Impact of left ventricular assist device (LVAD) support on the cardiac reverse remodeling process

With improved technology and expanding indications for use, left ventricular assist devices (LVADs) are assuming a greater role in the care of patients with end-stage heart failure. Following LVAD implantation with the intention of bridge to transplant, it became evident that some patients exhibit substantial recovery of ventricular function. This prompted explantation of some devices in lieu of transplantation, the so-called bridge-to-recovery (BTR) therapy. However, clinical outcomes following these experiences are not always successful. Patients treated in this fashion have often progressed rapidly back to heart failure. Special knowledge has emerged from studies of hearts supported by LVADs that provides insights into the basic mechanisms of ventricular remodeling and possible limits of ventricular recovery. In general, it was these studies that spawned the concept of reverse remodeling now recognized as an important goal of many heart failure treatments. Important examples of myocardial and/or ventricular properties that do not regress towards normal during LVAD support include abnormal extracellular matrix metabolism, increased tissue angiotensin levels, myocardial stiffening and partial recovery of gene expression involved with metabolism. Nevertheless, studies of LVAD-heart interactions have led to the understanding that although we once considered the end-stage failing heart of patients near death to be irreversibly diseased, an unprecedented degree of myocardial recovery is possible, when given sufficient mechanical unloading and restoration of more normal neurohormonal milieu. Evidence supporting and unsupporting the notion of reverse remodeling and clinical implications of this process will be reviewed.     

Vasoplegia after implantation of a continuous flow left ventricular assist device: incidence,outcomes and predictors

Background

Vasoplegia after routine cardiac surgery is associated with severe postoperative complications and increased mortality. It is also prevalent in patients undergoing implantation of pulsatile flow left ventricular assist devices (LVAD). However, less is known regarding vasoplegia after implantation of newer generations of continuous flow LVADs (cfLVAD). We aim to report the incidence, impact on outcome and predictors of vasoplegia in these patients.

Methods

Adult patients scheduled for primary cfLVAD implantation were enrolled into a derivation cohort (n?=?118, 2006–2013) and a temporal validation cohort (n?=?73, 2014–2016). Vasoplegia was defined taking into consideration low mean arterial pressure and/or low systemic vascular resistance, preserved cardiac index and high vasopressor support. Vasoplegia was considered after bypass and the first 48?h of ICU stay lasting at least three consecutive hours. This concept of vasoplegia was compared to older definitions reported in the literature in terms of the incidence of postoperative vasoplegia and its association with adverse outcomes. Logistic regression was used to identify independent predictors. Their ability to discriminate patients with vasoplegia was quantified by the area under the receiver operating characteristic curve (AUC).

Results

The incidence of vasoplegia was 33.1% using the unified definition of vasoplegia. Vasoplegia was associated with increased ICU length-of-stay (10.5 [6.9–20.8] vs 6.1 [4.6–10.4] p?=?0.002), increased ICU-mortality (OR 5.8, 95% CI 1.9–18.2) and one-year-mortality (OR 3.9, 95% CI 1.5–10.2), and a higher incidence of renal failure (OR 4.3, 95% CI 1.8–10.4). Multivariable analysis identified previous cardiothoracic surgery, preoperative dopamine administration, preoperative bilirubin levels and preoperative creatinine clearance as independent preoperative predictors of vasoplegia. The resultant prediction model exhibited a good discriminative ability (AUC 0.80, 95% CI 0.71–0.89, p?<? 0.01). Temporal validation resulted in an AUC of 0.74 (95% CI 0.61–0.87, p?<? 0.01).

Conclusions

In the era of the new generation of cfLVADs, vasoplegia remains a prevalent (33%) and critical condition with worse short-term outcomes and survival. We identified previous cardiothoracic surgery, preoperative treatment with dopamine, preoperative bilirubin levels and preoperative creatinine clearance as independent predictors.

