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Several investigations suggest that complexin may be a schizophrenia-susceptibility factor. We conducted a genetic association analysis between complexin genes (CPLX1 and CPLX2) and schizophrenia in Japanese patients (377 cases and 341 controls). Ten and eleven haplotype-tagging (ht)SNPs in CPLX1 and CPLX2, respectively, were selected. Only one htSNP (rs930047 in CPLX2) in allele-wise analysis showed significance, and even this disappeared with an increased sample size (563 cases and 519 controls: P = .757). Haplotype-wise analysis showed a weak association with a combination of htSNPs in CPLX2 (P = .0424), but this may be a result of type I error due to multiple testing. Our results suggest that complexin genes do not play a major role in schizophrenia in Japanese patients.

Recent evidence suggests that the AKT1-GSK3beta signalling cascade partially mediates dopamine-dependent behaviours. In relation to the pathophysiology of schizophrenia or methamphetamine (Meth) use disorder, AKT1 is a good candidate gene for such conditions. For schizophrenia, positive associations of SNPs and AKT1 haplotypes were reported in US and Japanese samples. To evaluate the association between AKT1 and Meth-use disorder, we conducted a case-control study of Japanese samples (182 patients and 437 controls). A positive association between a SNP and haplotypes was found, and the 'signal' SNP was the same SNP found to be associated with US schizophrenia, but not with Japanese schizophrenia. Our results indicate that AKT1 may play a possible role in the development of Meth-use disorder. Further investigation of these associations, together with evidence from previous animal studies, may open the way to elucidation of the pathophysiology of this condition.

Background: Vesicle-associated membrane protein 2 (VAMP2) is a key component of the synaptic vesicle docking/fusion machinery and its mRNA reportedly increases in the frontal cortex of rats following chronic antidepressant and electroconvulsive treatment. VAMP2 is therefore thought to be involved in the mechanism of action of antidepressants and may alter their efficacy. The purpose of this study was to investigate whether the VAMP2 gene is associated with clinical responses to a specific antidepressant, fluvoxamine., Methods: A total of 106 patients with major depressive disorder were given fluvoxamine (50-200 mg/day) for 8 weeks and assessed for severity of depression using the Semi-Structured Interview Guide of the Hamilton Depressive Scale (SIGH-D; 17 items) at 0 and 8 weeks. We defined a clinical response as more than a 50% reduction in baseline SIGH-D within 8 weeks, and defined clinical remission as a SIGH-D score of less than 7 at 8 weeks. Genotyping was performed by PCR-RFLP., Results: Analysis of haplotype tagging single nucleotide polymorphisms as well as haplotype analysis did not reveal any significant associations., Conclusion: Our results suggest that the VAMP2 gene is unlikely to play a major role in the efficacy of fluvoxamine., ((c) 2006 S. Karger AG, Basel.)

Recent study of linkage disequilibrium mapping showed one of the trace amine receptor (TRAR) genes, TRAR4, was associated with schizophrenia. We conducted a replication study of TRAR4 with schizophrenia in Japanese patients. We used two large independent sets of samples in a first-set analysis (cases=405, controls=401) and second-set analysis (cases=503, controls=440). In the first-set analysis, one Marker (Marker5) showed a significant association, but this significance was not seen in the second-set analysis. Our results indicate that TRAR4 may not play a major role in Japanese schizophrenia patients, and that it is important to examine the possibility of false positives in genetic association analysis.

Background: Several investigations suggest that abnormalities in gamma-amino butyric acid (GABA) neurotransmission systems may be related to the pathophysiology of schizophrenia. A GABA(A) receptor gene cluster on 5q31-35 (beta2 [GABRB2], alpha6 [GABRA6], alpha1 [GABRA1], and gamma2 [GABRG2] subunit genes) is one of the most attractive candidate regions for schizophrenia susceptibility., Methods: We performed 1) systematic polymorphism search of GABRB2, GABRA6, and GABRA1, in addition to our colleague's study of GABRG2; 2) evaluation of linkage disequilibrium (LD) within this cluster with 35 single nucleotide polymorphisms (SNPs); 3) "selection of haplotype-tagging (ht) SNPs"; and 4) two-stage association analysis that comprised first-set screening analysis of all htSNPs (288 Japanese schizophrenia patients and 288 control subjects) and second-set replication analysis of the positive htSNPs (901 schizophrenic patients and 806 control subjects)., Results: In the first-set scan, we found a significant association of two htSNPs in GABRA1, but no association of GABRB2, GABRA6, and GABRG2. In the following second-set analysis, however, we could not confirm these significant associations., Conclusions: These results indicate that this gene cluster may not play a major role in Japanese schizophrenia. They also raised an alert with regard to preliminary genetic association analysis using a small sample size.

Several lines of evidence indicate that glycogen synthase kinase-3beta (GSK3beta) is one of the candidates for schizophrenia-susceptibility factor. However, it has not been reported the association analysis between GSK3beta gene (GSK3B) and Japanese schizophrenia based on linkage disequilibrium (LD). We provide an association analysis using relatively large samples (381 schizophrenia, and 352 controls) after determination of "tag single nucleotide polymorphisms (SNPs)." In this LD mapping, we selected and genotyped for eight polymorphisms (seven SNPs and one diallelic (CAA)(n) repeat), which covered the entire region of GSK3B, and determined two "tag SNPs." In the following association analysis using these two "tag SNPs," we could not find association with Japanese schizophrenia. Furthermore, we also include subgroup analysis considering age-at-onset and subtypes, neither could we find associations. Because our samples provided quite high power, these results indicate that GSK3B may not play a major role in Japanese schizophrenia., (Copyright 2005 Wiley-Liss, Inc.)

