Desarrollo experimental de un elemento constructivo de envolvente, no estructural, a partir de una matriz de plástico reciclado, reforzado con fibras naturales y/o sintéticas

Esta Tesis trata sobre el diseño y desarrollo de un material constructivo de fachada (tras ventilada), empleando plástico reciclado (granza de caucho, de neumáticos fuera de uso) para su elaboración. El uso de materiales reciclados para la elaboración de nuevos materiales constructivos, es a día de hoy, un valor agregado que contribuye tanto a la disminución de desechos tóxicos, como a la fabricación de productos de alta calidad. La investigación partió de la necesidad de comprender qué es un plástico, cómo son producidos, cuáles son los factores que permitían su reciclaje y qué propiedades podrían ser aprovechadas para desarrollar un nuevo material constructivo. En el estado del arte, fueron analizados los aspectos del plástico relacionados a su composición, propiedades, tipologías, producción, consumo, legislación europea y española, reciclaje y valorización energética. Para analizar más profundamente los materiales desarrollados a partir de plásticos reciclados, desde textiles hasta elementos constructivos. Con el conocimiento adquirido mediante este análisis previo, se diseñó una metodología de experimentación, utilizando caucho reciclado y derivados del yeso como agregados, en una matriz de resinas poliméricas reforzada con fibras naturales y sintéticas. Los resultados obtenidos en los ensayos físicos y térmicos, con los elementos producidos, demostraron que el material tiene una excelente resistencia a tensión así como una baja conductividad térmica. Esta investigación, servirá como precedente para el desarrollo de nuevos materiales y sistemas constructivos, utilizando agregados de plástico reciclado, en los procesos de fabricación. Ya que ha comprobado el enorme potencial que ofrecen, creando nuevos materiales, y contribuyendo a reducir la contaminación medio ambiental. "La mayor recompensa de nuestro trabajo no es lo que nos pagan por él, sino aquello en lo que nos convierte". John Ruskin Material compuesto (Composite) de caucho reciclado, fibras y resinas poliméricas. ABSTRACT This thesis deals with the design and development of a new facade construction material using recycled plastic (rubber pellets from used tires) for processing. The use of recycled materials for the development of new building materials, today is an added value which contributes both to the reduction of toxic waste, as well as the processing of products of good quality. The research derives from the need to understand what a plastic is, how they are produced, what the factors that allowed recycling are and what properties can be exploited to develop a new building material. In the prior art, were analyzed plastic aspects related to its composition, properties, typologies, production, consumption, European and Spanish legislation, recycling and energy recovery. To further analyze the materials developed from recycled plastics, from textiles to construction elements. With the knowledge gained from this previous analysis, we designed an experimental approach using recycled rubber and plaster derivatives as aggregates in a polymeric resin matrix reinforced with natural and synthetic fibers. The results obtained in physical and thermal testing, with the elements produced, showed that the material has excellent tensile strength and a low thermal conductivity. This research will serve as a precedent for the development of new materials and building systems, using recycled plastic aggregates in the manufacturing processes. Since it was found the enormous potential, creating new materials, and helping reduce environmental pollution. "The greatest reward of our work is not what we get paid for it, but what they make us."

The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors.

Due to lack of effective therapy, primary brain tumors are the focus of intense investigation of novel experimental approaches that use vectors and recombinant viruses. Therapeutic approaches have been both indirect, whereby vectors are used, or direct to allow for direct cell killing by the introduced virus. Genetically engineered herpes simplex viruses are currently being evaluated as an experimental approach to eradicate malignant human gliomas. Initial studies with gamma (1)34.5 mutants, R3616 (from which both copies of the gamma (1)34.5 gene have been deleted) and R4009 (a construct with two stop codons inserted into the gamma (1)34.5 gene), have been assessed. In a syngeneic scid mouse intracranial tumor model, recombinant herpes simplex virus can be experimentally used for the treatment of brain tumors. These viruses and additional engineered viruses were subsequently tested in human glioma cells both in vitro and in vivo. Using a xenogeneic scid mouse intracranial glioma model, R4009 therapy of established tumors significantly prolonged survival. Most importantly, long-term survival was achieved, with histologic evidence that R4009 eradicated intracranial tumors in this model. Furthermore, the opportunity to evaluate gamma (1)34.5 mutants that have enhanced oncolytic activity, e.g., R8309 where the carboxyl terminus of the gamma (1)34.5 gene has been replaced by the murine homologue, MyD116, are considered.

