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PubMed2006

Application of a PDMS microstencil as a replaceable insulator toward a single-use planar microelectrode array.

Here we present a novel idea for a replaceable insulator, and thus advance toward the goal of a single-use planar microelectrode array (MEA) for the study of electrogenic tissues. The concept of a replaceable insulator is motivated by insulator degradation after repeated usage of an MEA. Instead of fabricating a more durable insulator for repeated MEA usage, we propose replacing the insulator and effectively producing a fresh MEA for each experiment. We chose a polydimethylsiloxane (PDMS) microstencil as a candidate for the replaceable insulator as it is biocompatible, shows reversible adhesion to surfaces, and can be easily and controllably fabricated. As a proof-of-concept, we demonstrate two applications using microstencils: the rejuvenation of an old MEA and the fabrication of a single-use MEA. These MEAs were tested with dissociated neural cell cultures and neural recordings were performed at 14 days in vitro. Inexpensive and quick supply of insulators with micrometer-sized holes provides a way of constructing an MEA that can be treated as a disposable component in high throughput cell-based biosensor applications.

Animals↗

PubMed1990

The accuracy of estimating the thermal insulation of clothing ensembles - the effect of appraisers.

The effect of the appraisers on the estimation of the thermal insulation of clothing ensembles was investigated. Nine appraisers, four experienced and five inexperienced, estimated the total thermal insulation by summing the values for individual garments. Lists of individual garments worn by workers were given during thermal comfort measurements carried out in shops and stores during one winter and summer. The beginners estimated the thermal insulation as accurately as the experienced appraisers. There were, however, great individual differences, for which three main reasons were found. Interpolation between the insulation provided by two garments was insufficient, and the insulation of these garments should be checked in more precise tables. Classification of the garments into heavy, medium and light clothing items was not adequate, and garments not listed by the workers confused the estimation given by different appraisers. The effect of error in thermal insulation on the PMV index is negligible if more than one appraiser estimates the thermal insulation and the mean of the estimates is used.

Journal Article↗

PubMed1987

Immunologic studies of subjects with asthma exposed to formaldehyde and urea-formaldehyde foam insulation (UFFI) off products.

There has been concern in recent years as to the health hazards of exposure to potentially carcinogenic or immunotoxic substances in the environment. This study was done to determine the effects of exposure to urea-formaldehyde foam insulation (UFFI) off products on various hematologic and immunologic parameters in subjects with asthma: complete blood count and differential, erythrocyte sedimentation rate, lymphocyte subpopulations (E-rosetting, T3, T4, T8, B73.1, and Fc receptor positive lymphocytes and large granular lymphocytes), lymphocyte response to phytohemagglutinin and formalin-treated red blood cells (Form-RBC), serum antibody against the Thomsen-Friedenreich RBC antigen and against Form-RBC, and natural killer (NK), interferon (IFN)-boosted NK (IFN-NK), and antibody-dependent cell-mediated cytotoxicity. Four control subjects with asthma from conventionally insulated homes (control group) and 23 subjects with asthma from UFFI-insulated homes (home group) were exposed to placebo, formaldehyde, dust, and UFFI off gas at levels ordinarily found in UFFI-containing homes for four separate periods in an environmental chamber. Immunologic testing was carried out before the exposure series and 1 day after completion 7 days later as part of an investigation of respiratory and possible allergic effects of such exposure. Data from the UFFI-insulated home group were not significantly different from data of the normal conventionally insulated home control group for any of the variables studied, either before or after UFFI exposure. Paired t tests comparing data from each of the two groups before and after UFFI exposure demonstrated minimal but statistically significant increases in percent eosinophils and T8 positive cells in the UFFI-insulated home group only. Although NK, relative NK, and IFN-NK were normal in all groups, IFN-NK assays by use of a low concentration of alpha-interferon demonstrated a statistically significant decrease in NK response to IFN in both the control and UFFI-insulated home groups after UFFI exposure. These differences were not observed at optimum levels of IFN stimulation. These data indicate that long-term exposure to UFFI off products in the home apparently had no effect on the immunologic parameters studied. Short-term exposure resulted in minor immunologic changes in this subject population.

