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PubMed1997

Transcription and translation in bovine nuclear transfer embryos.

The development of bovine embryos reconstructed by nuclear transfer (NT) is poor compared to that of embryos produced by in vitro fertilization. One reason for this could be incomplete reprogramming of the transferred nucleus. Therefore, with a view to optimizing the conditions for NT, the reprogramming of blastomere nuclei from 16- to 32-cell-stage in vitro-fertilized (IVF) embryos was investigated following NT by fusion of individual blastomeres with cytoplasts prepared from oocytes at two different stages of maturation. Heterogeneous RNA (hnRNA) production, nucleolar ultrastructure, and protein profiles of the NT embryos up to the 8-cell stage were analyzed. In all NT embryos analyzed for their hnRNA production (n = 133), [3H]uridine incorporation was higher at the 1-, 2-, and 4-cell stages than in control IVF embryos (n = 50). Ultrastructural examination of 11 NT embryos revealed evidence of transcriptional activity; fibrillar and granular components were seen in the nucleolus at the 1-cell stage. At the 2-, 4-, and 8-cell stages, fibrillar components were still evident but granular components had become scarce. The hnRNA synthesis, however, was not reflected in the one-dimensional electrophoretic patterns of protein production in the NT embryos (n = 56); these were largely similar to those of IVF embryos (n = 34) of corresponding stages. Thus, NT embryos made in this way do not behave like equivalent IVF embryos, suggesting that reprogramming of the transferred nucleus is absent or incomplete.

Animals↗

PubMed2002

Enhanced survivability of cloned calves derived from roscovitine-treated adult somatic cells.

Nuclear transfer to produce cattle is inefficient because 1) donor cells are not easily synchronized in the proper phase of the cell cycle, 2) the nucleus of these cells is not effectively reprogrammed, 3) the rate of attrition of late-term pregnancies is high, and 4) the health of early postnatal calves is compromised. The cyclin dependent kinase 2 inhibitor, roscovitine, was used to maximize cell cycle synchrony and to produce cells that responded more reliably to nuclear reprogramming. Roscovitine-treated adult bovine granulosa cells (82.4%) were more efficiently synchronized (P < 0.05) in the quiescent G0/G1 phase of the cell cycle than were serum-starved cells (76.7%). Although blastocyst development following nuclear transfer was elevated (P < 0.05) in the serum-starved group (21.1%) relative to the roscovitine-treated cells (11.8%), the number of cells in the blastocysts derived from roscovitine-treated cells was higher (P < 0.05) than those derived from the serum-starved group (roscovitine-treated group: 142.8 +/- 6.0 cells; serum-starved group: 86.8 +/- 14.5 cells). The resulting fetal and calf survival after embryo transfer was enhanced in the roscovitine-treated group (seven surviving calves from six pregnancies) compared with serum-starved controls (two calves born, one surviving beyond 60 days, from five pregnancies). Roscovitine culture can predictably synchronize the donor cell cycle and increase the nuclear reprogramming capacity of the cells, resulting in enhanced fetal and calf survival and increased cloning efficiency.

Animals↗

PubMed1992

Atrial arrhythmias in dual chamber pacing and their influence on long-term mortality.

A retrospective study of 252 patients who received a DDD pacemaker between October 1982 and December 1990 was performed. During a mean follow-up of 30 months, reprogramming to the VVI mode was necessary in 39 patients (15.5%). Technical problems causing downgrading occurred 15 times, of which 13 problems became permanent. A total number of 24 patients had sustained atrial arrhythmias, including 14 with atrial fibrillation and 10 with atrial flutter. In this group, conversion to sinus rhythm could be obtained in 38%. After 2 years, reliable DDD pacing was maintained in 86% of the surviving patients. The survival after 1 and 2 years was 94% and 89%, respectively, and was not influenced by arrhythmias or technical problems. We conclude that atrial arrhythmias including flutter are the most important reasons for reprogramming to the VVI mode, although in an important number of patients, predominantly those with flutter, restoration of AV synchrony can be obtained. The high number of patients with atrial flutter could imply some role for DDD devices offering the option of antitachycardia pacing. Reprogramming of the pacing mode did not influence mortality.