ZDHHC8 is a new and attractive candidate for a schizophrenia-susceptibility factor. First, several lines of linkage studies showed that 22q11, on which ZDHHC8 is located, is a "hot" region. Second, fine linkage disequilibrium mapping revealed a significant association around ZDHHC8. Moreover, a very recent study reported that one single nucleotide polymorphism (SNP: rs175174) in ZDHHC8 might affect the splicing process, the ZDHHC8 knock-out mice showed the gender-specific phenotype, and the transmission disequilibrium test (TDT) using this SNP also showed significant association with human female schizophrenia. Thus, we attempted a replication study of this SNP using relatively large Japanese case-control samples (561 schizophrenics and 529 controls). No association was found between schizophrenia and controls even after dividing samples by gender. Because our sample size provided quite high power, ZDHHC8 may not play a major role in Japanese schizophrenia. And our results did not support the gender-specific effect of this SNP.

We report the case of a 52-year-old man with variant Brugada syndrome who was successfully resuscitated from ventricular fibrillation (VF). Resting ECG showed J wave and ST-segment elevation in the inferior leads but no coved or saddleback ST-segment elevation in the right precordial leads. Pilsicainide infusion provoked coved-type ST-segment elevation in the right precordial leads and mild ST-segment elevation 80 ms after the J point in the inferior leads. During an emergency, 12-lead ECG showed that spontaneous onset of VF was preceded by left bundle branch block and superior axis-type ventricular extrasystoles. The present case provides additional information on the site of origin of VF in patients with Brugada syndrome.

We report a rare case in which a myxoid chondrosarcoma originated from the petrous bone and invaded the cerebellar hemisphere with hemorrhage. Neuroimaging showed the characteristic feature of multiple small cysts along the solid tumor, and the cystic formation was confirmed as a mucoid secretion by Alcian blue staining and electron microscopic examination. This tumor recurred following partial removal and stereotaxic radiosurgery.

Background: Abnormality of the V-akt murine thymoma viral oncogene homologue 1 (AKT1) may be a predisposing factor in schizophrenia. Recent evidence supporting this hypothesis showed decreased AKT1 protein levels in patients with schizophrenia and significant association of AKT1 haplotypes according to the transmission disequilibrium test., Methods: We provide the first replication of this evidence using a relatively large case-control sample (507 Japanese schizophrenia and 437 control subjects). We genotyped five single nucleotide polymorphisms (SNPs) from the original study and one additional SNP., Results: We found a positive association with an SNP (SNP5) different from the original study's findings (SNP3) and also significance in the haplotypes constructed from the combination of SNP5. Linkage disequilibrium around SNP5 was complex and may produce this positive association., Conclusions: Our study provides support for the theory that AKT1 is a susceptibility gene for Japanese schizophrenia. Fine linkage disequilibrium mapping is required for a conclusive result.

We have developed a field-worthy, high-definition, real-time depth-mapping television camera called the HDTV Axi-Vision Camera. The camera can simultaneously capture both an ordinary HDTV color image and a depth image of objects on more than 1280 x 720 pixels at a frame rate of 29.97 Hz, or on 853 x 480 pixels at a frame rate of 59.94 Hz. The number of detectable pixels per unit time was increased by about 5 times that of the prototype camera by improving the sensitivity and resolution of the depthmapping camera. Short video clips demonstrate how depth information from the camera can be used to create a virtual image in actual television program production.

Case Report: We present a case of solitary myofibromatosis of the skull in a 4-year-old girl. Surgery was performed and the final diagnosis of myofibromatosis was made histopathologically., Discussion: Solitary myofibromatosis of the skull is rare and we found approximately 20 reported cases in the English-language literature. We reviewed eight well-described cases., Conclusion: Neuroradiologically, common features such as a lytic lesion with a sclerotic rim on roentgenogram and intra-diploic lesion with periosteal new bone formation both in the outer and inner table of the skull on computed assisted tomography are noticed.

It has been reported that there is an inverse correlation between the immunohistochemical expression of Rb2/p130, a member of the retinoblastoma gene family, and the degree of malignancy in at least some histological types. In order to investigate the expression of this protein in gliomas, we evaluated 58 samples from patients with resected gliomas. We focused on the relationship between the degree of malignancy of the glioma and the immunohistochemical detection of Rb2/p130. Expression of Rb2/p130 was observed in 38 glioma specimens (65.5%), including a high expression level in low-grade glioma specimens (> 30% positive cells in 84% of tumors) and a low expression level in high-grade glioma specimens (> 30% positive cells in 12% of tumors). The most aggressive of the gliomas exhibited very low to undetectable levels of Rb2/p130. Moreover, we observed an inverse correlation between Rb2/p130 expression and the degree of malignancy. These findings suggest that the differentiation of gliomas might be partially mediated by the Rb2/p130 gene, and that Rb2/ p130 expression can additionally be an indicator of a better prognosis in patients with gliomas.

