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Previous studies in our laboratory have shown that muscarinic receptors become uncoupled from G-proteins in brains of patients with Alzheimer’s disease (AD). Interestingly, this process began prior...

Background Remote catheter navigation systems protect interventionalists from scattered ionizing radiation. However, these systems typically require specialized catheters and extensive operator training. Methods A new compact and sterilizable telerobotic system is described, which allows remote navigation of conventional tip-steerable catheters, with three degrees of freedom, using an interface that takes advantage of the interventionalist's existing dexterity skills. The performance of the system is evaluated ex vivo and in vivo for remote catheter navigation and ablation delivery. Results The system has absolute errors of 0.1 ± 0.1 mm and 7 ± 6° over 100 mm of axial motion and 360° of catheter rotation, respectively. In vivo experiments proved the safety of the proposed telerobotic system and demonstrated the feasibility of remote navigation and delivery of ablation. Conclusion The proposed telerobotic system allows the interventionalist to use conventional steerable catheters; while maintaining a safe distance from the radiation source, he/she can remotely navigate the catheter and deliver ablation lesions. Copyright © 2015 John Wiley & Sons, Ltd.

Tele-Operated Catheter Ablation, In Vivo. Introduction: The close proximity between the interventionalist and patient during catheter-based interventions for cardiac arrhythmia exposes the interventionalist to harmful radiation. A prototype remote catheter navigation system (RCNS) has been developed to reduce occupational dose. The safety, feasibility of this RCNS and a comparison of remote and conventional navigation techniques is investigated in vivo. Methods: Seven anatomical locations in the right side of the heart in porcine models were chosen as navigation targets. Using fluoroscopy and electrogram analysis, an experienced electrophysiology interventionalist manipulated a radiofrequency (RF) ablation catheter to each target using the RCNS and conventional navigation. Success rate, navigation time, exposure, exposure time and procedure time was recorded for all anatomical targets. Time to integrate the RCNS with the procedure suite was also measured. Results: All targets were successfully reached with the RCNS and conventional navigation. No erratic catheter motion was observed with the RCNS whereas 1 operation failure occurred. The anatomical targets were found to have the largest effect on navigation time (P < 0.05), exposure (P < 0.05), and exposure time (P < 0.01), although the navigation method had little to no effect on the metrics. These results suggest that remote navigation procedures can be performed with navigation times comparable to conventional bedside navigation. Conclusion: Remote navigation with the RCNS may present a safe method of reducing occupational dose, while providing comparable navigation time with conventional bedside navigation. (J Cardiovasc Electrophysiol, Vol. 23, pp. 81-87, January 2012)

Spinal Cord Stimulation Modulates Vagal Atrial Influences. Introduction: Experimental evidence suggests that spinal cord stimulation (SCS) can cause augmentation of parasympathetic influences on the heart via enhanced vagus nerve (VgN) activity. Herein, we investigated whether this might lead to enhanced inducibility of vagally mediated atrial tachyarrhythmias (AT) and whether such actions depend on intact autonomic neural connections with central neurons. Method and Results: Epidural SCS electrodes were implanted at T1-T4 in anesthetized canines. Sinus cycle length prolongation, atrial repolarization changes (191 epicardial electrode sites), and AT inducibility in response to right VgN stimuli applied at the cervical level were determined before and during SCS. VgN-induced sinus cycle length prolongation was potentiated during SCS among the animals with intact neural connections or bilateral vagotomy proximal to the stimulation site, whereas such prolongation was unaffected by SCS among animals with bilateral decentralization of stellate ganglia. Likewise, the atrial surface area in which VgN-induced repolarization wave form changes were identified was significantly augmented during SCS among the former but not among the latter. AT facilitation occurred during SCS in the majority of animals with intact neural connections, particularly among those displaying relatively greater potentiation of vagally mediated sinus cycle length prolongation. Conclusion: The data indicate that SCS may cause potentiation of parasympathetic influences on the atria in response to cervical VgN stimulation. Such SCS effects appear to be mediated via decreased tonic inhibitory sympathetic influences in the presence of intact stellate ganglion connections to central neurons. (J Cardiovasc Electrophysiol, Vol. 22, pp. 440-447)

