Safety, pharmacokinetics and pharmacodynamics of BI 135585, a selective 11ß-hydroxysteroid dehydrogenase-1 (HSD1) inhibitor in humans: liver and adipose tissue 11ß-HSD1 inhibition after acute and multiple administrations over 2 weeks.

AIMS: To assess the safety and pharmacokinetic and pharmacodynamic characteristics of BI 135585, a selective 11ß-hydroxysteroid dehydrogenase-1 (11ß-HSD1) inhibitor, after single- and repeated-dose administration. METHODS: The single-dose study included open-label administration of 200 mg BI 135585 in healthy volunteers, while in the multiple-dose study, we carried out randomized, double-blind administration of 5-200 mg BI 135585 or placebo once daily over 14 days in patients with type 2 diabetes (T2DM). Assessments included 11ß-HSD1 inhibition in the liver (urinary tetrahydrocortisol (THF)/tetrahydrocotisone (THE) ratio) and in subcutaneous adipose tissue (AT) ex vivo and determination of hypothalamus-pituitary-adrenal (HPA) axis hormone levels. RESULTS: No major safety issues occurred with BI 135585 administration. The HPA axis was mildly activated with slightly increased, but still normal adrenocorticotropic hormone levels, increased total urinary corticoid excretion but unchanged plasma cortisol levels. After multiple doses of 5-200 mg BI 135585, exposure (area under the curve) increased dose-proportionally and half-life was 55-65 h. The urinary THF/THE ratio decreased, indicating liver 11ß-HSD1 inhibition. Median 11ß-HSD1 enzyme inhibition in the AT reached 90% after a single dose of BI 135585, but was low (31% or lower) after 14 days of continuous treatment. CONCLUSIONS: BI 135585 was safe and well tolerated over 14 days and can be dosed once daily. Future studies are required to clarify the therapeutic potential of BI 135585 in view of its effects on 11ß-HSD1 inhibition in AT after single and multiple doses. Enzyme inhibition in the AT was not adequately predicted by the urinary THF/THE ratio.

Disease-promoting and -protective genomic loci on mouse chromosomes 3 and 19 control the incidence and severity of autoimmune arthritis.

Proteoglycan (PG)-induced arthritis (PGIA) is a murine model of rheumatoid arthritis. Arthritis-prone BALB/c mice are 100% susceptible, whereas the major histocompatibility complex-matched DBA/2 strain is completely resistant to PGIA. To reduce the size of the disease-suppressive loci for sequencing and to find causative genes of arthritis, we created a set of BALB/c.DBA/2-congenic/subcongenic strains carrying DBA/2 genomic intervals overlapping the entire Pgia26 locus on chromosome 3 (chr3) and Pgia23/Pgia12 loci on chr19 in the arthritis-susceptible BALB/c background. Upon immunization of these subcongenic strains and their wild-type (BALB/c) littermates, we identified a major Pgia26a sublocus on chr3 that suppressed disease onset, incidence and severity via controlling the complex trait of T-cell responses. The region was reduced to 3 Mbp (11.8 Mbp with flanking regions) in size and contained gene(s) influencing the production of a number of proinflammatory cytokines. Additionally, two independent loci (Pgia26b and Pgia26c) suppressed the clinical scores of arthritis. The Pgia23 locus (∼3 Mbp in size) on chr19 reduced arthritis susceptibility and onset, and the Pgia12 locus (6 Mbp) associated with low arthritis severity. Thus, we have reached the critical sizes of arthritis-associated genomic loci on mouse chr3 and chr19, which are ready for high-throughput sequencing of genomic DNA.

T cell receptor (TCR) signal strength controls arthritis severity in proteoglycan-specific TCR transgenic mice.