The shape of the shock waveform influences defibrillation efficacy. However, the optimal combination between capacitance size and truncation/tilt which can determine monophasic waveform's shape, has not been determined for external defibrillation. The purpose of this study was to assess the effects of varying capacitance and tilt on external defibrillation using exponential monophasic waveforms. In a pig model of external defibrillation (n = 10, 30 +/- 6 kg), nine exponential monophasic waveforms combining three capacitance values (30 microF, 60 microF, and 120 microF) and three tilt values (55%, 75%, and 95%) were tested randomly. The energy and leading edge voltage at 50% defibrillation success (E50 and V50) were used to evaluate defibrillation efficacy. E50 and V50 were determined by the Bayesian technique. The lowest stored E50 for the 30microF, 60 microF, and 120 microF waveforms were 90 +/- 12 J (95% tilt), 106 +/- 45 J (55% tilt), and 107 +/- 52 J (75% tilt), respectively. The lowest V50 for the 30 microF, 60 microF, and 120 microF waveforms were 2,439 +/- 166 V (95% tilt), 1,849 +/- 375 V (55% tilt), and 1,301 +/- 322 V (75% tilt), respectively. The average current at external defibrillation threshold demonstrated a strength versus pulse duration relationship similar to that seen with pacing. Reducing capacitance has the same effect as truncating the waveform. The E50 is more sensitive to tilt values changes in larger capacitance waveforms. This study suggests that the optimal combination between capacitance and tilt may be 120 microF and 55%-75% for external defibrillation.

Background: Ewing's sarcomas account for approximately 10% of primary malignant bone tumors. While most of the primary Ewing's sarcomas occur in the long bones, pelvis, or ribs, approximately 1-6% of these sarcomas arise in the skull. We found approximately 50 cases of Ewing's sarcoma of the calvarium reported in our search of the literature. Of these, 36 cases were reported in detail., Case Report and Discussion: In this article we describe a rare case of primary Ewing's sarcoma of the occipital bone presenting with acute obstructive hydrocephalus and review the literature.

A Japanese girl was diagnosed as true hermaphroditism with 46,X,+mar/46,XY and the marker chromosome was determined on the short arm of chromosome 22 without alpha-satellite by fluorescence in situ hybridization (FISH) and spectral karyotyping (SKY) methods. At birth, she showed intersexual external genitalia, urethral-vaginal fistula and right inguinal hernia. The right gonad was revealed as an ovotestis, and the left was as an undifferentiated testis. The gonadal mosaicism was demonstrated directly in gonadal tissue by interphase FISH.

To investigate the role of adhesion molecules [intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and integrin alpha 5 beta 1] in the progression of encapsulating peritoneal sclerosis (EPS) under peritoneal dialysis, we examined changes in the expression of those adhesion molecules in Wistar-Kyoto (WKY) rats treated with acidic dialysis solution with or without angiotensin II type 1a receptor blocker (ARB). We divided 48 WKY rats into 4 groups and dialyzed them with various solutions as follows: (1) pH 7 1.5% glucose dialysis solution (control group, n = 12); (2) pH 3.5 1.5% glucose dialysis solution (EPS group, n = 12); (3) pH 3.5 1.5% glucose dialysis solution, plus oral administration of CS866 5 mg/kg daily (ARB group, n = 12); and (4) pH 3.5 1.5% glucose dialysis solution, plus oral administration of amlodipine (CA group, n = 12). We injected the dialysis solutions into the abdominal cavity and administered the ARB and CA daily for 42 days. On days 3, 7, 14, and 42, three rats in each group were humanely killed by decapitation, and we studied the expression of adhesion molecules in peritoneum by the immunofluorescence method. In the EPS rats, expression of adhesion molecules was observed in peritoneum on day 3 after start of acidic solution treatment, in conjunction with an increment of interleukin 6 (IL-6) in the dialysate. The peritoneum of EPS rats showed peritoneal fibrosis with interstitial cell infiltration. Treatment with ARB significantly suppressed expression of adhesion molecules in the peritoneum and suppressed peritoneal fibrosis. Treatment with a neutral solution induced no peritoneal fibrosis nor expression of adhesion molecules in the peritoneum. Our results suggest that adhesion molecules play an important role in the progression of peritoneal fibrosis and resultant EPS. Treatment with ARB prevents the progression of peritoneal fibrosis and suppresses expression of adhesion molecules in the peritoneum.

The optimal capacitance for defibrillation is calculated to be 40 to 80 muF by theoretical models, assuming a heart chronaxie of 2 to 4 ms and a mean impedance of 40 ohms. The 60 muF capacitor is optimal for providing maximum defibrillation efficacy, which can reduce defibrillation energy. The purpose of the present study was to determine the optimal tilt to maximize defibrillation efficacy in a 60/60 muF biphasic waveform and to compare these waveforms with an optimized 60/15 muF waveform. The defibrillation thresholds (DFTs) were evaluated for five different 60/60 muF biphasic waveforms having 40%, 50%, 60%, 70% and 80% phase 1 tilt and a 60/15 muF biphasic waveform having 50% phase 1 tilt with a hot can electrode system in 15 pigs (20+/-2 kg). Phase 2 pulse widths were held constant at 3 ms in all waveforms. The DFT was measured by 'down-up, down-up' technique and was random in each waveform. The DFT energy in 60/60 muF waveforms (40%, 50%, 60%, 70% and 80%) and a 60/15 muF waveform (50%) were 6.9*, 6.9*, 7.1*, 7.8*, 8.4* and 6.0, respectively (*P<0.05 versus 60/15 muF waveform). A phase 1 tilt of 40% to 50% maximizes defibrillation efficacy for biphasic waveforms using 60/60 muF capacitors. Additionally, switching to a 15 muF capacitor for phase 2 can further reduce the DFT energy.