Our project is the reintroduction of off-pump intracardiac surgery using the Universal Cardiac Introducer (UCI) for safe intracardiac access. The purpose of this study was to evaluate multimodality visualization using three ultrasound modalities and ultrasound augmented with virtual reality. Image guidance was tested on implanting a mitral valve prosthesis via the UCI in 12 pigs. Initially, two-dimensional (2-D) transesophageal echocardiography (TEE) ultrasound, intravascular ultrasound (intracardiac echocardiography [ICE]), and three-dimensional (3-D) epicardial ultrasound were utilized. Ultrasound augmented with virtual reality was used in the last three experiments. A 2-D TEE assisted navigating the prosthesis into the orifice. Positioning was not intuitive and required trial and error method. A 3-D epicardial ultrasound allowed positioning of the valve into the orifice. Positioning of the clip was difficult because of artifacts with multiple reflections and shadowing. Augmented reality displayed the entire prosthesis and the tools without artifacts; provided intuitive information on navigation, positioning, and orientation of tools; and improved significantly image guidance and surgical skill. Augmented virtual reality, with tracked 2-D or 3-D ultrasound imaging, provides guidance that can effectively substitute for direct vision during beating heart intracardiac surgery.

Two reasons for the recent rise in radiation exposure from CT are increases in its clinical applicability and the desire to maintain high SNR while acquiring smaller voxels. To address this emerging dose problem, several strategies for reducing patient exposure have already been proposed. One method employed in cardiacimaging is ECG-driven modulation of the tube current between 100% at one time point in the cardiac cycle and a reduced fraction at the remaining phases. In this paper, we describe how images obtained during such acquisition can be used to reconstruct 4D data of consistent high quality throughout the cardiac cycle. In our approach, we assume that the mid-diastole (MD) phase is imaged with full dose. The MD image is then independently registered to lower dose images (lower SNR) at other frames, resulting in a set of transformations. Finally, the transformations are used to warp the MD frame through the cardiac cycle to generate the full 4D image. In addition, the transformations may be interpolated to increase the temporal sampling or to generate images at arbitrary time points. Our approach was validated using various data obtained with simulated and scanner-implemented dose modulation. We determined that as little as 10% of the total dose was required to reproduce full quality images with a 1 mm spatial error and an error in intensity values on the order of the imagenoise. Thus, our technique offers considerable dose reductions compared to standard imaging protocols, with minimal effects on the quality of the final data.

Cryoablation in the Distal Coronary Sinus. Introduction: The aim of this study was to assess the safety and feasibility of catheter-based cryothermal ablation lesions in the mid- and distal coronary sinus. Methods and Results: Cryothermal ablation lesions were delivered using a 7-French catheter at the mid-(n = 13) and distal (n = 12) coronary sinus in 14 swine under general anesthesia. Lesions were delivered for 2 or 4 minutes in a 1:2 randomized ratio such that seven 2-minute lesions and eighteen 4-minute lesions were delivered to a maximum negative temperature of -70°C. Integrity of the circumflex artery was assessed by angiography before and after each lesion application. In five animals, arterial Doppler flow velocity was continuously monitored and coronary flow reserve assessed. Histologic assessment of the left AV ring was made after a 48-hour survival period and lesions graded for depth and transmurality. Eighteen of 25 lesions were >3 mm deep: five of seven 2-minute lesions and thirteen of eighteen 4-minute lesions. Lesions were transmural in 18 of 25 cases. Two transmural lesions were limited in depth due to their epicardial position. One 2-minute mid-coronary sinus lesion was not found. Adherent thrombus was seen grossly in the coronary sinus at one site and only on microscopic examination in three other lesions. Angiography demonstrated no arterial spasm or thrombosis. Continuous-flow Doppler remained unchanged throughout lesion production. Coronary flow reserve was unchanged (1.7 ′ 0.8 preablation vs 1.7 ′ 1.0 postablation, P = 0.6). The media and intima were preserved in all cases. Necrosis of the adventitia was seen in one arterial segment. Conclusion: Catheter-based cryoablation can produce lesions in the musculature of the adjacent atrium and ventricle when accessed from the coronary sinus without significant injury to the coronary sinus or adjacent artery. This method has potential application as the ablation method of choice when such lesions are required.

