Sildenafil preserves diastolic relaxation after reduction by L-NAME and increases phosphodiesterase-5 in the intercalated discs of cardiac myocytes and arterioles

OBJECTIVES: We investigated the influence of sildenafil on cardiac contractility and diastolic relaxation and examined the distribution of phosphodiesterase-5 in the hearts of hypertensive rats that were treated with by NG-nitro-L-arginine methyl ester (L-NAME). METHODS: Male Wistar rats were treated with L-NAME and/or sildenafil for eight weeks. The Langendorff method was used to examine the effects of sildenafil on cardiac contractility and diastolic relaxation. The presence and location of phosphodiesterase-5 and phosphodiesterase-3 were assessed by immunohistochemistry, and cGMP plasma levels were measured by ELISA. RESULTS: In isolated hearts, sildenafil prevented the reduction of diastolic relaxation (dP/dt) that was induced by L-NAME. In addition, phosphodiesterase-5 immunoreactivity was localized in the intercalated discs between the myocardial cells. The staining intensity was reduced by L-NAME, and sildenafil treatment abolished this reduction. Consistent with these results, the plasma levels of cGMP were decreased in the L-NAME-treated rats but not in rats that were treated with L-NAME + sildenafil. CONCLUSION: The sildenafil-induced attenuation of the deleterious hemodynamic and cardiac morphological effects of L-NAME in cardiac myocytes is mediated (at least in part) by the inhibition of phosphodiesterase-5.

Evaluation of left ventricular diastolic echocardiographic parameters in healthy dogs by pulsed-wave Doppler

Left ventricular diastolic dysfunction plays an important role on heart failure progression. In order to obtain additional reference values of left ventricular diastolic parameters and investigate influence of common variables, peak E wave (peak E), peak A wave (peak A), E/A ratio (E/A), E wave deceleration time (EDT) and isovolumic relaxation time (IRVT) were studied in 40 clinically healthy dogs, by pulsed wave Doppler. The following values were obtained: peak E = 0.747 ± 0.117 m/s, peak A = 0.487 ± 0.062 m/s, E/A = 1.533 ± 0.198, EDT = 88.7 ± 9.2 ms and IRVT = 0.080 ± 0.009 s. Some parameters were influenced by heart rate (peak E, peak A and IRVT), by age (peak A and E/A) and by body weight (TRIV). Gender influence was absent. Values obtained can be used as reference for canine specimens but its interpretation should consider on the influence of related variables.

Rat Adipose Tissue-Derived Stem Cells Transplantation Attenuates Cardiac Dysfunction Post Infarction and Biopolymers Enhance Cell Retention

Background: Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI). Methodology/Principal Findings: (99m)Tc-labeled ASCs (1 x 10(6) cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. Conclusions: We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administrating co-injection of ASCs with biopolymers.

Changes in cardiac heparan sulfate proteoglycan expression and streptozotocin-induced diastolic dysfunction in rats

Background: Changes in the proteoglycans glypican and syndecan-4 have been reported in several pathological conditions, but little is known about their expression in the heart during diabetes. The aim of this study was to investigate in vivo heart function changes and alterations in mRNA expression and protein levels of glypican-1 and syndecan-4 in cardiac and skeletal muscles during streptozotocin (STZ)-induced diabetes. Methods: Diabetes was induced in male Wistar rats by STZ administration. The rats were assigned to one of the following groups: control (sham injection), after 24 hours, 10 days, or 30 days of STZ administration. Echocardiography was performed in the control and STZ 10-day groups. Western and Northern blots were used to quantify protein and mRNA levels in all groups. Immunohistochemistry was performed in the control and 30-day groups to correlate the observed mRNA changes to the protein expression. Results: In vivo cardiac functional analysis performed using echocardiography in the 10-day group showed diastolic dysfunction with alterations in the peak velocity of early (E) diastolic filling and isovolumic relaxation time (IVRT) indices. These functional alterations observed in the STZ 10-day group correlated with the concomitant increase in syndecan-4 and glypican-1 protein expression. Cardiac glypican-1 mRNA and skeletal syndecan-4 mRNA and protein levels increased in the STZ 30-day group. On the other hand, the amount of glypican in skeletal muscle was lower than that in the control group. The same results were obtained from immunohistochemistry analysis. Conclusion: Our data suggest that membrane proteoglycans participate in the sequence of events triggered by diabetes and inflicted on cardiac and skeletal muscles.

