Syncytial heterogeneity as a mechanism underlying cardiac far-field stimulation during defibrillation-level shocks

INTRODUCTION: The mechanisms by which a defibrillation shock directly stimulates regions of cardiac tissue distal to the stimulus electrodes ("far-field" stimulation) are still not well understood. Existing hypotheses have proposed that intercellular discontinuities and/or fiber curvatures induce the requisite membrane polarizations. This article hypothesizes a third potential mechanism: one based on the existence and influences of syncytial (anatomic) heterogeneities inherent throughout the bulk myocardium itself. METHODS AND RESULTS: We simulated the effects of such heterogeneities in a model of a two-dimensional region of passive cardiac tissue subjected to uniform 1 V/cm longitudinal or transverse field stimuli. Heterogeneities were manifested via random spatial variations of intracellular volume fractions (fi) over multiple length scales, with mean fi of 80% and standard deviation of fi (sigma[fi]) ranging from 0% to 10%. During field stimulation, many interspersed and variously shaped and sized islands of hyperpolarization and depolarization developed across the tissue, with their locations and extents correlated to the spatial gradients of the underlying heterogeneities. Increases in sigma(fi) correspondingly increased the shock-induced magnitudes of resulting membrane polarizations. The ratio of maximal polarizations for equivalent longitudinal and transverse shocks approximated 2:1 across all sigma(fi) tested. At sigma(fi) = 5%, these maximal induced polarizations were 17.4 +/- 2.4 mV and 8.18 +/- 1.5 mV, respectively. Assuming an excitation threshold of 25 mV, these data suggest corresponding diastolic thresholds of 1.47 +/- 0.20 V/cm and 3.14 +/- 0.50 V/cm, respectively. CONCLUSION: This study predicts that syncytial heterogeneities inherent within cardiac tissue could represent a significant-and heretofore unappreciated-mechanism underlying field-induced polarizations throughout the bulk myocardium.     

Effects of atrial defibrillation shocks on the ventricles in isolated sheep hearts

BACKGROUND: The effects of cardioversion of atrial fibrillation on the activation sequence of the ventricles have not been previously studied. In this study we examined the events in the ventricle that follow the application of atrial defibrillatory shocks. METHODS AND RESULTS: We used video imaging technology to study the sequence of activation on the surface of the ventricles in the Langendorff-perfused sheep heart. We recorded transmembrane potentials simultaneously from over 20000 sites on the epicardium before and after biphasic shocks applied by a programmable atrial defibrillator. The first epicardial activation after the shock depended on both the voltage and timing of the shock. During ventricular diastole shocks as low as 10 V produced ventricular excitation, although the time between the shock and the first epicardial activation (latency) was approximately 30 ms. As the shock voltage was increased to 120 V, latency decreased to zero and the entire epicardium was depolarized within 30 ms. For 120-V shocks delivered late in systole, the depolarization sequence produced by the shock was similar to the previous repolarization sequence. Shocks of 120 V applied 150 to 300 ms after the previous ventricular excitation induced ventricular fibrillation. Ventricular fibrillation was induced by multiple focal beats after the shock, which produced waves that propagated but broke down into reentry within regions of high repolarization gradients. CONCLUSIONS: These results demonstrate that atrial defibrillation shocks excite the ventricles even at low shock voltages. In addition, ventricular fibrillation can be induced by shocks given in the vulnerable period by producing focal patterns that break down into reentrant waves.     

