Evaluation of a novel ventricular support device with defibrillation capabilities in canine and porcine animal models.

INTRODUCTION: Sudden death is prevalent in heart failure patients. We tested an implantable ventricular support device consisting of a wireform harness with one or two pairs of integrated defibrillation electrode coils. METHODS AND RESULTS: The device was implanted into six pigs (36-44 kg) through a subxiphoid incision. Peak voltage (V) defibrillation thresholds (DFT) were determined for five test configurations compared with a control transvenous lead (RV to CanPect). Defibrillator can location (abdominal or pectoral) and common coil separation on the implant (0 degrees or 60 degrees ) were studied.(.) The DFT for RV60 to LV60 + CanPect was significantly less than control (348 +/- 57 vs 473 +/- 27 V, P < 0.05). The DFTs for other vectors were similar to control except for RV0 to LV0 + CanAbd (608 +/- 159 V). The device was implanted into 12 adult dogs for 42, 90, or 180 days with DFT and pathological examination performed at the terminal study. Cardiac pressures were determined at baseline, after implantation, and at the terminal study. The DFT was also determined in a separate group of four dogs at 42 days following implantation of the support device with one pair of defibrillation electrodes. The DFTs at implant and explant in dogs with one pair (8 +/- 1.5 Joules [J] and 6 +/- 1.9 J) or two pairs (8 +/- 3.4 J and 7 +/- 1.9 J) of defibrillation electrodes were not significantly different from each other but significantly less than control measured at the terminal study (18 +/- 3.4 J). Left-sided pressures were significantly decreased at explant but within expected normal ranges. Right-sided pressures were not different except for RV systolic. Histopathology indicated mild to moderate epicardial inflammation and fibrosis, consistent with a foreign body healing response. CONCLUSIONS: This defibrillation-enabled ventricular support system maintained mechanical functionality for up to 6 months while inducing typical chronic healing responses. The DFT was equal to or lower than a standard transvenous vector.

A semi-implantable multichannel telemetry system for continuous electrical, mechanical and hemodynamical recordings in animal cardiac research.

We have developed an eight-channel telemetry system for studying experimental models of chronic cardiovascular disease. The system is an extension of a previous device that has been miniaturized, reduced in power consumption and provided with increased functionality. We added sensors for ventricular dimension, and coronary artery blood flow and arterial blood pressure that are suitable for use with the system. The telemetry system consists of a front end, a backpack and a host PC. The front end is a watertight stainless steel case with all sensor electronics sealed inside; it acquires dimension, flow, pressure and five cardiac electrograms from selected locations on the heart. The backpack includes a control unit, Bluetooth radio, and batteries. The control unit digitizes eight channels of data from the front end and forwards them to the host PC via Bluetooth link. The host PC has a receiving Bluetooth radio and Labview programs to store and display data. The whole system was successfully tested on the bench and in an animal model. This telemetry system will greatly enhance the ability to study events leading to spontaneous sudden cardiac arrest.

Right-sided vagus nerve stimulation inhibits induced spinal cord seizures.

We have previously shown that left-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. To test our hypothesis that right-sided vagus nerve stimulation will also abort seizure activity, we have initiated seizures in the spinal cord and then performed right-sided vagus nerve stimulation in an animal model. Four pigs were anesthetized and placed in the lateral position and a small laminectomy performed in the lumbar region. Topical penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord, was next applied to the dorsal surface of the exposed cord. With the exception of the control animal, once seizure activity was discernible via motor convulsion or increased electrical activity, the right vagus nerve previously isolated in the neck was stimulated. Following multiple stimulations of the vagus nerve and with seizure activity confirmed, the cord was transected in the midthoracic region and vagus nerve stimulation performed. Right-sided vagus nerve stimulation resulted in cessation of spinal cord seizure activity in all animals. Transection of the spinal cord superior to the site of seizure induction resulted in the ineffectiveness of vagus nerve stimulation in causing cessation of seizure activity in all study animals. As with left-sided vagus nerve stimulation, right-sided vagus nerve stimulation results in cessation of induced spinal cord seizures. Additionally, the effects of right-sided vagus nerve stimulation on induced spinal cord seizures involve descending spinal pathways. These data may aid in the development of alternative mechanisms for electrical stimulation for patients with medically intractable seizures and add to our knowledge regarding the mechanism for seizure cessation following peripheral nerve stimulation.