     

Structure,stability and water permeation of ([D-Leu-L-Lys-(D-Gln-L-Ala)3]) cyclic peptide nanotube: a molecular dynamics study

The structural stability of 8 × ([D-Leu-L-Lys-(D-Gln-L-Ala)₃]) cyclic peptide nanotube (CPN) in water and different phospholipid bilayers were explored by 100 ns independent molecular dynamics (MD) simulations. The role of non-bonded interaction energy between the side and main chains of cyclic peptide rings in different membrane environments assessed, wherein the repulsive electrostatic interaction energy between neighbouring cyclic peptide rings was found adequate to break hydrogen bond energy thereby to crumple CPN. Further, the water permeation across the CPN channel was studied in four types of phospholipid bilayers- DMPG (1,2-Dimyristoyl-sn-glycero-3-phosphorylglycerol), DMPS (1,2-Dimyristoyl-sn-glycero-3-phosphoserine), POPC (1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and POPE (1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine) from MD simulations. DMPS membrane shows higher non-bonded interaction energies (?1913.06 kJ/mol of electrostatic interaction energy and ?994.13 kJ/mol of van der Waals interaction energy) with CPN due to the presence of polar molecules in lipid structure. Thusly, the non-bonded interaction energies were essential towards the stability of CPN than hydrogen bonds between the nearby cyclic peptides. The result also reveals the role of side chains, hydrogen bonds and non-bonded interaction energies in an aqueous environment. The diffusion coefficient of water obtained from means square deviation calculation shows similar coefficients irrespective of the lipid surroundings. However, the permeation coefficients demonstrate water flow in the channel relies upon the environment.     

Use of exclusion by a chimpanzee (Pan troglodytes) during speech perception and auditory-visual matching-to-sample

An adult female chimpanzee showed responding through use of exclusion in an auditory to visual matching-to-sample procedure. The chimpanzee had previously learned to associate specific visuographic symbols called lexigrams with real world referents and the spoken English words and photographs for those referents. On some trials, an unknown spoken English word was presented as the sample, and the match choices could consist of photographs or lexigrams that already were associated with known English words as well as unknown lexigrams or photos of objects without associated lexigrams. The chimpanzee reliably avoided choosing known comparisons for these unknown samples, instead relying on exclusion to choose comparisons that were of unknown lexigrams or photographs of items without associated lexigram symbols.     

Physiological acclimation of a desert antelope, Arabian oryx (Oryx leucoryx), to long-term food and water restriction

Desert mammals often experience scarcity of drinking water and food for prolonged periods. In this study, the first long-term acclimation experiment in a non-domesticated desert-adapted ungulate, we investigated the mechanisms used by the Arabian oryx Oryx leucoryx, to adjust its physiology to progressive food and water restriction over 5 months, an experimental regimen and time course chosen to mimic what it typically experiences between spring and late summer in the desert. At the end of the acclimation period, oryx consumed less than one and half of food and water of animals in the control group and lost 8.2±2.6% of their initial body mass. Experimental animals reduced their mass-specific resting metabolic rate (RMR) and total evaporative water loss (TEWL) by 16.2 and 25.7%, respectively, and maintained a digestive efficiency of about 70%. We found no support for the idea that reduced RMR in oryx correlated with a decreased thyroid hormone concentration in plasma. At the end of the 5 months acclimation, oryx continued to mobilize fatty acids to fuel metabolism, and did not use protein breakdown as a major source of gluconeogenesis. Oryx in the experimental group reduced their water intake by 70% and maintained constant plasma osmolality. They adjusted their water budget by reducing mass-specific TEWL, increasing urine osmolality and reducing urine volume by 40%, and excreting feces with <50% water content. Oryx have an unusually low TEWL compared with other arid-zone ungulates; both hydrated and water-deprived individuals have TEWL values, 51.7 and 39.3%, respectively, of allometric predictions for arid-zone ungulates. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Chloride cell responses to long-term exposure to distilled and hard water in the gill of the armored catfish, Hypostomus tietensis (Loricariidae)

The morphological changes in the gill chloride cells of the armored catfish, Hypostomus tietensis , were investigated after 15 days' exposure to either distilled or hard water. The thickness of the water–blood barrier in the lamellae increased significantly in fish kept in distilled water due to the high proliferation of chloride cells. The apical surface of about 68% of chloride cells was sharply reduced by the development of an apical crypt with a sponge-like surface, although no change in the chloride cell fractional area was found. In contrast, H. tietensis kept in Na⁺, Cl⁻ and Ca²⁺ rich water displayed no significant changes in the number of chloride cells or in their apical surface morphology compared with the control fish. Chloride cell response to ion challenge in H. tietensis suggested the involvement of different strategies to maintain homeostasis in ion-poor water, which may be related to the life history of species.     

