Identification of constrained sequence elements across 239 primate genomes.

Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3-9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.

The landscape of tolerated genetic variation in humans and primates.

Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.

The landscape of tolerated genetic variation in humans and primates.

Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole genome sequencing data for 809 individuals from 233 primate species, and identified 4.3 million common protein-altering variants with orthologs in human. We show that these variants can be inferred to have non-deleterious effects in human based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases. One Sentence Summary: Deep learning classifier trained on 4.3 million common primate missense variants predicts variant pathogenicity in humans.

Bilateral vestibulopathy and disabling vertigo: A CARE case series.

INTRODUCTION: The term bilateral vestibulopathy (BV) was recently defined by the Bárány Society. Loss of otolith function was not included in their criteria. Although spontaneous progression to complete bilateral impairment of vestibular function is expected, it is unlikely that patients with advanced BV will continue to present episodes of intense vertigo. Here, following CARE case report guidelines, we report the case of patients meeting the criteria for BV and still disabled by vertigo. CASE SERIES: Three patients evaluated in our department meeting the Bárány criteria for definite BV but still complaining of disabling rotatory vertigo were included. All underwent clinical and instrumental vestibular examination. The observations are reported. CONCLUSION: In case of BV, the conservation of a stable otolithic reference frame could allow patients to optimize postural strategy. It would be useful to revisit a classification of BV by stages, by introducing an evaluation of otolithic function and postural control for possible subsequent vestibular implantation.

Anesthesia for Ambulatory Pediatric Surgery in Sub-Saharan Africa: A Pilot Study in Burkina Faso.

BACKGROUND: Long surgical wait times and limited hospital capacity are common obstacles to surgical care in many countries in Sub-Saharan Africa (SSA). Introducing ambulatory surgery might contribute to a solution to these problems. The purpose of this study was to evaluate the safety and feasibility of introducing ambulatory surgery into a pediatric hospital in SSA. METHODS: This is a cross-sectional descriptive study that took place over 6 months. It includes all patients assigned to undergo ambulatory surgery in the Pediatric University Hospital in Ouagadougou, Burkina Faso. Eligibility criteria for the ambulatory surgery program included >1 year of age, American Society of Anesthesiologists (ASA) 1 status, surgery with a low risk of bleeding, lasting <90 minutes, and with an expectation of mild to moderate postoperative pain. The family had to live within 1 hour of the hospital and be available by telephone. RESULTS: During the study period, a total of 1250 patients underwent surgery, of whom 515 were elective cases; 115 of these met the criteria for ambulatory surgery; 103 patients, with an average age of 59.74 ± 41.57 months, actually underwent surgery. The principal indications for surgery were inguinal (62) and umbilical (47) hernias. All patients had general anesthesia with halothane. Sixty-five percent also received regional or local anesthesia consisting of caudal block in 79.23% or nerve block in 20.77%. The average duration of surgery was 33 ± 17.47 minutes. No intraoperative complications were noted. All the patients received acetaminophen and a nonsteroidal anti-inflammatory drug in the recovery room. Twelve (11.7%) patients had complications in recovery, principally nausea and vomiting. Eight (7.8%) patients were admitted to the hospital. CONCLUSIONS: No serious complications were associated with ambulatory surgery. Its introduction could possibly be a solution to improving pediatric surgical access in low-income countries.

Choking under monitoring pressure: being watched by the experimenter reduces executive attention.

Performing more poorly given one's skill level ("choking") is likely in situations that offer an incentive if a certain outcome is achieved (outcome pressure) or when one is being watched by others-especially when one's performance is being evaluated (monitoring pressure). According to the choking literature, outcome pressure is associated with reduced executive control of attention, whereas monitoring pressure is associated with increased, yet counterproductive, attention to skill processes. Here, we show the first evidence that monitoring pressure-being watched by the experimenter-may lead individuals with higher working memory to choke on a classic measure of executive control-just the task effect thought to result from outcome pressure. Not only does this finding help refine our understanding of the processes underlying choking under monitoring pressure, but it also leads to a new look at classic audience effects, with an important implication for experimental psychology.

Arrhythmia and thyroid dysfunction.

