Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/38—Applying electric currents by contact electrodes alternating or intermittent currents for producing shock effects
  • A61N1/39—Heart defibrillators
  • A61N1/3956—Implantable devices for applying electric shocks to the heart, e.g. for cardioversion
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/38—Applying electric currents by contact electrodes alternating or intermittent currents for producing shock effects
  • A61N1/39—Heart defibrillators
  • A61N1/3918—Heart defibrillators characterised by shock pathway, e.g. by electrode configuration

Definitions

• the present invention relates to methods and an implantable apparatus for treating cardiac arrhythmia, particularly ventricular fibrillation.
• Implantable defibrillators employ pacing, or pretreatment, pulses.
• U.S. Patent No. 5,366,485 to Kroll et al. and U.S. Patent No. 4,559,946 to Mower et al. both describe defibrillation apparatus in which pacing or pretreatment pulses are delivered through the same electrodes as the defibrillation pulse.
• U.S. Patent No. 4,693,253 to Adams and U.S. Patent No. 5,431,682 to Hedberg both describe defibrillation apparatus in which pacing pulses are delivered after defibrillation.
• U.S. Patent No. 5,282,836 to Kreyenhagen et al. describes an atrial defibrillator wherein pacing pulses are delivered through a pacing electrode prior to defibrillation pulses being delivered through a separate set of defibrillation electrodes.
• U.S. Patent No. 5,489,293 to Pless et al. describes an apparatus for treating cardiac tachyarrhythmia which uses a lower voltage defibrillation apparatus by providing a rapid sequence of defibrillation shocks synchronized with sensed sequential cardiac or electrogram events or features during an arrhythmia.
• U.S. Patent No. 5,464,429 to Hedberg et al. describes an apparatus in which a stimulation pulse is delivered through an electrode that ordinarily serves as a pacing electrode, with the stimulation pulse being delivered prior to a defibrillation pulse (the latter being delivered through separate defibrillation electrodes).
• the stimulation pulse is of a magnitude greater than that of a pacing pulse, but less than that of a defibrillation pulse, and is said to produce a refractory area around the stimulation electrode.
• the stimulation pulse is delivered via an electrode that also serves as a pacing electrode, rather than an electrode specifically positioned in a weak field area of the defibrillation electrodes.
• the use of a stimulation pulse of a reverse polarity to the first phase of a biphasic defibrillation pulse is not disclosed.
• a first (right ventricle) lead 252 includes an elongate large surface area electrode 256, a distal or tip sense electrode 258, and a ring or proximal sense electrode 260.
• Sense electrodes 258, 260 are positioned in and in contact with the wall of the right ventricle, and elongate electrode 256 is in the right atrium.
• a second (coronary sinus) lead 254 includes a tip, or distal sense electrode 264, a ring or proximal sense electrode 266, and a second elongate, large surface area electrode 262.
• Distal and proximal sense electrodes 264, 266 are both adjacent the left ventricle within the great vein, and elongate electrode 262 is within the coronary sinus beneath the left atrium.
• the right ventricle sense electrodes 258, 260 are coupled to inputs 50a, 50b of first sense amplifier 50; the great vein sense electrodes 264, 266 are coupled to inputs 52a, 52b of second sense amplifer 52.
• ventricular defibrillation electrode system in which on electrode is placed through the coronary sinus into a peripheral vein of the heart.
• peripheral vein is defined therein as to encompass "the venous side of the coronary vessels running between the base and the apex of the heart.
• the [sic] include the middle and small cardiac veins, and the portion of the great cardiac vein which runs between the base and apex of the heart.
• peripheral veins used herein, therefore, excludes that portion of the great cardiac vein which runs along the base plane of the heart, which has been used [as] a site for electrode placement in prior art electrode systems.”
• the electrodes are in the shape of a helix to apply pressure against the inner wall (col. 4, lines 14-17), with blood being able to flow unobstructed through the interior of the helix (column 4, lines 46-48)(S ⁇ e also U.S. Patent No. 5,423,865 to Bowald).
• Such stent-type electrodes can be difficult to adjust or remove. Only a simple shock pattern is described in Bowald, and efficacious electrode configurations and shock patterns are neither suggested nor disclosed.
• a third object of the invention is to provide an implantable system for treating cardiac arrythmia that can enable reduction of cardioversion, and particularly defibrillation, shock strength.
• a first aspect of the present invention is an implantable system for the defibrillation or cardioversion of a patient's heart, or the administration of antitachycardia pacing to a patient's heart.
• the system comprises a plurality of primary electrodes, a power supply, and a control circuit.