An Evidence to Use Cotes/a plutellae (Kurdjumov) (Hymenoptera: Braconidae) as a Field Control Agent against Diamondback Moth,Plutella xylostella L (Lepidoptera: Plutellidae)

The parasitic effectiveness of Cotesia plutellae Kurdjumov for the control of diamondback moth (DBM), Plutella xylostella L., was investigated without spraying pesticides in the greenhouse, and the damage degrees of Brassica rapa cv. Pakchoi grown in parasitoid-applied plot and control plot were evaluated. Among the 961 fourth instar DBM larvae collected in the common cabbage fields at Kwanshan region in Taiwan, 336 cocoons of C. plutellae were harvested from DBM larvae, which showed a parasitism rate of 35.0%. A total of 650 DBM adults and 600 C. plutellae adults were released according to the releasing scheme in the experiment plot. As a result, 56.7% of the DBM larvae were parasitized by C. plutellae adults 12 days before harvest, and the parasitism reached 80.8% at six days before harvest. At the harvest time, a population density of C. plutellae cocoons in the experiment plot was 2.2/plant, and that of normal DBM larvae was 0.5/plant. The density of DBM in the control plot was much higher than in the parasitoid-released plot by 7.7/plant. In the first survey, the density of DBM larvae on a Pakchoi plant was quite low, 0.3 ∼ 0.8 larvae. However, the DBM population increased dramatically after six days later, 5.7-10.1 larvae/plant. The population density of DBM larvae showed clear difference between the parasitoid-released plot and control plot. The parasitism increased to nearly two fold within a week after the release of DBM adults. As a further study, a combining use of two or more species para-sitoids could be considered to improve a parasitism against DBM in the fields.     

Use of low temperature sem to locate free water in frozen,hydrated seed tissues of Glycine max (Leguminosae)

Low temperature field emission electron microscopy was used to determine the location of free water in soybean seeds. Frozen, hydrated soybean seeds were fractured, the water etched from the fractured surface, and then part of the etched surface was refractured. The resulting surface, which contained a freeze-fractured face as well as a freeze-etched face was coated with platinum and viewed on the cryostage of a low temperature field emission electron microscope. Two surfaces could be viewed simultaneously to determine the location of water in the seed tissue. Viewing the fractured surface gave an indication of the extent of hydration of the tissue. Viewing the etched surface detailed the macro- and microanatomy of the tissue. Viewing the intersection between the fractured and etched surfaces allowed observation of the environment of partially etched cells and organelles. The technique avoids artifacts associated with chemical fixation, dehydration, and critical-point drying, procedures that affect the water content of the seed. The technique does not affect the degree of hydration of the seed and can be used to localize water in the inter- and intracellular environment of the seed. This technique could find wide application in studies of water relationships of seeds during development, maturation, and imbibition.     

Response of soil mites (Acari,Mesostigmata) to long-term Norway spruce plantation along a mountain stream

Hydrogen peroxide (H₂O₂) and hydroxyl radicals (HO·) are generated through partial reduction of oxygen. The HO· are the most reactive and have a shorter half-life than H₂O₂, they are produced from comparatively stable H₂O₂ through Fenton reaction. Although controlling HO· is important and biologically advantageous for organisms, it may be difficult. Ticks are obligate hematophagous arthropods that need blood feeding for development. Ticks feed on vertebrate blood containing high levels of iron. Ticks also concentrate iron-containing host blood, leading to high levels of iron in ticks. Host-derived iron may react with oxygen in the tick body, resulting in high concentrations of H₂O₂. On the other hand, ticks have antioxidant enzymes, such as peroxiredoxins (Prxs), to scavenge H₂O₂. Gene silencing of Prxs in ticks affects their blood feeding, oviposition, and H₂O₂ concentration. Therefore, Prxs could play important roles in ticks’ blood feeding and oviposition through the regulation of the H₂O₂ concentration. This review discusses the current knowledge of Prxs in hard ticks. Tick Prxs are also multifunctional molecules related to antioxidants and immunity like other organisms. In addition, tick Prxs play a role in regulating the host immune response for ticks’ survival in the host body. Tick Prx also can induce Th2 immune response in the host. Thus, this review would contribute to the further understanding of the tick’s antioxidant responses during blood feeding and the search for a candidate target for tick control.     