Antibody Formation↗

PubMed1997

Alleviation of insulitis in NOD mice is associated with expression of transgenic MHC E molecules on primary antigen-presenting cells.

Major histocompatibility complex (MHC) class II genes are important in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) both in the mouse and in man. The non-obese diabetic (NOD) mouse, which is a good model for human IDDM, has a particular MHC class II with an A complex consisting of A alpha d and the unique A beta g7 chain, as well as an absent E molecule due to a deletion in the Ea promoter region. Transgenic insertion of a functional Ea gene protects against insulitis and diabetes, but when the transgene expression is restricted to certain compartments of the immune system by deleting parts of the promoter region, the protection against insulitis is disrupted. We have analysed three promoter-mutated lines where one lacks expression on B cells and has a reduced expression on approximately 1/3 of the dendritic cells and macrophages (Sma), one lacks thymic cortical expression and has a slightly reduced B-cell expression (delta X), and one lacks expression in the thymic medulla, on macrophages, dendritic cells and about half of the B cells (delta Y). None of these lines is protected against insulitis, but Sma and delta X display a reduced intensity of insulitis, with an average of 10-15% of the islets infiltrated in each mouse, while delta Y resembles non-transgenic mice with 30-35% infiltrated islets. Bone-marrow chimeras between Sma and delta Y mice demonstrate that peripheral cells of Sma origin reduce insulitis significantly when developed in the delta Y host, while insulitis is enhanced when delta Y bone marrow is given to Sma mice. This shows that E expression on the primary antigen-presenting macrophages and dendritic cells is of crucial importance to the alleviation of insulitis.

Animals↗

PubMed2003

An endogenous suppressor of hairy-wing insulator separates regulatory domains in Drosophila.

Insulators define independent domains of gene function throughout the genome. The Drosophila gypsy insulator was isolated from the gypsy retrotransposon as a region that contains a cluster of binding sites for the Suppressor of Hairy-wing [Su(Hw)] protein. To study the effects of the gypsy insulator on gene expression within a single genomic domain, targeted gene replacement was used to exchange the endogenous yellow gene, located at cytological location 1A, with a set of gypsy-modified yellow genes. Replaced yellow genes carried a gypsy insulator positioned between the yellow promoter and either the upstream or the downstream tissue-specific enhancers. Whereas the gypsy insulator blocked the function of the upstream enhancers at the endogenous location, the downstream enhancers were not blocked. Investigation of the 1A region revealed two clustered Su(Hw)-binding sites downstream of the yellow gene, named 1A-2, that bind Su(Hw) in vivo and possess enhancer blocking function. We propose that interaction between 1A-2 and the gypsy insulator permits activation of yellow expression by enhancers in the neighboring achaete-scute complex, causing an apparent absence of the block of the downstream yellow enhancers. Based on these data, we suggest that 1A-2 is an endogenous Su(Hw) insulator that separates regulatory domains within the Drosophila genome.

Animals↗

PubMed1982

Multiple low-dose streptozotocin-induced hyperglycemia and insulitis in C57BL mice: influence of inbred background, sex, and thymus.

Insulin-dependent diabetes induced in susceptible strains of mice by multiple, low-dose streptozotocin treatment has been proposed to entail a thymus-dependent, autoimmune destruction of beta cells. In this study, thymectomized and genetically athymic mice have been tested for susceptibility to streptozotocin. Thymectomy was performed on newborn (day 1) to 3-day-old C57BL/KsJ mice. At 8 wk of age, thymectomized and sham-operated mice of both sexes were tested for susceptibility to diabetes induction by multiple, low-dose streptozotocin treatment (35 mg/kg of body weight per day for 6 consecutive days). Thymectomy failed to block susceptibility of males to induction of severe hyperglycemia. Beta cell necrosis and inflammatory cell infiltrates (insulitis) were consistent histopathological features. In general, females-both thymus-intact and thymectomized-were less susceptible than males to streptozotocin-induced hyperglycemia, and females exhibited an equally severe insulitis by experimental day 14; thus, the detection of an underlying insulitis did not predict the development of a more severe hyperglycemia because most streptozotocin-treated females at experimental day 35 continued to show only a modest hyperglycemia (about 200 mg/dl) compared to males (>400 mg/dl). That streptozotocin-induced hyperglycemia could occur in the absence of an intact thymus was further demonstrated in genetically athymic C57BL/6J NIcrOu nu/nu males and thymus-intact +/? littermate controls. C57BL/6J mice were resistant to streptozotocin-induced insulitis. This study shows that the presence of insulitis does not necessarily presage onset of severe hyperglycemia (e.g., C57BL/KsJ females), and conversely, the presence of severe hyperglycemia after low-dose streptozotocin treatment is not necessarily diagnostic of an underlying insulitis (e.g., C57BL/6J +/? and nu/nu males). These data stress the need for caution in the interpretation of studies of streptozotocin-insulitis sensitivities of nude mice.

