Exotic Dark Matter Search with the Majorana Demonstrator.

With excellent energy resolution and ultralow-level radiogenic backgrounds, the high-purity germanium detectors in the Majorana Demonstrator enable searches for several classes of exotic dark matter (DM) models. In this work, we report new experimental limits on keV-scale sterile neutrino DM via the transition magnetic moment from conversion to active neutrinos ν_{s}→ν_{a}. We report new limits on fermionic dark matter absorption (χ+A→ν+A) and sub-GeV DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), and new exclusion limits for bosonic dark matter (axionlike particles and dark photons). These searches utilize the (1-100)-keV low-energy region of a 37.5-kg y exposure collected by the Demonstrator between May 2016 and November 2019 using a set of ^{76}Ge-enriched detectors whose surface exposure time was carefully controlled, resulting in extremely low levels of cosmogenic activation.

Final Result of the Majorana Demonstrator's Search for Neutrinoless Double-ß Decay in

The Majorana Demonstrator searched for neutrinoless double-ß decay (0νßß) of ^{76}Ge using modular arrays of high-purity Ge detectors operated in vacuum cryostats in a low-background shield. The arrays operated with up to 40.4 kg of detectors (27.2 kg enriched to ∼88% in ^{76}Ge). From these measurements, the Demonstrator has accumulated 64.5 kg yr of enriched active exposure. With a world-leading energy resolution of 2.52 keV FWHM at the 2039 keV Q_{ßß} (0.12%), we set a half-life limit of 0νßß in ^{76}Ge at T_{1/2}>8.3×10^{25} yr (90% C.L.). This provides a range of upper limits on m_{ßß} of (113-269) meV (90% C.L.), depending on the choice of nuclear matrix elements.

α -event characterization and rejection in point-contact HPGe detectors.

P-type point contact (PPC) HPGe detectors are a leading technology for rare event searches due to their excellent energy resolution, low thresholds, and multi-site event rejection capabilities. We have characterized a PPC detector's response to α particles incident on the sensitive passivated and p + surfaces, a previously poorly-understood source of background. The detector studied is identical to those in the Majorana Demonstrator experiment, a search for neutrinoless double-beta decay ( 0 ν ß ß ) in 76 Ge. α decays on most of the passivated surface exhibit significant energy loss due to charge trapping, with waveforms exhibiting a delayed charge recovery (DCR) signature caused by the slow collection of a fraction of the trapped charge. The DCR is found to be complementary to existing methods of α identification, reliably identifying α background events on the passivated surface of the detector. We demonstrate effective rejection of all surface α events (to within statistical uncertainty) with a loss of only 0.2% of bulk events by combining the DCR discriminator with previously-used methods. The DCR discriminator has been used to reduce the background rate in the 0 ν ß ß region of interest window by an order of magnitude in the Majorana Demonstrator  and will be used in the upcoming LEGEND-200 experiment.

First Limit on the Direct Detection of Lightly Ionizing Particles for Electric Charge as Low as e/1000 with the Majorana Demonstrator.

The Majorana Demonstrator is an ultralow-background experiment searching for neutrinoless double-beta decay in ^{76}Ge. The heavily shielded array of germanium detectors, placed nearly a mile underground at the Sanford Underground Research Facility in Lead, South Dakota, also allows searches for new exotic physics. Free, relativistic, lightly ionizing particles with an electrical charge less than e are forbidden by the standard model but predicted by some of its extensions. If such particles exist, they might be detected in the Majorana Demonstrator by searching for multiple-detector events with individual-detector energy depositions down to 1 keV. This search is background-free, and no candidate events have been found in 285 days of data taking. New direct-detection limits are set for the flux of lightly ionizing particles for charges as low as e/1000.

New Limits on Bosonic Dark Matter, Solar Axions, Pauli Exclusion Principle Violation, and Electron Decay from the Majorana Demonstrator.

We present new limits on exotic keV-scale physics based on 478 kg d of Majorana Demonstrator commissioning data. Constraints at the 90% confidence level are derived on bosonic dark matter (DM) and solar axion couplings, Pauli exclusion principle violating (PEPV) decay, and electron decay using monoenergetic peak signal limits above our background. Our most stringent DM constraints are set for 11.8 keV mass particles, limiting g_{Ae}<4.5×10^{-13} for pseudoscalars and (α^{'}/α)<9.7×10^{-28} for vectors. We also report a 14.4 keV solar axion coupling limit of g_{AN}^{eff}×g_{Ae}<3.8×10^{-17}, a 1/2ß^{2}<8.5×10^{-48} limit on the strength of PEPV electron transitions, and a lower limit on the electron lifetime of τ_{e}>1.2×10^{24} yr for e^{-}→ invisible.