Differentiation of the thermo-/hygrosensitive (no-pore) sensilla on the antenna of Antheraea pernyi (Lepidoptera,Saturniidae): a study of cryofixed material

Summary The morphogenesis of the thermo- and hygro-sensitive sensilla styloconica of Antheraea pernyi was studied, exclusively by cryomethods, during the second half of pupal development. The three major processes taking place during this period are (1) the differentiation of the dendritic outer segments of the sensory cells, especially of the lamellated type-2 receptor, (2) the formation of the receptor-lymph cavities, (3) the formation of tubular structures of unknown function in the inner receptor-lymph cavity, and (4) the elongation of the dendrite sheath. The formation of lamellae in the type-2 dendritic outer segment is achieved by the enfolding of its originally cylindrical cytoplasmic membrane. Autocellular junctions, previously described in the sensilla of adult animals, are found to join the forming lamellae. Close similarities between the junctions and smooth septate junctions are demonstrated. Both the extensive inner and outer receptor-lymph cavities are formed by invagination and folding of the apical cytoplasmic membranes of the three enveloping cells. Formation starts at the most apical projection of the cells and proceeds in a proximal direction. Up to 4-m-long tubular structures appear, exclusively in developmental stages, in the inner receptor-lymph cavity. They are composed of plasma membranes whose inner surface is studded with regularly spaced electron-dense particles. Contacts with the cytoplasmic membrane of the innermost enveloping cell demonstrate that the structures are composed of lipid membranes. During elongation of the dendrite sheath, which in these sensilla is apically attached to the hair wall, an 2-m-long growth-zone is observed at its proximal end. By addition of sheath-forming material to the growth-zone, the latter continuously moves proximally until the sheath is completed.     

Response of cold-acclimated,farmed South African abalone (Haliotis midae) to short-term and long-term changes in temperature

In its natural environment, the South African abalone, Haliotis midae, occurs at average monthly water temperatures between 12 and 21 °C. In the present study we aimed to describe selected physiological and molecular responses of winter acclimated, cultured H. midae after acute and chronic exposure to 16, 19 and 22 °C.     

Use of a mitochondrial COI sequence to identify species of the subtribe Aphidina (Hemiptera, Aphididae)

Aphids of the subtribe Aphidina are found mainly in the North Temperate Zone. The relative lack of diagnostic morphological characteristics has hindered the identification of species in this group. However, DNA-based taxonomic methods can clarify species relationships within this group. Sequence variation in a partial segment of the mitochondrial COI gene was highly effective for identifying species within Aphidina. Thirty-six species of Aphidina were identified in a neighbor-joining tree. Mean intraspecific sequence divergence in Aphidina was 0.52%, with a range of 0.00% to 2.95%, and the divergences of most species were less than 1%. Mean interspecific divergence within previously recognized genera or morphologically similar species groups was 6.80%, with a range of 0.68% to 11.40%, with variation mainly in the range of 3.50% to 8.00%. Possible reasons for anomalous levels of mean nucleotide divergence within or between some taxa are discussed.     

Use of desmids to assess the natural conservation value of a Hungarian oxbow (Malom-Tisza,NE-Hungary)

A method recently proposed by Coesel that uses the desmid flora to assess the conservation value of aquatic habitats was applied to an alkaline and hypertrophic oxbow of the Upper Tisza river (NE Hungary). According to the macrophyte community the oxbow contains two distinct habitats, both of which provide suitable conditions for the development of a rich desmid flora. High temporal and spatial differences in the algal flora were observed in periphyton and plankton samples taken in June and August 2004. The sample of Utricularia vulgaris periphyton collected in August was characterised by the most species-rich desmid flora. The conservation value of this sample was the maximum according to Coesel’s method. The latter also proved to be useful for the assessment of the conservation value of plankton net samples taken from among the macrophytes. The use of modified rarity value calculations as recently proposed by Fehér did not significantly affect the conservation value, but different enumeration methods to quantify the floristic diversity did result in different conservation values. We found that Coesel’s desmid based method is a useful tool for assessing the conservation value of the studied oxbow. Based our results the Coesel method’s applicability and usefulness depended on (i) the sampling location (open water or macrophytic region) samples were taken from open water or from macrophytic region; and (ii) species enumeration procedures (up to 400 specimens counted, or whole droplets counted). Presented at the International Symposium Biology and Taxonomy of Green Algae V, Smolenice, June 26–29, 2007, Slovakia.     

