A polyhydroxybutyrate biodegradable stent: preliminary experience in the rabbit.

PURPOSE: The lifelong persistence of foreign bodies within the arteries may contribute to restenosis. Thus, biodegradable devices might decrease recurrence rates. METHODS: Eleven polyhydroxybutyrate biodegradable stents and 13 tantalum stents were implanted into the iliac arteries of New Zealand white rabbits for up to 30 weeks. After killing the animals, the specimens were harvested, fixed in formalin, processed in paraffin, and stained. RESULTS: Polyhydroxybutyrate instigated intense inflammatory and proliferative reactions with an increase in collagen (2.4- to 8-fold vs native segments), thrombosis and in-stent lumen narrowing (375.5-606.6 mm vs 655.6 +/- 268.8 mm in native segments). The elastic membranes were destroyed in all specimens. The tantalum stents increased the in-stent lumen progressively (769.7 +/- 366.6 mm vs 1309.9 +/- 695.3 mm), penetrated the external elastic membrane, and increased mural collagen content (6- to 8.6-fold vs native segments). Neither restenoses nor thromboses occurred. CONCLUSIONS: In the rabbit iliac artery, polyhydroxybutyrate stents caused intensive inflammatory vascular reactions which ban them from clinical use.

A new detection algorithm for implantable cardioverter defibrillator.

One of the most important subsystems of implantable cardioverter defibrillator (ICD) is the sensing stage, since it determines the sensitivity and specificity of the device to detect the heart rate and the underlying arrhythmia. This paper aims to investigate a new detection algorithm for ICD, which operates fully automatically. The algorithm ARGUS was implemented as a computer model and tested with intracardiac electrograms recorded (band-pass: 0.05 to 500 Hz; sampling rate: 1-4 kHz) under different rhythm condition like sinus rhythm (n = 18), atrial tachycardia (n = 16), and ventricular tachycardia as well as fibrillation (n = 139) during electrophysiological tests or ICD implantation. The results of the tests were visually inspected on a beat-to-beat basis. In total 31,934 events were classified by the algorithm (18,758 as long intervals (LI) with cycle length > 300 ms; 13,176 as short intervals (SI)). 195 out of the 13,176 SI and 572 out of 18,758 LI were incorrectly classified (SI: 1.48%; LI: 3.05%). In conclusion the new algorithm yield high sensitivity (99.9%) and specificity (97.0%) as known from conventional ICD algorithms but need no manual adjustments.

Prevention of surface encrustation of urological implants by coating with inhibitors.

The encrustation of materials used for urological implants is as yet an unresolved problem. The crystallisation-inhibiting effect of the glycosaminoglycan heparin was used to reduce encrustation. Heparin was covalently bound to the surface of slotted-tube stents of tantalum and stainless steel using a spacer molecule. To verify the inhibition of crystallisation processes, reproducible in vitro tests and in vivo tests using the rat as animal model were carried out. The in vitro and in vivo experiments showed that the heparin coating has a significant influence on the encrustation of the surface. After 7 days in vitro and 120 days in vivo, heparin coated stents were free of encrustation, whereas the uncoated reference stents were extensively covered.

Closed-loop stimulation using intracardiac impedance as a sensor principle: correlation of right ventricular dP/dtmax and intracardiac impedance during dobutamine stress test.