Striatal volume abnormalities in treatment-naive patients diagnosed with pediatric major depressive disorder

Objective: The striatum, including the putamen and caudate, plays an important role in executive and emotional processing and may be involved in the pathophysiology of mood disorders. Few studies have examined structural abnormalities of the striatum in pediatric major depressive disorder (MDD) patients. We report striatal volume abnormalities in medication-naive pediatric MDD compared to healthy comparison subjects. Method: Twenty seven medication-naive pediatric Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) MDD and 26 healthy comparison subjects underwent volumetric magnetic resonance imaging (MRI). The putamen and caudate volumes were traced manually by a blinded rater, and the patient and control groups were compared using analysis of covariance adjusting for age, sex, intelligence quotient, and total brain volumes. Results: MDD patients had significantly smaller right striatum (6.0% smaller) and right caudate volumes (7.4% smaller) compared to the healthy subjects. Left caudate volumes were inversely correlated with severity of depression in MDD subjects. Age was inversely correlated with left and right putamen volumes in MDD patients but not in the healthy subjects. Conclusions: These findings provide fresh evidence for abnormalities in the striatum of medication-naive pediatric MDD patients and suggest the possible involvement of the striatum in the pathophysiology of MDD.

HORMONAL RESPONSES TO DIFFERENT RESISTANCE EXERCISE SCHEMES OF SIMILAR TOTAL VOLUME

Uchida, MC, Crewther, BT, Ugrinowitsch, C, Bacurau, RFP, Moriscot, AS, and Aoki, MS. J Strength Cond Res 23(7): 2003-2008, 2009-This study assessed the effect of different resistance exercise scheme (RES) designs of similar total of load lifted on the responses of testosterone, cortisol, and creatine kinase (CK). Twenty-seven healthy males performed 1 of 4 bench press workouts described by the 1 repetition maximum (1RM) load: 4 sets of maximum repetitions at 50%-1RM (50%-1RM RES), 5 sets of maximum repetitions at 75%-1RM (75%-1RM RES), 10 sets of maximum repetitions at 90%-1RM (90%1RM RES), or 8 sets of maximum repetitions at 110%-1RM (110%-1RM RES). Each RES was equated by the total volume of load lifted (repetitions x sets x load). Blood samples, collected pre-exercise (Pre) and post-exercise (Post) at 1 and 24 hours (24 h), were analyzed for total and free testosterone, total cortisol, and CK. In general, testosterone and cortisol showed little change within or between the different RES (p > 0.05), possibly because of the relatively low volume lifted and/ or the small muscle mass activated by the bench press exercise. Cortisol was elevated after the 75%-1RM RES at the Post sample, with this response also exceeding the other RES (p < 0.05). The 24 h CK response was also elevated after the 75%-1RM RES (p < 0.05), thereby suggesting greater training strain for the same volume of load. These results confirm previous recommendations regarding the prescription of resistance exercise and the importance of total volume as a stimulus for activating the endocrine system and achieving long-term adaptation.