CONTEXT: Arrhythmia is a major cause of morbidity and mortality in Europe and in the United States. The aim of this review article was to assess the results of the prospective studies that evaluated the risk of arrhythmia in patients with overt and subclinical thyroid disease and discuss the management of this arrhythmia. EVIDENCE ACQUISITION: A literature search was carried out for reports published with the following terms: thyroid, hypothyroidism, hyperthyroidism, subclinical hyperthyroidism, subclinical hypothyroidism, levothyroxine, triiodothyronine, antithyroid drugs, radioiodine, deiodinase, atrial flutter, supraventricular arrhythmia, ventricular arrhythmia, ventricular tachycardia, ventricular fibrillation, torsade de pointes, amiodarone and atrial fibrillation. The investigation was restricted to reports published in English. EVIDENCE ANALYSIS: The outcome of this analysis suggests that patients with untreated overt clinical or subclinical thyroid dysfunction are at increased risk of arrhythmia. Hyperthyroidism increased atrial arrhythmia; however, hypothyroidism increased ventricular arrhythmia. CONCLUSION: The early recognition and effective treatment of thyroid dysfunction in patients with arrhythmia is mandatory because the long-term prognosis of arrhythmia may be improved with the appropriate treatment of thyroid dysfunction.

Efficacy of signal-averaged electrocardiography in the young orthotopic heart transplant patient to detect allograft rejection.

Endomyocardial biopsy is the gold standard survey for cardiac graft rejection. Signal-averaged electrocardiography (SAECG) identifies slowly conducting, diseased myocardium. We sought to determine whether SAECG is a sensitive, noninvasive transplant surveillance method in the young.Ninety-four SAECGs recorded prior to biopsy in 20 young transplant (OHT) patients and those from 15 healthy age-matched controls (CTL) were analyzed. In the OHT group, 56 no-rejection (NOREJ) (ISHLT grades 0 or 1 A) and 37 acute rejection (REJ) (ISHLT grades IB, 2, and 3A) SAECGs were compared, SAECGs were filtered at 40-255 Hz. Total QRS duration (QRSd), duration of terminal low amplitude of QRS under 40 microV (LAS), and root mean square amplitude of terminal 40 msec of QRS (RMS40) were compared.SAECGs were significantly different in CTL vs NOREJ but not in NOREJ vs REJ: QRSd, 81.7 +/- 8, 107.2 +/- 18.4, and 112.3 +/- 21.6 msec, respectively; LAS, (18 +/- 5.8, 23.6 +/- 10.7, and 27 +/- 14.8 msec, respectively; and RMS40, (169.3 +/- 100.4, 68 +/- 48.8, and 57.5 +/- 45.6 microV, respectively. Children following OHT exhibited significant differences in the SAECG compared to controls. Differences between the NOREJ and REJ groups were negligible. Therefore, SAECG may not be effective in detecting OHT rejection in the young.

Chronic asymptomatic contralateral wrist scapholunate dissociation.

BACKGROUND: The authors report a series of six patients who presented with scapholunate dissociation, with no significant contralateral antecedent trauma and no rheumatoid arthritis or congenital ligamentous laxity. Such patients may present with pain or a snapping/popping sensation in one wrist, undergo radiographs of both wrists, and are discovered to have scapholunate gapping bilaterally. The literature contains few reports of this condition, and this series of six is a relatively large one for this infrequently reported condition. METHODS: The six charts were reviewed retrospectively; each patient was asked to return for follow-up and radiographic examination and each participated in a telephone questionnaire about pain, activity changes, new treatments, and exacerbation of wrist problems. The average follow-up was 39 months, with a range of 6 months to 13.5 years. RESULTS: One patient with severe unilateral instability and persistent pain underwent soft-tissue surgical repair (Blatt reconstruction); another demonstrated unilateral dorsal intercalated segment instability with moderate pain symptoms but declined surgical reconstruction. The other 10 wrists, despite radiographically demonstrated widened scapholunate angles and rotatory subluxation of the scaphoid, had mild or no pain and no dorsal intercalated segment instability deformity. CONCLUSIONS: The evolution of the bilateral form of scapholunate dissociation seems to be benign unless dorsal intercalated segment instability deformity is present, which may then rapidly progress to degenerative arthritis and scapholunate advanced collapse wrist. Severe or minor repetitive trauma, inflammation, infection, tumors, and congenital ligamentous laxity have been etiologically implicated in scapholunate dissociation. The natural history of scapholunate dissociation involves volar rotation of the scaphoid and dorsal rotation of the lunate, progressing to malalignment and eventual arthrosis between the scaphoid and radius, the capitate and lunate, and the lunate and hamate bones.