Characterization of the recombinant Brettanomyces anomalus ß-glucosidase and its potential for bioflavouring.

AIM: Plant materials used in the food industry contain up to five times more aromas bound to glucose (glucosides) than free, unbound aromas, making these bound aromas an unused flavouring potential. The aim of this study was to identify and purify a novel ß-glucosidase from Brettanomyces yeasts that are capable of releasing bound aromas present in various food products. METHODS AND RESULTS: We screened 428 different yeast strains for ß-glucosidase activity and are the first to sequence the whole genome of two Brettanomyces yeasts (Brettanomyces anomalus and Brettanomyces bruxellensis) with exceptionally high ß-glucosidase activity. Heterologous expression and purification of the identified B. anomalus ß-glucosidase showed that it has an optimal activity at a higher pH (5·75) and lower temperature (37°C) than commercial ß-glucosidases. Adding this B. anomalus ß-glucosidase to cherry beers and forest fruit milks resulted in increased amounts of benzyl alcohol, eugenol, linalool and methyl salicylate compared to Aspergillus niger and Almond glucosidase. CONCLUSIONS: The newly identified B. anomalus ß-glucosidase offers new possibilities for food bioflavouring. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to sequence the B. anomalus genome and to identify the ß-glucosidase-encoding genes of two Brettanomyces species, and reports a new bioflavouring enzyme.

[Relationship between pre-dialysis period and mortality and morbidity; the importance of timely pre-dialysis care]. / Relatie predialyseduur met mortaliteit en morbiditeit; het belang van een tijdige voorbereiding op dialyse.

OBJECTIVE: To investigate if the duration of pre-dialysis nephrology care is a predictive factor for mortality and morbidity in the first year of renal replacement therapy (RRT). DESIGN: Cohort study. METHOD: We included all patients with chronic or acute-on-chronic renal failure whose estimated glomerular filtration time (eGFR) was < 30 ml/min/1.73 m2 6 months before starting RRT and in whom RRT was initiated in 2005-2006 or 2009-2010. Depending on the duration of the pre-dialysis period we allocated patients to the short (< 6 months) or the long (≥ 6 months) pre-dialysis group. Data regarding mortality and morbidity were registered at the initiation of RRT (T0), after 3 (T3), 6 (T6) and 12 (T12) months. RESULTS: Thirty-nine patients with a short pre-dialysis period and 49 patients with a long pre-dialysis period were included. Patients with a short pre-dialysis period had higher mortality (T6: 23.1% vs. 8.2%; p = 0.05), more hospital stays (2 vs. 1 stay; p = 0.02), and longer hospital stays (16 vs. 3 days; p < 0.01). Additionally, in this group RRT more often had to be started through an acute route of administration for dialysis, which was associated with a higher mortality at T6 (23.8% vs. 6.5%; p = 0.02). CONCLUSION: A too short pre-dialysis period is predictive for higher mortality and morbidity in the first year after initiation of RRT. The necessity for an acute route of administration for dialysis seems to be the most important predictor.

Switching mechanism in two-terminal vanadium dioxide devices.

Two-terminal thin film VO2 devices show an abrupt decrease of resistance when the current or voltage applied exceeds a threshold value. This phenomenon is often described as a field-induced metal-insulator transition. We fabricate nano-scale devices with different electrode separations down to 100 nm and study how the dc switching voltage and current depend on device size and temperature. Our observations are consistent with a Joule heating mechanism governing the switching. Pulsed measurements show a switching time to the high resistance state of the order of one hundred nanoseconds, consistent with heat dissipation time. In spite of the Joule heating mechanism which is expected to induce device degradation, devices can be switched for more than 10(10) cycles making VO2 a promising material for nanoelectronic applications.

Benzoate treatment and the glycine index in nonketotic hyperglycinaemia.