Encapsulating peritoneal sclerosis (EPS) is an important complication of peritoneal dialysis in which all or part of the intestine is enveloped in a fibrous ball resulting in a cocoon. Previously, we reported that acid dialysis solution (DS) induces peritoneal fibrosis. In the present study, we examined the effect of treatment with glucocorticoid (GC) in a model of EPS in rats. We divided 20 male Wistar-Kyoto rats into four groups and dialyzed them with various solutions for 40 days as follows: (1) pH 3.5 DS, 10 mL (pH 3.5, containing 1.35% glucose, n = 5); (2) pH 3.5 DS, 10 mL + GC (0.1 mg dexamethasone daily, n = 5); (3) pH 7.0 DS, 10 mL (n = 5); and (4) pH 7.0 DS, 10 mL + GC (n = 5). At the end of 40 days, all rats were humanely killed by decapitation. Expression of mRNA of aquaporins (AQPs) and glucose transporters (GLUTs) were studied by reverse-transcriptase polymerase chain reaction. In rats treated with pH 3.5 DS, necropsy findings showed evidence of EPS. The typical appearance was multiple surfaces covered with granulation tissue or fibrotic tissue or both. Multiple adhesions were present. Microscopic findings revealed that low-pH DS induced peritoneal fibrosis and loss of mesothelium. In the dialyzed rats, mRNA of AQP-1, AQP-4, GLUT-1, GLUT-4, and GLUT-5 was expressed in peritoneum. In rats treated with pH 3.5 DS, expression of AQPs was significantly suppressed and expression of GLUTs was significantly enhanced. However, glucocorticoid treatment prevented the progression of peritoneal fibrosis and adhesion of peritoneum. In rats treated with pH 7.0 DS, no signs of EPS were seen. Our study suggests that low-pH DS induced the development of EPS. Glucocorticoid protects against the development of EPS on peritoneal dialysis.

Objective: Encapsulating peritoneal sclerosis (EPS), in which all or part of the intestine is enveloped in a fibrous ball resembling a cocoon, is a serious complication of peritoneal dialysis (PD). The aim of the present study was to investigate whether pH-neutral or acidic dialysis solutions induce peritoneal fibrosis., Design: We divided 18 male Wistar-Kyoto (WKY) rats into three groups and dialyzed them with various solutions as follows: group I, 10 mL acidic dialysis solution (pH 3.8, containing 1.35% glucose), n = 6; group II, 10 mL pH 5.0 dialysis solution, n = 6; and group III, 10 mL neutral dialysis solution (pH 7.0), n = 6. Peritoneal catheters were inserted, and dialysis solution was injected every day for 40 days. At the end of the experiment, a peritoneal equilibration test (PET) was performed. Expression of mRNA of aquaporins 1 and 4 (AQP-1 and AQP-4) in the peritoneum were studied by semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR)., Results: In rats treated with pH 3.8 dialysis solution, necropsy findings revealed features identical to those of EPS. The typical appearance was of granulation tissue or fibrotic tissue (or both) covering multiple surfaces. Multiple adhesions were present. In microscopic examinations, peritoneal fibrosis and loss of mesothelium were found. In rats treated with pH 7.0 dialysis solution, no signs of EPS were seen. In rats treated with pH 5.0 dialysis solution, milder changes (subserosal thickening and partial adhesion of the peritonea) were observed. The mRNA of AQP-1 and AQP-4 were expressed in the peritonea of the rats. The expression of the AQPs was significantly suppressed in rats treated with pH 3.8 dialysis solution., Conclusions: In rats, long-term intraperitoneal injection of acidic dialysis solution produced features typical of EPS in humans. Newly developed neutral dialysis solutions protected the against the development of EPS during peritoneal dialysis in rats.

Vulnerability and defibrillation are mechanistically dependent upon shock strength, polarity, and timing. We have recently demonstrated that shock-induced virtual electrode polarization (VEP) may induce reentry. However, it remains unclear how the VEP mechanism may explain the vulnerable window and polarity dependence of vulnerability. We used a potentiometric dye and optical mapping to assess the anterior epicardial electrical activity of Langendorff-perfused rabbit hearts (n = 7) during monophasic shocks (+/-100 V and +/-200 V, duration of 8 ms) applied from a transvenous defibrillation lead at various coupling intervals. Arrhythmias were induced in a coupling interval and shock polarity dependent manner: (i) anodal and cathodal shocks induced arrhythmias in 33.2 +/- 30.1% and 53.1 +/- 39.3% cases (P < 0.01), respectively, and (ii) the vulnerable window was located near the T-wave. Optical maps revealed that VEP was also modulated by the coupling interval and shock polarity. Recovery of excitability produced by negative polarization, known as de-excitation, and the resulting reentry was more readily achieved during the relative refractory period than the absolute refractory period. Furthermore, anodal shocks produced wavefronts propagating in an inward direction with respect to the electrode, whereas cathodal shocks propagated in an outward direction. Wavefronts produced by anodal shocks were more likely to collide and annihilate each other than those caused by cathodal shocks. The probability of degeneration of the VEP-induced phase singularity into a sustained arrhythmia depends upon the gradient of VEP and the direction of the VEP-induced wavefront. The VEP gradient depends upon the coupling interval, while the direction depends upon shock polarity; these factors explain the vulnerable window and polarity-dependence of vulnerability, respectively.