A MULTICHANNEL FIBER-OPTIC MAPPING SYSTEM FOR INTRAMURAL RECORDING OF CARDIAC ACTION POTENTIALS.

Measuring cardiac action potentials at many sites within the ventricular wall is important for understanding cardiac arrhythmias; however, recording in the depth of the heart wall presents many difficulties. We have developed a multichannel optical mapping system for recording cardiac action potentials transmurally. Each channel uses a single small-diameter optical fiber to transmit and collect light from the cardiac tissue. Excitation light is supplied by low-power green lasers. Wavelength separation is performed with a dichroic mirror, and fluorescence is detected with a photodiode. We have recorded action potentials with an unfiltered signal-to-noise ratio (SNR) as high as 60:1 and a temporally filtered SNR as high as 200:1. The collection of fluorescence is optimized so that low excitation light intensity can be used, which increases the available recording time. Channels are modular and compact, and the system can be easily expanded to include additional channels, ratiometry or dual-dye mapping. In addition, the system is highly flexible and can be used for virtually any experiment from single cell recording to surface and transmural mapping of the whole heart.

Marginal adaptation of class II resin composite restorations using incremental and bulk placement techniques: an ESEM study.

This in vitro study compared marginal gap formation in class II resin composite restorations. Forty caries-free extracted molars were prepared in a standardized manner for class II restoration by one of four methods: bulk- or incrementally-placed light-activated resin composite (Amelogen), and bulk- or incrementally-placed chemically activated composite (Rapidfill). The restored teeth, after finishing and polishing, and thermocycling, were examined using environmental scanning electron microscopy. Marginal gap measurements at predetermined facial and lingual margin sites showed no significant differences between the two sites within any of the groups. Both the light- and the chemically-activated restorations showed no significant differences in mean marginal gap sizes whether they were placed by incremental or bulk techniques. Amelogen restorations placed by both methods had significantly larger margin gaps than those of each of the Rapidfill groups (P<0.05). Thus, although method of placement of a given material had no significant effect on the quality of marginal adaptation, both of the chemically activated resin composite restorations produced significantly smaller marginal gaps than both the bulk- and incrementally-placed light-activated composites.

Real-time three-dimensional intracardiac echocardiography.

Using catheter-mounted 2-D array transducers, we have obtained real-time 3-D intracardiac ultrasound (US) images. We have constructed several transducers with 64 channels inside a 12 French catheter lumen operating at 5 MHz. The transducer configuration may be side-scanning or beveled, with respect to the long axis of the catheter lumen. We have also included six electrodes to acquire simultaneous electrocardiograms. Using an open-chest sheep model, we inserted the catheter into the cardiac chambers to study the utility of in vivo intracardiac 3-D scanning. Images obtained include a cardiac four-chamber view, mitral valve, pulmonic valve, tricuspid valve, interatrial septum, interventricular septum and ventricular volumes. We have also imaged two electrophysiological interventional devices in the right atrium, performed an in vitro ablation study, and viewed the pulmonary veins in vitro.

Effect of pacing site on ventricular fibrillation initiation by shocks during the vulnerable period.

The critical point hypothesis for the upper limit of vulnerability (ULV) states that the site of S1 pacing should not affect the ULV S2 shock strength for a single S2 shock electrode configuration but may affect the S1-S2 interval at which sub-ULV shocks induce ventricular fibrillation (VF). Furthermore, early post-S2 activations leading to VF should arise in areas with low potential gradients of similar magnitude, regardless of the S1 site. This hypothesis was tested in 10 pigs by determining ULVs for three S1 sites [left ventricular apex (LVA), LV base (LVB), and right ventricular outflow tract (RVOT)] with one S2 configuration (LVA patch to superior vena cava catheter). T-wave scanning was performed with biphasic S2 shocks incremented from 60 V in 40-V steps and stepped up or down in 20- and 10-V steps. Activations and S2 potential gradients were recorded at 528 epicardial sites. Although shocks just below the ULV induced VF significantly earlier in the T wave when the S1 site was the RVOT than when it was the LVA or LVB, ULVs were not significantly different for the three S1 pacing sites. Early post-S2 activations arose closer to the S2 electrode for weak S2s but moved to distant low potential gradient areas as the S2 strengthened. Just below the ULV, early post-S2 activations arose in the RVOT when the S1 site was the LVA or LVB but arose along the RV base when the S1 site was the RVOT. Early site potential gradients were not significantly different just below the ULV (LVA: 8.2 +/- 4.1 V/cm; LVB: 8.6 +/- 4. 9 V/cm; RVOT: 8.7 +/- 4.4 V/cm). At the ULV, early post-S2 activations arose from the same areas but did not induce VF. The results support the critical point hypothesis for the ULV. For this S2 configuration, no single point in the T wave could be used to determine the ULV for all S1 sites.