T cell receptor transgenic (TCR-Tg) mice specific for the arthritogenic 5/4E8 epitope in the G1 domain of cartilage proteoglycan were generated and back-crossed into arthritis-prone BALB/c background. Although more than 90% of CD4(+) T cells of all TCR-Tg lines were 5/4E8-specific, one (TCR-TgA) was highly sensitive to G1-induced or spontaneous arthritis, while another (TCR-TgB) was less susceptible. Here we studied whether fine differences in TCR signalling controlled the onset and severity of arthritis. Mice from the two TCR-Tg lines were immunized side by side with purified recombinant human G1 (rhG1) domain for G1 domain of cartilage proteoglycan (PG)-induced arthritis (GIA). TCR-TgA mice developed severe and early-onset arthritis, whereas TCR-TgB mice developed weaker arthritis with delayed onset, although TCR-TgB CD4(+) T cells expressed approximately twice more TCR-Vß4 chain protein. The more severe arthritis in TCR-TgA mice was associated with higher amounts of anti-G1 domain-specific antibodies, larger numbers of B cells and activated T helper cells. Importantly, TCR-TgB CD4(+) T cells were more sensitive to in vitro activation-induced apoptosis, correlating with their higher TCR and CD3 expression and with the increased TCR signal strength. These findings indicate that TCR signal strength determines the clinical outcome of arthritis induction: 'optimal' TCR signal strength leads to strong T cell activation and severe arthritis in TCR-TgA mice, whereas 'supra-optimal' TCR signal leads to enhanced elimination of self-reactive T cells, resulting in attenuated disease.

History-dependent domain and skyrmion formation in 2D van der Waals magnet Fe3GeTe2.

The discovery of two-dimensional magnets has initiated a new field of research, exploring both fundamental low-dimensional magnetism, and prospective spintronic applications. Recently, observations of magnetic skyrmions in the 2D ferromagnet Fe3GeTe2 (FGT) have been reported, introducing further application possibilities. However, controlling the exhibited magnetic state requires systematic knowledge of the history-dependence of the spin textures, which remains largely unexplored in 2D magnets. In this work, we utilise real-space imaging, and complementary simulations, to determine and explain the thickness-dependent magnetic phase diagrams of an exfoliated FGT flake, revealing a complex, history-dependent emergence of the uniformly magnetised, stripe domain and skyrmion states. The results show that the interplay of the dominant dipolar interaction and strongly temperature dependent out-of-plane anisotropy energy terms enables the selective stabilisation of all three states at zero field, and at a single temperature, while the Dzyaloshinksii-Moriya interaction must be present to realise the observed Néel-type domain walls. The findings open perspectives for 2D devices incorporating topological spin textures.

Osteoarthritis-like damage of cartilage in the temporomandibular joints in mice with autoimmune inflammatory arthritis.

OBJECTIVE: To study temporomandibular joint (TMJ) involvement in an autoimmune murine model of rheumatoid arthritis (RA), a disease characterized by inflammatory destruction of the synovial joints. Although TMJ dysfunction is frequently found in RA, TMJ involvement in RA remains unclear, and TMJ pathology has not been studied in systemic autoimmune animal models of RA. METHODS: Proteoglycan (PG) aggrecan-induced arthritis (PGIA) was generated in genetically susceptible BALB/c mice. TMJs and joint tissues/cartilage were harvested for histological and immunohistochemical analyses and RNA isolation for quantitative polymerase chain-reaction. Serum cytokine levels were measured in mice with acute or chronic arthritis, and in non-arthritic control animals. RESULTS: Despite the development of destructive synovitis in the limbs, little or no synovial inflammation was found in the TMJs of mice with PGIA. However, the TMJs of arthritic mice showed evidence of aggrecanase- and matrix metalloproteinase-mediated loss of glycosaminoglycan-containing aggrecan, and in the most severe cases, structural damage of cartilage. Serum levels of pro-inflammatory cytokines, including interleukin (IL)-1ß, were elevated in arthritic animals. Expression of the IL-1ß gene was also high in the inflamed limbs, but essentially normal in the TMJs. Local expression of genes encoding matrix-degrading enzymes (aggrecanases and stromelysin) was upregulated to a similar degree in both the limbs and the TMJs. CONCLUSION: We propose that constantly elevated levels of catabolic cytokines, such as IL-1ß, in the circulation (released from inflamed joints) create a pro-inflammatory milieu within the TMJ, causing local upregulation of proteolytic enzymes and subsequent loss of aggrecan from cartilage.