The present study was carried out to investigate changes in the expression of aquaporins (AQPs) in the peritoneum. The effects of the renin-angiotensin system on the expression of AQPs with and without angiotensin converting enzyme inhibitor (ACEI) or angiotensin II type 1a receptor blocker (ARB) were then examined. We divided 20 male Wistar Kyoto (WKY) rats into four groups, dialyzed with these solutions: saline; 10% glucose (TZ); 10% glucose plus benazepril (ACEI: 4 mg/kg daily); and 10% glucose plus valsartan (ARB: 10 mg/kg daily). The ACEI and ARB were administered into the peritoneum for 7 days. Expression of AQP-1-AQP-4 mRNA was studied by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR). Ultrafiltration volume (UFV) and peritoneal function were measured by peritoneal equilibration test (PET). In the TZ group, expression of AQP-1 and AQP-4 was enhanced in parallel with an increment in UFV. Expression of AQP-1 and AQP-4 was also observed in the mesothelium by immunofluorescence microscopy. On the other hand, in ACEI- and ARB-treated rats, expression of AQP-1 and AQP-4 was significantly suppressed, accompanied by loss of UFV. Our results suggest that the renin-angiotensin system plays an important role in the regulation of water transport in the peritoneum. Administration of ACEI or ARB in patients undergoing continuous ambulatory peritoneal dialysis should be carried out with caution.

Objectives: Combined administration of propranolol and disopyramide treatment often leads to better results in patients with atrial fibrillation refractory to only disopyramide administration. The electrophysiological mechanism of this combination therapy was investigated., Methods: Nineteen patients with paroxysmal atrial fibrillation without organic heart disease were studied. The indices for atrial vulnerability were compared in the control state, 10 min after injection of disopyramide (2 mg/kg) and 10 min after additional administration of propranolol (0.2 mg/kg)., Results: Administration of both drugs did not significantly change the percentage fragmented atrial activity and the interatrial conduction delay. Disopyramide increased the atrial effective refractory period and the wavelength index, defined as the ratio of the atrial effective refractory period to the interatrial conduction delay and represented the length of the reentry circuit. Additional injection of propranolol caused further increases in both values., Conclusions: Combination therapy with disopyramide and propranolol improves atrial vulnerability by increasing the wavelength.

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 be responsible for defibrillation failure. The aim of this study was to experimentally support this hypothesis., Methods and Results: We used the voltage-sensitive dye di-4-ANEPPS and fast imaging to assess electrical activity in Langendorff-perfused rabbit hearts. Ventricular arrhythmias were induced by monophasic shocks applied during T wave. Three types of defibrillation shocks (n = 79) were delivered from an intravenous right ventricular electrode: monophasic (8 msec), optimal biphasic (8/8 msec, 2/1 leading-edge voltage ratio), and nonoptimal biphasic (8/8 msec, 1/1 leading-edge voltage ratio). We found that a monophasic shock extinguished arrhythmic pattern of electrical activity via a virtual electrode polarization effect. However, the virtual electrode polarization was likely to produce phase singularities, leading to another arrhythmia and defibrillation failure. Nonoptimal biphasic shocks produced similar effects. Optimal biphasic shocks were successful because the first phase of the shock erased the arrhythmia via the virtual electrodes effect, whereas the second phase canceled the virtual electrodes, eliminating the substrate for phase singularities and arrhythmia resulting from them., Conclusion: Our data provide the first experimental support of the hypothesis implicating virtual electrode-induced phase singularity in defibrillation failure in the Langendorff-perfused rabbit heart. Optimal biphasic shock has a higher defibrillation efficacy because it does not produce virtual electrode-induced phase singularities.

Introduction: The use of two independent, fully discharging capacitors for each phase of a biphasic defibrillation waveform may lead to the design of a simpler, smaller, internal defibrillator. The goal of this study was to determine the optimal combination of capacitor sizes for such a waveform., Methods and Results: Eight full-discharge (95/95% tilt), biphasic waveforms produced by several combinations of phase-1 capacitors (30, 60, and 90 microF) and phase-2 capacitors (1/3, 2/3, and 1.0 times the phase-1 capacitor) were tested and compared to a single-capacitor waveform (120 microF, 65/65% tilt) in a pig ventricular fibrillation model (n = 12, 23+/-2 kg). In the full-discharge waveforms, phase-2 peak voltage was equal to phase-1 peak voltage. Shocks were delivered between a right ventricular lead and a left pectoral can electrode. E50s and V50s were determined using a ten-step Bayesian process. Full-discharge waveforms with phase-2 capacitors of < or =40 microF had the same E50 (6.7+/-1.7 J to 7.3+/-3.9 J) as the single-capacitor truncated waveform (7.3+/-3.7 J), whereas waveforms with phase-2 capacitors of > or =60 microF had an extremely high E50 (14.5+/-10.8 J or greater, P < 0.05). Moreover, of the former set of energy-efficient waveforms, those with phase-1 capacitors of > or =60 microF additionally exhibited V50s that were equivalent to the V50 of the single-capacitor waveform (344+/-65 V to 407+/-50 V vs 339+/-83 V)., Conclusion: Defibrillation efficacy can be maintained in a full-discharge, two-capacitor waveform with the proper choice of capacitors.