Arrhythmia, Sinus↗

PubMed1992

Incidence and timing of activity parameter changes in activity responsive pacing systems.

The incidence and timing of rate response parameter reprogramming in activity responsive pacing systems during the year after implantation was evaluated in two groups of patients: 24 patients in whom a VVI,R system was implanted (Activitrax, Medtronic, Inc.), and 21 patients in whom a DDD,R system was implanted (Synchrony, Siemens Pacesetter, Inc.). Activity parameter changes in Activitrax patients were made based on the presence of symptoms, while in Synchrony patients, changes were based on objective data obtained using a sensor indicated rate histogram with a slow and fast walk protocol. No significant difference in the incidence of activity parameter reprogramming was noted at various time intervals during the first year in Activitrax patients; in Synchrony patients a greater incidence of reprogramming changes was noted at the 1-month follow-up visit compared to later follow-up visits (P less than 0.02). Further, the incidence of changes at 1 month was greater for Synchrony compared to Activitrax patients (P less than 0.001), while no difference was detected between groups at subsequent follow-up intervals. Use of the slow and fast walk protocol, by permitting serial evaluation of sensor response, demonstrated alterations in sensor drive rates with similar levels of activity over the initial 4 to 6 postimplant weeks. This may result from postoperative changes at the pacemaker insertion site. Based on this experience, predischarge programming may not predict long-term rate response requirements. We recommend evaluation of sensor function using an exercise protocol performed at 4 to 6 postimplant weeks in all rate responsive pacing systems that utilize a piezoelectric crystal.

Aged↗

PubMed1996

Comparative evaluation of acute and long-term clinical performance of two single lead atrial synchronous ventricular (VDD) pacemakers: diagonally arranged bipolar versus closely spaced bipolar ring electrodes.

Floating P wave sensing can be derived from bipolar atrial electrodes with different electrode configurations, although the relative clinical efficacy of these methods of atrial sensing has not been studied. We evaluated 32 sex and age matched patients with advanced AV block who received AV synchronous pacers using either a single lead with diagonally arranged bipole (Unity VDDR, Model 292, Intermedics Inc.) or closely spaced bipolar complete ring electrodes (Thera VDD, Model 8948, Medtronic Inc.). The total surface area of the atrial electrodes were 17.2 and 25 mm2, and the highest programmable atrial sensitivities were 0.1 and 0.25 mV, respectively. Atrial electrogram amplitude and sensing threshold were evaluated at implant and at each follow-up clinic visit (1, 3, and 6 months). Stability of atrial sensing was assessed during physical maneuvers, treadmill exercise test, and Holter recording. Atrial electrogram amplitude at implantation was higher in the Thera VVD (2.08 +/- 0.79 vs 1.45 +/- 0.59 mV in Unity VDDR; P < 0.05), but the value of atrial sensing threshold was lower during follow-up than Unity VDDR. P wave undersensing was additionally observed with both pacemakers during physical maneuvers and exercise testing (6%-19% of patients). Two and four patients had atrial undersensing on Holter in the Unity VDDR and Thera VDD, respectively, and the percentage P wave undersensing were 0.88% +/- 2.41% versus 3.63% +/- 8.16%, respectively. Reprogramming of the atrial sensitivity in the Unity VDDR and the use of investigational software allowing 0.18 mV atrial sensitivity to be programmed in the Thera VDD substantially reduced the percentage of P wave undersensing on Holter to 0.46% +/- 1.67% and 0.10% +/- 0.24%, respectively. Beginning at discharge with a programmed atrial sensitivity level at least twice the sensing margin, the mean atrial sensitivity level was reprogrammed from 0.29 to 0.26 mV for Unity VDDR and 0.33 to 0.24 mV for Thera VDD at 6 months. There was no incidence of atrial oversensing. Despite differences in atrial amplitudes at implantation between the diagonally arranged bipole and closely spaced full ring single lead systems, the clinical performances of atrial sensing were similar at an appropriately high atrial sensitivities. The absence of atrial oversensing suggests that single pass VDD pacemakers should probably be programmed at the highest available atrial sensitivity to ensure adequate P wave sensing as guided by physical maneuvers and Holter recording to minimize the need of subsequent reprogramming.