Metal abundances in hot white dwarfs with signatures of a superionized wind.

About a dozen hot white dwarfs with effective temperatures T eff = 65 000 K - 120 000 K exhibit unusual absorption features in their optical spectra. These objects were tentatively identified as Rydberg lines of ultra-high excited metals in ionization stages v-x, indicating line formation in a dense environment with temperatures near 106 K. Since some features show blueward extensions, it was argued that they stem from a superionized wind. A unique assignment of the lines to particular elements is not possible, although they probably stem from C, N, O, and Ne. To further investigate this phenomenon, we analyzed the ultraviolet spectra available from only three stars of this group; that is, two helium-rich white dwarfs, HE 0504-2408 and HS 0713+3958 with spectral type DO, and a hydrogen-rich white dwarf, HS 2115+1148 with spectral type DAO. We identified light metals (C, N, O, Si, P, and S) with generally subsolar abundances and heavy elements from the iron group (Cr, Mn, Fe, Co, Ni) with solar or oversolar abundance. The abundance patterns are not unusual for hot WDs and can be interpreted as the result of gravitational settling and radiative levitation of elements. As to the origin of the ultra-high ionized metals lines, we discuss the possible presence of a multicomponent radiatively driven wind that is frictionally heated.

Topological Crystalline Insulator in a New Bi Semiconducting Phase.

Topological crystalline insulators are a type of topological insulators whose topological surface states are protected by a crystal symmetry, thus the surface gap can be tuned by applying strain or an electric field. In this paper we predict by means of ab initio calculations a new phase of Bi which is a topological crystalline insulator characterized by a mirror Chern number nM = -2, but not a strong topological insulator. This system presents an exceptional property: at the (001) surface its Dirac cones are pinned at the surface high-symmetry points. As a consequence they are also protected by time-reversal symmetry and can survive against weak disorder even if in-plane mirror symmetry is broken at the surface. Taking advantage of this dual protection, we present a strategy to tune the band-gap based on a topological phase transition unique to this system. Since the spin-texture of these topological surface states reduces the back-scattering in carrier transport, this effective band-engineering is expected to be suitable for electronic and optoelectronic devices with reduced dissipation.

Humoral immune response during coronary artery bypass grafting: A comparison of limited approach, "off-pump" technique, and conventional cardiopulmonary bypass.

BACKGROUND: The introduction of limited approaches to the heart and the avoidance of cardiopulmonary bypass (CPB) aim to reduce the invasiveness of CABG by decreasing the systemic release of inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8, as well as the anti-inflammatory agent IL-10. This study compares the humoral immune response in patients undergoing CABG with standard, minimally invasive, and "off-pump" techniques. METHODS AND RESULTS: Thirty patients were divided into 3 operative groups: full sternotomy approach plus CPB (group A); full sternotomy approach, off pump (group B); and limited left anterior thoracotomy, off pump (group C). Plasma levels of TNF-alpha receptors p55 and p75, IL 6, IL-8, and IL-10 were taken at baseline, during CPB, and at 4, 24, and 48 hours and 6 days after surgery. A significant increased release of activated complement factors C5a and C3d, IL-8, and IL-10 was observed in patients subjected to CPB (group A) during the initial period and for a short time after perfusion (P:<0.05). TNF-alpha receptors p55 and p75 showed a prolonged elevation (up to 48 hours) in the CPB group compared with the 2 off-pump groups. IL-6 showed no different release among the 3 surgical groups throughout the entire period. There was no significant difference in any parameter measured in relation to the type of operative approach. CONCLUSIONS: There is an inflammatory, as well as an anti-inflammatory, response during CABG that is related to the general surgical trauma. The release of immune mediators is enhanced by the use of CPB during various perioperative and postoperative phases. The type of operative approach did not influence this immune response.