High-dose benzoate treatment aimed at reducing plasma glycine levels to normal reduces seizures and increases wakefulness in patients with nonketotic hyperglycinaemia (NKH). Since benzoate metabolism is dependent on the available glycine pool, and since the glycine pool is variably affected by the deficiency in the glycine cleavage enzyme system, we examined the importance of interpatient variability in benzoate requirement. To correct for the dietary glycine contribution, the glycine index was introduced as the molar requirement of benzoate dose necessary to normalize plasma glycine levels and subtracting from that the dietary glycine intake, both corrected for weight. The glycine index varied between 3.62 and 4.87 mmol/kg per day in five patients with a poor neurodevelopmental outcome and between 0.92 and 1.90 mmol/kg per day in four patients with a better neurodevelopmental outcome, and was 2.54 mmol/kg per day in a single patient with an intermediate outcome. The glycine index was stable over time within each patient. Exceeding the balance by either increasing food glycine intake or decreasing the benzoate dose resulted in increased glycine levels. Exceeding the glycine tolerance by increasing benzoate resulted in elevated and toxic levels of benzoate. The glycine index is a stable, individually specific parameter in patients with NKH. It has clinical consequences for the dose of benzoate required and the role of dietary management. Through its correlation with neurodevelopmental outcome, the glycine index points to potential genetic factors that could contribute to the psychomotor retardation in NKH.

Fertilization and early embryonic development in heifers and lactating cows in summer and lactating and dry cows in winter.

Two experiments in two seasons evaluated fertilization rate and embryonic development in dairy cattle. Experiment 1 (summer) compared lactating Holstein cows (n = 27; 97.3 +/- 4.1 d postpartum [dppl; 40.0 +/- 1.5 kg milk/d) to nulliparous heifers (n = 28; 11 to 17 mo old). Experiment 2 (winter) compared lactating cows (n = 27; 46.4 +/- 1.6 dpp; 45.9 +/- 1.4 kg milk/d) to dry cows (n = 26). Inseminations based on estrus included combined semen from four high-fertility bulls. Embryos and oocytes recovered 5 d after ovulation were evaluated for fertilization, embryo quality (1 = excellent to 5 = degenerate), nuclei/embryo, and accessory sperm. In experiment 1, 21 embryos and 17 unfertilized oocytes (UFO) were recovered from lactating cows versus 32 embryos and no UFO from heifers (55% vs. 100% fertilization). Embryos from lactating cows had inferior quality scores (3.8 +/- 0.4 vs. 2.2 +/- 0.3), fewer nuclei/embryo (19.3 +/- 3.7 vs. 36.8 +/- 3.0) but more accessory sperm (37.3 +/- 5.8 vs. 22.4 +/- 5.5/embryo) than embryos from heifers. Sperm were attached to 80% of UFO (17.8 +/- 12.1 sperm/UFO). In experiment 2, lactating cows yielded 36 embryos and 5 UFO versus 34 embryos and 4 UFO from dry cows (87.8 vs. 89.5% fertilization). Embryo quality from lactating cows was inferior to dry cows (3.1 +/- 0.3 vs. 2.2 +/- 0.3), but embryos had similar numbers of nuclei (27.2 +/- 2.7 vs. 30.6 +/- 2.1) and accessory sperm (42.0 +/- 9.4 vs. 36.5 +/- 6.3). From 53% of the flushings from lactating cows and 28% from dry cows, only nonviable embryos were collected. Thus, embryos of lactating dairy cows were detectably inferior to embryos from nonlactating females as early as 5 d after ovulation, with a surprisingly high percentage of nonviable embryos. In addition, fertilization rate was reduced only in summer, apparently due to an effect of heat stress on the oocyte.

Hemodynamic changes with right lateral decubitus body positioning in the tilted porcine heart.

BACKGROUND: In beating-heart coronary surgical procedures, exposure of posterior vessels through sternotomy causes cardiac function to deteriorate. We hypothesized that turning the subject to the right lateral decubitus position before cardiac retraction improves exposure of posterior vessels and preserves cardiac pump function on displacement. METHODS: Eight 80-kg open-chest pigs were instrumented with catheter-tip manometers. After a stepwise 60-degree turn to the right lateral decubitus position of the body, the heart was retracted anteriorly to 90 degrees with a suction stabilizer. RESULTS: Right lateral body positioning caused an approximately 45-degree right deviation of the apex, thereby exposing the left atrial groove. Stroke volume, mean arterial pressure, right atrial pressure, and right ventricular end-diastolic pressure increased to 106% +/- 5% (mean +/- standard error of the mean, p = 0.31), 106% +/- 3% (p = 0.01), 129% +/- 8% (p = 0.001), and 171% +/- 14% (p = 0.002), respectively, compared with control values. In contrast, left atrial pressure decreased to 73% +/- 6% (p = 0.007), whereas left ventricular preload remained unchanged (110% +/- 8%, p = 0.26). Additional anterior displacement to 90 degrees fully exposed the posterior vessels, and stroke volume decreased to 90% +/- 3% (p = 0.01) and mean arterial pressure to 93% +/- 5% (p = 0.07) at the expense of further increased right ventricular preload (256% +/- 28%, p < 0.001). CONCLUSIONS: By placing the subject in the right lateral decubitus position, exposure through sternotomy of posterior vessels in the beating porcine heart was facilitated while mean arterial pressure was maintained.