Relationship between efficacy of defibrillation shocks and frequency characteristics of shock waveforms

INTRODUCTION: Using the Fourier transform, it is possible to replace each time domain representation of a defibrillatory shock by a unique frequency domain representation in which the shock waveform is defined in terms of a complex number function of frequency and typically described as an amplitude in amperes per hertz (or, closely related, joules per hertz) and an associated frequency-dependent phase angle. METHODS AND RESULTS: The present article describes the conceptual basis of the Fourier transform, sketches a simplified mathematical framework for deriving frequency domain parameters, considers properties crucial to interpreting defibrillatory-type shocks when expressed in the frequency domain, and then presents a series of shock waveforms in the frequency domain. Although not definitive, knowledge of the energy distribution with frequency alone, usually presented in joules per hertz, is shown to yield considerable insight into the probable comparable efficacy of uniphasic/biphasic rectangular, untruncated/truncated uniphasic exponential, and various biphasic "single capacitor" waveforms. CONCLUSION: In general, efficacy in achieving ventricular defibrillation is improved by parameter changes that shift a larger percentage of the delivered energy into a mid-frequency range (very roughly, 40 to 160 Hz). With further study, the frequency domain approach may prove to be a useful tool in the a priori selection of optimal defibrillatory shock waveforms.     

Spatiotemporal effects of syncytial heterogeneities on cardiac far-field excitations during monophasic and biphasic shocks

INTRODUCTION: It has recently been postulated that syncytial (anatomic) heterogeneities inherent within cardiac tissue might represent a significant mechanism underlying field-induced polarization of the bulk myocardium. This simulation study examines and characterizes the spatiotemporal excitatory dynamics associated with this newly hypothesized mechanism. METHODS AND RESULTS: Two-dimensional regions of syncytially heterogeneous cardiac tissue were simulated with active membrane kinetics. Heterogeneities were manifested via random spatial variations of intracellular volume fractions over multiple length scales. Excitation thresholds were determined for uniform rectangular monophasic (M) and symmetric biphasic (B) far-field stimuli, from which strength-duration and strength-interval relationships were constructed. For regions measuring 5.4 x 5.4 mm, baseline diastolic thresholds for longitudinal (L) and transverse (T) shocks of 5-msec total duration averaged (in V/cm, n = 10) M-L = 2.87+/-0.26, M-T = 6.71+/-0.83, B-L = 3.22+/-0.25, and B-T = 7.93+/-0.51. These thresholds decreased by 15% to 25% when the region sizes were increased to 10.8 x 10.8 mm. Strength-duration relationships correlated strongly with the Weiss-Lapicque hyperbolic relationship, with rheobases and chronaxies of 2.33 V/cm and 1.15 msec for M-L stimuli, and 2.28 V/cm and 2.04 msec for B-L stimuli. Strength-interval relationships for M-L and B-L stimuli decreased monotonically with increasing coupling intervals, with similar minimum coupling intervals at absolute refractoriness. However, the B-L thresholds were substantially less sensitive to changes in coupling intervals than their M-L counterparts. CONCLUSION: This study provides strong additional support for and understanding of the syncytial heterogeneity hypothesis and its manifested properties. Furthermore, these results predict that syncytial heterogeneities of even modest proportions could represent a significant mechanism contributing to the far-field excitation process.     

The relationship of transmembrane potential to surface morphology of human atrial muscle and cardiac hemodynamics

A correlative study of transmembrane potential characteristics, surface morphological features of human atrial muscle, and cardiac hemodynamics was carried out in 41 patients, who were divided into 2 groups based on the level of the mean maximum diastolic potentials (MDP). Group A consisted of 19 patients with MDP values ranging from -60.0 to -82.0 mV (mean +/- S.D. = -65.70 +/- 6.63 mV). Group B included 22 patients who had abnormally low MDP (range -36.0- -58.5 mV, mean +/- S.D. = -48.14 +/- 6.72 mV). The differences in electrophysiological data were statistically significant. However, there were no significant differences in the hemodynamic data between the 2 groups. Furthermore, there was poor correlation between the electrophysiological and hemodynamic data in both groups. In group A, scanning and transmission electron microscopy revealed either no changes or only mild alterations in the surface morphology of the atrial myocardium. Various degrees of surface morphological changes, including a focal loss of the endothelium which was always associated with endocardial fibrosis, irregular thickening and lamination of the glycocalyx, disruption of the sarcolemma and complete destruction of the surface membrane structures were more often observed in group B. These results provide valuable evidence that sarcolemmal changes may underlie the electrophysiological alterations in diseased human atria. We suggest that the principal pathogenetic mechanisms leading to the transmembrane potential changes are the altered surface morphology of atrial myocardial cells, resulting from underlying disease processes.     