Vagus nerve stimulation for induced spinal cord seizures: insights into seizure cessation.

OBJECT: Vagus nerve stimulation is known to decrease the frequency, duration, and intensity of some types of intracranial seizures in both humans and animals. Although many theories abound concerning the mechanism for this action, the true cause remains speculative. To potentially elucidate a pathway in which vagus nerve stimulation aborts seizure activity, seizures were initiated not in the cerebral cortex but in the spinal cord and then vagus nerve stimulation was performed. METHODS: Ten pigs were anesthetized and placed in the lateral position, and a small laminectomy was performed in the lumbar region. Topical penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord, was applied to the dorsal surface of the exposed cord. With the exception of two animals that were used as controls, once seizure activity was discernible via motor convulsion or increased electrical activity the left vagus nerve, which had been previously isolated in the neck, was stimulated. Following multiple stimulations of the vagus nerve and with seizure activity confirmed, the cord was transected in the midthoracic region and vagus nerve stimulation was performed. Vagus nerve stimulation resulted in cessation of spinal cord seizure activity in all (87.5%) but one experimented animal. Transection of the spinal cord superior to the site of seizure induction resulted in the ineffectiveness of vagus nerve stimulation to cause cessation of seizure activity in all study animals. CONCLUSIONS: The effects of vagus nerve stimulation on induced spinal cord seizures involve descending spinal pathways. The authors believe that this experiment is the first to demonstrate that spinal cord neuronal hyperactivity can be suppressed by stimulation of a cranial nerve. These data may aid in the development of alternative mechanisms for electrical stimulation in patients with medically intractable seizures. Further studies are now necessary to isolate which specific tracts, nuclei, and neurotransmitters are involved in this process.

Mechanisms for the maintenance of ventricular fibrillation: the nonuniform dispersion of refractoriness, restitution properties, or anatomic heterogeneities?

INTRODUCTION: The relative importance of nonuniform dispersion of refractoriness, steep restitution slopes, and anatomic heterogeneities in causing conduction block during ventricular fibrillation (VF) remains unknown. METHODS AND RESULTS: In six open-chest pigs, ventricular refractoriness and restitution curves were estimated from activation recovery intervals (ARIs) calculated from 504 (21 x 24) unipolar electrode recordings 2 mm apart in a plaque sutured to the left ventricular (LV) free wall. A steady-state restitution protocol was performed twice at each of two pacing sites: the LV base and near the left anterior descending artery. VF was electrically induced four times and the incidence of conduction block at each electrode during the first 20 seconds was determined by an automated algorithm. The gradient of the ARI was calculated at each electrode to estimate the spatial dispersion of refractoriness. An exponential curve was fit to the restitution plots of ARIs versus the corresponding diastolic intervals (DIs) for all pacing cycle lengths at each electrode. The locations of epicardial blood vessels were noted after the study. Spatial patterns of conduction block were significantly correlated between the four VF episodes in the same animal (r = 0.66 +/- 0.07, P < 0.05). At the shortest pacing cycle length, the spatial distribution of ARIs, ARI gradients, and restitution slopes was not random but formed clusters of similar values. However, none of these variables was significantly correlated with the incidence of conduction block, even though ARI gradients >2 msec/mm were present between many clusters and approximately 90% of restitution slopes were >1. Instead, conduction block frequently appeared to cluster along epicardial vessels. CONCLUSION: Neither the dispersion of refractoriness nor action potential duration restitution determined during rapid pacing by itself is the major determinant of the location of conduction block during early VF in normal pigs. It may be that these factors interact synergistically with each other as well as with other factors, including anatomic heterogeneities such as those caused by blood vessels, which may be particularly important for the formation of conduction block and maintenance of VF.

Design and initial evaluation of an implantable sonomicrometer and CW Doppler flowmeter for simultaneous recordings with a multichannel telemetry system.