Use of a Silicone Rubber (Clear Seal) as a Section Adhesive Resistant to Acid, Alkali and Heat

An optically clear silicone rubber adhesive is recommended for use in histochemical procedures in which detachment of tissue sections is likely. Procedure: Cut paraffin sections and float on a 45-50 C water bath; leave frozen sections on the microtome knife in the cryostat; spread the silicone rubber thinly and evenly over 2/3 of the slide (Clear Seal—General Electric, was used); pick up paraffin sections directly from the floatation water and frozen sections from the microtome knife with a warm slide; dry for 1.5 hr at 25 C; place paraffin sections in a 60 C oven for 0.5 hr, deparaffinize through xylene and hydrate through alcohols to water. Stain sections as desired, but avoid clearing agents before mounting after strong acid or alkaline treatment, and mount rapidly if a synthetic resin is used because of the solvent effect on the silicone rubber. Of the adhesives tried, silicone rubber is the only one capable of withstanding boiling 10% HCl for any period of time without detachment of sections.     

Electrolyte changes,cell volume regulation and hormonal influences during acclimation of rainbow trout (Salmo gairdnerii) to salt water

• 1.1. Rainbow trout were acclimated to salt water (1.5, 2.0 or 3.0%, which means 40, 60 or 85% concentrated sea-water) and the electrolyte, glucose and cortisol concentrations of the plasma as well as the extra- and intracellular muscle space, the muscle electrolyte concentrations and the ATPase activity were analysed.
• 2.2. Plasma osmolality, Na⁺, Ca²⁺ and Mg²⁺ concentrations of the plasma had a maximum at 24 hr after the start of acclimation when acclimated to 3.0% salt water. Plasma osmolality, Na⁺ and Mg²⁺ concentrations were significantly higher during the whole acclimation time when exposed to 3.0% salt water.
• 3.3. Variations and regulations of ECS and ICS were clearly demonstrated. The intracellular electrolyte concentrations were also maximal at 24 hr.
• 4.4. The plasma glucose level was just slightly elevated, but the cortisol level clearly indicated a stress response at 24 hr.
• 5.5. The activity of gill Na-K-ATPase increased during the acclimation time.
• 6.6. The regulatory processes in trout during acclimation to salt water are compared with those occurring in tilapia and carp.

     

Physiological adjustments of sand gazelles (Gazella subgutturosa) to a boom-or-bust economy: standard fasting metabolic rate, total evaporative water loss, and changes in the sizes of organs during food and water restriction

To test the hypothesis that desert ungulates adjust their physiology in response to long-term food and water restriction, we established three groups of sand gazelles (Gazella subgutturosa): one that was provided food and water (n = 6; CTRL) ad lib. for 4 mo, one that received ad lib. food and water for the same period but was deprived of food and water for the last 4.5 d (n = 6; EXPT(1)), and one that was exposed to 4 mo of progressive food and water restriction, an experimental regime designed to mimic conditions in a natural desert setting (n = 6; EXPT(2)). At the end of the 4-mo experiment, we measured standard fasting metabolic rate (SFMR) and total evaporative water loss (TEWL) of all sand gazelles and determined lean dry mass of organs of gazelles in CTRL and EXPT(2). Gazelles in CTRL had a mean SFMR of 2,524 +/- 194 kJ d(-1), whereas gazelles in EXPT(1) and EXPT(2) had SFMRs of 2,101+/- 232 and 1,365 +/- 182 kJ d(-1), respectively, values that differed significantly when we controlled for differences in body mass. Gazelles had TEWLs of 151.1 +/- 18.2, 138.5 +/- 17.53, and 98.4 +/- 27.2 g H(2)O d(-1) in CTRL, EXPT(1), and EXPT(2), respectively. For the latter group, mass-independent TEWL was 27.1% of the value for CTRL. We found that normally hydrated sand gazelles had a low mass-adjusted TEWL compared with other arid-zone ungulates: 13.6 g H(2)O kg(-0.898) d(-1), only 17.1% of allometric predictions, the lowest ever measured in an arid-zone ungulate. After 4 mo of progressive food and water restriction, dry lean mass of liver, heart, and muscle of gazelles in EXPT(2) was significantly less than that of these same organs in CTRL, even when we controlled for body mass decrease. Decreases in the dry lean mass of liver explained 70.4% of the variance of SFMR in food- and water-restricted gazelles. As oxygen demands decreased because of reduced organ sizes, gazelles lost less evaporative water, probably because of a decreased respiratory water loss.