We report on a 9-year-old boy with a rare rearranged Y chromosome and borderline short stature (-2.0 SD). Standard metaphase chromosome analysis indicated a 46,X,i(Y)(q1O) karyotype, but high resolution G-banding showed an asymmetric band pattern for the rearranged Y chromosome. FISH and DNA studies for a total of 15 different Y chromosomal loci or regions showed that the rearranged Y chromosome was accompanied by: 1) a partial deletion of the short arm pseudoautosomal region (PAR1) involving SHOX, with the breakpoint distal to DXYS85; and 2) a partial duplication of Yq, with the breakpoint proximal to DAZ. The karyotype was determined as 46,X,?i(Y)(q1O).ish der(Y)(Yqter--> Yp11.3::Yq11.2-->Yqter)(DAZ++,DYZ3+,SRY +, SHOX-). The X chromosome and the autosomes were normal. The results suggest that haploinsufficiency of SHOX is primarily responsible for the borderline short stature, and that the deletion of the PAR1 may result in spermatogenic failure due to defective X-Y pairing and recombination in the PAR1.

We report on an 18-month-old Japanese girl with 46,XX,del(22)(q13.1q13.2). To our knowledge, this is the first report of a case of interstitial deletion of a 22q13.1-q13.2 segment. Clinical features included hearing loss accompanied by inner ear anomalies, hypotonia and minor anomalies, such as a long philtrum, full eyelids, epicanthus, left transverse palmar crease and psychomotor developmental delay. Despite the chromosomal deletion, her physical growth was accelerated: her height was between the 75th and 90th percentiles for her age. Her brain MRI showed signs of delayed myelination. The three-dimensional MRI of the inner ear showed abnormalities of the cochlea and vestibule in both ears. Clinical features of the patient are similar to those of a patient with a del(22)(q13.1q13.33) karyotype previously reported by Romain et al.

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.

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 microF, 70% tilt), B1 (60/60 microF, 70% tilt/3 ms pulse width), and B2 (60/20 microF, 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 often defibrillation 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.

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.

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.

Objective: To study the interaction between salicylate and class 1 antiarrhythmic agents., Methods: The effects of salicylate on class 1 antiarrhythmic agent-induced tonic and phasic block of the Na+ current (INa) of ventricular myocytes and the upstroke velocity of the action potential (Vmax) of papillary muscles were examined by both the patch clamp technique and conventional microelectrode techniques., Results: Salicylate enhanced quinidine-induced tonic and phasic block of INa at a holding potential of -100 mV but not at a holding potential of -140 mV; this enhancement was accompanied by a shift of the hinfinity curve in the presence of quinidine in a further hyperpolarized direction, although salicylate alone did not affect INa. Salicylate enhanced the tonic and phasic block of Vmax induced by quinidine, aprindine and disopyramide but had little effect on that induced by procainamide or mexiletine; the enhancing effects were related to the liposolubility of the drugs., Conclusions: Salicylate enhanced tonic and phasic block of Na+ channels induced by class 1 highly liposoluble antiarrhythmic agents. Based on the modulated receptor hypothesis, it is probable that this enhancement was mediated by an increase in the affinity of Na+ channel blockers with high lipid solubility to the inactivated state channels.

The inhibitory effects of amlodipine besilate (CAS 11470-99-6) on the native Na+ current (INa) and cloned human cardiac Na+ channel alpha subunit (hH1) were studied by whole cell patch clamp techniques. Amlodipine produced tonic block of INa in a concentration- and holding potential (HP)-dependent manner with hyperpolarization of H infinity. Amlodipine produced phasic blockade of INa, which was dependent on HP and pulse duration. Amlodipine produced tonic blockade of hH1 in a concentration-dependent manner with 1 : 1 stoichiometry, and phasic blockade of hH1 which was dependent on the pulse duration. Amlodipine blocked INa in a voltage- and frequency-dependent manner via affinity to the resting as well as inactivated conformations of the alpha subunit.

Introduction: A single lead active can configuration has been widely used in patients with life-threatening ventricular arrhythmias. Occasionally, however, such a defibrillation lead configuration may not achieve adequate defibrillation threshold (DFT). The purpose of this study was to determine whether addition of a left ventricular (LV) lead can improve defibrillation efficacy., Methods and Results: Three transvenous defibrillation leads (8.3-French with a 5-cm long unipolar coil) were placed in the right ventricle (RV), LV, and superior vena cava (SVC), along with an active can (92 cm2) in the left subpectoral area. The DFT stored energy of seven combinations of these defibrillation leads were compared in a pig ventricular fibrillation model using a biphasic defibrillation waveform (125 microF, 6.5/3.5 msec). A biventricular leads active can configuration in which the RV and LV leads were of the same polarity reduced the DFT stored energy by approximately 35% when compared to a single RV lead active can configuration (9.6 +/- 3.0 J vs 15.0 +/- 7.2 J, respectively, P = 0.02). Moreover, adding a SVC lead further reduced the DFT energy (8.4 +/- 3.3 J)., Conclusion: A biventricular leads active can configuration can significantly improve defibrillation efficacy as compared to a single lead active can configuration. In such a defibrillation lead configuration, the polarity of RV and LV leads should be the same.