• the plurality of primary electrodes are configured for delivering a defibrillation pulse, cardioversion pulse, or antitachycardia pacing along a predetermined current pathway in a first portion of the heart, with a first one of the primary electrodes configured for positioning through the coronary sinus and within a vein on the surface of the left ventricle of the heart.
• the control circuit is operatively associated with the power supply and the primary electrodes, and the control circuit is configured for delivering a defibrillation pulse through the primary electrodes.
• a second aspect of the present invention is an implantable system for the defibrillation or cardioversion of the heart of a patient in need of such treatment.
• the system comprises a plurality of primary electrodes, at least one auxiliary electrode, a power supply, and a control circuit.
• the plurality of primary electrodes are configured for delivering a defibrillation pulse along a predetermined current pathway in a first portion of the heart, the current pathway defining a weak field area in a second portion of the heart.
• the weak field area is the portion of the heart where the defibrillation shock field intensity is at or near a minimum.
• At least one auxiliary electrode is configured for delivering an auxiliary pulse to the weak field area.
• the control circuit is operatively associated with the primary electrodes, the auxiliary electrode, and the power supply, with the control circuit configured for delivering a cardioversion sequence comprising an auxiliary pulse sufficient to alter transmembrane potential in the weak field area through the auxiliary electrode, followed by a defibrillation pulse through the primary electrodes delivered while the electrophysiological effects imparted by the auxiliary pulse in the weak field area are present.
• One preferred embodiment of the foregoing apparatus is an implantable system for the defibrillation of the ventricles of the heart of a patient in need of such treatment.
• the system comprises a plurality of primary electrodes, at least one auxiliary electrode, a power supply, and a control circuit.
• the plurality of primary electrodes are configured for delivering a defibrillation pulse along a predetermined current pathway in a first portion of the heart, the current pathway defining a weak field area in a second portion of the heart.
• At least one auxiliary electrode is configured for delivering an auxiliary pulse to the weak field area, with the at least one auxiliary electrode configured for positioning through the coronary sinus and in a vein on the surface of the left ventricle of the heart.
• a still further object of the present invention is an electrode lead useful for the cardioversion or defibrillation of a patient's heart.
• the lead comprises an elongate transveneous electrode lead having a distal end portion, with the lead configured for positioning the distal end portion within the right atrial appendage or the right ventricular outflow track, and a primary electrode connected to the electrode lead and positioned on the distal end portion thereof.
• Figure 1 illustrates a preferred set of electrode placements in an apparatus for carrying out the present invention
• FIG. 2 schematically illustrates the control circuitry employed in an apparatus of the present invention
• Figure 3 illustrates a waveform that may be used to carry out the present invention
• Figure 4 illustrates a preferred waveform that may be used to carry out the present invention
• Figure 5 illustrates an alternate set of cardiac electrode placements in an apparatus for carrying out the present invention
• Figure 7 schematically illustrates how an apparatus of the present invention is modified to control the therapy delivered
• FIG 8 schematically illustrates the thirteen treatment procedures, including control, used in Example 1 below;
• Figure 9 provides histograms of the mean delivered energy at defibrillation threshold for pulsing schema utilizing auxiliary shocks according to Figure 8;
• Figure 10 is similar to Figure 9 above, except delivered energy is expressed as leading edge voltage rather than in Joules;
• Figure 11 schematically illustrates transvenous electrode placement in the closed- chest dog model described in Example 2 below;
• FIG 12 schematically illustrates seven treatment protocols used in Example 2 below;
• Figure 13a illustrates a set of waveforms and electrode configurations that may be used to practice the present invention
• Figure 13b illustrates a set of waveforms and electrode configurations that may be used to practice the present invention
• Figure 13c illustrates a set of waveforms and electrode configurations that may be used to practice the present invention
• Figure 13d illustrates a set of waveforms and electrode configurations that may be used to practice the present invention.
• the present invention may be used to treat all forms of cardiac tachyarrythmias, including ventricular fibrillation, with defibrillation (including cardioversion) shocks or pulses, including antitachycardia pacing.
• defibrillation including cardioversion shocks or pulses, including antitachycardia pacing.
• the treatment of polymorphic ventricular tachycardia and ventricular fibrillation are particularly preferred.
• the antitachycardia pacing may be delivered from the primary electrode placed through the coronary sinus ostium and within a vein on the surface of the left ventricle alone, or may be coupled to or yolked to an additional electrode, such as an electrode positioned in the right ventricle.
• An independent right ventricle may be provided as an alternate source of antitachycardia pacing, based upon the origin of the trigger and cross- channel syntactic patterns.