Low temperature of GroEL/ES overproduction permits growth of Escherichia coli cells lacking trigger factor DnaK.

Escherichia coli trigger factor (TF) and DnaK cooperate in the folding of newly synthesized proteins. The combined deletion of the TF-encoding tig gene and the dnaK gene causes protein aggregation and synthetic lethality at 30 degrees C. Here we show that the synthetic lethality of deltatigdeltadnaK52 cells is abrogated either by growth below 30 degrees C or by overproduction of GroEL/GroES. At 23 degrees C deltatigdeltadnaK52 cells were viable and showed only minor protein aggregation. Overproduction of GroEL/GroES, but not of other chaperones, restored growth of deltatigdeltadnaK52 cells at 30 degrees C and suppressed protein aggregation including proteins >/= 60 kDa, which normally require TF and DnaK for folding. GroEL/GroES thus influences the folding of proteins previously identified as DnaK/TF substrates.

Low temperature or GroEL/ES overproduction permits growth of Escherichia coli cells lacking trigger factor and DnaK.

Escherichia coli trigger factor (TF) and DnaK cooperate in the folding of newly synthesized proteins. The combined deletion of the TF-encoding tig gene and the dnaK gene causes protein aggregation and synthetic lethality at 30 degrees C. Here we show that the synthetic lethality of DeltatigDeltadnaK52 cells is abrogated either by growth below 30 degrees C or by overproduction of GroEL/GroES. At 23 degrees C DeltatigDeltadnaK52 cells were viable and showed only minor protein aggregation. Overproduction of GroEL/GroES, but not of other chaperones, restored growth of DeltatigDeltadnaK52 cells at 30 degrees C and suppressed protein aggregation including proteins >/=60 kDa, which normally require TF and DnaK for folding. GroEL/GroES thus influences the folding of proteins previously identified as DnaK/TF substrates.

Neuromonitoring and neurocognitive outcome in off-pump versus conventional coronary bypass operation.

BACKGROUND: Cardiopulmonary bypass seems to be a major cause for both intraoperative microemboli and cerebral hypoperfusion. This study investigates high intensive transient signals (HITS) in transcranial Doppler ultrasound (TCD) and serum levels of the neurobiochemical marker protein S-100 in patients who underwent coronary artery bypass operation without cardiopulmonary bypass (off-pump CABG) in comparison with the conventional procedure using cardiopulmonary bypass (CPB). The results are related to the neuropsychologic outcome in both surgical groups. METHODS: Forty patients were randomized in 2 groups (20 conventional and 20 off-pump CABG). Neurocognitive status was assessed preoperatively and postoperatively. Venous serum levels of S-100 protein were measured before and after coronary operation, HITS were measured in the middle cerebral artery during the operation. RESULTS: The median value of HITS was 394.5 (0 to 2217) in the conventional versus 11 (0 to 50) in the off-pump group, p less than 0.0001. Postoperative S-100 serum levels were: 3.76 (0.13 to 11.2) microg/L (conventional) versus 0.13 (0.04 to 1.01) microg/L (off-pump), p less than 0.0001. Postoperative cognitive testing showed significantly different results with a postoperative impairment of 90% of the patients in the conventional group versus no impairment in the off-pump group. CONCLUSIONS: Cognitive impairment seems to be strongly associated to CPB and the occurrence of micro-emboli. The off-pump technique appears to be promising in order to eliminate the source of these neuropyschologic impairments following CABG operation.

Comparison of different anticalcification treatments for stentless bioprostheses.