Influence of polarity reversal on defibrillation success with biphasic shocks and a transvenous/subcutaneous defibrillator system in a porcine animal model

Clinical studies show that polarity reversal affects defibrillation success in transvenous monophasic defibrillators. Current devices use biphasic shocks for defibrillation. We investigated in a porcine animal model whether polarity reversal influences defibrillation success with biphasic shocks. In nine anesthetized, ventilated pigs, the defibrillation efficacy of biphasic shocks (14.3 ms and 10.8 ms pulse duration) with "initial polarity" (IP, distal electrode = cathode) and "reversed polarity" (RP, distal electrode = anode) delivered via a transvenous/subcutaneous lead system was compared. Voltage and current of each defibrillating pulse were recorded on an oscilloscope and impedance calculated as voltage divided by current. Cumulative defibrillation success was significantly higher for RP than for IP for both pulse durations (55% vs 44%, P = 0.019) for 14.3 ms (57% vs 45%, P < 0.05) and insignificantly higher for 10.8 ms (52% vs 42%, P = ns). Impedance was significantly lower with RP at the trailing edge of pulse 1 (IP: 44 +/- 8.4 vs RP: 37 +/- 9.3 with 14.3 ms, P < 0.001 and IP: 44 +/- 6.2 vs RP: 41 +/- 7.6 omega with 10.8 ms, P < 0.001) and the leading edge of pulse 2 (IP: 37 +/- 5 vs RP: 35 +/- 4.2 omega with 14.3 ms, P = 0.05 and IP: 37.5 +/- 3.7 vs RP: 36 +/- 5 omega with 10.8 ms, P = 0.02). In conclusion, in this animal model, internal defibrillation using the distal coil as anode results in higher defibrillation efficacy than using the distal coil as cathode. Calculated impedances show different courses throughout the shock pulses suggesting differences in current flow during the shock.     

Alteration in diaphragmatic function during cardiac insufficiency: potential pharmacology modulation

Respiratory muscle dysfunction has been demonstrated in several clinical situations including chronic respiratory disease, such as chronic obstructive pulmonary disease, as well as cardiac insufficiency. In the latter case, respiratory muscle dysfunction has been demonstrated in acute situation (cardiogenic shock) and in chronic cardiac insufficiency. In the former case, it has been shown in an animal model that respiratory muscle dysfunction could influence markedly the outcome of cardiogenic shock. In chronic cardiac insufficiency histologic, biochemical and contractile abnormalities of the respiratory muscles have been demonstrated in an animal model as well as in humans. These alterations may account, at least in part, for the sensation of dyspnea that these patients encountered. Finally, several pharmacological agents such as angiotensin-converting enzyme inhibitors have been shown to restore muscle abnormalities observed during chronic cardiac insufficiency.     

Gender differences in strength and muscle fiber characteristics

Strength and muscle characteristics were examined in biceps brachii and vastus lateralis of eight men and eight women. Measurements included motor unit number, size and activation and voluntary strength of the elbow flexors and knee extensors. Fiber areas and type were determined from needle biopsies and muscle areas by computerized tomographical scanning. The women were approximately 52% and 66% as strong as the men in the upper and lower body respectively. The men were also stronger relative to lean body mass. A significant correlation was found between strength and muscle cross-sectional area (CSA; P < or = 0.05). The women had 45, 41, 30 and 25% smaller muscle CSAs for the biceps brachii, total elbow flexors, vastus lateralis and total knee extensors respectively. The men had significantly larger type I fiber areas (4597 vs 3483 microns2) and mean fiber areas (6632 vs 3963 microns2) than the women in biceps brachii and significantly larger type II fiber areas (7700 vs 4040 microns2) and mean fiber areas (7070 vs 4290 microns2) in vastus lateralis. No significant gender difference was found in the strength to CSA ratio for elbow flexion or knee extension, in biceps fiber number (180,620 in men vs 156,872 in women), muscle area to fiber area ratio in the vastus lateralis 451,468 vs 465,007) or any motor unit characteristics. Data suggest that the greater strength of the men was due primarily to larger fibers. The greater gender difference in upper body strength can probably be attributed to the fact that women tend to have a lower proportion of their lean tissue distributed in the upper body.(ABSTRACT TRUNCATED AT 250 WORDS)     