• Antitachycardia pacing may be delivered from the right ventricle and then the left ventricle electrode, or may be delivered from the left ventricle and then the right ventricle electrode.
• the heart includes a fibrous skeleton, valves, the trunks of the aorta, the pulmonary artery, and the muscle masses of the cardiac chambers (i.e., right and left atria and right and left ventricles).
• the schematically illustrated portions of the heart 30 illustrated in Figure 1 includes the right ventricle “RV” 32, the left ventricle “LV” 34, the right atrium “RA” 36, the left atrium “LA” 38, the superior vena cava 48, the coronary sinus "CS" 42, the great cardiac vein 44, the left pulmonary artery 45, and the coronary sinus ostium or "os" 40.
• the driving force for the flow of blood in the heart comes from the active contraction of the cardiac muscle.
• This contraction can be detected as an electrical signal.
• the cardiac contraction is triggered by electrical impulses traveling in a wave propagation pattern which begins at the cells of the SA node and the surrounding atrial myocardial fibers, and then traveling into the atria and subsequently passing through the AV node and, after a slight delay, into the ventricles.
• the beginning of a cardiac cycle is initiated by a P wave, which is normally a small positive wave in the body surface electrocardiogram.
• the P wave induces depolarization of the atria of the heart.
• the P wave is followed by a cardiac cycle portion which is substantially constant with a time constant on the order of 120 milliseconds
• the system includes a first catheter 20 and a second catheter 21, both of which are insertable into the heart (typically through the superior or inferior vena cava) without the need for surgical incision into the heart.
• catheter as used herein includes
• the system includes an electrode A; 50 that resides in the superior vena cava or innominate vein, an electrode B; 51 positioned in the right ventricle, and an electrode C; 52 positioned within a vein on the postero lateral surface of the left ventricle (e.g., in the apical third of the posterior cardiac vein or the apical half of the great cardiac vein).
• the active external portion of the housing 16 serves as a fourth electrode D.
• Designations "A" through “D” herein refer to electrodes in the aforesaid positions.
• Electrode C may be a hollow electrode to allow the flow of blood through the electrode (e.g., a stent-type electrode that engages the vessel wall) when positioned in the vein, or may be a solid electrode configured (that is, of a shape and size) to allow the flow of blood around the electrode when positioned within the vein. A solid electrode is preferred. Electrode C may be positioned entirely within a vein on the postero-lateral surface of the left ventricle, or may also extend into the coronary sinus (as in the case of an elongate electrode).
• the position of electrode C may be achieved by first engaging the coronary sinus with a guiding catheter through which a conventional guidewire is passed. The tip of the torqueable guidewire is advanced under fluoroscopic guidance to the desired location. The lead 21 on which electrode C is mounted passes over the guidewire to the proper location. The guidewire is withdrawn and electrode C is incorporated into the lead system. Such an electrode is considered a solid-type electrode herein.
• the defibrillation electrodes may alternately be configured to sense cardiac cycles, or may have smaller sensing electrodes placed adjacent thereto and thereby provide input to the electronics package as well as provide a predetermined stimulation shock output to predetermined cardiac areas as directed by the controller.
• the electronic circuit 15 also includes a cardiac cycle monitor ("synchronization monitor 72") for providing synchronization information to the controller 74.
• synchronization monitor 72 for providing synchronization information to the controller 74.
• the synchronization is typically provided by sensing cardiac activity in the RV, but may also include other sensing electrodes which can be combined with the defibrillation electrodes or employed separately to provide additional assurance that defibrillation shock pulses are not delivered during sensitive portions of the cardiac cycle so as to reduce the possibility of inducing ventricular fibrillation.
• the power supply may include a single capacitor, and the control circuit may be configured so that both the auxiliary pulse and the defibrillation pulse are generated by the discharge of the single capacitor.
• the power supply may include a first and second capacitor, with the control circuit configured so that the auxiliary pulse is generated by the discharge of the first capacitor and the defibrillation pulse is generated by the discharge of the second capacitor.
• the power supply includes a first and second capacitor, and the control circuit may be configured so that the auxiliary pulse is generated by the discharge (simultaneous or sequential) of both the first and second capacitors, and the defibrillation pulse likewise generated by the discharge of the first and second capacitors.
• FIG 3 shows a schematic illustration of a biphasic truncated exponential waveform. While a variety of different waveforms can be used, as discussed herein, surprisingly good results are achieved when an auxiliary pulse is delivered prior to the primary, or defibrillation, pulse, with the auxiliary pulse being delivered along a different current pathway. A particularly surprising finding was that better results can be achieved when the auxiliary pulse is of an opposite polarity than the first phase of the defibrillation pulse.