Post-concurrent exercise hemodynamics and cardiac autonomic modulation

Concurrent training is recommended for health improvement, but its acute effects on cardiovascular function are not well established. This study analyzed hemodynamics and autonomic modulation after a single session of aerobic (A), resistance (R), and concurrent (A + R) exercises. Twenty healthy subjects randomly underwent four sessions: control (C:30 min of rest), aerobic (A:30 min, cycle ergometer, 75% of VO(2) peak), resistance (R:6 exercises, 3 sets, 20 repetitions, 50% of 1 RM), and concurrent (AR: A + R). Before and after the interventions, blood pressure (BP), heart rate (HR), cardiac output (CO), and HR variability were measured. Systolic BP decreased after all the exercises, and the greatest decreases were observed after the A and AR sessions (-13 +/- 1 and -11 +/- 1 mmHg, respectively, P < 0.05). Diastolic BP decreased similarly after all the exercises, and this decrease lasted longer after the A session. CO also decreased similarly after the exercises, while systemic vascular resistance increased after the R and AR sessions in the recovery period (+4.0 +/- 1.7 and +6.3 +/- 1.9 U, respectively, P < 0.05). Stroke volume decreased, while HR increased after the exercises, and the greatest responses were observed after the AR session (SV, A = -14.6 +/- 3.6, R = -22.4 +/- 3.5 and AR = -23.4 +/- 2.4 ml; HR, A = +13 +/- 2, R = +15 +/- 2 vs. AR = +20 +/- 2 bpm, P < 0.05). Cardiac sympathovagal balance increased after the exercises, and the greatest increase was observed after the AR session (A = +0.7 +/- 0.8, R = +1.0 +/- 0.8 vs. AR = +1.2 +/- 0.8, P < 0.05). In conclusion, the association of aerobic and resistance exercises in the same training session did not potentiate postexercise hypotension, and increased cardiac sympathetic activation during the recovery period.

Baroreflex Sensitivity Impairment Is Associated With Cardiac Diastolic Dysfunction in Rats

Background: Studies have shown that the autonomic dysfunction accompanied by impaired baroreflex sensitivity was associated with higher mortality. However, the influence of decreased baroreflex sensitivity on cardiac function, especially in diastolic function, is not well understood. This study evaluated the morpho-functional changes associated with baroreflex impairment induced by chronic sinoaortic denervation (SAD). Methods and Results: Animals were divided into sinoaortic denervation (SAD) and control (C) groups. Baroreflex sensitivity was evaluated by tachycardic and bradycardic responses, induced by vasoactive drugs. Cardiac function was studied by echocardiography and by left ventricle (LV) catheterization. LV collagen content and the expression of regulatory proteins involved in intracellular Ca(2+) homeostasis were quantified. Results showed higher LV mass in SAD versus C animals. Furthermore, an increase in deceleration time of E-wave in the SAD versus the C group (2.14 +/- 0.07 ms vs 1.78 +/- 0.03 ms) was observed. LV end-diastolic pressure was increased and the minimum dP/dt was decreased in the SAD versus the C group (12 +/- 1.5 mm Hg vs 5.3 +/- 0.2 mm Hg and 7,422 +/- 201 vs 4,999 +/- 345 mm Hg/s, respectively). SERCA/NCX ratio was lower in SAD than in control rats. The same was verified in SERCA/PLB ratio. Conclusions: The results suggest that baroreflex dysfunction is associated with cardiac diastolic dysfunction independently of the presence of other risk factors. (J Cardiac Fail 2011;17:519-525)

Altered left ventricular diastolic function in subjects with spinal cord injury

Study design: This is cross-sectional study. Objectives: The aim of this study is to investigate the cardiac structure and function of subjects with spinal cord injury (SCI) and the impact of metabolic, hemodynamic and inflammatory factors on these parameters. Setting: Sao Paulo, Brazil. Methods: Sixty-five nondiabetic, nonhypertensive, sedentary, nonsmoker men (34 with SCI and 31 healthy subjects) were evaluated by medical history, anthropometry, laboratory tests, analysis of hemodynamic and inflammatory parameters and echocardiography. Results: Subjects with SCI had lower systolic blood pressure and higher levels of C-reactive protein and tumor necrosis factor receptors than the healthy ones. Echocardiography data showed that the SCI group presented similar left ventricular (LV) structural and systolic parameters, but lower initial diastolic velocity (Em) (9.2 +/- 0.5 vs 12.3 +/- 0.5 cm s(-1); P<0.001) and higher peak early inflow velocity (E)/Em ratio (7.7 +/- 0.5 vs 6.1 +/- 0.3; P = 0.009) compared with the able-bodied group, even after adjustment for systolic blood pressure and C-reactive protein levels. Furthermore, injured subjects with E/Em >8 had lower peak spectral longitudinal contraction (Sm) (9.0 +/- 0.7 vs 11.6 +/- 0.4cm s(-1); P<0.001) and cardiac output (4.2 +/- 0.2 vs 5.0 +/- 0.21 min(-1); P = 0.029), as well as higher relative wall thickness (0.38 +/- 0.01 vs 0.35 +/- 0.01; P = 0.005), than individuals with SCI with E/Em<8, but similar age, body mass index, blood pressure, injury level, metabolic parameters and inflammatory marker levels. Conclusion: Subjects with SCI presented impaired LV diastolic function in comparison with able-bodied ones. Moreover, worse LV diastolic function was associated with a pattern of LV concentric remodeling and subclinical decreases in systolic function among injured subjects. Overall, these findings might contribute to explain the increased cardiovascular risk reported for individuals with SCI. Spinal Cord (2011) 49, 65-69; doi: 10.1038/sc.2010.88; published online 27 July 2010