Abordagem experimental para avaliação de manobras de navios em modelos físicos de espaços náuticos.

Em um mercado de comércio internacional cada vez mais competitivo existe a necessidade de a infraestrutura do sistema portuário brasileiro modernizar-se, tornando-se mais eficiente do ponto de vista operacional e com capacidade para receber navios de maior porte. Neste cenário, as técnicas de projeto de espaços náuticos precisam ser revistas, utilizando-se de ferramentas mais sofisticadas que permitam otimizar os dimensionamentos sem deixar de lado as questões da eficiência e, principalmente, da segurança operacional. O presente trabalho apresenta uma abordagem experimental para análise do projeto das dimensões de canais de acesso e bacias portuárias, fundamentada no desenvolvimento de um simulador de manobras de navios em modelo físico de escala reduzida, denominado Simulador Analógico de Manobras SIAMA 2014. Além disso, é proposto um sistema completo para avaliação das condições de manobrabilidade de espaços náuticos portuários, desde a calibração da ferramenta de simulação, até a verificação de cenários complexos e situações de emergência. O SIAMA 2014 e o sistema desenvolvido foram aplicados em um estudo de caso, que contou com a participação de práticos e autoridades portuárias na realização de simulações de manobras para verificação das condições de atracação no novo berço do Terminal Portuário Marítimo de Ponta da Madeira, em São Luís do Maranhão. Os resultados deste estudo foram apresentados e discutidos, de forma a mostrar a importância da utilização de modelos físicos reduzidos na simulação de manobra de navios.

Trends in research on the possible effects of climate change concerning aquatic ecosystems with special emphasis on the modelling approach

Knowledge on the expected effects of climate change on aquatic ecosystems is defined by three ways. On the one hand, long-term observation in the field serves as a basis for the possible changes; on the other hand, the experimental approach may bring valuable pieces of information to the research field. The expected effects of climate change cannot be studied by empirical approach; rather mathematical models are useful tools for this purpose. Within this study, the main findings of field observations and their implications for future were summarized; moreover, the modelling approaches were discussed in a more detailed way. Some models try to describe the variation of physical parameters in a given aquatic habitat, thus our knowledge on their biota is confined to the findings based on our present observations. Others are destined for answering special issues related to the given water body. Complex ecosystem models are the keys of our better understanding of the possible effects of climate change. Basically, these models were not created for testing the influence of global warming, rather focused on the description of a complex system (e. g. a lake) involving environmental variables, nutrients. However, such models are capable of studying climatic changes as well by taking into consideration a large set of environmental variables. Mostly, the outputs are consistent with the assumptions based on the findings in the field. Since synthetized models are rather difficult to handle and require quite large series of data, the authors proposed a more simple modelling approach, which is capable of examining the effects of global warming. This approach includes weather dependent simulation modelling of the seasonal dynamics of aquatic organisms within a simplified framework.

Conversão da lactose e síntese de galacto-oligossacarídeos: uma abordagem experimental e teórica

O presente trabalho avaliou, na etapa experimental, um processo simultâneo de catálise e fermentação láctica visando obter um iogurte com potenciais características nutracêuticas e, na sua etapa teórica, estabeleceu uma interlocução entre a vivência experimentalista e a teoria da cinética enzimática, no que se refere à conversão da lactose e à síntese de galactooligossacarídeos (GOS). Na abordagem experimental, para um substrato específico, avaliouse biocatálise conduzida simultaneamente à fermentação, defasando a adição da enzima em relação ao início do processo fermentativo. A fermentação foi realizada a partir de cultura láctica liofilizada comercial contendo dois micro-organismos probióticos, Bifidobacterium animalis e Lactobacillus acidophilus, associados aos micro-organismos característicos do iogurte, Lactobacillus bulgaricus e Streptococcus thermophilus. Foi utilizado um preparado enzimático contendo -galactosidases obtidas de duas origens distintas: Kluyveromyces lactis e Aspergillus niger. Foram avaliados os efeitos da concentração da enzima e do tempo de adição da enzima em um planejamento experimental 2 2 . As respostas foram às concentrações, ao final do processo, de lactose, de GOS, de glicose e de galactose e a hidrólise dos galactooligossacarídeos ao longo do tempo. No que se refere à abordagem teórica, o presente trabalho considerou modelos matemáticos de hidrólise de dissacarídeos e conversão da lactose, em que a inibição foi representada a partir do incremento da concentração dos produtos da reação. No que se refere à conversão da lactose e síntese de GOS, o presente trabalho buscou estabelecer um modelo matemático em que a inibição ocorreu por efeito do incremento das concentrações de glicose e de galactose, comparando-o com os modelos conhecidos na literatura. Verificou-se que o desempenho do modelo obtido no presente trabalho foi robusto em relação às premissas estabelecidas. Na comparação com resultados experimentais de conversão enzimática, o modelo mostrou-se capaz de minimizar o erro e de ajustar-se aos dados experimentais.