Autonomic tone may contribute to cardiac arrhythmogenesis and influence the efficacy of implantable defibrillators. Fifty-two anesthetized pigs were randomized to: (1) methacholine (n = 12); (2) nitroprusside (n = 12); (3) phenylephrine (n = 12); (4) carbachol (n = 8); and (5) saline (n = 8). Ventricular fibrillation threshold (VFT) and triplicate defibrillation thresholds (DFT) were obtained before and during each intervention. Mean (+/- SE) VFT was increased with: methacholine (76 +/- 10.6 V vs 39 +/- 7.1 V, P < 0.001); phenylephrine (68 +/- 10.5 V vs 38 +/- 6.2 V, P < 0.001); and carbachol (106 +/- 11.5 V vs 30 +/- 6.5 V, P < 0.0001). Nitroprusside and saline failed to alter VFT. Mean (+/- SE) DFT was decreased with: methacholine (7.7 +/- 0.8) vs 9.7 +/- 0.8 J, P < 0.001); phenylephrine (9.8 +/- 0.9 J vs 11.3 +/- 1.0 J, P < 0.05); and carbachol (9.2 +/- 0.7 J vs 12.2 +/- 0.8 J, P < 0.0001), remaining unchanged following nitroprusside and saline infusion. Thus, modulation of autonomic tone modified arrhythmia susceptibility and the energy necessary for defibrillation, increased parasympathetic tone, increased VFT, and decreased DFT. Evaluation of autonomic balance, particularly parasympathetic tone, may be useful with the implantation of automatic defibrillators.

BACKGROUND Patients with ischemic heart disease may require antianginal and/or antiarrhythmic regimes. These patients may also be candidates for implantable defibrillators. The effects of antiarrhythmics, such as bretylium, or calcium antagonists, such as verapamil, nifedipine, or diltiazem on internal defibrillation efficacy have been inconsistent or are unknown. METHODS AND RESULTS The effects of bretylium and verapamil on the energy requirements for ventricular defibrillation threshold (DFT) were determined in 92 open-chest anesthetized pigs. Triplicate DFTs were determined before and after intravenous administration of saline or one of four doses of verapamil, or saline or one of three doses of bretylium, in a balanced random order. Bretylium elicited a dose dependent reduction of DFT (F = 2.72 at 3 degrees and 36 degrees of freedom). DFT was significantly reduced with the highest dose of bretylium, (from 5.9 +/- 0.6 J to 4.7 +/- 0.6 J, mean +/- S.E.M.; P < 0.01). However, cardiac massage was sometimes needed at this dose due to low blood pressure immediately after defibrillation. In contrast, there was a positive correlation between DFT and serum verapamil concentration (r = 0.54, P < 0.001). The highest dose of verapamil significantly increased DFT (from 6.3 +/- 0.6 J to 8.2 +/- 1.1 J; P < 0.05), at a serum verapamil concentration of 86.6 +/- 6.8 ng/mL. CONCLUSIONS These data indicate that bretylium decreases while verapamil increases the minimum energy requirement for internal defibrillation. Caution is warranted in patients who may be hemodynamically comprised and may be candidates for bretylium therapy or in patients who have marginal DFT value who might be candidates for verapamil therapy.