A discussion on volume change in the plastic phase

This technical note discusses the possibility of using a more simplified scheme to estimate the plastic multiplier when some material shows volume changes, e.g. soil, balsa wood foam and other similar materials. Two procedures regarding volume changes during the plastic phase are discussed here. The first one is the classic procedure applied to non-associative plasticity, for which a Drucker-Prager-like surface is adopted to represent the plastic potential. For the second procedure, the plastic potential is not explicitly known, however, its orthogonal direction is chosen respecting a plastic volume change parameter similar to Poisson`s ratio. Copyright (C) 2007 John Wiley & Sons, Ltd.

AnSBBR Applied to a Personal Care Industry Wastewater Treatment: Effects of Fill Time, Volume Treated Per Cycle, and Organic Load

A study was performed regarding the effect of the relation between fill time, volume treated per cycle, and influent concentration at different applied organic loadings on the stability and efficiency of an anaerobic sequencing batch reactor containing immobilized biomass on polyurethane foam with recirculation of the liquid phase (AnSBBR) applied to the treatment of wastewater from a personal care industry. Total cycle length of the reactor was 8 h (480 min). Fill times were 10 min in the batch operation, 4 h in the fed-batch operation, and a 10-min batch followed by a 4-h fed batch in the mixed operation. Settling time was not necessary since the biomass was immobilized and decant time was 10 min. Volume of liquid medium in the reactor was 2.5 L, whereas volume treated per cycle ranged from 0.88 to 2.5 L in accordance with fill time. Influent concentration varied from 300 to 1,425 mg COD/L, resulting in an applied volumetric organic load of 0.9 and 1.5 g COD/L.d. Recirculation flow rate was 20 L/h, and the reactor was maintained at 30 A degrees C. Values of organic matter removal efficiency of filtered effluent samples were below 71% in the batch operations and above 74% in the operations of fed batch followed by batch. Feeding wastewater during part of the operational cycle was beneficial to the system, as it resulted in indirect control over the conversion of substrate into intermediates that would negatively interfere with the biochemical reactions regarding the degradation of organic matter. As a result, the average substrate consumption increased, leading to higher organic removal efficiencies in the fed-batch operations.

Effect of specific feed volume on the performance of an anaerobic sequencing batch biofilm reactor (AnSBBR) with circulation treating different wastewaters under different organic loads