Random costs in combinatorial optimization

The random cost problem is the problem of indentifying the minimum in a list of random numbers. By definition, this problem cannot be solved faster than by exhaustive search. It is shown that a classical NP-hard optimization problem, number partitioning, is essentially equivalent to the random cost problem. On the one hand this explains the bad performance of heuristic approaches to the number partitioning problem, but on the other hand it allows one to calculate the probability distributions of the optimum and suboptimum costs.

Effect of perfluorodecalin on human retinal pigment epithelium and human corneal endothelium in vitro.

BACKGROUND: Perfluorocarbon liquids are useful intraoperative tools in complicated vitreoretinal surgery. They are usually removed at the end of the procedure, but small amounts may remain in the eye. Recently, contradictory results have been reported on the damage in association with residual perfluorocarbon liquids in the eye. This study examined the effects of perfluorodecalin on human retinal pigment epithelium and corneal endothelium in vitro. METHODS: Vitality and proliferative capacity of cell cultures were measured after incubation with perfluorodecalin. Vitality of cell cultures were measured using the Life-Dead assay. Cell proliferation was determined by measuring incorporation of 5-bromo-2'-deoxyuridine into cellular DNA. Furthermore, endothelium of organ-cultured human corneas was examined after incubation with perfluorodecalin by photodocumentation. RESULTS: Both cell types showed less extinctions in the Life-Dead assay after incubation with perfluorodecalin. After removing perfluorodecalin from the cultures, cells showed the same capacity of proliferation as the control cells. Compared to control corneas, perfluorodecalin induced a decrease in endothelial cell density. In four corneas, endothelial cell necrosis was observed. CONCLUSION: Decreasing extinctions in the Life-Dead assay after incubation with perfluorodecalin can be interpreted as showing a decreasing amount of vital cells. Because cell proliferation showed no significant changes the results suggest that perfluorodecalin may not be directly toxic to cells in vitro. It may exert an indirect or mechanical effect on cell function by impeding the normal metabolic exchange between endothelium and medium. Based on these results perfluorodecalin should be completely removed after operation.

A conformational switch at the 3' end of a plant virus RNA regulates viral replication.

3' untranslated regions of alfamo- and ilar-virus RNAs fold into a series of stem-loop structures to which the coat protein binds with high affinity. This binding plays a role in initiation of infection ('genome activation') and has been thought to substitute for a tRNA-like structure that is found at the 3' termini of related plant viruses. We propose the existence of an alternative conformation of the 3' ends of alfamo- and ilar-virus RNAs, including a pseudoknot. Based on (i) phylogenetic comparisons, (ii) in vivo and in vitro functional analyses of mutants in which the pseudoknot has been disrupted or restored by compensatory mutations, (iii) competition experiments between coat protein and viral replicase, and (iv) investigation of the effect of magnesium, we demonstrate that this pseudoknot is required for replication of alfalfa mosaic virus. This conformation resembles the tRNA-like structure of the related bromo- and cucumo-viruses. A low but specific interaction with yeast CCA-adding enzyme was found. The existence of two mutually exclusive conformations for the 3' termini of alfamo- and ilar-virus RNAs could enable the virus to switch from translation to replication and vice versa. The role of coat protein in this modulation and in genome activation is discussed.

Population genetics and disease susceptibility: characterization of central European haplogroups by mtDNA gene mutations, correlation with D loop variants and association with disease.