Changes of the unipolar right ventricular impedance during the cardiac cycle are related to the changing content of blood (low impedance) and tissue (high impedance) around the tip of the pacing electrode. During myocardial contraction, the impedance continuously increases reaching its maximum in late systole. This impedance increase is thought to correlate with right ventricular contractility, and thus, with the inotropic state of the heart. In the new Inos2 DDDR pacemaker, integrated information from the changing ventricular impedance (VIMP) is used for closed-loop regulation of the rate response. The aim of this study was to analyze the effect of increasing dobutamine challenge on RV contractility and the measured impedance signals. In 12 patients (10 men, 68 +/- 12 years) undergoing implantation of an Inos2 DDDR pacemaker (Biotronik), a right ventricular pigtail catheter was inserted for continuous measurements of RV-dP/dtmax and simultaneous VIMP signals during intrinsic and ventricular paced rhythm. Then, a stress test with a stepwise increase of intravenous dobutamine (5-20 micrograms/kg per min) was performed. To assess the relationship between RV contractility and measured sensor signals, normalized values of dP/dtmax and VIMP were compared by linear regression. There was a strong and highly significant correlation between dP/dtmax and VIMP for ventricular paced (r2 = 0.93) and intrinsic rhythm (r2 = 0.92), although the morphologies of the original impedance curves differed quite substantially between paced and intrinsic rhythm in the same patient. Furthermore, VIMP correlated well with sinus rate (r2 = 0.82), although there were at least four patients with documented chronotropic incompetence. We conclude, that for intrinsic and ventricular paced rhythms sensor signals derived from right ventricular unipolar impedance curves closely correlate with dP/dtmax, and thus, with a surrogate of right ventricular contractility during dobutamine stress testing. Our results suggest that "inotropy-sensing" via measurement of intracardiac impedance is highly accurate and seems to be a promising sensor principle for physiological rate adaptation in a closed-loop pacing system.

Dynamic cardiomyoplasty: long-term clinical results in patients with dilated cardiomyopathy.

BACKGROUND: Dynamic cardiomyoplasty has been considered to be an effective method of surgical treatment of patients with end-stage heart failure, and is an alternative to heart transplantation. METHODS: We critically evaluated the long-term course of 52 patients with dilated cardiomyopathy who underwent dynamic cardiomyoplasty and were followed-up for up to 110 months. RESULTS: Dilated cardiomyopathy was due to undetermined cause in 42 patients (80.8%), Chagas disease in 8 (15.4%), viral infection in 1 (1.9%), and peripartum cardiomyopathy in 1 (1.9%). In the nonchagasic group the survival rates were 79.5% +/- 6.1%, 67.8% +/- 7.1%, 53.7% +/- 8.3%, 49.9% +/- 8.3%, 14.9% +/- 12.2%, and 14.9% +/- 12.2%, respectively, at 12, 24, 48, 60, 80 and 110 months of follow-up. In the chagasic patients the survival rates were 37.5% +/- 17.1%, 12.5% +/- 11.7%, 12.5% +/- 11.7% and 0%, respectively, at 12, 24, 48, and 60 months of follow-up, making chagasic cardiomyopathy a possible contraindication for dynamic cardiomyoplasty. CONCLUSIONS: There was no correlation between the clinical improvement and hemodynamic data. Ventricular fibrillation was a frequent cause of immediate and late death, suggesting the need for prophylactic use of antiarrhythmic drugs or implantable cardioverter/ defibrillators.

The ancient source of a distinct gene family encoding proteins featuring RING and C(3)H zinc-finger motifs with abundant expression in developing brain and nervous system.

Intronless genes can arise by germline retrotransposition of a cDNA originating as mRNA from an intron-containing source gene. Previously, we described several members of a family of intronless mammalian genes encoding a novel class of zinc-finger proteins, including one that shows imprinted expression and one that escapes X-inactivation. We report here the identification and characterization of the Makorin ring finger protein 1 gene (MKRN1), a highly transcribed, intron-containing source for this family of genes. Phylogenetic analyses clearly indicate that the MKRN1 gene is the ancestral founder of this gene family. We have identified MKRN1 orthologs from human, mouse, wallaby, chicken, fruitfly, and nematode, underscoring the age and conservation of this gene. The MKRN gene family encodes putative ribonucleoproteins with a distinctive array of zinc-finger motifs, including two to four C(3)H zinc-fingers, an unusual Cys/His arrangement that may represent a novel zinc-finger structure, and a highly conserved RING zinc-finger. To date, we have identified nine MKRN family loci distributed throughout the human genome. The human and mouse MKRN1 loci map to a conserved syntenic group near the T-cell receptor beta cluster (TCRB) in chromosome 7q34-q35 and chromosome 6A, respectively. MKRN1 is widely transcribed in mammals, with high levels in murine embryonic nervous system and adult testis. The ancient origin of MKRN1, high degree of conservation, and expression pattern suggest important developmental and functional roles for this gene and its expressed family members.

The effects of orthostasis on the ventricular-evoked response.

