Yoshio Yamanouchi

Autonomic Modification of the Atrioventricular Node During Atrial Fibrillation Role in the Slowing of Ventricular Rate

BACKGROUND Postganglionic vagal stimulation (PGVS) by short bursts of subthreshold current evokes release of acetylcholine from myocardial nerve terminals. PGVS applied to the atrioventricular node (AVN) slows nodal conduction. However, little is known about the ability of PGVS to control ventricular rate (VR) during atrial fibrillation (AF). METHODS AND RESULTS To quantify the effects and establish the mechanism of PGVS on the AVN, AF was simulated by random high right atrial pacing in 11 atrial-AVN rabbit heart preparations. Microelectrode recordings of cellular action potentials (APs) were obtained from different AVN regions. Five intensities and 5 modes of PGVS delivery were evaluated. PGVS resulted in cellular hyperpolarization, along with depressed and highly heterogeneous intranodal conduction. Compact nodal AP exhibited decremental amplitude and dV/dt and multiple-hump components, and at high PGVS intensities, a high degree of concealed conduction resulted in a dramatic slowing of the VR. Progressive increase of PGVS intensity and/or rate of delivery showed a significant logarithmic correlation with a decrease in VR (P<0.001). Strong PGVS reduced the mean VR from 234 to 92 bpm (P<0.001). The PGVS effects on the cellular responses and VR during AF were fully reproduced in a model of direct acetylcholine injection into the compact AVN via micropipette. CONCLUSIONS These studies confirmed that PGVS applied during AF could produce substantial VR slowing because of acetylcholine-induced depression of conduction in the AVN.

Direct Evidence of the Role of Virtual Electrode-Induced Phase Singularity in Success and Failure of Defibrillation

Virtual Electrodes in Defibrillation. Introduction: We recently demonstrated that virtual electrode‐induced phase singularity is responsible for arrhythmogenesis during T wave shocks and explains the upper and lower limits of vulnerability. Furthermore, we suggested that the same mechanism might he responsible for defibrillation failure. The aim of this study was to experimentally support this hypothesis.

Changes in left ventricular volume during head-up tilt in patients with vasovagal syncope: An echocardiographic study

We tested the hypothesis that patients who have vasovagal syncope during head-up tilt have a greater decrease in their left ventricular volume in response to tilt than do normal subjects. Measurements were done in the supine position and during graded tilt by using two-dimensional echocardiography. We compared seven patients with vasovagal syncope with nine normal volunteers. The rate of reduction of end-diastolic volume index during tilt was faster in the vasovagal group than in normal subjects. A more significant reduction of stroke index and ejection fraction during tilt was found in the vasovagal group than in normal subjects, possibly because of more peripheral translocation of blood volume in the venous system during tilt and an early vagal effect on ventricular contraction.

Usefulness of Plasma Catecholamines During Head‐Up Tilt as a Measure of Sympathetic Activation in Vasovagal Patients

Vasovagal syncope is a common clinical disorder which has been traditionally related to a vasovagal reflex precipitated by an initial excess sympathetic stimulation. We hypothesized that the increase in plasma Catecholamines during head‐up tilt is more accentuated in patients with tilt induced vasovagal syncope. To test this hypothesis, plasma Catecholamines were measured in supine posture and during head‐up tilt in patients with a history suggestive of vasovagal syncope. Of these, 13 had a normal response to tilt (nonvasovagal group; age 41 ± 19 [SD]years) and 11 had a vasovagal response to tilt (vasovagal group; 39 ± 20 years). In the supine posture at rest, plasma epinephrine and norepinephrine were not significantly different between the nonvasovagal and the vasovagal groups (39 ± 28 ng/L vs 46 ± 38 ng/L, P = 0.5792, 335 ± 158 ng/L vs 304 ± 124 ng/L, P = 0.6007, respectively). Furthermore, the tilt induced changes in plasma epinephrine and norepinephrine were not different between the two groups (20 ± 20 ng/L vs 35 ± 55 ng/L, P = 0.3562, 264 ± 158 ng/L vs 242 ± 205 ng/L, P = 0.7724, respectively) suggesting that differences in the hemodynamic response to tilt are not predictable by the supine levels of circulating plasma Catecholamines, and that the extent of plasma catecholamines increase during tilt does not determine the hemodynamic outcome of the tilt test. Since orthostatic changes of plasma Catecholamines could be influenced by volume factors, we assessed plasma renin activity and aldosterone as surrogates of blood volume. Baseline plasma renin activity and aldosterone were not significantly different between the two groups. We conclude that inasmuch as plasma catecholamines reflect the status of sympathetic activity, our data do not support the hypothesis that accentuation of sympathetic activity precedes necessarily the tilt induced vasovagal syncope. However, one should take in consideration that multiple factors may influence catecholamine levels and catecholamines kinetics. A hyperresponsiveness of β‐receptors to Catecholamines in patients with vasovagal syncope may be suggested but needs to be tested.