The objective of this research was to study the behavior of two anaerobic sequencing batch reactors, containing immobilized biomass (AnSBBR), as a function of the ratio of the volume of treated medium in each cycle to the total volume of reaction medium. The reactors, in which mixing was accomplished by recirculation of the liquid phase, were maintained at 30 +/- 1 degrees C and treated different wastewaters in 8-h cycles. The operational conditions imposed had the objective to investigate whether maintenance of a residual volume in the reactor would affect, at the end of each cycle, process efficiency and stability, as well as to verify the intensity of the effect for different types of wastewaters and organic loading rates. The first reactor, with work volume of 2.5 L, treated reconstituted cheese whey at an organic loading rate of 12 g COD.L(-1).d(-1) and presented similar effluent quality for the four conditions under which it was operated: renewal of 100, 70, 50 and 25 % of its work volume at each cycle. Despite the fact that reduction in the renewed volume did not significantly affect effluent quality, in quantitative terms, this reduction resulted in an increase in the amount of organic matter removed by the first reactor. The second reactor, with work volume of 1.8 L, treated synthetic wastewater at organic loading rates of 3 and 5 g COD.L(-1).d(-1) and operated under two conditions for each loading: renewal of 100 and 50 % of its work volume. At the organic loading rate of 3 g COD.L(-1).d(-1), the results showed that both effluent quality and amount of organic matter removed by the second reactor were independent of the treated volume per cycle. At the organic loading rate of 5 g COD.L(-1).d(-1), although the reduction in the renewed volume did not affect the amount of organic matter removed by the reactor, effluent quality improved during reactor operation with total discharge of its volume. In general, results showed process stability under all conditions, evidencing reactor flexibility and the potential to apply this technology in the treatment of different types of wastewater.

Cardiovascular Simulator Improvement: Pressure Versus Volume Loop Assessment

This article presents improvement on a physical cardiovascular simulator (PCS) system. Intraventricular pressure versus intraventricular volume (PxV) loop was obtained to evaluate performance of a pulsatile chamber mimicking the human left ventricle. PxV loop shows heart contractility and is normally used to evaluate heart performance. In many heart diseases, the stroke volume decreases because of low heart contractility. This pathological situation must be simulated by the PCS in order to evaluate the assistance provided by a ventricular assist device (VAD). The PCS system is automatically controlled by a computer and is an auxiliary tool for VAD control strategies development. This PCS system is according to a Windkessel model where lumped parameters are used for cardiovascular system analysis. Peripheral resistance, arteries compliance, and fluid inertance are simulated. The simulator has an actuator with a roller screw and brushless direct current motor, and the stroke volume is regulated by the actuator displacement. Internal pressure and volume measurements are monitored to obtain the PxV loop. Left chamber internal pressure is directly obtained by pressure transducer; however, internal volume has been obtained indirectly by using a linear variable differential transformer, which senses the diaphragm displacement. Correlations between the internal volume and diaphragm position are made. LabVIEW integrates these signals and shows the pressure versus internal volume loop. The results that have been obtained from the PCS system show PxV loops at different ventricle elastances, making possible the simulation of pathological situations. A preliminary test with a pulsatile VAD attached to PCS system was made.

Genetic variation for anatomic traits and volume shrinkage and their correlation with wood basic density in an Eucalyptus camaldulensis Dehn base population

Eucalyptus camaldulensis has great importance in Brazil because of their phenotypic plasticity for different environmental conditions, as soils, altitudes and rainfall. This study is an investigation of a base population of E. camaldulensis from Australia through a progeny test implanted in Selviria, MS. The trial was established in a randomized block design, with 25 families and 60 replications of single tree plots. Genetic parameters for anatomic traits and volume shrinkage were estimated, as well as their correlations with wood basic density. No significant differences among progenies were observed for the traits studied. The additive genetic variation coefficient at individual and among progeny levels ranged from low (0.26%) to high (16.98%). The narrow sense heritability at individual and family means levels also ranged from low (0.01) to high (0.87). This indicates that some traits are under strong genetic control and can be improved by selection. In the present situation, in order to attain the highest genetic gains, the sequential selection among and within progeny would be recommended.

A demonstration of artificial dissipation effects in some finite volume solution methods for the Navier-Stokes equations

The artificial dissipation effects in some solutions obtained with a Navier-Stokes flow solver are demonstrated. The solvers were used to calculate the flow of an artificially dissipative fluid, which is a fluid having dissipative properties which arise entirely from the solution method itself. This was done by setting the viscosity and heat conduction coefficients in the Navier-Stokes solvers to zero everywhere inside the flow, while at the same time applying the usual no-slip and thermal conducting boundary conditions at solid boundaries. An artificially dissipative flow solution is found where the dissipation depends entirely on the solver itself. If the difference between the solutions obtained with the viscosity and thermal conductivity set to zero and their correct values is small, it is clear that the artificial dissipation is dominating and the solutions are unreliable.