• Such a biphasic truncated exponential waveform primary pulse with a monophasic auxiliary pre-pulse is illustrated in Figure 4.
• the foregoing waveforms can be modified in ways that will be apparent to those skilled in the art (e.g., a chopped waveform can be delivered; the waveform can be time-based or fixed tilt; etc).
• the auxiliary pulse may be from .5 or 1 to 5 or 10 milliseconds in duration, with a 2 millisecond pulse currently preferred.
• the time interval from the end of the auxiliary pulse to the leading edge of the primary pulse may be from 1 or 2 milliseconds to 10, 15 or 20 milliseconds, with a delay of about 5 milliseconds currently preferred.
• the optimal auxiliary-to-primary interval may differ depending on the type of rhythm or condition of the myocardial tissue at the time the therapy is applied. Therefore, the control circuitry may also be configured to sense a characteristic of the cardiac rhythm (e.g., an activation interval or a dynamical pattern of consecutive activation intervals) and then select an optimum auxiliary-to-primary shock time interval (e.g., from a look up table stored in a microprocessor memory).
• a characteristic of the cardiac rhythm e.g., an activation interval or a dynamical pattern of consecutive activation intervals
• the control circuit is configured so that the auxiliary pulse is not more than 40% or 50% of the peak current and not more than 20% or 30% of the delivered energy (in Joules) of the defibrillation pulse.
• the trailing edge voltage of the auxiliary pulse is equal ( ⁇ 10 Volts) to the leading edge voltage of the defibrillation pulse.
• Particular voltage, current, and energy outputs will depend upon factors such as the condition of the tissue and the particular disorder being treated.
• the auxiliary pulse may have a peak voltage of from 20 or 30 volts to 200 or 250 volts, with a peak voltage range of 50 to 150 volts preferred.
• the energy of the auxiliary pulse may be from .01 or .05 to 1 or 2 Joules.
• the energy of the defibrillation pulse may be from 5 or 10 Joules to 30, 40 or 50 Joules.
• An object of the instant invention is to enable the reduction of the size of the implantable defibrillator, which is made possible by defibrillation pulse energy ranges as described.
• a further aspect of the present invention is an implantable defibrillator comprising a housing and a power supply contained within the housing, and a control circuit contained within the housing and operatively associated with the power supply.
• the control circuit is configured for delivering a cardioversion sequence as described above.
• the maximum storage capacity of the capacitor in the power supply may be from 5.01 to 52 Joules, and is most preferably from 10 or 15 to 20 Joules.
• the housing for such a power supply preferably has a volume less than 35 cubic centimeters (but typically at least 5 cubic centimeters) .
• Table 1 illustrates a first embodiment of the invention. After a tachyarrhythmic condition is detected and reconfirmed by algorithms running in the controller 74, therapy in the form of an electrical shock of Figure 3 is applied to the heart by discharging capacitor 78. A preferred pairing of electrodes for this embodiment is illustrated in Table 1 below. In all tables herein, a "+” indicates that the electrodes are electrically common, and an "->" indicating current flow (which may be reversed).
• Table 2 illustrates a second embodiment of the invention. This embodiment introduces the use of an auxiliary pulse, with four possible configurations being shown in Figure 4.
• the auxiliary pulse is delivered through a different set of electrodes than the primary, or defibrillation, pulse.
• control circuitry is configured so that only one capacitor is employed to deliver both pulses, and that the different sets of electrodes are switched in and out of the discharge circuit to achieve the therapeutic effect.
• the trailing edge of the auxiliary pulse is equal to the leading edge of the primary pulse.
• the control circuitry is configured so that the auxiliary pulse and the primary pulse arise from separate capacitors.
• time constant is the product of the resistance and the capacitance
• the resistance to the shock ratio of voltage to current
• the relative strength of the pulses can be made independent. In this way, the minimum auxiliary shock strength can be applied that produces the synergistic action between the auxiliary and primary shocks, thereby minimizing the shock strength requirements for effective defibrillation.
• Table 3 below and Figure 5 illustrate another embodiment of the invention, where the beneficial effects are augmented by placing an additional electrode E; 53 on endocardial transvenous elongate lead 23 in the area of the heart experiencing the weakest electric field when electrode C; 52 is present.
• the weak field area in this location is in the region of the right ventricular conus.
• the electrode E can be located within the right atrial appendage or the right ventricular outflow track. To accomplish this, the electrode should be located at the most distal portion of the lead body.