BACKGROUND: New anticalcificant treatments have been developed because tissue calcification is a major contributing factor for bioprosthetic valve failure. METHODS: Aortic valve leaflet and aortic root tissue samples from stentless bioprostheses treated with No-React (Biocor, Belo Horizonte, Brazil), AOA (Medtronic freestyle, Minneapolis, MN), and BiLinx (St. Jude Medical, St. Paul, MN) were compared to a control group by subcutaneous implantation in 60 male weanling Sprague-Dawley rats. RESULTS: Calcium levels were in the range of 0.3 to 2.2 mg/g dry tissue at 3 and 12 weeks in all three treated aortic valve leaflet implants. The BiLinx treatment proved anticalcificant effectiveness on aortic root samples as well. There were statistically significant differences for valve leaflet tissue samples: No-React = AOA < BiLinx < < Control and for aortic root tissue samples: BiLinx < < AOA < Control = No-React. CONCLUSION: Calcification of aortic valve leaflets was significantly reduced by all new anticalcificant treatments. Inhibition of cellular calcification (BiLinx) resulted in additional reduction of aortic root calcification. Maximum anticalcificant properties upon both leaflet and aortic root is important as these are considered a functional unit in stentless bioprostheses.

Tyrosine pretreatment reverses hypothermia-induced behavioral depression.

Cold exposure accelerates the firing frequency of norepinephrine (NE) neurons, enhancing NE release and leading to NE depletion in specific regions of the brain. The accelerated firing activates the enzyme tyrosine-hydroxylase, making it more tyrosine sensitive. The reduction of brain NE is accompanied by a behavioral depression on the open field test. Two experiments were performed on adult male rats. First, it was determined whether systematic lowering of core body temperature produced behavioral depression in the swim test. Second, treatment with the NE precursor tyrosine was employed in an attempt to prevent hypothermia-induced behavioral depression. In Experiment 1, two levels of hypothermia were highly effective in producing behavioral depression in rats forced to swim in a narrow cylinder. In Experiment 2, treatment with tyrosine (400 mg/kg, IP) thirty minutes prior to the hypothermia procedure completely reversed the behavioral depression found in Experiment 1. Tyrosine administration did not significantly influence the rate of deep body cooling during the hypothermia treatment.

Cyclo (His-Pro), d-amphetamine and striatal dopamine: a microdialysis study.

Extracellular levels of dopamine (DA) and its metabolites (DOPAC and HVA) were monitored in the striatum of rats using in vivo microdialysis, in an attempt to elucidate the mechanism of cyclo (His-Pro) (histidyl-proline-diketopiperazine, CHP) on dopaminergic activity. Pretreatment with CHP (0.5 mg/kg SC) (n = 5) or the equivalent volume of saline (n = 5) was followed 30 min later by 5 mg/kg IP of d-amphetamine. Dialysate samples were collected and analyzed by high performance liquid chromatography with electrochemical detection (HPLC-EC). Following the initial increase in DA caused by d-amphetamine, DA levels of CHP-treated rats were significantly lower than saline-treated rats across time (p less than 0.05). No difference was observed for DOPAC or HVA. It is therefore unlikely that CHP interferes with the d-amphetamine-induced inhibition of DA reuptake. Other neurotransmitter systems may be involved in the CHP-induced augmentation of amphetamine's behavioral effects. Our data, as well as previous findings, suggest that attenuation of the dopaminergic response to d-amphetamine might be best explained on the basis of striatal DA depletion, possibly via tyrosine hydroxylase (TH) inhibition. This study also indicates that a dissociation may exist between the behavioral and the striatal DA response to acute amphetamine. The data support the hypothesis that amphetamine releases DA from a newly synthesized, extravesicular cytoplasmic pool, and that intracellular striatal DA is present in considerable excess relative to the extracellular DA.

Retention of a spatial task after intraperitoneal, subcutaneous or intravenous injections of equal doses of atropine.

The retention of a well-learned spatial task was assessed in rats after equal doses of atropine sulfate (30 mg/kg) were administered by intraperitoneal, subcutaneous or intravenous injection. Atropine sulfate disrupted first choice accuracy and escape latency measures of spatial retention. Intravenous and intraperitoneal atropine sulfate produced significant impairments in choice accuracy. However, only intravenous atropine sulfate produced a significant impairment in escape latency. Atropine sulfate administered subcutaneously never produced a significant impairment in spatial retention compared to the intravenous saline control. One would predict from the present findings that a centrally active drug might produce a highly variable effect on a specific behavior as a function of the parenteral route of administration.