We have developed a sonomicrometer and continuous wavelength (CW) Doppler flowmeter for a multichannel telemetry system. These developments will enable us to measure ventricular dimension and coronary artery blood velocity, which are valuable parameters to characterize sudden cardiac death (SCD) in ambulatory animal models of ventricular arrhythmias. The design goals for the sensors were accuracy, low power consumption, small size and compatibility with each other. The circuits were designed successfully and tested simultaneously in vivo. The CW Doppler flowmeter draws 9 mA and the sonomicrometer draws 28 mA on a 5-V supply. The ability to measure heart dimension and blood velocity will add significantly to our understanding of the sequence of events leading up to spontaneous sudden cardiac death.

Regional variation in capture of fibrillating swine left ventricle during electrical stimulation.

INTRODUCTION: While it has been shown that electrical stimulation can capture a region of myocardium during ventricular fibrillation (VF), the ideal location to stimulate to maximize capture of the fibrillating in vivo left ventricle (LV) is not known. We previously demonstrated a mean directionality to the propagation of VF wavefronts in swine from posterior to anterior LV. We hypothesized that this directionality of VF wavefronts would affect capture of the LV epicardium while stimulating during VF. METHODS AND RESULTS: In seven open-chest swine, during different VF episodes, electrical stimulation was performed singly or simultaneously from two lines of 26 epicardial electrodes, one on the posterior LV adjacent to the posterior descending coronary artery and another on the anterior LV adjacent to the left anterior descending coronary artery. Mapping was performed between the line of stimulating electrodes with 768 recording electrodes 2-mm apart. The incidence and extent of epicardium captured by stimulation through the lines of stimulating electrodes were determined in the mapped region. Capture occurred during 67% of 78 VF episodes. Capture from the posterior LV line was achieved in 88% of the episodes and from the anterior LV line in 44% of the episodes (P = 0.001). The maximum amount of myocardium captured was also much greater for stimulating from the posterior as compared to the anterior LV line (232 +/- 168 mm(2) vs 64 +/- 124 mm(2), P = 0.003). A significant part of the variability in capture was related to the direction of the mean VF wavefront velocity vector in each animal (r = 0.84, P < 0.05). CONCLUSION: Electrical stimulation from the posterior LV resulted in a greater incidence and extent of LV capture than stimulation from the anterior LV. A significant component of the variability in capture is related to the mean direction of VF wavefronts.

Adaptive pacing during ventricular fibrillation.

While it has been shown that pacing during ventricular fibrillation (VF) can capture a portion of the epicardium, little is known about the characteristics of the area captured or about whether adaptively changing the pacing rate during VF will increase the area captured. In six open-chested pigs, pacing during VF was performed from the center of a plaque containing 504 electrodes 2 mm apart in a21 x 24 array on the anterior right ventricle. Simultaneous recordings from the 504 electrodes were used to construct activation maps from which the area of epicardium captured by pacing was determined. Four pacing algorithms were examined: (1) fixed rate pacing at 95% of the median VF activation rate, (2 and 3) adaptive pacing in which the pacing timing and/or rate is reset in real time if capture is not obtained, and (4) pacing at a slowly increasing rate after initial capture. Regional capture, defined as control of the myocardium under at least 10 plaque electrodes, was achieved in 71% (92/129) of pacing episodes. The incidence of capture was not significantly different for pacing algorithms 1-3. The maximum area captured for each pacing episode with algorithms 1-3 was 3.8 +/- 2.0 cm2(mean +/- SD). Within each animal, the pattern of capture was similar among all pacing episodes, no matter which algorithm was use dr = 0.85 +/- 0.25). The region of greatest capture extended away from the pacing site along the long axis of the myocardial fibers. However, the area of captured epicardium toward the right ventricular side of the pacing electrode was 9.7 times greater than toward the left ventricular side. This principal direction toward the right ventricular side of the pacing electrode was the same direction traveled by the majority of VF activation fronts before capture occurred. The absence of recorded activations at the pacing site for 20 consecutive stimuli predicted 83% of the time that regional capture was present. With algorithm 4, the pacing rate could be increased 7.1%+/- 4.3%while maintaining capture; however, the area of capture progressively decreased as the pacing rate increased. While pacing from the anterior right ventricular epicardium during VF, the area of capture is repeatable and is markedly asymmetrical with almost 10 times as much epicardium captured on the side of the pacing electrode closest to the acute margin of the right ventricle as on the opposite side. This marked asymmetry is associated both with myofiber orientation and with the direction of spread of activation and hence the direction of dispersion of refractoriness during VF just before pacing is initiated. It is possible to perform adaptive pacing algorithms in real time during VF; however, the two adaptive algorithms tested did not capture significantly more epicardium than a simple fixed-rate pacing algorithm. Although it is possible to maintain capture while increasing the pacing rate during VF, the area of capture decreases.