Animals↗

PubMed1983

In vitro and in vivo response after exposure to man-made mineral and asbestos insulation fibers.

The relative in vitro and in vivo toxicity of several types of manufactured fibrous glass insulation and crocidolite asbestos was investigated to aid in selection of a suitable glass fiber for subsequent use in inhalation exposures. The in vitro cytotoxicity to pulmonary alveolar macrophages of small glass fibers from microfiber insulation (count median diameter (CMD) approximately 0.1-0.2 micrometer) was greater than that of the larger fibers from household insulation (CMD approximately 2.4 micrometers). To screen for in vivo pulmonary toxicity, 2-21 mg of glass or asbestos fibers were administered in divided doses to male Syrian hamsters by intratracheal instillation. Animals were sacrificed at 1, 3.5 and 11 months following initial administration of material. One type of glass microfiber [count median diameter (CMD) approximately 0.1 micrometer] caused deaths from pulmonary edema at early times after instillation. High levels of asbestos, a second glass microfiber (CMD approximately 0.2 micrometer) and one type of household insulation fiber (CMD 2.3 micrometers) all resulted in increase in total collagen and mild pulmonary fibrosis at later times after instillation, although microfiber insulation produced a greater response than household insulation. Asbestos insulation produced the greatest response. A five-day inhalation exposure to a high level of glass microfibers deposited in lung less than 10 percent of the lowest instilled amount which elicited indications of lung injury. This amount did not produce significant biological changes at 1 to 12 months after exposure.

Animals↗

PubMed2002

A comparison of the suitabilities of rectal, gut, and insulated axilla temperatures for measurement of the circadian rhythm of core temperature in field studies.

Eight healthy males were studied for a total of 13 subject-days to assess if gut (from an ingested pill) and axilla (from a thermally insulated skin probe) temperatures would act as a substitute for rectal temperature in field studies of the circadian rhythm of core temperature. Subjects slept and went about their activities, indoors and outdoors, normally. Regular recordings (at 6 min intervals) were made of temperatures from the three sites. In addition, activity was measured (by a sensor on the nondominant wrist) so that the raw temperature data could be "purified," that is, corrected for the direct effects of sleep and activity. Inspection of the raw data indicated that there was a close parallelism between rectal and gut temperatures, but that the parallelism between rectal and insulated axilla temperatures was less reliable. This parallelism was supported by initial calculations of the correlations between rectal and gut temperatures (high and positive) and between rectal and insulated axilla (lower, though still positive) temperatures. Calculation of the limits of agreement between the parameters of the cosine curves fitted to the raw data confirmed that the rectal and gut temperatures were far closer with regard to acrophase and amplitude than were rectal and insulated axilla temperatures (-0.31 +/- 0.89 vs. +0.75 +/- 6.03 h and +0.002 +/- 0.116 vs. +0.083 +/- 0.625 degrees C, respectively). After purification of the temperature data, the limits of agreement for the cosine parameters acrophase and amplitude still indicated that there was a closer agreement between rectal and gut temperatures than between rectal and insulated axilla temperatures (-0.30 +/- 1.12 vs. +0.58 +/- 6.69 h, and +0.007 +/- 0.116 vs. +0.104 +/- 0.620 degrees C, respectively). Part of the explanation of this difference was the unreliable relationships between temperature changes in insulated axilla temperature and bursts of activity and going to bed. It is concluded that, whereas gut temperature is a viable alternativ to rectal temperature (from the viewpoints of both user acceptability and the reliability of data obtained), insulated axilla temperature, though acceptable to subjects, is unreliable from an experimental viewpoint.

