequency energy for control of atrioventricular nodal reentry tachycardia.

BACKGROUND: The utility of transcatheter application of radiofrequency energy to eliminate atrioventricular nodal reentrant tachycardia (AVNRT) was investigated. METHODS AND RESULTS: Thirty-nine patients (mean age, 53 +/- 20 years; range 14-86 years) with medically refractory AVNRT underwent perinodal ablation with radiofrequency energy. A custom-designed 6F catheter with a large (3-mm-long) distal electrode and interelectrode pacing of 2 mm was used in the majority of cases. The catheter used for ablation was initially positioned across the tricuspid anulus to obtain the largest His bundle electrogram, then withdrawn to obtain the largest atrial:ventricular electrogram ratio, with a small His bundle electrogram (less than or equal to 100 microV). Each application of radiofrequency energy (350-550 kHz, 16.2 +/- 5.2 W) was stopped after 60 seconds or if PR prolongation or an impedance rise was noted. The endpoints of the procedure were persistent modification of atrioventricular nodal conduction (either first-degree atrioventricular block or impairment of ventriculoatrial conduction) and noninducibility of AVNRT before and during isoproterenol administration. Radiofrequency energy was applied a mean of 6.8 +/- 3.5 times per session. After a mean follow-up of 8 +/- 3.0 months, 32 of the 39 patients (82%) have been free of AVNRT, and did not have high grade AV block. Three patients (8%) developed complete atrioventricular block and had pacemakers implanted. Two patients had unsuccessful initial procedures, and two patients had initially successful ablations but had recurrences of tachycardia 4-6 weeks later. Elimination of AVNRT appeared to be due to effects on the retrograde fast pathway in most patients. CONCLUSIONS: Radiofrequency ablation of the perinodal right atrium appears to be safe and effective for treatment of typical AVNRT:

A new single catheter technique for simultaneous measurement of action potential duration and refractory period in vivo.

In vivo correlations of action potential duration measured by a monophasic action potential catheter and effective refractory period measured by a separate pacing catheter have been poor, probably because of the known variability of both action potential duration and effective refractory period between different ventricular sites. In this study, a new quadripolar contact electrode catheter designed for simultaneous pacing and monophasic action potential recording at closely adjacent sites (2 mm separation between recording electrodes and pacing electrodes) was tested in five closed chest dogs and four patients. Dog studies: Pacing thresholds were extremely low, ranging from 0.02 to 0.25 mA (mean +/- SD 0.099 +/- 0.051, n = 36) and were stable over time (less than 20% increase during 1 h of continuous pacing). Because of the close proximity of pacing and recording electrodes, the pacing artifact nearly coincided with the monophasic action potential upstroke. Because of the low pacing threshold, however, pacing artifacts were small (33 +/- 17% of the monophasic action potential amplitude at twice diastolic threshold strength) and did not affect the duration or configuration of the simultaneously recorded monophasic action potential. The short stimulus response time and the undisturbed monophasic action potential signal fidelity during pacing allowed precise simultaneous measurements of action potential duration and effective refractory period at the same endocardial site.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiofrequency catheter ablation: the effect of electrode size on lesion volume in vivo.

Radiofrequency current is a promising alternative to high voltage direct current defibrillator discharges for catheter ablation of arrhythmias. However, lesions produced with radiofrequency current are relatively small and use of high power is limited by the impedance rise that occurs with desiccation of tissue and coagulum formation. The effect of electrode size on radiofrequency ablation was assessed by comparing results of radiofrequency application using a standard 6 French electrode catheter (distal electrode 2 mm in length) to those using catheters modified with longer distal electrodes (3, 4, 6, 8, and 10 mm in length). Radiofrequency ablation was performed at 47 left ventricular endocardial sites in 20 anesthetized dogs. A constant power of 13.3 +/- 1.3 watts at 550 kHz was applied between the distal catheter electrode and a skin electrode until a total of 500 joules had been delivered or a rise in impedance occurred. Increasing electrode length from 2 to 4 mm more than doubled lesion volume from a mean of 143 to 326 mm3 (P = 0.025). Increasing electrode length beyond 4 mm produced progressively smaller lesions (157 mm3, 155 mm3, and 67 mm3 for 6-, 8-, and 10-mm electrode lengths, respectively). Impedance rise was significantly less likely with larger electrodes and took longer to occur. Increasing the size of electrodes used for radiofrequency ablation allows application of higher power without an impedance rise. Optimizing electrode size (3 or 4 mm in this study) results in larger lesions and may improve the effectiveness of radiofrequency ablation of arrhythmias.