Mitochondrial (mt)DNA haplogroups in a German control group (n = 67) were characterized by screening mitochondrial coding regions encompassing most of the ND, tRNA and cyt b genes. We used a PCR-SSCP screening approach followed by direct sequencing of polymorphic mtDNA fragments. Five major mtDNA lineages, diverging in at least nine different haplogroups, could be defined by characteristic polymorphic sites in mitochondrial genes. Additional sequencing of two hypervariable segments (HVS-I and II) of the non-coding displacement (D) loop in all control subjects revealed that certain D loop variants were strongly correlated with lineages and haplogroups, while others represented hotspots occurring frequently in different haplogroups. The existence of identified lineages and haplogroups received support from data in the literature, obtained by use of different approaches. Subsequently, we investigated four disease groups for association with these haplogroups: (i) LHON patients (n = 55) carrying at least one of the primary/intermediate LHON mutations at nt 3460, 11778, 14484 and/or 15257; (ii) patients suffering from Wolfram or DIDMOAD syndrome (n = 8); (iii) MELAS patients (n = 9); (iv) a group of children, who died from 'sudden infant death syndrome' (SIDS) (n = 9). The distribution patterns among the haplogroups of the disease groups (LHON, DIDMOAD and SIDS) differed considerably from the control population. LHON and DIDMOAD were significantly under-represented in the most frequent German haplogroup DC, but were concentrated in a mtDNA lineage defined by polymorphisms at nt 4216 + 11251 + 16126. As this lineage diverged into two precisely defined haplogroups, LHON and DIDMOAD could be assigned to the two haplogroups separately. Strikingly, SIDS was often found in association with two rare German haplogroups. MELAS patients were equally distributed among German haplogroups and, moreover, did not reveal any accumulation of specific D loop variants. We conclude that certain European mtDNA haplogroups define a genetic susceptibility basis for various disorders.

Distress and coping among women with HIV infection: preliminary findings from a multiethnic sample.

In a multiethnic sample of 53 women with HIV/AIDS, nearly 40% reported clinically significant levels of depression symptomatology and anxiety. Compared to a nonpatient norm, distress levels were higher among the Latina, African-American, and white women who made up the HIV sample. Prayer and rediscovery of self were their most frequent coping responses, suggesting that clinicians working with HIV/AIDS populations not overlook the importance of spiritual faith and practices in adapting to HIV infection.

Wolfram (DIDMOAD) syndrome and Leber hereditary optic neuropathy (LHON) are associated with distinct mitochondrial DNA haplotypes.

Because Wolfram (or DIDMOAD) syndrome is supposed to be a mitochondrial (mt)-mediated disease, we investigated a group of eight DIDMOAD patients with respect to point mutations of the mtDNA thus far described as being associated with defined mitochondrial disorders such as MELAS, MERRF, and LHON. Furthermore, to screen DIDMOAD patients for other mtDNA defects we used Southern blot analysis to detect mtDNA length mutations and rearrangements as well as PCR-SSCP and direct sequencing to screen all ND genes (complex I of the respiratory chain), the 22 tRNAs, and a part of the cyt b gene for unknown mutations. As a disease control group, 17 LHON patients (harboring one of the primary LHON mutations) were included in this study because of the overlapping clinical symptoms (optic atrophy) in both syndromes. We compared mtDNA variants identified in DIDMOAD patients with those found in LHON patients as well as in a control group consisting of 67 healthy German blood donors. In total, the control group was characterized by 29 polymorphic sites in ND and tRNA genes that define certain major Caucasian haplotypes. We found that a cluster of nucleotide exchanges at nucleotide positions (nps) 4216 and 11,251 roughly discriminates controls (12/67 controls, 18%) from the disease groups (6/8 DIDMOAD patients, 75%; 10/17 LHON patients, 59%). All 4216-positive LHON patients (10 patients) were concentrated in a haplogroup defined by additional exchanges at nps 10,398, 12,612, and 13,708 (haplogroup A), while the bulk of 4216-positive DIDMOAD patients (5 patients) were found in a distinct haplogroup consisting of nucleotide exchanges at nps 4917, 10,463, 13,368, 14,233, and 15,928. The frequencies of both haplogroups were significantly lower in the control group versus the respective disease groups. A more detailed analysis was performed by sequencing the two hypervariable regions of the non-coding D-loop region from patients and controls and corroborated the ranging in the two major haplogroups. Thus, the different clinical features of the mitochondrial disease groups investigated here corresponded to different clusters of mtDNA variants, which might act as predisposing haplotypes, increasing the risk for disease.

SAP kinase-3, a new member of the family of mammalian stress-activated protein kinases.