Hypothermia impairs performance in the Morris water maze.

Fifteen rats were trained to learn the location of a spatially fixed platform hidden in a Morris water maze (14-16 degrees C). Asymptotic performance was achieved over six training days (10 trials/day). Then retention of the task was assessed immediately after lowering core body temperature (Tc) to 28 degrees or 30 degrees C or stabilizing at 37 degrees C (the normothermic control). The hypothermia treatment order was counterbalanced according to a Latin-square design. Hypothermia significantly impaired all measures of spatial performance. Hypothermic animals were then rewarmed in a 40 degrees C water bath to 37 degrees C Tc and spatial performance tested again. Artificial rewarming resulted in complete recovery of all measures of spatial performance. These results demonstrate that hypothermia impairs performance in the Morris water maze, possibly by an amnesic mechanism, and that returning Tc to normothermic levels initiates recovery of performance.

Discrepancy of sizers for conventional and stentless aortic valve implants.

BACKGROUND AND AIM OF THE STUDY: As the hemodynamic performance of an artificial heart valve is closely related to the size of the valve implanted, exact sizing of the prosthesis is important in aortic valve replacement. In the past, discrepancies have been recognized between the actual and labeled diameters of sizers used for conventional aortic valves; this study aimed to examine the accuracy of sizers for both conventional and stentless valves. METHODS: Currently used sets of sizers were analyzed using a high-precision digital micrometer with a resolution of 0.01 mm. Sizers of aortic bileaflet mechanical valves (ATS, CarboMedics, St. Jude Medical Standard, St. Jude Medical HP), conventional aortic bioprostheses (Carpentier Edwards) and stentless aortic bioprostheses (Freestyle, TorontoSPV) were analyzed. The diameters were recorded when the sizer could not be moved laterally while still able to be rotated. RESULTS: Results are given as mean +/- standard deviation for 20 repeat measurements. All mechanical valve sizers were 0.77 +/- 0.03 to 1.01 +/- 0.02 mm larger than labeled, whereas all bioprosthetic valve sizers proved to be sized as labeled (0 +/- 0.01 mm). CONCLUSIONS: Exact sizing is important in stentless valve replacement. The use of accurate sizers is recommended with other types of replacement valves as well. Results of valve replacement procedures worldwide would be more comparable if sizers of identical size were available in all operating rooms. As long as discrepancies between different sizers still exist, surgeons must be made aware of the problem.

Nimodipine improves spatial working memory and elevates hippocampal acetylcholine in young rats.

The calcium channel blocker nimodipine has been reported to improve cognitive performance in aged and brain-damaged animals. In the present study, the effects of nimodipine and placebo on spatial working memory and hippocampal acetylcholine were studied in young Fischer-344 rats. Nimodipine or placebo was administered via subcutaneously implanted, sustained-release pellets. Each active pellet contained 20 mg of nimodipine and released the drug over approximately 21 days. Two days after the drug or placebo pellets were implanted, training in the 8-arm radial maze started and continued for 12 days. Rats were required to learn a win-shift surgery. Nimodipine-treated animals learned the maze more rapidly than a placebo-treated group as indicated by the number of correct choices out of the first eight arms visited (p less than 0.001). Treated rats also made twice as many choices per unit time during the first week of training (p = 0.005). To assess hippocampal acetylcholine release, in vivo microdialysis was performed while animals were awake and unrestrained, 19-21 days after pellet implantation. A probe with a 3 mm semipermeable tip was placed in the hippocampus (CA1 and dentate gyrus), and individual microliters dialysate samples were collected at 2 microliters/min and immediately analyzed by high performance liquid chromatography with electrochemical detection. Significantly higher extracellular ACh levels were found in nimodipine-treated rats (71.4 +/- 3.6 nM; n = 4) compared to controls (52.5 +/- 2.5 nM; n = 5) (p = 0.003) and in another group of rats of the same age that received identical drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Effectiveness of two radiofrequency ablation systems in atrial tissue.