AIMS: The effects of orthostasis on the morphology of the ventricular-evoked response were investigated. METHODS AND RESULTS: Seven patients (five females; 74.9 +/- 4.6 years) with second- or third-degree atrioventricular block received DDD pacemakers Physios CTM 01 with fractal-coated ventricular leads (both Biotronik, Germany). At their 3-month follow-up sessions, these patients underwent tilt-table tests. Heart rate, mean arterial blood pressure and ventricular-evoked response were measured continuously. Signals were averaged over 15 consecutive beats. Coefficients of correlation between selected ventricular-evoked response parameters and heart rate or mean arterial blood pressure were calculated. Tilt upwards affected heart rate, mean arterial blood pressure and ventricular-evoked response extremes showed non-uniform, patient-specific changes that were not related directly to other parameters. Heart rates significantly increased in six patients following tilt upwards. For all patients, ventricular-evoked response plateau amplitudes immediately increased with tilt upwards. Furthermore, repolarization times correlated with changes in heart rates (r = -0.78). CONCLUSIONS: Monitoring of the ventricular-evoked response during tilt-table testing revealed that the plateau amplitude of the ventricular-evoked response depends on the patient's position; ventricular-evoked response increased in the upright position and decreased in the supine position. Furthermore, repolarization time and heart rate correlated inversely; higher heart rates resulted in a shortening of the ventricular-evoked response.

Concerted regulation and molecular evolution of the duplicated SNRPB'/B and SNRPN loci.

The human small nuclear ribonucleoprotein SNRPB ' /B gene is alternatively spliced to produce the SmB or SmB' spliceosomal core proteins. An ancestral duplication gave rise to the closely related SNRPN paralog whose protein product, SmN, replaces SmB'/B in brain. However, the precise evolutionary and functional relationship between these loci has not been clear. Genomic, cDNA and protein analyses presented here in chicken, two marsupials (South American opossum and tammar wallaby), and hedgehog, suggest that the vertebrate ancestral locus produced the SmB' isoform. Interestingly, three eutherians exhibit radically distinct splice choice expression profiles, producing either exclusively SmB in mouse, both SmB and SmB' in human, or exclusively SmB' in hedgehog. The human SNRPB ' /B locus is biallelically unmethylated, unlike the imprinted SNRPN locus which is unmethyl-ated only on the expressed paternal allele. Western analysis demonstrates that a compensatory feedback loop dramatically upregulates SmB'/B levels in response to the loss of SmN in Prader-Willi syndrome brain tissue, potentially reducing the phenotypic severity of this syndrome. These findings imply that these two genes encoding small nuclear ribonucleoprotein components are subject to dosage compensation. Therefore, a more global regulatory network may govern the maintenance of stoichiometric levels of spliceosomal components and may constrain their evolution.

Ventricular evoked response in patients with hypertrophic obstructive cardiomyopathy treated with DDD pacing.

OBJECTIVE: To assess the changes in ventricular evoked responses (VER) produced by the decrease in left ventricular outflow tract gradient (LVOTG) in patients with hypertrophic obstructive cardiomyopathy (HOCM) treated with dual-chamber (DDD) pacing. METHODS: A pulse generator Physios CTM (Biotronik, Germany) was implanted in 9 patients with severe drug-refractory HOCM. After implantation, the following conditions were assessed: 1) Baseline evaluation: different AV delay (ranging from 150 ms to 50 ms) were sequentially programmed during 5 to 10 minutes, and the LVOTG (as determined by Doppler echocardiography) and VER recorded; 2) standard evaluation, when the best AV delay (resulting in the lowest LVOTG) programmed at the initial evaluation was maintained so that its effect on VER and LVOTG could be assessed during each chronic pacing evaluation. RESULTS: LVOTG decreased after DDD pacing, with a mean value of 59 +/- 24 mmHg after dual chamber pacemaker, which was significantly less than the gradient before pacing (98 + 22 mmHg). An AV delay > 100 ms produced a significantly lower decrease in VER depolarization duration (VERDD) when compared to an AV delay < or = 100 ms. Linear regression analyses showed a significant correlation between the LVOTG values and the magnitude of VER (r = 0.69; p < 0.05) in the 9 studied patients. CONCLUSION: The telemetry obtained intramyocardial electrogram is a sensitive means to assess left ventricular dynamics in patients with HOCM treated with DDD pacing.