Stress-activated protein kinases are MAP kinase homologues that are activated by cellular stresses, bacterial endotoxin and inflammatory cytokines. They are activated by a dual threonine/tyrosine phosphorylation within a TPY sequence in the case of stress-activated protein kinase-1 and its isoforms (also called JNKs) or a TGY sequence in the case of stress-activated protein kinase-2 and its isoforms (also called p38, p40, RK, CSBPs, XMpk2 and Mxi2). Here we report the cloning and sequencing of a new protein kinase from rat with a TGY sequence in the activation domain. This stress-activated protein kinase-3 is 60% identical to mouse stress-activated protein kinase-2 and 45% identical to HOG1 from Saccharomyces cerevisiae. Transcripts encoding stress-activated protein kinase-3 are widely expressed, with high levels in skeletal muscle.

Molecular distinction of three N-methyl-D-aspartate-receptor subtypes in situ and developmental receptor maturation demonstrated with the photoaffinity ligand 125I-labeled CGP 55802A.

Activation of N-methyl-D-aspartate (NMDA) receptors is essential for synaptic plasticity in the central nervous system and contributes to neuronal death under various pathological conditions. Although several subunits have been cloned, the structure of NMDA receptors in situ is unresolved. By using a photoreactive antagonist with nanomolar affinity to the NMDA-binding site, three types of receptors were differentiated by their pattern of photoaffinity-labeled subunits. In adult brain, a protein of 175-kDa was photoreactive that displayed a profile of ligand binding and autoradiographical distribution corresponding to NMDA receptors. In contrast, in early postnatal brain, proteins of both 175 kDa and 115 kDa were photolabeled. This labeling pattern is switched to that of adult brain around postnatal day 10, pointing to a structural maturation of NMDA receptors. A third type of receptor could be identified in cerebellar granule cell cultures, where NMDA receptors mediate trophic effects and photolabeling was exclusively targeted to a 115-kDa protein. To identify the proteins labeled in situ, recombinant receptors were subjected to photolabeling. When the NR1 subunit was coexpressed with either the NR2A, NR2B, or NR2C subunit, only the combination of NR1/NR2A was photoreactive. Both the NR1 and NR2A subunits were photolabeled, corresponding in size to the proteins labeled in situ. However, the lack of subunit-selectivity in photolabeling the NR1/NR2A combination suggests the presence of additional receptor components in situ to explain the subunit-selective photoreactivity in adult brain (175 kDa) and in cerebellar granule cells (115 kDa). The subunit combination NR1/NR2A by itself appears insufficient to describe a major population of NMDA receptors, in particular, in adult brain.

Enoximone therapy as pharmacological bridging to cardiac transplantation.

Keeping pre-transplant patients alive while waiting for a suitable donor is still a major challenge. New pharmacological agents which can provide improved hemodynamics are urgently needed in patients with severe heart failure who are on the waiting list for cardiac transplantation. Intravenous enoximone therapy (an initial 0.5 mg/kg bolus, then 1.25-5.0 mcg/kg/min infusion) was administered to 35 transplant candidates with progressive heart failure despite optimal drug regimen including digoxin, diuretics, and ACE-inhibitors. In 18 out of 35 patients complete hemodynamic, echocardiographic, neurohumoral, and Holter-ECG studies were performed before and 24 hours after intravenous enoximone infusion. Patients were then continued on chronic oral therapy of 100 mg twice a day. Enoximone infusion increased the cardiac index (CI) (1.78 +/- 0.45 l/min/m2 vs 3.04 +/- 0.83 l/min/m2; p < 0.001) and stroke volume index (SVI)(22.33 +/- 9.45 ml/m2 vs 32.28 +/- 7.29 ml/m2; p < 0.05) and decreased wedge pressure (PCP)(24.1 +/- 11.98 mmHg vs 17.78 +/- 8.76 mmHg; p < 0.05) while mean arterial pressure (MAP) was unchanged. Left ventricular ejection time (LVET)(225.1 +/- 26.9 ms vs 242.2 +/- 25.8 ms; p < 0.05) was increased whereas other echocardiographic parameters were unchanged (Left ventricular end-diastolic dimension LVEDD, left ventricular end-systolic dimension LVESD, fractional shortening FS, early diastolic relaxation parameter Te). Plasma neurohumoral parameters did not change (Aldosterone, epinephrine, renin, atrial natriuretic factor) except for a significant drop in norepinephrine (936.7 +/- 443.2 pg/ml vs 522.4 +/- 287.6 pg/ml; p < 0.05). Holter-ECG parameters (ventricular premature beats VPB, couplets, ventricular tachycardia VT) were not influenced by enoximone infusion.(ABSTRACT TRUNCATED AT 250 WORDS)