Adult↗

PubMed2002

The gypsy insulators flanking yellow enhancers do not form a separate transcriptional domain in Drosophila melanogaster: the enhancers can activate an isolated yellow promoter.

The best-characterized insulator in Drosophila melanogaster is the Su(Hw)-binding region contained within the gypsy retrotransposon. In the y(2) mutant, Su(Hw) protein partially inhibits yellow transcription by blocking the function of transcriptional enhancers located distally from the yellow promoter with respect to gypsy. Previously we have shown that yellow enhancers can overcome inhibition by a downstream insulator in the y(rh1) allele, when a second gypsy element is located upstream of the enhancers. To understand how two insulators neutralize each other, we isolated various deletions that terminate in the regulatory region of the y(rh1) allele. To generate these alleles we used DNA elongation by gene conversion of the truncated chromosomes at the end of the yellow regulatory region. We found that gypsy insulator can function at the end of the truncated chromosome. Addition of the gypsy insulator upstream of the yellow enhancers overcomes the enhancer-blocking activity of the gypsy insulator inserted between the yellow enhancers and promoter. These results suggest that the gypsy insulators do not form separate transcriptional domains that delimit the interactions between enhancers and promoters.

Animals↗

PubMed2001

The gypsy insulator can act as a promoter-specific transcriptional stimulator.

Insulators define chromosomal domains such that an enhancer in one domain cannot activate a promoter in a different domain. We show that the Drosophila gypsy insulator behaves as a cis-stimulatory element in the larval fat body. Transcriptional stimulation by the insulator is distance dependent, as expected for a promoter element as opposed to an enhancer. Stimulation of a test alcohol dehydrogenase promoter requires a binding site for a GATA transcription factor, suggesting that the insulator may be facilitating access of this DNA binding protein to the promoter. Short-range stimulation requires both the Suppressor of Hairy-wing protein and the Mod(mdg4)-62.7 protein encoded by the trithorax group gene mod(mdg4). In the absence of interaction with Mod(mdg4)-62.7, the insulator is converted into a short-range transcriptional repressor but retains some cis-stimulatory activity over longer distances. These results indicate that insulator and promoter sequences share important characteristics and are not entirely distinct. We propose that the gypsy insulator can function as a promoter element and may be analogous to promoter-proximal regulatory modules that integrate input from multiple distal enhancer sequences.

Alcohol Dehydrogenase↗

PubMed2004

Human matrix attachment regions are necessary for the establishment but not the maintenance of transgene insulation in Drosophila melanogaster.

Human matrix attachment regions (MARs) can insulate transgene expression from chromosomal position effects in Drosophila melanogaster. To gain insight into the mechanism(s) by which chromosomal insulation occurs, we studied the expression phenotypes of Drosophila transformants expressing mini-white transgenes in which MAR sequences from the human apoB gene were arranged in a variety of ways. In agreement with previous reports, we found that a single copy of the insulating element was not sufficient for position-independent transgene expression; rather, two copies were required. However, the arrangement of the two elements within the transgene was unimportant, since chromosomal insulation was equally apparent when both copies of the insulator were upstream of the mini-white reporter as when the transcription unit was flanked by insulator elements. Moreover, experiments in which apoB 3' MAR sequences were removed from integrated transgenes in vivo by site-specific recombination demonstrated that MAR sequences were required for the establishment but not for the maintenance of chromosomal insulation. These observations are not compatible with the chromosomal loop model in its simplest form. Alternate mechanisms for MAR function in this system are proposed.

Animals↗

PubMed2005

Pairing between gypsy insulators facilitates the enhancer action in trans throughout the Drosophila genome.