Aged↗

PubMed2003

Nuclear transfer: progress and quandaries.

Cloning mammals by nuclear transfer is a powerful technique that is quickly advancing the development of genetically defined animal models. However, the overall efficiency of nuclear transfer is still very low and several hurdles remain before the power of this technique will be fully harnessed. Among these hurdles include an incomplete understanding of biologic processes that control epigenetic reprogramming of the donor genome following nuclear transfer. Incomplete epigenetic reprogramming is considered the major cause of the developmental failure of cloned embryos and is frequently associated with the disregulation of specific genes. At present, little is known about the developmental mechanism of reconstructed embryos. Therefore, screening strategies to design nuclear transfer protocols that will mimic the epigenetic remodeling occurring in normal embryos and identifying molecular parameters that can assess the developmental potential of pre-implantation embryos are becoming increasingly important. A crucial need at present is to understand the molecular events required for efficient reprogramming of donor genomes after nuclear transfer. This knowledge will help to identify the molecular basis of developmental defects seen in cloned embryos and provide methods for circumventing such problems associated with cloning the future application of this technology.

Animals↗

PubMed2003

5' exon replacement and repair by spliceosome-mediated RNA trans-splicing.

Spliceosome-mediated RNA trans-splicing (SMaRT) has been used previously to reprogram mutant endogenous CFTR and factor VIII mRNAs in human epithelial cell and tissue models and knockout mice, respectively. Those studies used 3' exon replacement (3'ER); a process in which the distal portion of RNA is reprogrammed. Here, we also show that the 5' end of mRNA can be completely rewritten by 5'ER. For proof-of-concept, and to test whether 5'ER could generate functional CFTR, we generated a mutant minigene target containing CFTR exons 10-24 (deltaF508) and a mini-intron 10, and a pretrans-splicing molecule (targeted to intron 10) containing CFTR exons 1-10 (+F508), and tested these two constructs in 293T cells for anion efflux transport. Cells cotransfected with target and PTM showed a consistent increase in anion efflux, but there was no response in control cells that received PTM or target alone. Using a LacZ reporter system to accurately quantify trans-splicing efficiency, we tested several unique PTM designs. These studies provided two important findings as follows: (1) efficient trans-splicing can be achieved by binding the PTM to different locations in the target, and (2) relatively few changes in PTM design can have a profound impact on trans-splicing activity. Tethering the PTM close to the target 3' splice site (as opposed to the donor site) and inserting an intron in the PTM coding resulted in a 65-fold enhancement of LacZ activity. These studies demonstrate that (1) SMaRT can be used to reprogram the 5' end of mRNA, and (2) efficiency can be improved substantially.

Cell Line↗

PubMed2025

Baculovirus enhances arginine uptake and induces mitochondrial autophagy to promote viral proliferation.

As obligatory intracellular parasites, viruses must rely on metabolic reprogramming of host cells to meet their replication needs. Baculovirus is an important biopesticide and a vector for the preparation of biological products. In addition, one of its representative species, Bombyx mori nucleopolyhedrovirus (BmNPV-Baculoviridae), also causes huge losses to the insect industry. In our previous study, amino acid metabolism has been found to play a crucial role in the BmNPV infection process. However, the mechanisms by which BmNPV reprograms host amino acid metabolism remains unclear. In fact, current insights in the importance of amino acid metabolism are limited to the impact of glutamine on viral infection. Therefore, unraveling the mechanism of amino acid metabolism reprogramming induced by baculovirus would advance this field of research to a great extent. In this study, targeted metabolomics revealed that the preferred amino acids of BmNPV budded virus (BV) include arginine, lysine, proline, isoleucine, histidine and others. In addition, most of the viral amino acids were found to be increased in the hemolymph of BmNPV infected silkworms at the later stage of infection, especially arginine, valine, phenylalanine and others. Furthermore, the importance of arginine for BmNPV proliferation was validated. Next, we confirmed that the expression of the arginine transporter Slc7a6 was strongly induced by BmNPV infection and that Slc7a6 could promote arginine uptake to support BmNPV proliferation in host cells. Moreover, using Slc7a6 knockout cells which eliminate extracellular arginine uptake, we confirmed that BmNPV could induce mitochondrial autophagy, thereby supplementing intracellular arginine and providing necessary amino acids for BmNPV proliferation. Overall, these findings support a model in which baculovirus (BmNPV) enhances the uptake of exogenous amino acids by inducing the expression of amino acid transporters and activating autophagy of organelles to maintain intracellular amino acid levels, thereby facilitating virus proliferation.