• Table 3 One configuration for pairing of electrodes in this embodiment is given in Table 3:
• the primary electrode is about 15 to 25 millimeters in length, most preferably 20 millimeters in length, and preferably about 4 to 6 French in diameter, the pair of ring electrodes (2-4 millimeters in length together, with a diameter at least equal to that of the lead body) being positioned 10 to 20 millimeters proximal to the primary electrode.
• Pacing and sensing capability on lead 23 are particularly important when the system 10 is configured to monitor electrical rhythm activity in both atrial and ventricular chambers.
• Table 4 taken together with the apparatus of Figure 3 implementing the waveform of Figure 4, illustrate three additional configurations of the present invention: Table 4: Electrode Pairings
• Figure 7 presents a flow chart schematically illustrating how the electrodes employed to carry out the present invention can be used to modify the therapy delivered.
• electrode C permits sensing of electrical rhythm information and furthermore, allows the implanted device to use that information to select therapy that is tailored to specific rhythm characteristics.
• electrodes C and B are electrically common during sensing and the combined signal is fed into a sensing module for subsequent feature extraction, therapy adaptation in light of the detected feature, and therapy delivery.
• the time at which the shock is delivered is determined by an algorithm that chooses the optimum time for the defibrillation shock to produce its most significant electrophysiological effects.
• Other therapy adaptations include the coupling interval between the auxiliary and primary pulses.
• Electrodes C and D are common, electrograms recorded between electrodes B and C and a common indifferent electrode (electrodes A or D) could be separately fed into the sensing module 60.
• the feature extraction algorithm can examine features from each electrogram signal alone or in a differential fashion. As previously, the features extracted are then used to guide therapy adaptation and optimize therapy delivery.
• Systems as described above may be implanted in a patient by conventional surgical techniques, or techniques readily apparent to skilled surgeons in light of the disclosure provided herein, to provide an implanted defibrillation or cardioversion system.
• Additional features can also be added to the invention without affecting the function of the invention and result thereof.
• additional features include, but are not limited to, safety features such as noise suppression or multiple wave monitoring devices
• Skeletal muscle paralysis was induced with intravenous succinylcholine (1 mg/kg) and maintained with a dosage of 0.25 to 0.50 mg/kg each hour. Additional intravenous injections of sodium pentobarbital (10-20 mg) were given to titrate the anesthesia to an appropriate level. Sterile 0.9% saline solution was infused (2-5 ml/kg/hr) through a central venous catheter placed in an internal jugular vein. A femoral artery was surgically exposed and isolated through an inguinal cutdown. A 4 French polyurethane catheter was inserted and its tip was advanced into the descending aorta. Central arterial pressure was continuously displayed on a monitor (Hewlett Packard Corp.).
• the chest was opened through a median sternotomy.
• a retractor was installed to improve exposure of the heart and surrounding organs.
• the pericardium was carefully incised along an axis connecting the base and apex of the heart.
• a pericardial cradle was fashioned to elevate the heart to a closed-chest position within the chest cavity.
• the surface of the heart was kept moist and warm by flushing its surface with normal saline and covering the chest cavity with a sheet of plastic.
• Defibrillation electrode placement Four defibrillation electrodes were used in this study; two for the primary shocks and two for the monophasic auxiliary shocks. Defibrillation electrodes mounted on a commercially available lead system (ENDOTAK® model 0094, CPI/Guidant Corp., St. Paul, MN) were introduced through a right jugular venotomy. The distal coil electrode (4.0 cm length) was advanced under fluoroscopic guidance to the right ventricular apex. The proximal coil (6.8 cm length) was positioned with its distal tip 1 to 2 cm cephalid to the junction of the right atrium and superior vena cava using fluoroscopic guidance.
• ENDOTAK® model 0094 CPI/Guidant Corp., St. Paul, MN
• the distal and proximal catheter electrodes were used to deliver all the biphasic shocks.
• an epicardial electrode formed by concentric ellipses fashioned from platinum coated titanium coils 2 mm in diameter was sutured to the lateral, apical aspect of the left ventricular free wall.
• This coil-patch electrode circumscribed about 15 cm " and extended from the apex to about two-thirds the distance from the apex to base.
• Fibrillation Ventricular fibrillation was induced with 60 Hz alternating current (50-100 mA peak to peak) applied to the pacing tip electrode of the endocardial lead positioned in the right ventricle. In all episodes, fibrillation was allowed to persist for at least 10 seconds but not more than 12 seconds prior to delivery of the defibrillation test shock. When the test failed to defibrillate, the heart was immediately defibrillated with a rescue shock given through the transvenous catheter lead system. The animal was allowed to recover at least four minutes between each test shock.