Haemodynamic response to an isometric exercise test in obese patients: influence of autonomic dysfunction.

OBJECTIVE: To investigate blood pressure (BP) and heart rate (HR) responses to an isometric exercise test in obese non diabetic patients and to correlate the results with vagal function and plasma insulin concentration. SUBJECTS: 63 obese patients, 36 of whom had abnormal cardiac parasympathetic control (PS+), and 35 healthy control subjects. METHODS: Analysis of HR variations during three standardized tests: deep-breathing, lying-to-standing and Valsalva. Isometric contraction (handgrip) for 5 min. RESULTS: In the PS+ obese patients, resting HR and body mass index (BMI) were significantly higher than in the PS- subjects and there was a trend to higher plasma insulin concentrations. Age-matched comparison showed that during the handgrip test, the increase in HR at the first minute was significantly higher in the PS- obese patients than in the controls. The increase in BP was significantly lower in the PS+ obese patients than in age-and-BMI-matched PS- obese patients. CONCLUSION: These data suggest that 1) there is an increase in cardiac vagal tone in PS- obese patients, since the early increase in HR at 1 min of the handgrip test, results from the withdrawal of vagal tone; 2) BP response to an isometric contraction is impaired in PS+ obese patients due to a lower sympathetic activation; 3) high plasma insulin concentrations may also contribute to limiting the BP response; and 4) autonomic disorders may account for alterations in the haemodynamic changes during exercise.

Nitric oxide regulation of gene transcription via soluble guanylate cyclase and type I cGMP-dependent protein kinase.

Nitric oxide (NO) regulates the expression of multiple genes but in most cases its precise mechanism of action is unclear. We used baby hamster kidney (BHK) cells, which have very low soluble guanylate cyclase and cGMP-dependent protein kinase (G-kinase) activity, and CS-54 arterial smooth muscle cells, which express these two enzymes, to study NO regulation of the human fos promoter. The NO-releasing agent Deta-NONOate (ethanamine-2,2'-(hydroxynitrosohydrazone)bis-) had no effect on a chloramphenicol acetyltransferase (CAT) reporter gene under control of the fos promoter in BHK cells transfected with an empty vector or in cells transfected with a G-kinase Ibeta expression vector. In BHK cells transfected with expression vectors for guanylate cyclase, Deta-NONOate markedly increased the intracellular cGMP concentration and caused a small (2-fold) increase in CAT activity; the increased CAT activity appeared to be from cGMP activation of cAMP-dependent protein kinase. In BHK cells co-transfected with guanylate cyclase and G-kinase expression vectors, CAT activity was increased 5-fold in the absence of Deta-NONOate and 7-fold in the presence of Deta-NONOate. Stimulation of CAT activity in the absence of Deta-NONOate appeared to be largely from endogenous NO since we found that: (i) BHK cells produced high amounts of NO; (ii) CAT activity was partially inhibited by a NO synthase inhibitor; and (iii) the inhibition by the NO synthase inhibitor was reversed by exogenous NO. In CS-54 cells, we found that NO increased fos promoter activity and that the increase was prevented by a guanylate cyclase inhibitor. In summary, we found that NO activates the fos promoter by a guanylate cyclase- and G-kinase-dependent mechanism.

Influence of parasympathetic dysfunction and hyperinsulinemia on the hemodynamic response to an isometric exercise in non-insulin-dependent diabetic patients.