Animals↗

PubMed1988

Physiologic pacing in the elderly. Effects on exercise capacity and exercise-induced arrhythmias.

It is not clear whether hemodynamic and other benefits from dual-chamber pacing also exist in elderly patients. We studied a group of 18 elderly patients (mean age 74 +/- 4 yrs) with exercise testing in DDD and VVI modes in a randomized way to compare the effects of these pacing modes on exercise capacity, atrial rate and exercise-induced arrhythmias. Patients were selected when complete heart block was present without clinical evidence of sinus node dysfunction. Significant differences were observed: atrial rate was lower during exercise in DDD-mode (p less than 0.01); exercise time and cumulative load increased (p less than 0.05); maximal oxygen uptake was improved (p less than 0.05). Some of these differences were less clear in a subgroup with replacement of a VVI-device by DDD-stimulation. No differences could be observed in severity of exercise-induced arrhythmias. No evidence of sinus node dysfunction was found during exercise. Reprogramming of atrial sensitivity was required in 3 patients, with reprogramming to DVI because of paroxysmal atrial fibrillation once. Two patients died within a mean follow-up period of 13 months. Sinus rhythm was present at the most recent evaluation in all patients, including the patient stimulated in the DVI mode. Physiologic stimulation is of value for elderly patients with an active life style and complete heart block. Reprogramming to another pacing mode is only seldom necessary.

Aged↗

PubMed2007

Erasure of cellular memory by fusion with pluripotent cells.

Pluripotent cells have been suggested as a prime source to reprogram somatic cells. We used F9 EC cells as a pluripotent partner to reprogram neurosphere cells (NSCs) because they exhibit a nonneural differentiation potential in the presence of retinoic acid. F9-NSC hybrid cells displayed various features of reprogramming, such as reactivation of pluripotency genes, inactivation of tissue-specific genes, and reactivation of the inactive X chromosome. As the hybrid cells undergo differentiation, the pluripotency markers Oct4 and Nanog were downregulated. Whereas neural marker genes were not upregulated, endodermal and mesodermal markers were, suggesting that NSCs lose memory of their neural origin and preferentially differentiate to the lineages corresponding to the F9 program. After fusion, the methylation status in the Xist region was similar to that of F9 EC cells. However, upon differentiation, the Xist region failed to resume the methylation patterns of differentiated cells, suggesting that the Xist in F9-NSC hybrids does not easily acquire a differentiated state.

Animals↗

PubMed2002

Adenoviral E1A: everlasting tool, versatile applications, continuous contributions and new hypotheses.

Adenoviral E1A is an indispensable protein for virus-host interaction. To provide a suitable environment for viral replication, E1A physically interacts with multiple cellular proteins to reprogram gene expression and other processes of the host cells. Proteins targeted by E1A include the pRb family of pocket proteins, p300/CBP, cyclin/Cdk, the carboxyl terminal binding protein (CtBP), transcriptional regulator YY1, and the recently identified RACK1 and SWI/SNF complex. Reprogramming activity of E1A and the host cell response to this reprogramming lead to transformation, growth arrest or apoptosis. Based on the ability of E1A to override the fundamental controls of host cells, E1A has been being utilized to make continuous contributions not only to a better understanding of the molecular mechanisms underlying the regulation of transcription, cell division, apoptosis and tumorigenesis but also to new therapeutics such as gene therapy.