Estudo numérico experimental de treliças espaciais feitas com tubos de aço com ponta amassada e espaçadores de madeira para corrigir as excentricidades nos nós de ligação

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Tecnologia, 2015.

Uma abordagem experimental de fatores da adesão à medicação em idosos: barreiras e facilitadores

Este estudo teve como objetivo perceber de que forma certos fatores mencionados como determinantes da adesão à medicação, nomeadamente severidade da condição clínica (SCC), confiança no clínico, complexidade do regime e custo dos medicamentos influenciam os juízos de adesão por parte de idosos. Replicando a investigação de Diniz, Oliveira, e Santos (2016) sobre a doença cardíaca (DC), recorreu-se a uma tarefa experimental composta pela combinação dos diferentes níveis dos fatores, pediu-se aos 72 participantes que avaliassem o nível de adesão percebida à medicação de um hipotético doente com diabetes Tipo II. Através da ANOVA mista de medidas repetidas verificou-se que a SCC surgiu como o único determinante da adesão, revelando, tal como na DC, a importância do afeto como informação. Contudo, a diabetes Tipo II gerou menos pavor do que a DC, com os restantes fatores a não influenciar a adesão por causa de preferências enviesadas para o presente; An experimental approach of factors of medication adherence in elderly: Barriers and facilitators Abstract: The purpose of this study was to understand how certain factors mentioned as determinants of adherence to medication, namely severity of clinical condition (SCC), trust in the clinician, regimen complexity and cost of medication, influence the judgments of adherence by the elderly. Replicating the investigation of Diniz, Oliveira, e Santos (2016) about heart precondition (HP), an experimental task composed by scenarios combining the different levels of the factors was used, asking 72 participants to rate the degree of perceived adherence to medication of a hypothetical patient with Type II diabetes. Through mixed repeated measures ANOVA it was found that SCC emerged as the only determinant of adherence, revealing, as in HP, the importance of affect as information. However, the clinical condition Type II diabetes generated less dread than the HP, not influencing adherence because of present-biased preferences.

Evaluating the effect of a patient education brochure on patients’ expectations and satisfaction with emergency department service