The handgrip test has long been used as a test for investigating cardiac autonomic neuropathy in diabetic patients. However, the factors involved in the hemodynamic response to the handgrip test have not been thoroughly studied. The aim of this study was to investigate blood pressure (BP) and heart rate (HR) responses to an isometric test in non-insulin-dependent diabetics (NIDDs) and to correlate the results with vagal function evaluated by three standardized tests and with plasma insulin levels. Fifty-five NIDDs, 35 of whom had one to three abnormal parasympathetic tests (PS+), were compared with 10 healthy control subjects. Fasting and postprandial plasma insulin levels were significantly higher in the PS+ than in the PS- patients. Resting HR correlated significantly with log fasting and postprandial insulin. In PS+ NIDDs, resting HR was significantly higher than in PS- patients. Age-matched comparisons also showed that resting systolic BP was significantly higher in PS+ patients than in controls. In PS- patients, the mean acceleration of HR was significantly higher than in the control group from the second to the fifth minute, and the BP response was also higher than in controls. These data suggest that (1) sympathetic response to an isometric exercise is increased in PS- NIDDs; (2) cardiac parasympathetic dysfunction is associated with a more severe insulin resistance; and (3) the subsequent higher plasma insulin level may contribute to the increase in resting HR and BP through sympathetic activation while limiting the hemodynamic response to an isometric exercise through its vasodilative effect.

Influence of epicardial patches on defibrillation threshold with nonthoracotomy lead configurations.

BACKGROUND: In previous studies, epicardial patch electrodes decreased transthoracic defibrillation efficacy. We studied the effects of two inactive epicardial 14-cm2 titanium mesh patches on defibrillation energy requirements with nonthoracotomy internal lead configurations. METHODS AND RESULTS: A 6/6-millisecond biphasic shock wave-form was delivered via several electrode configurations 10 seconds after ventricular fibrillation was initiated with a 60-Hz generator. In two series, a total of 16 dogs (weight, 23.3 +/- 2.4 kg) underwent an up-down defibrillation protocol. In the first series, the defibrillation threshold (DFT) was determined for each electrode configuration in the presence of two inactive epicardial patches. In the second series, DFTs were determined in the presence of an inactive right ventricular (RV) or left ventricular (LV) patch alone. For several nonthoracotomy lead configurations tested in the first 8 dogs, the mean +/- SD DFT energy increased 49% to 97% with two inactive patches on the heart compared with no patches on the heart as follows: RV to superior vena caval (SVC) electrode, from 8.9 +/- 2.6 to 18.0 +/- 14.3 J; RV to SVC plus subcutaneous array electrode, from 7.0 +/- 2.4 to 10.7 +/- 5.3 J; RV to subcutaneous pectoral plate electrode, from 6.2 +/- 1.3 to 11.4 +/- 4.0 J (P < or = .05). The lowest DFT was achieved by defibrillating between the epicardial patches (3.8 +/- 3.3 J). The second series showed that DFT voltage requirements increased significantly for all three nonthoracotomy lead configurations with the inactive LV patch alone (P < or = .05) but not with the inactive RV patch alone. CONCLUSIONS: Inactive epicardial patches can significantly increase the defibrillation energy requirements for nonthoracotomy lead configurations. This negative impact may be due to an insulating effect of the patches and to a disturbance of the potential gradient field under the patches. If the same holds true in patients, these results have clinical implications. Functioning epicardial patch leads should be incorporated in the defibrillation lead system if already present. If the LV patch is nonfunctioning, such as because of a lead fracture, the marked increase in DFT due to an inactive LV patch calls for thorough DFT testing during surgery and, in selected patients, may necessitate patch removal to produce an effective transvenous-based system.

Effect of rapid pacing and T-wave scanning on the relation between the defibrillation and upper-limit-of-vulnerability dose-response curves.