Adenovirus E1A Proteins↗

PubMed1999

Incidence and management of subdural hematoma/hygroma with variable- and fixed-pressure differential valves: a randomized, controlled study of programmable compared with conventional valves.

Shunt systems with differential pressure valves are prone to the complications of overdrainage. A programmable valve permits adjustment of the opening pressure of the valve. In this paper the authors report the incidence of subdural fluid collections in a randomized trial of programmable compared with conventional valves, and they describe methodologies used in management of this complication. A multiinstitutional, prospective, randomized trial of the Codman Hakim programmable valve and conventional fixed-pressure valves was undertaken. Two classes were defined: "new" and "replacement" valves. Randomization of the type of valve in each group was performed at each study site. Clinical and radiological studies were required at fixed intervals over a 104-week period. All complications were reported. The experimental valves were required to be reprogrammed after magnetic resonance imaging studies, but all other decisions regarding pressure setting were left to each investigator. Three hundred seventy-seven patients were randomized; 194 were treated with a programmable valve and 183 with a fixed-pressure valve. The two groups were statistically similar in demographic composition, as were the "new" and "replacement" categories. The investigators made 540 valve pressure changes (five per patient; range one-41 changes). More than half of the reprogramming adjustments were made in the first 3 months postplacement; 70% were made within 6 months. More than half of all reprogramming adjustments were required in a group of 30 patients. Four treatment modalities were observed: 1) 30% of the fluid collections resolved spontaneously (25% in the patients with programmable valves and 36.3% in those with conventional valves) and were largely found to be hygromas in infants and children; 2) four subdural fluid collections were unresolved and under observation; 3) the subdural hematoma was drained and the shunt removed (in 8.3% of patients with the programmable valve and 36.3% of those with the control valve); 4) the pressure of programmable valve was raised in 58% of patients (seven of 12), and this increase in opening pressure was a feature used by investigators to affect treatment. There was no significant difference in the incidence of subdural fluid collections between the programmable and fixed-pressure valve treatment groups. The programmable feature provided a considerable advantage in treatment when subdural collections occurred.

Journal Article↗

PubMed2026

Genome agnostic, multi-level non-oncogene addiction-based systems pharmacology for rescuing metastatic relapsed/refractory neoplasias.

Rescue therapies for relapsed/refractory (r/r) metastatic neoplasias present significant unmet needs. Tumor tissue editing regimen for 13 r/r tumor types, carcinomas, sarcomas and hematologic neoplasias, included in 15 phase I/II trials, nuclear/cytokine receptor agonists, pioglitazone, plus/minus dexamethasone or all-trans retinoic acid or interferon-α to counterbalance tumor tissue homeostasis and reprogramming of cancer hallmarks, stress response inhibitors, COX-2 inhibitor, everolimus, lenalidomide, or clarithromycin, and a stress response inducer, low-dose metronomic chemotherapy with treosulfan, trofosfamide, capecitabine, or azacitidine. CR in three, cCR in another five r/r neoplasias, as the best response occurred after transcriptional reprogramming of cancer hallmarks, inflammation control or differentiation induction. Receptor agonist combinations for cCR induction can be identical among quite different tumor types and diversified within the same tumor histology. Data reveal ubiquitous, differential transcriptional access to non-oncogene addiction (NOA) networks that cope with cancer hallmarks/stress responses and three levels of therapeutic NOA targeting. (1) Agonists of nuclear/cytokine receptor NOAs critically target tumor identity and viability, while (2) transcriptional reprogramming of NOA networks that contribute to tumor tissue addiction, thereby genome-agnostically counteracting oncogene addictions. (3) Targeting edited NOAs may improve long-term outcome with CR/cCR (everolimus, IMiD). Transcriptionally accessible NOA targets offer high specificity, modest toxicity profile, low cost of therapy and outpatient treatment, independent of comorbidities. Adaptive targeting of the transcriptomic landscapes of tumor cell compartments breaks tumor tissue addiction and overcomes M-CRAC, post-therapy metastasis, cancer cell recolonization, acquired resistance and genetic heterogeneity. Thus, editing approaches provide a template for controlling metastatic r/r tumors. In the future, diagnostics of NOA networks and transcription factors involved in tumor tissue addiction may be as valuable for therapy selection as histological/molecular genetic tumor typing for the establishment of personalized hematology/oncology.