Severe and early alteration of action potential during acute cardiac rejection in rats

INTRODUCTION: Alteration of cardiac action potential and its adaptation to heart rate could contribute to cardiac dysfunction and arrhythmias during acute cardiac rejection. METHODS AND RESULTS: Heterotopic heart transplantation was performed in allogeneic and syngeneic rats in which the action potentials of right and left ventricles were measured at 1, 2.5, 3.3, and 5.7 Hz successively using standard microelectrode techniques and compared with nontransplanted hearts. For each frequency, we measured action potential amplitude, action potential duration, transmembrane resting potential, and Vmax. In the right ventricle, at 1 Hz in the presence of rejection (n = 40), a significant increase was observed in action potential duration at 20%, 50%, and 70% repolarization (82.5%, 75.6%, and 70.8%, respectively) and in action potential amplitude (+17.9 mV), and the resting potential was decreased (-5.3 mV). A lack of adaptation of action potential duration to the driving frequency was observed in the rejecting heart group in contrast to controls (n = 20) and nonrejecting hearts (n = 13). Similar results were observed in the left ventricle and surprisingly in the native hearts (n = 11) of recipients with allografted rejecting hearts in the abdominal position. CONCLUSION: Action potential and its adaptation to the driving frequency is considerably altered during acute rejection. A humoral factor could contribute to cardiac dysfunction.     

Mitochondrial transmembrane potential and free radical production in excitotoxic neurodegeneration

OBJECTIVE: To evaluate quality-of-life (QOL) parameters in patients undergoing esophagectomy, curative or palliative, for carcinoma. DESIGN: Nonconsecutive case series. PATIENTS: Eighty-eight patients who underwent esophagectomy for cancer (curative, n=49 [56%]; palliative, n=39 [44%]) provided QOL assessments over an 18-month period. SETTING: Procedures for referral care were performed by a single team of clinicians in a tertiary referral center. Evaluations of QOL were made by 1 independent trained investigator. OUTCOME MEASURES: Data were documented by questionnaire at interview and parameters evaluated included an esophageal module for the type and quantity of food intake, severity of related symptoms on eating, Eastern Cooperative Oncology Groups (ECOG) performance status, sleep, pain, leisure activity, working capacity, outlook on life, general well-being, and support from family and friends. A summation of selected parameters was used to calculate a total score. RESULTS: Significant improvements were recorded in both the curative and palliative groups for at least 1 year following surgery in the type (P<.03) and quantity (P<.03) of food intake and severity of diet-related symptoms (P<.02), when compared with preoperative considerations. Findings were comparable between the groups with regard to dietary intake. Pain status and total scores were worse in the palliative group at 9 months postoperatively but no significant differences between the groups were evident at any time for sleep, leisure activity, and ECOG performance status. CONCLUSIONS: To our knowledge, there are no previous data regarding a comparison of QOL considerations in patients who have undergone either potentially curative or palliative esophagectomy for malignant disease. Data analysis revealed that palliative esophagectomy provided enhanced QOL with marked symptomatic benefits and enjoyment of daily living comparable to that observed following curative resection.     