• auxiliary pulse a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is a pulse that is referred to as the "auxiliary" pulse and the biphasic shock as the "primary" pulse herein.
• the auxiliary primary coupling interval is defined as the time between the trailing edge of the auxiliary pulse and the leading edge of the primary pulse.
• the monophasic shocks were delivered by a research defibrillator.
• the research defibrillator delivers fixed-duration shocks (1-20 ms) with an effective capacitance of 150 ⁇ F.
• the monophasic auxiliary pulses were always 5 ms in duration.
• the initiation of capacitor discharge for both shock generating devices could be externally triggered using a low-amplitude (1-5 volts) pulse.
• the polarity of the defibrillation electrodes was controlled in each experiment since it has been shown that defibrillation can be affected by electrode polarity.
• the left ventricular electrode was always connected to the anodic terminal (positive) of the defibrillator output circuit, while the right ventricular defibrillation coil electrode was always connected to the cathodic terminal (negative).
• each experiment consisted of multiple episodes of electrically-induced ventricular fibrillation that were intentionally terminated with test shocks, by applying an established set of rules to the observed outcome of each defibrillation trial, shock strengths were selected that permitted the definition of a defibrillation threshold for each experimental treatment.
• the modified Purdue technique was used to determine defibrillation thresholds.
• the strength of the test shock is adjusted according to the outcome (success or failure).
• the first defibrillation test shock for each treatment in the first animal was 400 V.
• the initial test shock strength was adjusted to the mean from the previous animals. If the first test shock failed the next shock voltage was increased 80 V and decreased 80 V if it succeeded.
• the shock strength step was reduced to 40 V. Trials continued until a second outcome reversal was encountered, after which the strength was increased 20 V for a failure and decreased 20 V for a success.
• the lowest shock strength that defibrillated the ventricles was defined as the defibrillation threshold.
• auxiliary pulse strength was tested in combination with an auxiliary-primary pulse coupling interval.
• Four auxiliary-primary pulse coupling intervals defined as the time between the trailing edge of the auxiliary pulse and the leading edge of the primary pulse, were tested: - 5 ms (simultaneous delivery), 1 ms, 20 ms and 40 ms.
• the combination of the two variables and the control yields thirteen treatments as shown in Figure 9.
• the experimental treatments were tested in randomized order in each animal. Data acquisition. Defibrillation threshold measurements are more accurate and precise when shock strength measurements are made directly across the defibrillation electrodes.
• the current and voltage during the defibrillation pulses were measured through 4:1 and 200:1 dividers by a waveform analyzer (model 6100, Data Precision, Inc., Danvers, MA).
• the analog current and voltage signals were digitized at 20 kHz and stored in a buffer.
• the digitized waveforms were displayed after each defibrillation attempt to permit visual inspection.
• Custom analysis software was used to define the time and amplitude of the leading and trailing edges and to compute the shock lmpedance and total energy delivered in each pulse Peak voltage, peak current, shock impedance and energy delivered was recorded for each test shock
• the mean total delivery energy values include the energy delivered in the monophasic pulse
• the mean peak current and peak voltage values always reflect the strength of the biphasic p ⁇ mary pulse
• the mean energy delivered at defibnllation threshold for each of the expe ⁇ mental treatments is presented m Figure 9
• the mean defibnllation threshold for the control treatment was 24 + 10 4 J
• the defibnllation thresholds were significantly lower (-50%) when a monophasic auxiliary pulse was delivered simultaneously with the biphasic pnmary pulse
• the mean energy delivered in the 50, 100 and 150 V monophasic pulses was 0 09 J, 0 38 J and 0 87 J, respectively
• there was no significant differences among the simultaneous treatments Similarly, the defibnllation thresholds for the treatments with a 1 ms auxiliary -pnmary pulse coupling interval were significantly lower than control, and unlike the simultaneous treatments, there was a trend suggesting that the strength of the monophasic pulse affected the amount of defibnllation threshold reduction
• Peak voltage requirements at defibnllation threshold followed trends very similar to the trends for energy delivered Figure 10 shows mean peak voltage of the pnmary pulse at defibnllation threshold with and without the auxiliary pulse
• the peak voltage defibnllation threshold was reduced about 25%
• the defibnllation thresholds were not different than control for auxiliary shocks of 50 V and 100 V
• the defibnllation threshold for the 150 V auxiliary shock with a 20 ms auxihary-pnmary coupling interval was significantly lower than the control treatment (P ⁇ 0 05) EXAMPLE 2
• Animal model preparation A total of six animals were studied. Methods of preparation were essentially equivalent for each animal.