The Suppressor of the Hairy wing [Su(Hw)] binding region within the gypsy retrotransposon is the best known chromatin insulator in Drosophila melanogaster. According to previous data, two copies of the gypsy insulator inserted between an enhancer and a promoter neutralize each other's actions, which is indicative of an interaction between the protein complexes bound to the insulators. We have investigated the role of pairing between the gypsy insulators located on homologous chromosomes in trans interaction between yellow enhancers and a promoter. It has been shown that trans activation of the yellow promoter strongly depends on the site of the transposon insertion, which is evidence for a role of surrounding chromatin in homologous pairing. The presence of the gypsy insulators in both homologous chromosomes even at a distance of 9 kb downstream from the promoter dramatically improves the trans activation of yellow. Moreover, the gypsy insulators have proved to stabilize trans activation between distantly located enhancers and a promoter. These data suggest that gypsy insulator pairing is involved in communication between loci in the Drosophila genome.

Animals↗

PubMed2001

Genomic context modulates insulator activity through promoter competition.

Chromatin insulators regulate gene expression by preventing inappropriate enhancer-promoter interactions. Our previous study showed that insulators do not merely function as rigid blockers, rather their activities are quantitative and selective. We have investigated the factors and mechanisms that determine the effectiveness of the suHw insulator in transgenic Drosophila. We show that the suHw-mediated blockage of the AE1 enhancer from a downstream promoter depends on the ability of the promoter to compete for AE1. Promoters that are highly competitive for the enhancer are blocked less effectively. Moreover, blockage of AE1 from its cognate ftz promoter can range from virtually complete to non-detectable, depending on the property of the neighboring upstream promoter. A highly competitive neighboring promoter enhances the suHw-mediated blockage, whereas a less competitive promoter reduces the insulator effectiveness. The influence on insulator effectiveness by both the interacting and the neighboring competing promoters correlates with their ability to compete for the enhancer, which was previously shown to depend on core promoter sequences. Our findings suggest a mechanism at the level of gene organization that modulates insulator effectiveness through promoter competition. The dependence of insulator function on its cis contexts may provide it with more regulatory flexibility while imposing organizational restraints on eukaryotic gene complexes.

Animals↗

PubMed2002

The chicken beta-globin insulator element conveys chromatin boundary activity but not imprinting at the mouse Igf2/H19 domain.

Imprinting of the mouse insulin-like growth factor 2 (Igf2) and H19 genes is regulated by an imprinting control region (ICR). The hypomethylated maternal copy functions as a chromatin insulator through the binding of CTCF and prevents Igf2 activation in cis, while hypermethylation of the paternal copy inactivates insulator function and leads to inactivation of H19 in cis. The specificity of the ICR sequence for mediating imprinting and chromatin insulation was investigated by substituting it for two copies of the chicken beta-globin insulator element, (Ch beta GI)(2), in mice. This introduced sequence resembles the ICR in size, and in containing CTCF-binding sites and CpGs, but otherwise lacks homology. On maternal inheritance, the (Ch beta GI)(2) was hypomethylated and displayed full chromatin insulator activity. Monoallelic expression of Igf2 and H19 was retained and mice were of normal size. These results suggest that the ICR sequence, aside from CTCF-binding sites, is not uniquely specialized for chromatin insulation at the Igf2/H19 region. On paternal inheritance, the (Ch beta GI)(2) was also hypomethylated and displayed strong insulator activity--fetuses possessed very low levels of Igf2 RNA and were greatly reduced in size, being as small as Igf2-null mutants. Furthermore, the paternal H19 allele was active. These results suggest that differential ICR methylation in the female and male germ lines is not acquired through differential binding of CTCF. Rather, it is likely to be acquired through a separate or downstream process.

Animals↗

PubMed2006

Thermal insulation and body temperature wearing a thermal swimsuit during water immersion.