EMT defibrillation does not increase survival from sudden cardiac death in a two-tiered urban-suburban EMS system

BACKGROUND: The aim of this article was to analyze the perioperative mortality and stroke risk rates and late benefits of carotid endarterectomy (CE) contralateral to an occluded internal carotid artery (ICA), on the basis of our surgical experience from July 1990 to June 1996. METHODS: In 57 (14.7%) of 336 patients undergoing 388 CEs, the contralateral ICA was occluded (group I). All operations were performed under general anesthesia with selective shunting based on electroencephalographic criteria. Shunting was used in 36 (63.1%) of 57 revascularizations in group I and 47 (14.2%) of 331 operations performed on the remaining 279 patients with patent contralateral ICAs (group II) (p < 0.001). RESULTS: Perioperative strokes occurred in two patients (3.5%) in group I and three patients (1%) in group II (difference not significant). The only perioperative death, which occurred in one patient (1.7%) in group I, was the result of a perioperative stroke; two patients (0.7%) in group II died within 30 days of operation (difference not significant). Life-table cumulative stroke-free rates at 1, 3, and 5 years were 95%, 95%, 95% in group I and 98.8%, 98.2%, and 98.2% in group II, respectively (p = 0.272). Life-table cumulative survival rates at 1, 3, and 5 years were 97.5%, 94.2%, and 78.1% in group I and 99.2%, 94.8%, and 71.7% in group II, respectively (p = 0.306). CONCLUSIONS: The results of this analysis indicate that CE contralateral to an occluded ICA can be performed with acceptable perioperative mortality and stroke risk rates and late stroke-free and survival rates comparable to those seen in patients without contralateral ICA occlusion who have undergone operation. Nevertheless, we think it is misleading to imply that the risks of operating on the two groups are the same. Moreover, because no late stroke-related death occurred in patients with contralateral ICA occlusion, it would appear that superior late stroke-free rates did not translate into a prolonged survival advantage.     

Finite element analysis of defibrillation fields in a human torso model for ventricular defibrillation

In order to optimize defibrillation electrode systems for ventricular defibrillation thresholds (DFTs), a Finite Element Torso model was built from fast CT scans of a patient who had large cardiac dimensions (upper bound of normal) but no heart disease. Clinically used defibrillation electrode configurations, i.e. Superior Vena Cava (SVC) to Right Ventricle (RV) (SVC-RV), left pectoral Can to RV (Can-RV) and Can + SVC-RV, were analyzed. The DFTs were calculated based on 95% ventricular mass having voltage gradient > 5 V/cm and these results were also compared with clinical data. The low voltage gradient regions with voltage gradient < 5 V/cm were identified and the effect of electrode dimension and location on DFTs were also investigated for each system. A good correlation between the model results and the clinical data supports the use of Finite Element Analysis of a human torso model for optimization of defibrillation electrode systems. This correlation also indicates that the critical mass hypothesis is the primary mechanism of defibrillation. Both the FEA results and the clinical data show that Can + SVC-RV system offers the lowest voltage DFTs when compared with SVC-RV and Can-RV systems. Analysis of the effect of RV, SVC and Can electrode dimensions and locations can have an important impact on defibrillation lead designs.     

Fiber strength and fiber/matrix bond strength in single crystal Al2O3 fiber reinforced Ni3Al based composites

A series of single-crystal A1₂O₃ fiber (Saphikon), reinforced Ni₃Al-based composites were fabricated by a liquid metal infiltration technique, pressure casting. Tensile testing and indentation techniques have been employed to measure fiber strength and fiber/matrix interfacial debond shear stress. The Weibull mean strength of the fiber has been observed to decrease drastically upon handling, exposure to high temperature, and casting. Alloying of Ni₃Al with Ti has resulted in a further decrease in fiber strength. Thermal expansion mismatch between the fiber and matrix led to the formation of compressive twins in the fiber. These twins, forming on planes, produced cracks at their intersections, which were parallel to the fiber axis,c-axis. Twin-induced fiber cracking was observed in all cases, but most predominantly when Cr was present. While addition of Cr at the 1 at. pct level had no appreciable effect on the interfacial debond shear stress, addition of 0.5 at. pct Cr resulted in an approximately threefold increase in debond stress, from 19 MPa to about 54.5 MPa. Alloying of Ni₃Al with Cr has also resulted in partial dissolution of the A1₂O₃ fiber. Addition of Ti had a moderate effect on increasing the fiber/matrix bond strength.     