• Mixed-breed canines (26-36 kg) were tranquilized via an intramuscular injection of ketamine (10 mg/kg), if necessary. After about 15 minutes, anesthesia was induced with an intravenous bolus injection of sodium pentobarbital (30 mg/kg) through a catheter placed in a cephalic vein. An endotracheal tube was inserted and the cuff was inflated to provide closed circuit ventilation. Electrocardiographic monitoring leads were placed on the cleaned and shaved portions of the fore limbs and hind limbs. The animal was placed in dorsal recumbence and secured to the table with limb restraints.
• a deep surgical plane of anesthesia was maintained with continuous intravenous infusion of sodium pentobarbital (0.05 mg/kg/min).
• Skeletal muscle paralysis was induced with intravenous succinylcholine (1 mg/kg) and maintained with a dosage of 0.25 to 0.50 mg/kg each hour.
• Additional intravenous injections of sodium pentobarbital (10-20 mg) were given to titrate the anesthesia to an appropriate level prior to performing any surgical procedures.
• Sterile 0.9% saline solution was infused (2-5 ml/kg/hr) through a central venous catheter placed in an internal jugular vein.
• a femoral artery was surgically exposed and isolated.
• a 4 French polyurethane catheter was inserted and its tip was advanced into the descending aorta.
• Central arterial pressure was continuously displayed on a monitor
• Anesthesia level was routinely monitored by testing cardiac reflex response to intense pedal pressure, jaw tone and basal heart rate and blood pressure. Both arterial blood electrolytes, blood gasses, as well as pH were measured every 30-60 minutes. Abnormal values were corrected by adding electrolytes to the hydration fluids and by adjusting ventilation rate and tidal volume. Esophageal temperature was continuously monitored. Heated water-circulating mats were used to maintain a normothermia (36°-38°C). The chest was opened through a median sternotomy. A retractor was installed to improve exposure of the heart and surrounding organs. The pericardium was carefully incised along an axis connecting the base and apex of the heart.
• a pericardial cradle was fashioned to elevate the heart to a closed-chest position within the chest cavity.
• the surface of the heart was kept moist and warm by flushing its surface with normal saline and covering the chest cavity with a sheet of plastic.
• Defibrillation electrode placement Four defibrillation electrodes were used in this study; two for the primary shocks and two for the monophasic auxiliary shocks (see Figure 11). Defibrillation electrodes mounted on a commercially available lead system (ENDOTAK® model 0094, CPI/Guidant Corp., St. Paul, MN) were introduced through a right jugular venotomy. The distal coil electrode (4.0 cm length) was advanced under fluoroscopic guidance to the right ventricular apex. The proximal coil (6.8 cm length) was positioned with its distal tip 1 to 2 cm cephalid to the junction of the right atrium and superior vena cava using fluoroscopic guidance. The distal and proximal catheter electrodes were used to deliver all the biphasic shocks.
• ENDOTAK® model 0094 CPI/Guidant Corp., St. Paul, MN
• the return electrode for the monophasic auxiliary shocks a 6 French titanium coil electrode, 6.8 cm in length, was positioned in the left jugular vein. See Figure 11.
• Fibrillation Ventricular fibrillation was induced with 60 Hz alternating current (50-100 mA peak to peak) applied to the pacing tip electrode of the endocardial lead positioned in the right ventricle. In all episodes, fibrillation was allowed to persist for at least 10 seconds but not more than 12 seconds prior to delivery of the defibrillation test shock. When the test failed to defibrillate, the heart was immediately defibrillated with a rescue shock given through the transvenous catheter system. The animal was allowed to recover at least four minutes between each test shock.
• Defibrillation waveforms External defibrillators were used to deliver the monophasic and biphasic truncated exponential shocks over two different current pathways.
• the monophasic shock is refened to as the "auxiliary" pulse and the biphasic shock as the "primary" pulse herein.
• Biphasic primary shocks were delivered by the VENTAK® external cardioverter defibrillator as described in Example 1 above or by a research defibrillator.
• the research defibrillator was programmed to emulate a single capacitor truncated exponential waveform.
• the first phase duration was 4 ms and the second phase duration was 3 ms.
• the trailing edge of phase one was equal (+10 V) to the leading edge voltage of phase two.
• the research defibrillator delivers fixed-duration shocks (1-20 ms) with an effective capacitance of 150 ⁇ F.
• the monophasic auxiliary pulses were always 5 ms in duration.
• the initiation of capacitor discharge for both shock generating devices could be externally triggered using a low-amplitude (1-5 volts) pulse.