Fully Discharging Phases A New Approach to Biphasic Waveforms for External Defibrillation

BACKGROUND Phase-2 voltage and maximum pulse width are dependent on phase-1 pulse characteristics in a single-capacitor biphasic waveform. The use of 2 separate output capacitors avoids these limitations and may allow waveforms with lower defibrillation thresholds. A previous report also suggested that the optimal tilt may be >70%. This study was designed to determine an optimal biphasic waveform by use of a combination of 2 separate and fully (95% tilt) discharging capacitors. METHODS AND RESULTS We performed 2 external defibrillation studies in a pig ventricular fibrillation model. In group 1, 9 waveforms from a combination of 3 phase-1 capacitor values (30, 60, and 120 microF) and 3 phase-2 capacitor values (0=monophasic, 1/3, and 1.0 times the phase-1 capacitor) were tested. Biphasic waveforms with phase-2 capacitors of 1/3 times that of phase 1 provided the highest defibrillation efficacy (stored energy and voltage) compared with corresponding monophasic and biphasic waveforms with the same capacitors in both phases except for waveforms with a 30-microF phase-1 capacitor. In group 2, 10 biphasic waveforms from a combination of 2 phase-1 capacitor values (30 and 60 microF) and 5 phase-2 capacitor values (10, 20, 30, 40, and 50 microF) were tested. In this range, phase-2 capacitor size was more critical for the 30-microF phase-1 than for the 60-microF phase-1 capacitor. The optimal combinations of fully discharging capacitors for defibrillation were 60/20 and 60/30 microF. Conclusions-Phase-2 capacitor size plays an important role in reducing defibrillation energy in biphasic waveforms when 2 separate and fully discharging capacitors are used.

Effects of Polarity on Defibrillation Thresholds Using a Biphasic Waveform in a Hot Can Electrode System

The polarity of a monophasic and biphasic shocks have been reported to influence DFTs in some studies. The purpose of this study was to evaluate the effect of the first phase polarity on the DFTofa biphasic shock utilizing a nonthoracotomy “hot can” electrode configuration which had a 90‐μF capacitance. We tested the hypothesis that anodal first phase was more effective than cathodal ones for defibrillation using biphasic shocks in ten anesthetized pigs weighing 38.9 ± 3.9 kg. The lead system consisted of a right ventricular catheter electrode with a surface area of 2.7 cm2 and a left pectoral “hot can” electrode with 92.9 cm2 surface area. DFT was determined using a repeated “down‐up” technique. A shock was tested 10 seconds after initiation of ventricular fibrillation. The mean delivered energy at DFT was 11.2 ± 1.7 J when using the right ventricular apex electrode as the cathode and 11.3 ± 1.2 J (P = NS) when using it as the anode. The peak voltage at DFT was also not significantly different (529.0 ± 41.3 and 531.8 ± 28.6 V, respectively). We concluded that the first phase polarity of a biphasic shock used with a nonthoracotomy “hot can” electrode configuration did not affect DFT.

External Exponential Biphasic Versus Monophasic Shock Waveform: Efficacy in Ventricular Fibrillation of Longer Duration

Ventricular fibrillation (VF) duration may be a factor in determining the defibrillation energy for successful defibrillation. Exponential biphasic waveforms have been shown to defibrillate with less energy than do monophasic waveforms when used for external defibrillation. However, it is unknown whether this advantage persists with longer VF duration. We tested the hypothesis that exponential biphasic waveforms have lower defibrillation energy as compared to exponential monophasic waveforms even with longer VF duration up to 1 minute. In a swine model of external defibrillation (n = 12, 35 ± 6 kg), we determined the stored energy at 50% defibrillation success (E50) after both 10 seconds and 1 minute of VF duration. A single exponential monophasic (M) and two exponential biphasic (B1 and B2) waveforms were tested with the following characteristics: M (60 μF, 70% tilt), B1 (60/60 μF, 70% tilt/3 ms pulse width), and B2 (60/20 μF, 70% tilt/3 ms pulse width) where the ratio of the phase 2 leading edge voltage to that of phase 1 was 0.5 for B1 and 1.0 for B2. E50 was measured by a Bayesian technique with a total of ten defibriilation shocks in each waveform and VF duration randomly. The E50 (J) for M, B1, and B2 were 131 ± 41, 57 ± 18* and 60 ± 26* with 10 seconds of VF duration, respectively, and 114 ± 62, 77 ± 45* and 72 ± 53* with 1 minute of VF duration, respectively (*P < 0.05 vs M). There was no significant difference in the E50 between 10 seconds and 1 minute of VF durations for each waveform. We conclude that (1) the E50 does not significantly increase with lengthening VF durations up to 1 minute regardless of the shock waveform, and (2) external exponential biphasic shocks are more effective than monophasic waveforms even with longer VF durations.