BACKGROUND: The critical-point and upper-limit-of-vulnerability (ULV) hypotheses predict that the ULV dose-response curve should be steeper and to the right of the defibrillation (DF) curve. Yet, some recent experimental data contradict this prediction. Two studies are presented that test two explanations for the contradiction: (1) Testing at a single point in the T wave underestimates the ULV dose-response curve and (2) ULV testing at normal heart rates does not mimic the mechanical or electrical state of the heart in ventricular fibrillation (VF). METHODS AND RESULTS: A nonthoracotomy lead system with a biphasic waveform was used throughout. In eight dogs, the dose-response curve widths (a measure of steepness) were compared between DF data and ULV data gathered at the peak (ULVPK), middownslope (ULVDWN), midupslope (ULVUP), and all times (scanning or ULVSCN) in the T wave. In another eight dogs, ULV data (ULVRAP) were gathered by scanning the T wave after 15 rapidly paced beats (166- to 198-ms pacing interval). The rapid pacing interval was chosen to more closely mimic the hemodynamics and activation rate of early VF. ULV data (ULVSTD) at normal heart rates were gathered for all animals. In the first study, scanning significantly reduced the ULV curve width (ULVSCN, 63.5 +/- 29.7 V; ULVPK, 81.9 +/- 45.2 V; ULVDWN, 116 +/- 36.5 V; DF, 105 +/- 22.0 V; P < .03) and significantly shifted the ULV curve to the right (ULV80 SCN, 410 +/- 62.6 V; ULV80 PK, 266 +/- 35.3 V; ULV80 DWN, 355 +/- 80.4 V; DF80, 427 +/- 60.9 V; P < .001). The subscript 80 signifies that the subject was left in normal sinus rhythm 80% of the time after that stimulus strength was delivered. In the second study, the ULVRAP curve was shifted dramatically to the right, the average ULV50 RAP being greater than the average DF90. Furthermore, 92% of the ULVRAP VF inductions occurred between 10 ms before and 50 ms after the peak of the T wave, suggesting that scanning of the entire T wave may not be necessary. CONCLUSIONS: With a single rapidly paced ULV sequence with limited T-wave scanning, it may be possible to estimate highly effective defibrillation doses with few VF episodes and high-voltage stimuli.

Predicting the potential gradient field in ventricular fibrillation from shocks delivered in paced rhythm.

A method of defibrillation threshold determination that utilizes low-strength shocks delivered in a benign rhythm would be desirable. Because the two-dimensional epicardial potential gradient (PG) is a shock parameter that is linked to defibrillation, we examined whether the epicardial PG measured for shocks delivered in paced rhythm could be used to predict the PG for defibrillation-strength shocks delivered in ventricular fibrillation (VF). In six open-chest pentobarbital-anesthetized pigs with left ventricular apex and right atrial internal defibrillation patches, we measured the epicardial PG field for shocks delivered in paced rhythm and during VF. We determined that there was a linear relationship between epicardial PG and shock strength for shocks delivered in paced rhythm. However, prediction of the PG measured for shocks in VF from those measured in paced rhythm resulted in a statistically significant overestimation of the PG in VF. We conclude that, for equivalent strength shocks, the epicardial PG field is weaker for shocks delivered in VF. This change in the potential gradient field can have an effect on defibrillation threshold estimates that are based on shocks delivered in paced rhythm.

Comparison of defibrillation probability of success curves for an endocardial lead configuration with and without an inactive epicardial patch.

OBJECTIVES: This study sought to assess the effect of passive "bystander" epicardial electrodes on defibrillation efficacy. BACKGROUND: We hypothesized that an inactive epicardial patch placed in an area of low potential gradient from an endocardial electrode shock might affect defibrillation efficacy through its effects on the shock field and the underlying potential gradient. METHODS: We studied the effects of an inactive 18-cm2 titanium mesh patch placed on the anterolateral left ventricular epicardium on the 50% probability of successful defibrillation. A biphasic shock with both phases 6 ms in duration was delivered between superior vena cava and right ventricular catheter electrodes 10 s after the electrical induction of ventricular fibrillation. Six dogs underwent an up/down defibrillation protocol randomized with or without the patch on the heart. RESULTS: Mean 50% (+/-) probability point for energy doubled with the conductive patch on the heart, from 8.0 +/- 3.2 to 16.8 +/- 7.0 J (p < 0.01), and leading-edge voltage increased from 334 +/- 64 to 477 +/- 98 V (p < 0.01). Mean 50% probability points for energy and leading-edge voltage were not significantly changed when the procedure was repeated using a nonconductive patch in another six dogs as a control group. In a saline-saturated foam model, measurements from electrodes placed around and under the patch revealed a 72% mean decrease in the potential gradient in the foam under the conductive patch. CONCLUSIONS: A passive defibrillator patch can markedly increase the energy requirements for defibrillation, probably by decreasing the potential gradient under the patch. These results suggest the use of caution when passive electrodes are present, for example, when a patient receives a nonthoracotomy defibrillator system while epicardial electrodes from a previously implanted system are left in place.