Regional differences in ventricular fibrillation in the open-chest porcine left ventricle.

It has been hypothesized that during ventricular fibrillation (VF), the fastest activating region, the dominant domain, contains a stable reentrant circuit called a mother rotor. This hypothesis postulates that the mother rotor spawns wavefronts that propagate to maintain VF elsewhere and implies that the ratio of wavefronts propagating off a region to those propagating onto it (propoff/propon) should be >1 for the dominant domain but <1 elsewhere. To test this prediction in the left ventricular (LV) epicardium of a large animal, most of the LV free wall was mapped with 1008 electrodes in 7 pigs. VF activation rate was faster in the posterior than in the anterior LV (10.0+/-1.3Hz versus 9.3+/-1.3Hz; P<0.001). The anterior LV had a higher fraction of wavefronts that blocked than did the posterior LV and had a propoff/propon ratio <1 (P<0.001). The mean conduction velocity vectors of the VF wavefronts pointed in the direction from the posterior to the anterior LV. Although these findings favor a dominant domain in the posterior LV, the facts that the anterior LV had a higher incidence of reentry than did the posterior LV and that the posterior LV did not have propoff/propon significantly different from 1 do not. Thus, quantitative regional differences are present over the porcine LV epicardium during VF. Although these differences are not totally consistent with the presence of a dominant domain within the LV free wall, the mean conduction velocity vector is consistent with one in the septum.

Discernment of adipose versus nervous tissue: a novel adjunct solution in lipomyelomeningocele surgery.

OBJECTIVE: To determine a solution capable of discerning adipose versus nervous tissue, to aid in surgical separation of the adipose tissue which appears to be visually indistinguishable from nervous tissue in lipomyelomeningoceles (LMMs). METHODS: The following solutes (in normal saline) were investigated, both at 25 and 37 degrees C: beta-carotene, vitamin D, vitamin E, lecithin, hydrogen peroxide, lipase, protease, hyaluronidase, partially purified collagenase, purified collagenase, trypsin, trypsin plus purified collagenase and non-solute-containing saline (control). Each solution was applied to a pediatric lipoma to determine gross effects over a period of approximately 30 min. If a solution appeared to affect the adipose tissue grossly, studies of functional in vivo sensory evoked and spontaneous potentials using that particular solution were conducted upon sheep spinal cord, nerve roots, dura and peripheral nerve. Additionally, histological studies were conducted to determine the effect of that solution upon adipose tissue, spinal cord, myelin, dura and nerve roots. RESULTS: Of all solutions investigated, partially purified collagenase type 1 (T1C; Lot M0M4322, Code CLS-1, Worthington Biochemical Corporation, Lakewood, N.J., USA) at 37 degrees C was the most successful in grossly altering the consistency and appearance of adipose tissue. This change was more apparent over 20-30 min following application of the solution to the adipose tissue. Solutions not containing T1C did not show appreciable results; purified collagenase plus trypsin did not appear comparable or superior to T1C. No significant histological or functional change was noted when comparing the spinal cord, nerve rootlets, myelin, dura or peripheral nerve from the T1C-treated group versus normal (untreated) control groups. CONCLUSION: T1C appears to be a potentially effective solution for application during LMM surgery in the acute setting, and such use of an adjunct solution may significantly aid in the safe surgical resection of LMMs. Pending further research, this technique may be applied for other indications which require discernment or alteration of adipose versus nervous tissue.

Ninth cranial nerve stimulation for epilepsy control. Part 1: efficacy in an animal model.