Effects of multipolar electrode radiofrequency energy delivery on ventricular endocardium.

This study examined the effects of radiofrequency energy applied in a bipolar fashion with single as compared with multiple sequential applications at the canine endocardium. In this closed-chest model, radiofrequency energy (750 kHz) was delivered between two adjacent poles of an electrode catheter. Single applications were performed at distinct sites in the left (n = 30) and right ventricles (n = 29) of 13 normal dogs. A multiple sequential technique, which enlarges the ablated endocardial surface, was applied in the left (n = 13) and right ventricles (n = 4) of seven normal dogs and six dogs with remote myocardial infarction. Single applications (199 +/- 200 joules) resulted in lesions with a volume of 0.12 +/- 0.06 cm3 (range 0.03 to 0.31 cm3) and an endocardial surface area of 0.29 +/- 0.15 cm2 (range 0.06 to 0.63 cm2). Changes at the catheter/tissue interface led to a rise in impedance, restricting further enlargement of the necrosis. Sequential delivery of radiofrequency energy between poles 1 and 2, 2 and 3, and 3 and 4 of a quadripolar electrode catheter repeated 9 to 11 times in slightly different positions allowed a cumulative energy of 6571 +/- 3857 joules to be applied to the endocardium, resulting in a lesion volume of 0.84 +/- 0.38 cm3, with an endocardial lesion surface area of 3.7 +/- 1.2 cm2 (range 2.9 to 5.1 cm2). Histologically, all radiofrequency lesions were restricted to the endocardium/subendocardium with a small border zone of injury. Aggressive stimulation techniques did not induce ventricular tachycardia in any of the dogs before and 19 +/- 11.4 days after multiple sequential ablations.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of radiofrequency catheter ablation on permanent pacemakers: an experimental study.

Radiofrequency current is being investigated as an alternative to direct current shock for transcatheter ablation of cardiac arrhythmias. Permanent pacemakers are known to be susceptible to high frequency electromagnetic interference. This study was performed to examine the effects of transcatheter radiofrequency ablation on permanent pacemakers in a worst-case scenario. Nineteen pulse generators representing 16 models from seven manufacturers were acutely implanted in 12 dogs to assess their function during and after ablation. Pulse generators were implanted subcutaneously in the neck and connected to a transvenous permanent pacing lead positioned in the right ventricular apex. A 6F quadripolar electrode catheter was positioned approximately 1 cm from the tip of the permanent pacing lead. Radiofrequency current from an electrosurgical unit was applied between the distal electrode of the catheter and a large diameter skin electrode placed below the left scapula. Three additional ablation sessions were performed with the catheter situated 4-5 cm from the permanent pacing lead. Each ablation consisted of 15 W of radiofrequency power, delivered for up to 30 seconds. Twelve pulse generators were falsely inhibited during radiofrequency ablation while programmed to the VVI or DDD mode, nine of which continued to be inhibited while programmed to the VOO or DOO mode. Five pulse generators paced at abnormal rates, including three examples of one pulse generator model that displayed pacemaker runaway. Runaway was observed during eight ablations, resulting in two episodes of ventricular fibrillation. Eleven pulse generators reverted to noise mode behavior during ablation. Only three pulse generators were unaffected during ablation. No reprogramming or pacing system malfunctions were observed after cessation of radiofrequency current application or during ablations greater than 4 cm from the permanent lead.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheter ablation of the atrioventricular junction with radiofrequency energy.