Transthoracic resistance in human defibrillation. Influence of body weight, chest size, serial shocks, paddle size and paddle contact pressure

Successful defibrillation depends on delivery of adequate electrical current to the heart; one of the major determinants of current flow is transthoracic resistance (TTR). To study the factors influencing TTR, we prospectively collected data from 44 patients undergoing emergency defibrillation. Shocks of 94-450 J delivered energy were administered from specially calibrated Datascope defibrillators that displayed peak current flow, thereby permitting determination of TTR. Shocks were applied from standard (8.5-cm diameter) or large (13 cm) paddles placed anteriorly and laterally. First-shock TTR ranged from 15-143 omega. There was a weak correlation between TTR and body weight (r = 0.45, p less than 0.05) and a stronger correlation between TTR and chest width (r = 0.80, p less than 0.01). Twenty-three patients who were defibrillated using standard 8.5-cm paddles had a mean TTR of 67 +/- 36 omega (+/- SD), whereas 21 patients who received shocks using paddle pairs with at least one large (13 cm) paddle had a 21% lower TTR of 53 +/- 24 omega (p = 0.05, unpaired t test). Ten patients received first and second shocks at the same energy level; TTR declined only 8%, from 52 +/- 19 to 48 +/- 16 omega (p less than 0.01, paired t test). In closed chest dogs, shocks were administered using a spring apparatus that regulated paddle contact pressure against the thorax. Firmer contact pressure caused TTR to decrease 25%, from 48 +/- 22 to 36 +/- 17 omega (p less than 0.01, paired t test). Thus, human TTR varies widely and is related most closely to chest size. TTR declines only slightly with a second shock at the same energy level. More substantial reductions in TTR and declines only slightly with a second shock at the same energy level. More substantial reductions in TTR and increases in current flow can be achieved by using large paddles and applying firm paddle contact pressure.     

Cotton fiber annexins: a potential role in the regulation of callose synthase

Cotton fibers contain a characteristic set of proteins which interact with plasma membranes in a Ca(2+)-dependent manner. The association of these proteins with the membrane is correlated with a reduced level of UDP-glucose: (1-->3)-beta-glucan (callose) synthase activity. Analysis of the proteins released from membranes by EDTA treatment shows that the most abundant proteins comprise a family of at least three polypeptides (p34) which resemble annexins. This resemblance includes similarity in size (about 34 kDa), sequence homology, Ca(2+)-dependent precipitation or interaction with the plasma membrane, and ability to serve as a substrate for phosphorylation by endogenous protein kinase(s) which also bind to the membranes in a Ca(2+)-dependent manner. A purified fraction of these annexins binds to, and inhibits, the activity of a partially purified cotton fiber callose synthase. These findings suggest that one possible function of annexin(s) in plants is to modulate the activity and/or localization of callose synthase.     

Interfacial shear strength of cast and directionally solidified NiAl-sapphire fiber composites

The feasibility of fabricating intermetallic NiAl-sapphire fiber composites by casting and zone directional solidification has been examined. The fiber-matrix interfacial shear strengths measured using a fiber push-out technique in both cast and directionally solidified composites are greater than the strengths reported for composites fabricated by powder cloth process using organic binders. Microscopic examination of fibers extracted from cast, directionally solidified (DS), and thermally cycled composites, and the high values of interfacial shear strengths suggest that the fiber-matrix interface does not degrade due to casting and directional solidification. Sapphire fibers do not pin grain boundaries during directional solidification, suggesting that this technique can be used to fabricate sapphire fiber reinforced NiAl composites with single crystal matrices.