OBJECTIVE: To characterize the effects of stimulation of the nerve of Hering (HN; cranial nerve nine) in controlling seizure activity using a canine model. METHODS: Using penicillin applied topically to a region of the cerebral cortex, 16 seizure-type continuous epileptiform discharges were generated. Ten specimens of HN (five left-sided and five right-sided) were dissected from the cervical region in five dogs and stimulated at varying parameters to determine the effects in controlling epileptiform activity. Electroencephalography (using a multielectrode array), electrocardiography and other vital signs were continuously monitored for side effects. RESULTS: Resolution of continuous epileptiform activity following stimulation was found in 12 of 16 trials (75%); no spontaneous resolution was noted in the absence of stimulation, and stimulation significantly shortened seizure duration (p < 0.05). Mean epileptiform activity duration was 139 s prior to stimulation (range 1-432 s), with a mean poststimulation delay of 17 s until resolution and a mean interictal time of 399 s. Two specimens became free of seizure activity for the duration of our study (p < 0.001). No significant side effects (such as the potentially life-threatening cardiac problems seen with right-sided cervical vagal nerve stimulation) were found with stimulation of either left- or right-sided HN. Stimulation of other regional nerves (e.g. twelfth cranial nerve, nerves of the cervical plexus) failed to yield similar control of epileptiform activity. CONCLUSIONS: The results of this pilot study suggest that stimulation of the HN can successfully control focal seizure activity in the majority of cases. Pending further study, stimulation of the HN may have a role in the management of patients suffering from medically and otherwise surgically refractory epilepsy.

Impact of myocardial ischemia and reperfusion on ventricular defibrillation patterns, energy requirements, and detection of recovery.

BACKGROUND: Shocks that have defibrillated spontaneous ventricular fibrillation (VF) during acute ischemia or reperfusion may seem to have failed if VF recurs before the ECG amplifier recovers after shock. This could explain why the defibrillation threshold (DFT) for spontaneous VF appears markedly higher than for electrically induced VF. METHODS AND RESULTS: The DFT for electrically induced VF (E-DFT) was determined in 15 pigs before ischemia, followed by left anterior ascending or left circumflex artery occlusion. VF was electrically induced 20 minutes after occlusion, followed 5 minutes later by reperfusion. Whether spontaneous or electrically induced, VF during occlusion or reperfusion was treated with up to 3 shocks at 1.5xE-DFT. If all 3 shocks failed, shock strength was increased. Thirty minutes after reperfusion, the other artery was occluded and the protocol was repeated. Defibrillation was considered successful if postshock sinus/idioventricular rhythm was present for > or = 30 seconds. VF recurring within 30 seconds after the shock was considered immediate or delayed if the first postshock activation complex in a rapidly restored ECG recording was VF or sinus/idioventricular rhythm, respectively. Defibrillation efficacy at 1.5xE-DFT was significantly higher for electrically induced ischemic VF (76%) than for spontaneous VF (31%). The incidence of delayed recurrence after electrically induced nonischemic (3%) or ischemic (20%) VF was significantly lower than after spontaneous VF (75%). Mean VF recurrence time after spontaneous VF was 4.6+/-5.3 seconds. CONCLUSIONS: Spontaneous VF can be halted by a shock but then quickly restart before a standard ECG amplifier has recovered from postshock saturation, making it appear that the shock failed.

Intelligent multichannel stimulator for the study of cardiac arrhythmias.

An intelligent multichannel stimulator (IMS) has been designed and built for use in a cardiac research environment. The device is capable of measuring and responding to cardiac electrophysiological phenomena in real time with carefully timed and placed electrical stimuli. The system consists of 16 channels of sense/stimulation electronics controlled by a digital signal processor (DSP) data acquisition card and a host computer and can be expanded to include more channels. The DSP allows for powerful and flexible algorithms to be implemented for real-time interaction with the cardiac tissue. Although a number of possible uses can be conceived for such a device, the initial motivation was to improve upon attempts to terminate fibrillation by pacing. The IMS was tested in an open-chest animal model, both in sinus rhythm and during fibrillation. It was shown to be an effective research tool by demonstrating the ability to measure and respond to cardiac activations in real time using complex numerical algorithms and appropriately timed stimuli.