Spontaneous remission of Graves' disease with a decrease of thyroid stimulating antibody (TSAb) activity is commonly observed in pregnancy. In this article, however, a Graves' patient who developed primary hypothyroidism with an appearance of thyroid stimulation-blocking antibody (TSBAb) activity in late pregnancy is reported. A 25-year-old woman presented with clinical and biochemical hyperthyroidism with an elevation of 99mTcO4- thyroid uptake (4.7%; normal range, 0.7%-3.0%) and mildly elevated activity of thyrotropin-binding inhibitory immunoglobulin (TBII; 30.4%). She was euthyroid with normal TBII (8.0%) and TSAb (126%) before pregnancy, when the patient was taking a 5-mg daily dose of methimazole (MMI). MMI was stopped by the patient when she became pregnant. Subsequently, the patient progressed into primary hypothyroidism with a marked elevation of TBII activity (78.4%) in the third trimester of the pregnancy (at that time, TSAb activity was not detected). TSBAb measured 2 weeks later was detected at the activity of 85.0%. Replacement therapy was initiated with levothyroxine (LT4) (0.05-0.1 mg/day), which was discontinued on the 55th day postpartum because of the onset of mild thyrotoxicosis followed by short-term euthyroid state despite high TSBAb activity. Subsequently, because the patient developed primary hypothyroidism 5 months after delivery, replacement therapy with LT4 (0.1-0.125 mg/day) was readministered. Thus, it is suggested that the development of hypothyroidism with the appearance of TSBAb in Graves' patients can occur even in late pregnancy.

The objective of this study was to determine whether graded isoproterenol infusion test identifies a specific hypersensitivity response of the LV diastolic relaxation properties in nonpheochromocytoma patients with paroxysmal symptoms of hyperadrenergic surges. We hypothesized that patients with hyperadrenergic surges, not due to pheochromocytoma, have hypersensitivity of cardiac beta-adrenergic receptor responses to exogenous catecholamines, resulting in enhancement of LV relaxation. We assessed the physiological beta 1 and beta 2 receptor responsiveness to graded isoproterenol infusion (0.01, 0.02, 0.03 and 0.04 microgram/kg per min) in 32 patients presented with hyperadrenergic surges not due to pheochromocytoma. Two major observations were made. First, systemic hemodynamic evaluation using 99m Technetium first pass method revealed hyperkinetic state only in 21 patients (20 females and 1 male; aged 31 +/- 9 years); the other 11 patients were without hyperkinetic circulatory state (10 females and 1 male; aged 41 +/- 9 years). At baseline, plasma catecholamines were not significantly different between the two groups. The baseline corrected LV peak filling and ejection rates (cPFR and cPER) were significantly higher in hyperkinetic group (cPFR: 10 +/- 2 vs 8 +/- 2 x 10(-2) Hz/ms, P = 0.03; cPER: 11 +/- 2 vs 8 +/- 1 x 10(-2) Hz/ms, P = 0.002) and their baseline HR was faster (85 +/- 16 vs 70 +/- 9 beats/min, P = 0.006). Second, the cardiac and vascular responses to isoproterenol infusion were compared between these two groups. During the graded isoproterenol infusion, the response of HR, systolic, and diastolic BP were not significantly different between the two groups at all doses of isoproterenol, but cPFR and cPER had a more marked response to the lowest dose of 0.01 mg/kg per min in the hyperkinetic group. Thus, the graded isoproterenol infusion test can differentiate between two groups of nonpheochromocytoma patients presenting with paroxysmal symptoms of hyperadrenergic surges. Only patients with baseline hyperkinetic hemodynamic profile had accentuated cardiac hyperresponsiveness to a low dose of isoproterenol. We concluded that cPFR and cPER is a more sensitive index to assess the response to isoproterenol, because of metabolic determinants affecting the rate of change in LV volume.

Background: Biphasic waveforms have been reported to be more efficacious than monophasic waveforms for external defibrillation. This study examined the optimal phase-1 tilts and phase-2 leading-edge voltages with small capacitors (60 and 20 microF) for external defibrillation. We also assessed the ability of the "charge-burping" model to predict the optimal waveforms., Methods and Results: Two groups of studies were performed. In group 1, 9 biphasic waveforms from a combination of 3 phase-1 tilt values (30%, 50%, and 70%) and 3 phase-2 leading-edge voltage values (0.5, 1.0, and 1.5 times the phase-1 leading-edge voltage, V1) were tested. Phase-2 pulse width was held constant at 3 ms in all waveforms. Two separate 60- microF capacitors were used in each phase. The energy value that would produce a 50% likelihood of successful defibrillation (E50) decreased with increasing phase-1 tilt and increased with increasing phase-2 leading-edge voltage except for the 30% phase-1 tilt waveforms. In group 2, 9 waveforms were identical to the waveforms in group 1, except for a 20- microF capacitor for phase 2. E50 decreased with increasing phase-1 tilt. Phase-2 leading-edge voltage of 1.0 to 1.5 V1 appeared to minimize E50 for phase-1 tilt of 50% and 70% but worsened E50 for phase-1 tilt of 30%. There was a significant correlation between E50 and residual membrane voltage at the end of phase 2, as calculated by the charge-burping model in both groups (group 1, R2=0.47, P<0.001; group 2, R2=0.42, P<0.001)., Conclusions: The waveforms with 70% phase-1 tilt were more efficacious than those with 30% and 50%. The relationship of phase-2 leading-edge voltage to defibrillation efficacy depended on phase-2 capacitance. The charge-burping model predicted the optimal external biphasic waveform.