• We used a commercially- available current source (Bloom Stimulator, Bloom & Assoc, Reading, PA) to generate 1 ms trigger pulses on two independent output channels that were used to control the relative timing between the auxiliary and primary pulses.
• the polarity of the defibrillation electrodes was controlled in each experiment since it has been shown that defibrillation can be affected by electrode polarity.
• the left ventricular electrode was always connected to the anodic terminal (positive) of the defibrillator output circuit, while the right ventricular defibrillation coil electrode was always connected to the cathodic terminal (negative).
• the left ventricular electrode was connected along with the right ventricular electrode to the cathodic terminal of the external defibrillator.
• an ENDOTAK® lead (available from Guidant Corporation Cardiac Pacemakers (CPI)) was inserted via a jugular venotomy into the right ventricle.
• CPI Guidant Corporation Cardiac Pacemakers
• a 3 cm DBS electrode was used as the LVA lead in this study.
• To implant the LVA lead first a median sternotomy was performed. The exposed pericardium was then incised and the electrode was sutured to the epicardium in a position approximating the path of the lateral coronary vein. The pericardium was then sutured closed. The LVA lead was brought out through the chest wall at the fifth intercostal space. A chest tube was added for drainage. The sternotomy was then closed and the chest evacuated. Fifteen ohms of external resistance was connected to the LVA lead to simulate a prototype LVA lead.
• the RV vector for preshocks and postshocks was RV -> superior vena cava (SVC) + can.
• the LV vector for preshocks and postshocks was LV->SVC + can.
• the protocol had eleven test configurations:
• LV preshock 20% tilt preshock/60% tilt postshock 5.
• LV preshock 40% tilt preshock/20% tilt postshock
• RV preshock 5 ms fixed duration preshock/40% tilt postshock (control).
• the LV preshock test waveforms (numbers 2-10 above) corresponded to the waveform of Figure 13c number 5 and Table 5 number 5, and were consistently a fixed tilt biphasic, 60:40 duration ratio, truncated exponential preshock, followed by a 5 ms delay, and then a fixed tilt, 60:40 duration ratio, biphasic, truncated exponential postshock.
• the RV preshock waveform (11) was a 5 ms fixed duration monophasic preshock followed by a 5 ms delay and a 40% fixed tilt, 60:40 biphasic postshock.
• Simulated capacitance was 225 ohms for all sequential test configurations.
• Waveforms were delivered using an AWAG arbitrary waveform generator. Voltage, current and energy data were collected with an automated data collection system.
• Fibrillation was induced by two 9 volt batteries placed in series across the shock coils. Fibrillation was confirmed by disorganization of the surface ECG and loss of blood pressure. Fibrillation was allowed to run ten seconds before a test shock was attempted. In the event of a failure, the animal was rescued using a 2815 ECD. Leading edge current of the preshock was increased ten percent after failures, decreased ten percent after successes. In either instance, animals were allowed to recover two minutes between fibrillation induction attempts. The up-down procedure was continued until three reversals were observed.
• Waveforms with lower first shock tilts performed better from a delivered energy standpoint, but not from a voltage and stored energy standpoint.
• LV preshocks did not noticeably outperform RV preshocks (see number 11 above).
• the best overall waveform was the 40/40 LV preshock waveform (number 6 above), which had significantly lowered current, voltage and energy as compared to a TRIAD waveform (number 1 above), while still having a low stored energy requirement.
• RV biphasic (bi) preshock 40% tilt preshock/20% tilt postshock positive positive;
• RV bi preshock 40% tilt preshock 40% tilt postshock positive positive
• RV bi preshock 60% tilt preshock/20% tilt postshock positive positive
• RV bi preshock 60% tilt preshock/40% tilt postshock positive positive
• RV bi preshock 40% tilt preshock/40% tilt postshock positive negative (the first phase of the postshock was in opposite polarity to the first phase of the preshock);
• RV monophasic (mono) preshock 40% tilt preshock/40% tilt postshock positive negative
• RV mono preshock 40% tilt preshock/40% tilt postshock positive positive
• LV bi preshock 40% tilt preshock/40% tilt postshock positive positive. Positive indicates a polarity of RV negative -> SVC positive + can positive.
• Waveforms 2-5 were designed to test the preshock/postshock tilt relationship of RV preshock waveforms. Preshock tilts of 40% and 60% and postshock tilts of 20% and 40% were used. Waveforms 6, 7, and 8, in combination with waveform 3, were designed to study the effect of using a reverse polarity postshock and of using a monophasic or biphasic preshock. Waveform 9, an LV preshock waveform found to be efficacious in the immediately preceeding example, was included as an additional control. Results. The results are summarized in Table 7 below.

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