Alcohol ingestion has been associated with cardiac arrhythmias and may initiate fibrillation in patients with automatic defibrillators. The effect of alcohol on defibrillation efficacy is unknown. To assess the acute effects of alcohol on defibrillation efficacy, triplicate defibrillation thresholds (DFTs) were determined before and after intravenous administration of 25% ethanol. Fifty-two pigs were randomized into four groups: (1) control, 6 mL/kg of saline over 10 minutes (n = 12); (2) low dose, 6 mL/kg of 25% ethanol over 10 minutes (n = 12); (3) mid dose, 0.45 mL/kg per minute for 30 minutes followed by 0.045 mL/kg per minute for 45 minutes (n = 12); and (4) high dose, 0.6 mL/kg per minute for 30 minutes followed by 0.06 mL/kg per minute for 45 minutes (n = 16). Three coil defibrillating electrodes (Medtronic 6888) were sutured to the epicardium of the right and left ventricles for defibrillation shocks. Ventricular fibrillation was induced using alternating current and after 10 seconds of fibrillation, the minimum energy for defibrillation was established using sequential pulse defibrillation. Triplicate determinations were obtained before and after saline or ethanol infusion. Alcohol elevated DFT in a dose related manner. Control and low dose groups thresholds were unchanged, but the mid dose approached statistical significance (6.8 +/- 0.7 vs 7.6 +/- 0.9 J, 0.05 < P < 0.1) and the high dose was significantly elevated (8.5 +/- 0.7 vs 11.2 +/- 1.1 J, P < 0.01). Ventricular effective refractory periods and cycle lengths between fibrillatory waves did not differ before and after the high dose ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)

Some antiarrhythmic drugs may influence the ability of a shock to defibrillate a patient but the effect of lidocaine on defibrillation efficacy has been controversial, suggesting multiple influencing factors. We determined the effects of three doses of lidocaine on defibrillation thresholds, using single and sequential shocks, in 36 open chest halothane-anesthetized pigs. An additional eight pigs were anesthetized with barbiturate and received the highest infusion regime of lidocaine. Shocks were delivered through three mesh electrodes sutured over the anterior right ventricle, posterior right ventricle, and lateral left ventricle for sequential pulse shocks and between a lateral right to a lateral left ventricular mesh electrode for single pulse shocks. Triplicate defibrillation thresholds (DFTs) were obtained before and after lidocaine (n = 32) or saline (n = 12) administration, either with halothane or barbiturate anesthesia. Lidocaine did not alter DFT at any dose with either the single pulse (control 17.4 +/- 3.7 joules [J], highest dose of lidocaine 13.5 +/- 1.7 J, P = NS) or sequential pulse shocks (control 7.6 +/- 0.8 J, highest dose lidocaine 6.6 +/- 0.7 J, P = NS), when halothane anesthesia was used. Similar results were obtained with lower doses. In contrast, lidocaine in pentobarbital anesthetized pigs produced a significant increase of the DFT with single (control 13.7 +/- 1.9, during lidocaine 16.6 +/- 3.1, P less than 0.01) and sequential shocks (control 11.1 +/- 2.2, during lidocaine 14.5 +/- 3.4, P less than 0.01). Interaction between barbiturates and lidocaine, and/or pH may account for the inconsistency in previous studies and must be considered for animal and clinical experiments.

1. Noradrenaline (NA) was microinjected into the anterior hypothalamic/preoptic area(AH/POA) of unanaesthetized cats held at ambient temperatures of 10, 22 or 35 degrees C. Loci in which injection of NA caused body temperature changes were also found to be sensitive to the febrile action of PGE1. 2. At all ambient temperatures, NA caused a dose-dependent fall in body temperature. However the mechanisms by which these temperature changes were brought about varied at different ambient temperatures. In cats maintained at the higher ambient temperature, NA activated heat loss mechanisms whereas in the cats maintained in the 10degrees C environment, the major effect of NA injection was an inhibition of heat conservation and heat production mechanisms. 3. We conclude that NA acts in cats not only as an inhibitor of heat conservation and production, but also acts in an excitatory manner on an active heat loss pathway within the AH/POA.