Venous Dysfunction and the Change of Blood Viscosity During Head-Up Tilt

The precise stimulus that induces vasovagal syncope is still unclear. We have previously demonstrated that the peripheral distribution of blood volume (venous pooling) is a strong predictor of tilt induced vasovagal reaction. We hypothesized that an increase in venous pooling during tilt accentuates the measured increase in blood viscosity. This hypothesis is based on the previously demonstrated increase in venous pressure and subsequent increase in transcapillary fluid transudation during tilt. The increased blood viscosity, in turn, increases vascular shear rate, which may alter the vasoconstrictive and other cardiovascular responses to decreased preload. We measured blood viscosity (supine and tilt) in 56 patients with a history of orthostatic intolerance (37 with venous pooling [VP] and 19 without venous pooling [non‐VP]). VP and non‐VP were separated into subgroups based on blood pressure and heart rate response to tilt. There was a positive correlation between blood viscosity and plasma aldosterone in the supine. In the group as a whole, neither supine blood viscosity nor its increase during tilt differed between VP and non‐VP. However, the tilt induced increase of blood viscosity was significant only in patients with tilt provoked tachycardia plus normal blood pressure response in VP group. We suggest that the increase of blood viscosity in this group led to the normal blood pressure response. The positive correlation between supine blood viscosity and supine plasma aldosterone indicates that the normal blood pressure response in this group possibly was via stimulation of the renin‐angiotensin‐aldosterone system.

Voltage Dependence of ICD Lead Polarization and the Effect of Iridium Oxide Coating

Nonthoracotomy leads (NTLs) with an iridium oxide (IROX) coating exhibit lower defibrillation thresholds (DFTs) than uncoated NTLs. We tested whether adding an IROX coating to an active pectoral can would influence defibrillation efficacy. However, the primary purpose of this study was to examine the impedance changes that occur at different voltages for uncoated titanium NTLs and identical NTLs with an IROX coating. We studied anesthetized pigs with an NTL placed in the right ventricle and coupled this to an active pectoral can. Biphasic waveform DFTs were obtained for the four NTLs and can combinations: uncoated NTL and uncoated can, uncoated NTL and IROX can, IROX NTL and uncoated can. and IROX NTL and IROX can. The respective energy DFTs were: 23.6 ± 6.9, 24.1 ± 6.7, 21.3 ± 6.0, and 21.4 ± 7.0 J. The IROX NTL DFTs were significantly lower (P < 0.05) than the uncoated NTL DFTs (either can), confirming our previous study. We then used a low tilt monophasic waveform to assess impedance changes. The impedance rise for each NTL/can combination was measured at 50, 100, 300, and 700 V. Comparisons of impedance changes between voltage levels showed that the impedance rise was inversely related to voltage and was greatest with uncoated NTLs. The IROX coating of the NTL reduced the impedance rise at all shock voltages, but was particularly beneficial at the lower voltages. No advantage was seen when the pectoral can was coated with IROX regardless of which NTL was used. Our results suggest that low voltage applications, such as atrial defibrillation, would benefit most from the IROX‐coated NTL, and further studies are warranted in this area.

EFFECTS OF RESPIRATION PHASE ON VENTRICULAR DEFIBRILLATION THRESHOLD IN A HOT CAN ELECTRODE SYSTEM

The impedance of defibrillation pathways is an important determinant of ventricular defibrillation efficacy. The hypothesis in this study was that the respiration phase (end‐inspiration versus end‐expiration) mayalter impedance and/or defibrillation efficacy in a “hot can” electrode system. Defibrillation threshold (DFT) parameters were evaluated at end‐expiration and at end‐inspiration phases in random order by a biphasic waveform in ten anesthetized pigs (body weight: 19.1 ±2.4 kg; heart weight: 97 ± 10g). Pigs were intubated with a cuffed endotracheal tube and ventilated through a Drager SAVrespirator with tidal volume of 400–500 mL. A transvenous defibrillation lead (6 cm long, 6.5 Fr) was inserted into the right ventricular apex. A titanium can electrode (92‐cm2 surface area) was placed in the left pectoral area. The right ventricular lead was the anode for the first phase and the cathode for the second phase. The DFT was determined by a “down‐up down‐up” protocol. Statistical analysis was performed with a Wilcoxon matched pair test. The median impedance at DFT for expiration and inspiration phases were 37.8 ±3.1 Ω and 39.3 ± 3.6 Ω, respectively (P = 0.02). The stored energy at DFT for expiration and inspiration phases were 5.7 ± 1.9 J and 6.0 ± 1.0 J, respectively (P = 0.594). Shocks delivered at end‐inspiration exhibited a statistically significant increase in electrode impedance in a “hot can” electrode system. The finding that DFT energy was not significantly different at both respiration phases indicates that respiration phase does not significantly affect defibrillation energy requirements.