The purpose of this study was to examine the anatomic relationship between the mitral annulus (MA) and the coronary sinus (CS). Fifty consecutive hearts of 31 men and 19 women, 63.5 +/- 13.7 years of age, were examined at autopsy. MA was divided perpendicularly to the annular plane into an anteromedial block and a posterolateral block by sectioning from the CS ostium through the center of MA. The posterolateral block was subdivided radially into five equal sections at 36 degrees, 72 degrees, 108 degrees, 144 degrees, and 180 degrees. The distance from the ventricular endocardium under MA to the nearest wall of CS (D) was measured in each cross-section. D measured 9.7 +/- 2.3, 10.9 +/- 3.3, 10.2 +/- 3.6, 9.2 +/- 3.4, and 8.2 +/- 2.9 mm at 36 degrees, 72 degrees, 108 degrees, 144 degrees, and 180 degrees, respectively. D at 72 was significantly longer than at 144 degrees and 180 degrees (P < 0.01). Likewise, D at 108 degrees was significantly longer than at 144 degrees and 180 degrees (P < 0.05). The population was divided according to the morphology into five patterns. "Type C," the pattern that separated in the middle section and then reapproximated, was more common (66%) than any other pattern. D was confirmed to be longest at the level of the 72 degrees section, corresponding to a left posterolateral free-wall location. The potential mapping in CS would be easily modified by this anatomic feature. When mapping activation from the CS, the electrophysiological data should be interpreted in light of these anatomic findings.

We evaluated the renal handling of urate in 12 Japanese renal hypouricemia patients, and studied the relationship between the renal handling of urate and the urinary pH. The patients were classified into the 4 subtypes of renal hypouricemia: (defective presecretory reabsorption (Pre), defective postsecretory reabsorption (Post), enhanced tubular secretion (Secretion), and defective presecretory and postsecretory reabsorption (Pre&Post) as based on a pharmacological test. Seven patients showed acid urine with a urinary pH of less than 5.9, although this was not accompanied by any abnormality of blood pH, partial pressure of carbon dioxide (PaCO2), or blood HCO3-. The urinary pH in the morning significantly correlated with the ratio of urate clearance to creatinine clearance in the morning, whereas the urinary urate concentration in the morning did not correlate with the urinary pH in the morning. In the Pre&Post patients, the urate excretion was higher and the urinary pH was more acidic compared to the other subtypes. The administration of K+-, Na+-citrate significantly alkalized the urinary pH in the patients with renal hypouricemia. These results suggest that the acidic urine was significantly related to the Pre&Post subtype of renal hypouricemia with the higher urate excretion, and that this subtype might be a risk factor for complications in renal hypouricemia. The alkalization of urine might be a useful treatment for the complication of renal hypouricemia.

We performed radiofrequency current catheter ablation in a patient with idiopathic LV. While mapping the inferoapical LV septum during tachycardia, spontaneous termination of tachycardia was observed with block between Purkinje (P) potential and ventricular electrogram (P-V block). The cycle length of the tachycardia was associated with prolongation of P-P interval and P-V interval. P potential recording at this site was earliest and at very low amplitude during tachycardia. The radiofrequency current at this site was successful. These findings indicated that Purkinje fiber was a critical part of the tachycardia circuit. Ablation was successful at a site where both an earliest and low amplitude P potential was recorded during tachycardia, and where P-V block that was induced by catheter manipulation was observed during tachycardia.

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 beta-receptors to catecholamines in patients with vasovagal syncope may be suggested but needs to be tested.

The unc-51 gene, isolated from mutants of Caenorhabditis elegans exhibiting abnormal axonal extension and growth, encodes a novel serine/threonine kinase (K. Ogura, et al., 1994, Genes Dev. 8: 2389-2400). Here we report the molecular cloning and characterization of the human homologue of UNC-51, designated ULK1, for UNC-51 (C. elegans)-like kinase 1. Sequence analysis of the human ULK1 cDNA showed that an open reading frame is composed of 1050 amino acids with a calculated MW of 112.6 kDa and a pI of 8.80. Homology search analysis showed that ULK1 has 41% overall similarity to UNC-51 and 29% similarity to Apg1p of Saccharomyces cerevisiae. Phylogenetic analysis of ULK1, UNC-51, and Apglp suggested that they constitute a novel subfamily of serine/threonine kinases. Southern blot analyses suggested that the ULK1 gene spans 30-40 kb in the human genome as a single-copy gene. Zoo blot analysis indicated that ULK1 kinase is conserved among vertebrates including mammals, birds, reptiles, amphibians, and fish. Northern blot analysis revealed that ULK1 is ubiquitously expressed in adult human tissues such as skeletal muscle, heart, pancreas, brain, placenta, liver, kidney, and lung, whereas UNC-51 is specifically detected in the nervous system of C. elegans. Both FISH and RH mapping confirmed the regional localization of ULK1 to human chromosome 12q24.3., (Copyright 1998 Academic Press.)

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) may alter 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 +/- 10 g). Pigs were intubated with a cuffed endotracheal tube and ventilated through a Drager SAV respirator 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 omega, and 39.3 +/- 3.6 omega, 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.

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.