Elective subtotal injury to the AV node-His bundle region may create a negative dromotropic effect to provide a therapeutic advantage in some patients with supraventricular tachycardia without creating complete AV block. We examined the effects of cryosurgery to the AV nodal region, varying temperature and time using a 15 mm circular cryoprobe applied directly to the canine AV node-His bundle region. Twelve dogs were anesthetized and the heart was exposed through a right thoracotomy. Electrophysiological data obtained included conduction intervals, incremental pacing, and extrastimulus testing. Under inflow occlusion, the cryoprobe was positioned over the AV node-His bundle region using anatomical landmarks and a single freeze was applied (-15 degrees C to -60 degrees C, 15 to 60 seconds). Dogs were allowed to recover for 1 month, after which time electrophysiological testing was repeated under similar conditions; then the animals were sacrificed. With probe temperatures of -60 degrees C for 15 to 60 seconds, five of six dogs experienced complete heart block with dense fibrosis observed in the AV nodal-His bundle region. After freezing with higher temperatures, the remaining seven dogs had return of atrioventricular conduction postoperatively with prolongation of AH time observed in five and marked prolongation of the Wenckebach cycle length in three of the five. We conclude that controlled cryothermal injury to the AV node-His bundle region may be useful to create a desirable negative dromotropic response without creating complete AV block.

We compared single to sequential pulse shocks with different pulse separations on internal cardiac defibrillation by using a catheter and plaque electrodes in open-chest halothane-anesthetized pigs. Ten seconds after fibrillation onset, defibrillation was attempted using trapezoidal pulses of 65% tilt, approximately 5 ms duration and fixed outputs from 1.0 to 50 joules (J). With single pulses, minimum defibrillation energy for the catheter alone was 2.4 +/- 0.3 J/kg (mean +/- standard error) and 2.1 +/- 0.2 J/kg for the catheter tip to plaque configuration. With sequential pulse shocks, the first pulse delivered via the catheter and the second pulse from the catheter tip to the plaque electrode, the energy necessary for defibrillation was dependent on the separation time between the two pulses (2.0 +/- 0.2, 1.5 +/- 0.2, 0.9 +/- 0.1, 1.3 +/- 0.3, 0.6 +/- 0.2, and 1.2 +/- 0.2 J/kg at 100, 10, 1, 0.5, 0.2, and 0.1 ms, respectively). Further, at the 0.2 ms separation, 100% of the animals could be defibrillated with less than 2.0 J/kg (35 J total). We conclude that sequential pulse defibrillation provides a significant improvement over single pulse defibrillation. The optimum separation between the sequential pulses in this study was 0.2 ms.

The experiments investigated the hypothesis that the occurrence of repetitive ventricular responses elicited by the ventricular extrasystole (VES) technique are an indicator of ventricular vulnerability to fibrillation. A comparison was made between the incidence of repetitive responses elicited by the VES technique and the minimum electrical energy (VFT technique) necessary to elicit repetitive responses and ventricular fibrillation in normal dogs, dogs with acute infarction, and dogs with chronic infarction. The VES technique produced repetitive responses in 14 of 46 sites. Responses were of at least three types: (1) bundle branch re-entry; (2) activation at the pacing site, and (3) activation at the infarct zone. In contrast repetitive responses and the onset of fibrillation produced by the VFT technique appeared to be a single type with earliest activation at the pacing site. There were no differences in the ventricular fibrillation thresholds between dogs with and without repetitive responses produced by the VES technique. Thus the incidence of VES technique-induced repetitive responses is not a reasonable predictor of ventricular vulnerability to fibrillation. However, in 2 dogs with lower ventricular fibrillation thresholds, repetitive responses originating at the infarct zone were induced by the VES technique. Occurrence of these repetitive responses may be indicative of ventricular vulnerability to fibrillation.

The perturbation correction factors for a 0.03 cc parallel plate chamber and a 0.6 cc cylindrical ionization chamber have been compared. The current from these ion chambers was measured in electron beams of energy in the range 7 to 12 MeV and in a cobalt-60 gamma ray beam. It is concluded that there is no difference between the perturbation correction factor for these two chambers. A significant polarity effect was observed for the parallel plate chamber, which was a function of energy and depth in the phantom. This work supports the ICRU recommendation for displacement correction.

The Northwest Center for Radiological Physics has used a well‐defined protocol in the review of radiotherapy machines. The central axis depth dose and off‐axis factor of fifteen Clinac‐4’s are reported. The range in depth dose was on the order of 3.5% and the range in off‐axis factor on the order of 8%. Similar measurements on a Theratron‐80 Cobalt‐60 teletherapy machine are reported to demonstrate the reproducibility of the measurement technique.