This study evaluated the effects of a thermal swimsuit on body temperatures, thermoregulatory responses and thermal insulation during 60 min water immersion at rest. Ten healthy male subjects wearing either thermal swimsuits or normal swimsuits were immersed in water (26 degrees C or 29 degrees C). Esophageal temperature, skin temperatures and oxygen consumption were measured during the experiments. Metabolic heat production was calculated from oxygen consumption. Heat loss from skin to the water was calculated from the metabolic heat production and the change in mean body temperature during water immersion. Total insulation and tissue insulation were estimated by dividing the temperature difference between the esophagus and the water or the esophagus and the skin with heat loss from the skin. Esophageal temperature with a thermal swimsuit was higher than that with a normal swimsuit at the end of immersion in both water temperature conditions (p<0.05). Oxygen consumption, metabolic heat production and heat loss from the skin were less with the thermal swimsuit than with a normal swimsuit in both water temperatures (p<0.05). Total insulation with the thermal swimsuit was higher than that with a normal swimsuit due to insulation of the suit at both water temperatures (p<0.05). Tissue insulation was similar in all four conditions, but significantly higher with the thermal swimsuit in both water temperature conditions (p<0.05), perhaps due to of the attenuation of shivering during immersion with a thermal swimsuit. A thermal swimsuit can increase total insulation and reduce heat loss from the skin. Therefore, subjects with thermal swimsuits can maintain higher body temperatures than with a normal swimsuit and reduce shivering thermo-genesis.

Adult↗

PubMed1988

Induction of insulitis by adoptive transfer with L3T4+Lyt2- T-lymphocytes in T-lymphocyte-depleted NOD mice.

To clarify the pathogenesis of insulitis in the nonobese diabetic (NOD) mouse, an animal model for human insulin-dependent diabetes mellitus, T-lymphocyte-depleted NOD mice (B mice) were adoptively transferred with spleen and lymph node cells from cyclophosphamide-treated NOD mice after separating the cells with monoclonal antibodies against various T-lymphocyte surface antigens plus complement. Light-microscopic and immunohistochemical studies were also performed to investigate the lymphocytic infiltrations. The incidence of insulitis detected in B mice was much lower when compared with that of the lesion naturally occurring in the NOD mouse. However, higher incidence of insulitis was inducible in B mice by transferring unfractionated lymphoid cells from NOD mice. When the Thy1+ cell-depleted fraction was transferred into the B mice, no increase in the incidence of insulitis was observed. The Lyt1+ or L3T4+ cell-eliminated fraction was also unable to transfer insulitis. Conversely, donor cells depleted of Lyt2+ components successfully induced insulitis in the recipient B mice. These data were consistent with the immunohistochemical study, which showed that the main phenotype of the cells infiltrating the islets was L3T4+. These results suggest the importance of L3T4+Lyt2- T-lymphocytes in the pathogenesis of insulitis in NOD mice.

Animals↗

PubMed1993

Insulitis-caused redistribution of heat-shock protein HSP60 inside beta-cells correlates with induction of HSP60 autoantibodies.

We recently reported that sera of NOD mice contain autoantibodies to the endogenous HSP60. Under physiological conditions, the HSP60 antigen was located to secretory granules and mitochondria of beta-cells, but in islets affected by insulitis, the antigen accumulated rapidly in cytoplasm and on beta-cell surface membranes. The relationship was examined between insulitis-dependent redistribution of the HSP60 inside beta-cells and induction of the HSP60 autoantibodies. By use of quantitative immunoelectron microscopy and monoclonal antibodies to human HSP60, changes were monitored in levels of the cytoplasmic HSP60 with progression of insulitis. Development of insulitis was accompanied by reduction of the HSP60 levels in secretory granules and increased levels in the cytoplasm. Mean concentration of cytoplasmic HSP60 in 4-, 7-, and 13-wk-old NOD mice representing 0, 85, and 100% incidence of insulitis, gradually increased from 4.6 to 11.2 to 35.9 immunogold grains/micron2, respectively, and this increase was statistically significant (P < 0.001). Simultaneously, the time course of an appearance of HSP60 antibodies was established by testing sera of > 4- to 25-wk-old NOD mice, for their cross-reactivity to human recombinant HSP60 on Western blots. HSP60 antibodies developed in both sexes between 7 and 13 wk of age but were found with the highest frequency in sera of 10- to 15-wk-old mice. Antibodies declined rapidly with the onset of diabetes. HSP60 antibodies were not observed in sera of 4-wk-old NOD mice devoid of insulitis or in 7-wk-old males with delayed onset of insulitis. The cytoplasmic HSP60 levels in these cases were the same as in control mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMedDate not supplied

Bipolar leads for use with permanently implantable cardiac pacing systems: a review of limitations of traditional and coaxial configurations and the development and testing of new conductor, insulation, and electrode designs.