Hodgkin’s lymphoma↗

PubMed2026

Extravascular coagulation stabilizes pro-fibrotic stromal states via tumor-intrinsic PAR1 signaling in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) exhibits a desmoplastic stroma with context-dependent tumor-restraining and tumor-promoting functions, highlighting the need to selectively reprogram stromal states. Extravascular coagulation is a prominent feature of the PDAC tumor microenvironment, yet whether it functions as an upstream regulator of fibrotic stromal states, rather than merely a byproduct of tumor-associated vascular dysfunction, has remained unclear. Here, we identify extravascular coagulation as a tumor-amplified regulatory module that stabilizes pro-fibrotic stromal states via tumor-intrinsic protease-activated receptor-1 (PAR1) signaling. To interrogate this axis mechanistically, we integrated human tumor bioinformatics with microphysiological tumor-stroma (MPTS) models that reconstruct tumor-stroma interactions under controlled coagulation exposure, followed by cross-scale validation in vivo. Analysis of The Cancer Genome Atlas (TCGA) revealed heterogeneous F2R (PAR1) expression across tumors, with elevated expression associated with fibrotic transcriptional programs and reduced survival. Consistently, thrombin induced coordinated pro-fibrotic programs in tumor cells and cancer-associated fibroblasts (CAFs), which were recapitulated in MPTS where tumor-intrinsic PAR1 was required for amplification of extracellular matrix deposition and CAF activation. Mechanistically, PAR1 signaling amplified tumor-stroma communication, in part through induction of TGF-β1-dependent pathways, establishing a reinforcing feedback loop that stabilizes fibrotic remodeling. Pharmacologic inhibition of PAR1 selectively suppressed the fibrotic transcriptional program within myofibroblastic CAFs while reducing the abundance of other CAF subtypes, reprogramming stromal states and attenuating tumor progression across MPTS and in vivo models. These findings establish a coagulation-PAR1 axis as an upstream organizer of PDAC stromal architecture and identify pharmacologic PAR1 inhibition as a mechanistically grounded strategy for selectively reprogramming the tumor-promoting stroma.

Journal Article↗

PubMed2003

[Effects of 50 to 60 Hz and of 20 to 50 kHz magnetic fields on the operation of implanted cardiac pacemakers].

UNLABELLED: The effect of 50 Hz and 60 Hz (frequencies of current distribution) and 20 kHz to 50 kHz (frequencies of induction cooktop) magnetic interference on implanted pacemakers have been assessed with the present generation of device technology. Sixty patients implanted in 1998 and 1999 with dual chamber pacemakers from 9 different manufacturers were monitored with telemetry while passing through, and standing between a system of two coils. They generated a 50 Hz or a 60 Hz magnetic field at 50 microT. Then, patients used a cooktop at different power. The recordings were made with the standard setting of "medically correct" sensing parameters chosen for the patients. Then pacemakers were reprogrammed to the unipolar mode, with the highest atrial (A) and ventricular (V) sensitivity that did not induce muscular inhibition while moving. Between each exposure (50 Hz, 60 Hz or 20 kHz to 50 kHz), the pacemaker programmation was controlled. At the end of the tests, pacemakers will be reprogrammed with the standard setting. The medical observer being blind to the existence or not of the magnetic field. No pacemaker was influenced by the vicinity of the magnetic field at medically correct settings. At unipolar high sensitivity, no inhibition nor reprogramming was observed. Transient reversion to interference mode was observed in 6 cases, 3 transient acceleration due to atrial detection of the interference, and one T wave detection by the ventricular lead. All were observed with the 60 Hz, and only 3 with the 50 Hz magnetic field. One device (Biotronik) shifted out of its special program (hysteresis research) during the tests with the induction cooktop, but it maintained its standard program, and the event could not be repeated despite further testing. CONCLUSION: Actual pacemakers do not present any electromagnetic interference with 50 Hz and 60 Hz or induction cooktop frequency working. They are insensitive with medically correct settings. Unusual high sensitivity leads only to noise reversion mode, or transient ventricular tracking.