OBJECTIVE: The efficacy of the left atrial radiofrequency ablation procedure, for the curative treatment of atrial fibrillation, is dependent upon obtaining a confluent transmural line of hyperthermic cellular death. We compare the in vitro effectiveness of obtaining transmural hyperthermic cellular death (>55 degrees C) of both the Osypka single electrode and Boston Scientific Thermaline multi-electrode radiofrequency systems. METHODS: Isolated cadaver porcine hearts were used to measure epicardial temperatures either 'central' or at the 'edge' in relation to an endocardial applied radiofrequency electrode. Reference set point was 70 degrees C, and 4-6-mm thick atrial tissue was used for all applications. 'Edge' temperatures with the Boston Scientific unit were measured whilst activating both adjacent electrodes. RESULTS: Boston Scientific: Probe temperature closely approximated the set point. 'Central' epicardial temperature was lower than probe temperature until after 40 s application (P<0.05), 55 degrees C was reached at 50 s, maximal mean temperature 63.0+/-8.9 degrees C was reached at 100 s. Epicardial 'edge' temperature remained lower than probe temperature for the entire 120 s (P<0.05). Osypka: Probe temperature tended to overshoot the set point. 'Central' epicardial temperature paralleled and occasionally exceeded probe temperature reaching 55 degrees C within 10 s, maximal mean temperature 76.3+/-12.7 degrees C was reached at 10 s and exceeded the set point thereafter. 'Edge' temperature was no different to probe temperature or 'central' epicardial temperature. The mean epicardial temperatures produced with a 65 degrees C set point was no different to that with the 70 degrees C set point, except for a lower final temperature at 60 s. CONCLUSIONS: The Boston Scientific system (70 degrees C set point) requires a minimum in vitro application of 40 s to transmurally increase 4-6 mm atrial tissue temperature above 55 degrees C, and 120-s duration per application would appear to be a reasonable clinical recommendation. The Osypka system transfers thermal energy more effectively, requiring less than 10 s in vitro to achieve a similar transmural temperature, and a 30-s application can be recommended. However, a tendency to overshoot both probe and set point temperature, suggests that a lower set point of 65 degrees C might be safer and as effective.

Endothelial function of human vena saphena magna prepared with different minimally invasive harvesting techniques.

OBJECTIVES: Minimally invasive saphenous harvesting techniques have been shown to reduce post-operative morbidity. However, when applying new techniques of vein harvesting, endothelial integrity should be preserved in order to guarantee graft quality. We investigated the impact of two different minimally invasive saphenous vein harvesting techniques on endothelial function compared with the traditional 'open' technique by inducing endothelium-dependent in vitro relaxation. METHODS: Two different minimally invasive techniques for harvesting the greater saphenous vein were used in 66 patients, either using a video-assisted dissector (ETHI, n=33) or a light coupled retractor (AUTS, n=33); other patients were treated conventionally (CONV, n=30). The physiological response was tested in vitro using an organ chamber on vein segments exposed to acetylcholine after precontraction with potassium. RESULTS: In both minimally invasive groups, two patients each had to be converted to the traditional open technique and dropped out of the study. The endothelial function of the other veins harvested by either of the minimally invasive techniques showed no significant difference compared with veins harvested conventionally. Reactivity was measured as the percentage relaxation of pharmacological contraction and was significant in all groups (P<0.05); ETHI, 49.1+/-4.2%; AUTS, 48.8+/-5.1%; and CONV, 51.7+/-6. 0%. The responder/non-responder ratio was similar in all groups: ETHI (two drop-outs), 28/3 (90.3%); AUTS (two drop-outs), 28/3 (90. 3%); and CONV, 27/3 (90.0%). CONCLUSION: Veins harvested by minimally invasive techniques have not shown an impaired reactivity of the endothelium compared with the conventional technique.