The unacceptable rate of mechanical failures, threshold problems, and recalls experienced with many coaxial bipolar cardiac pacing lead designs are reviewed in detail. To address these problems, redundant insulation coradial atrial and ventricular tined leads (AL and VL, respectively) with iridium oxide electrodes were developed and subjected to extensive accelerated testing. There were no mechanical failures. The new lead body design proved to be much more durable than widely used trifilar MP35N configurations. The data reviewed and early and current test results are strongly supportive of tightly coupled insulation being a major factor in improving lead durability as long as the insulating material is not stressed. In addition to improving flex life, insulation adherence to the conductor may reduce the potential for ionic degradation. Pacing and sensing thresholds in animal studies of the new leads were within the reported range for leads with steroid eluting electrodes. A multicenter Canadian clinical trial was initiated with the first implant in early January 1994. By November 1995, 110 VL and 82 AL had been placed in 124 patients and followed for a mean of 11 +/- 6 months; maximum 21, total 1355. There were 60 males and 64 females with a mean age of 64 +/- 16 years, range 15-88. Primary indications for pacing were AV block in 61 patients, sick sinus syndrome in 53, vasovagal syncope in 4, and congestive heart failure in 7. Many patients had associated or primary tachyarrhythmias, including 111 with supraventricular and 12 with ventricular. Forty-two percent of patients (52/124) had prior cardiac procedures, including 18 open heart surgeries and 20 AV nodal ablations. At implant, 8 lead characteristics were rated good or excellent in 90% (746/829) of evaluations. X-ray visibility was of concern in 10% of patients (12/124). Three perioperative complications occurred, including displacement of one AL (1.2%) and one VL (0.9%). There were no subsequent mechanical (connector, conductor, or insulation) or functional (exit block, micro or macro displacement, or over- or undersensing) problems. Implant pacing thresholds (PT) at 0.45 ms were AL, 0.6 +/- 0.2 (74) and VL 0.4 +/- 0.2 V; impedance (Z) at 3.5 V output AL 373 +/- 77 (82) and VL 497 +/- 117 omega. Sensing thresholds (ST) were AL 3.1 +/- 1.6 (74) and VL 10.3 +/- 4.9 mV. Ventricular lead data were obtained for all patients (N = 110). Atrial lead data are incomplete, because some patients were in atrial fibrillation during implantation. After 12 months, AL PT at 1.5 V output was 0.18 +/- 0.10 ms (21) and at 2.5 V was 0.10 +/- 0.053 (22). Associated AL ST was 3.3 +/- 0.9 mV (21) AL Z 500 +/- 65 omega (25). After 18 months VL PT at 1.5 V was 0.15 +/- 0.10 ms (9) and at 2.5 V output was 0.09 +/- 0.04 ms (9). Associated VL ST was > 7.5 +/- 2.4 mV (9) and VL Z 497 +/- 105 omega (9). Follow-up time discrepancy is due to the VL being available 6 months earlier than the AL. There were no 30-day deaths and only one late death at 10 months in a patient with chronic atrial fibrillation. Death was unrelated to pacer or lead function. At 1 year, 68% AL (15/22) and 62% (24/39) captured at 0.5 V and < or = 1 ms pulse width output. Innovative adherent insulation coradial bipolar lead conductors of the design studied combined with coated iridium oxide electrodes provide for a negligible incidence of mechanical or functional failure with clinical follow-up now approaching 3 years. Excellent acute and chronic sensing and pacing thresholds have been documented. Late thresholds have continued to improve gradually. Long-term clinical pacing at < or = 1.5 V output with a large safety margin is feasible in essentially all patients. This coradial design produces very flexible < 5 French bipolar redundantly insulated lead bodies allowing both AL and VL to simultaneously pass through a single 10 French introducer sheath. (ABSTRACT TRUNCATED)

Cardiac Surgical Procedures↗