Dose-Response Relationship, Radiation↗

PubMedDate not supplied

[Aging and limited capacity for division of normal, diploid amphibian fibroblasts in vitro in relation to cell nucleus transplantations in amphibia].

In many experiments Hayflick had proved the limited division capacity of lung fibroblasts derived from different mammalian species, chicken and tortoise. Gurdon transplanted the nuclei of differentiated Xenopus cells into enucleated eggs yielding a complete development of the hybrid individuals. These results arise the question about a reprogramming of cell nuclei concerning their division capacity. On the other hand, amphibian cells may not show any proliferative limit. Thus, primary cultures were established from tadpoles, recently metamorphosed frogs and adult animals, respectively. The latent period of the tissue explants proved to be dependent on donor age. The cell strain I401 showed the characteristic degeneration phenomena after six subcultivations and ceased to proliferate. These results lead to the conclusion that nuclear transplantation into an enucleated egg yields reprogramming of the nucleus, including the reprogramming of the division capacity as much as the biological age of the nucleus.

Animals↗

PubMed1983

Early experience with a universal (DDD) pacing device.

To assess the advantages and complications of a new universal (DDD) pacemaker, we studied retrospectively the initial 38 patients who received such a pacing device. This group consisted of 27 men and 11 women whose ages ranged from 23 to 89 years. The pacemaker was the initial one for 32 patients and was the replacement unit for 6. Indications for dual-chamber pacing included a need to maintain atrioventricular synchrony, the previous occurrence of the pacemaker syndrome or the presence of intact ventriculoatrial conduction, and previous success with atrioventricular sequential pacing. Pacemaker-mediated tachycardia developed in six patients during the follow-up period. All six were successfully treated by a change in pacing mode. Eighteen pacemakers remained in the DDD mode, 17 were reprogrammed to the DVI mode, and 3 were reprogrammed to the VVI mode. Seven patients experienced difficulties with loss of capture or undersensing, the most common problem being failure of atrial sensing. This was corrected in four of five patients by noninvasive reprogramming. Pacemaker-mediated tachycardia is a frequent complication that can be avoided by assessing ventriculoatrial conduction before implantation of the pacemaker. Use of the DDD device should be considered in patients in whom atrioventricular synchrony must be maintained or who have previously had the pacemaker syndrome with VVI pacing.

Adult↗

PubMedDate not supplied

Long term performance of atrial leads.

Long term performance of 163 atrial leads implanted in 158 patients between July 1981 and June 1993 was evaluated. There were 122 DDD and 36 AAI units, with 125 (77%) polyurethane and 38 (23%) silicone leads. One hundred and nine (67%) unipolar and 54 (33%) bipolar leads were used. Patients were followed in the Pacemaker Clinic for 6 to 124 months (mean 50 +/- 39 months). Five patients were lost to follow up. Transient malfunction was observed in 18 cases (sensing 13, pacing 5) within the first 2 weeks. In 13 cases failure to sense subsided spontaneously and in 4 pacing malfunction could be corrected by reprogramming. Lead dislodgement occurred in 4 patients (2.5%), all within the first week. After the 1st month malfunction was uncommon. Between 1 and 12 months undersensing occurred in 4 (2.5%). In 3 cases it could be corrected by reprogramming. In the first year, reoperation was performed in 5 cases for lead related problems (3 dislodgements, 2 insulation failures). Beyond 12 months complications were as follows: failure to sense-8 (5%), failure to pace-3 (2%), insulation break -1 (0.6%). Majority of these problems could be managed by reprogramming. Reoperation was performed in 1 case with insulation break. The pacing mode had to be changed in 5 (3%) patients with dual chamber units who had loss of P wave sensing. During follow-up 98%, 98%, 96%, 95% and 83% of the leads were working satisfactorily at 1,2,3,4 and 9 years respectively. Thus atrial leads have excellent long term performance and an acceptable rate of late malfunction.

Adolescent↗