Catheter ablation of the atrioventricular junction using direct-current defibrillator discharges requires general anesthesia and may have serious side effects. Sixteen patients with drug-refractory supraventricular tachycardia underwent catheter ablation of the atrioventricular junction using radiofrequency energy. A standard 7F quadripolar electrode catheter was positioned to record the largest unipolar His potential (580 +/- 640 microV) from the distal electrode. An electrocoagulator (Microvasive Bicap 4005) supplied continuous, unmodulated energy at 550 kHz. One to 14 applications of radiofrequency current were delivered between the distal electrode and a large-diameter chest wall electrode. Transient, mild chest discomfort was reported by seven of 16 patients. None had significant arrhythmias or blood pressure changes during radiofrequency ablation. Complete atrioventricular block was produced in nine of 16 patients and high-grade second-degree atrioventricular block was produced in one patient with radiofrequency current. Attenuated His bundle electrograms could still be recorded in the remaining six patients, four of whom underwent successful atrioventricular junctional ablation using direct-current shock during the same session. Atrioventricular block persisted in all 10 patients successfully treated with radiofrequency ablation during a mean follow-up of 4.2 months. Compared with a group of historic control subjects treated with direct-current shock ablation, the 10 patients successfully treated with radiofrequency current had significantly less creatine kinase-MB isoenzyme release (5.7 +/- 5.1 vs. 22 +/- 13 IU, p = 0.006). A junctional escape rhythm was present in all patients after radiofrequency-induced atrioventricular block. In contrast, three of 10 control patients had an idioventricular escape after direct current shock ablation, and four patients had no escape rhythm at all.(ABSTRACT TRUNCATED AT 250 WORDS)

Scintigraphic assessment of regional cardiac adrenergic innervation.

To assess the feasibility of noninvasively imaging the regional distribution of myocardial sympathetic innervation, we evaluated the distribution of sympathetic nerve endings, using 123I metaiodobenzylguanidine (MIBG), and compared this with the distribution of myocardial perfusion, using 201Tl. Twenty dogs were studied: 11 after regional denervation, and nine as controls. Regional denervation was done by left stellate ganglion removal, right stellate ganglion removal, and application of phenol to the epicardial surface. Computer-processed functional maps displayed the relative distribution of MIBG and thallium in multiple projections in vivo and excised heart slices in all animals. In six animals, dual isotope emission computed tomograms were acquired in vivo. Tissue samples taken from innervated and denervated regions of the MIBG images were analyzed for norepinephrine content to validate image findings. Normal controls showed homogeneous and parallel distributions of MIBG and thallium in the major left ventricular mass. In the left stellectomized hearts, MIBG was reduced relative to thallium in the posterior left ventricle; whereas in right stellectomized hearts, reduced MIBG was in the anterior left ventricle. Phenol-painted hearts showed a broad area of decreased MIBG extending beyond the area of phenol application. In both stellectomized and phenol-painted hearts, thallium distribution remained homogeneous and normal. Norepinephrine content was greater in regions showing normal MIBG (550 +/- 223 ng/g) compared with regions showing reduced MIBG (39 +/- 44 ng/g) (p less than 0.001), confirming regional denervation. Combined MIBG-thallium functional maps display the regional distribution of sympathetic innervation. This new ability to noninvasively map the distribution of sympathetic nerves with simultaneous comparison to regional perfusion may provide important new insights into mechanisms, whereby an imbalance in sympathetic activity may relate to clinical disorders.

Catheter ablation of accessory pathways using radiofrequency energy in the canine coronary sinus.

Ablation of a left-sided accessory pathway with high energy direct-current shocks delivered by an electrode catheter in the coronary sinus is associated with the risk of coronary sinus rupture. The safety and effectiveness of closed chest catheter desiccation in the coronary sinus with use of radiofrequency energy was studied. Radiofrequency energy (174 +/- 74 J) was applied between the distal electrode of a standard electrode catheter placed 3 to 6 cm inside the coronary sinus and a large posterior chest wall patch in 16 dogs. No arrhythmias or hemodynamic changes were observed. Three dogs were killed approximately 1 h after ablation and 13 after 2 to 4 weeks. Lesions in the atrioventricular (AV) sulcus were observed in 14 of 16 dogs. Lesions were 11.6 +/- 6 mm in length, 4.3 +/- 2.3 mm in width and 2.8 +/- 1.4 mm in depth. Microscopic examination showed well circumscribed areas of necrosis and fibrosis in the fat of the AV sulcus. The media and intima of the circumflex coronary artery were not involved nor was the endocardium or mitral apparatus damaged in any dog. Coronary sinus thrombus was present in 3 of 16 dogs. Large amounts of radiofrequency energy can be safely applied to the coronary sinus. The size and location of the lesions produced suggest that this technique may be useful for the interruption of left-sided accessory AV connections in humans.