Introduction: The purpose of this study was to assess the capacity of a written intervention, in this case a patient information brochure, to improve patient satisfaction during an Emergency Department (ED) visit. For the purpose of measuring the effect of the intervention the ED journey was conceptualised as a series of distinct areas of service comprising waiting time, service by the triage nurse, care from doctors and nurses and information giving Background of study: Research into patient satisfaction has become a widespread activity endorsed by both governments and hospital administrations. The literature on ED patient satisfaction has consistently indicated three primary areas of patient dissatisfaction: waiting time, nursing care and communication. Recent developments in the literature on patient satisfaction studies however have highlighted the relationship between patients. expectations of a service encounter and their consequent assessment of the experience as dissatisfying or satisfying. Disconfirmation theory posits that the degree to which expectations are confirmed will affect subsequent levels of satisfaction. The conceptual framework utilised in this study is Coye.s (2004) model of disconfirmation. Coye while reiterating satisfaction is a consequence of the degree expectations are either confirmed or disconfirmed also posits that expectations can be modified by interventions. Coye.s work conceptualises these interventions as intra encounter experiences (cues) which function to adjust expectations. Coye suggests some cues are unintended and may have a negative impact which also reinforces the value of planned cues intended to meet or exceed consumer expectations. Consequently the brochure can be characterized as a potentially positive cue, encouraging the patient to understand processes and to orient them in what can be a confronting environment. Only a limited number of studies have examined the effect of written interventions within an ED. No studies could be located which have tested the effect of ED interventions using a conceptual framework which relates the effect of the degree to which expectations are confirmed or disconfirmed in terms of satisfaction with services. Method: Two studies were conducted. Study One used qualitative methods to explore patients. expectations of the ED from the perspective of both patients and health care professionals. Study One was used in part to direct the development of the intervention (brochure) in Study Two. The brochure was an intervention designed to modify patients. expectations thus increasing their satisfaction with the provision of ED service. As there was no existing tools to measure ED patients. expectations and satisfaction a new tool was also developed based on the findings and the literature of Study One. Study Two used a non-randomised, quasi-experimental approach using a non-equivalent post-test only comparison group design used to investigate the effect of the patient education brochure (Stommel and Wills, 2004). The brochure was disseminated to one of two study groups (the intervention group). The effect of the brochure was assessed by comparing the data obtained from both the intervention and control group. These two groups consisted of 150 participants each. It was expected that any differences in the relevant domains selected for examination would indicate the effect of the brochure both on expectation and potentially satisfaction. Results: Study One revealed several areas of common ground between patients and nurses in terms of relevant content for the written intervention, including the need for information on the triage system and waiting times. Areas of difference were also found with patients emphasizing communication issues, whereas focus group members expressed concern that patients were often unable to assimilate verbal information. The findings suggested the potential utility of written material to reinforce verbal communication particularly in terms of the triage process and other ED protocols. This material was synthesized within the final version of the written intervention. Overall the results of Study Two indicated no significant differences between the two groups. The intervention group did indicate a significant number of participants who viewed the brochure of having changed their expectations. The effect of the brochure may have been obscured by a lack of parity between the two groups as the control group presented with statistically significantly higher levels of acuity and experienced significantly shorter waiting times. In terms of disconfirmation theory this would suggest expectations that had been met or exceeded. The results confirmed the correlation of expectations with satisfaction. Several domains also indicated age as a significant predictor with older patients tending to score higher satisfaction results. Other significant predictors of satisfaction established were waiting time and care from nurses, reinforcing the combination of efficient service and positive interpersonal experiences as being valued by patients. Conclusions: Information presented in written form appears to benefit a significant number of ED users in terms of orientation and explaining systems and procedures. The degree to which these effects may interact with other dimensions of satisfaction however is likely to be limited. Waiting time and interpersonal behaviours from staff also provide influential cues in determining satisfaction. Written material is likely to be one element in a series of coordinated strategies to improve patient satisfaction during periods of peak demand.

Human atrial beta1L-adrenoceptor but not beta3-adrenoceptor activation increases force and Ca2+ current at physiological temperature

BACKGROUND AND PURPOSE It has been proposed that BRL37344, SR58611 and CGP12177 activate b3-adrenoceptors in human atrium to increase contractility and L-type Ca2+ current (ICa-L). b3-adrenoceptor agonists are potentially beneficial for the treatment of a variety of diseases but concomitant cardiostimulation would be potentially harmful. It has also been proposed that (-)-CGP12177 activates the low affinity binding site of the b1-adrenoceptor in human atrium. We therefore used BRL37344, SR58611 and (-)-CGP12177 with selective b-adrenoceptor subtype antagonists to clarify cardiostimulant b-adrenoceptor subtypes in human atrium. EXPERIMENTAL APPROACH Human right atrium was obtained from patients without heart failure undergoing coronary artery bypass or valve surgery. Cardiomyocytes were prepared to test BRL37344, SR58611 and CGP12177 effects on ICa-L. Contractile effects were determined on right atrial trabeculae. KEY RESULTS BRL37344 increased force which was antagonized by blockade of b1- and b2-adrenoceptors but not by blockade of b3-adrenoceptors with b3-adrenoceptor-selective L-748,337 (1 mM). The b3-adrenoceptor agonist SR58611 (1 nM–10 mM) did not affect atrial force. BRL37344 and SR58611 did not increase ICa-L at 37°C, but did at 24°C which was prevented by L-748,337. (-)-CGP12177 increased force and ICa-L at both 24°C and 37°C which was prevented by (-)-bupranolol (1–10 mM), but not L-748,337. CONCLUSIONS AND IMPLICATIONS We conclude that the inotropic responses to BRL37344 are mediated through b1- and b2-adrenoceptors. The inotropic and ICa-L responses to (-)-CGP12177 are mediated through the low affinity site b1L-adrenoceptor of the b1-adrenoceptor. b3-adrenoceptor-mediated increases in ICa-L are restricted to low temperatures. Human atrial b3-adrenoceptors do not change contractility and ICa-L at physiological temperature.

The benefits of not managing change and not communicating : towards a complex systems view of communication in evolving organisations

The relationship between change in organisations and communication about change in organisations can be analysed as a particular case of a general debate in social theory about the extent to which reality is socially constructed. Social constructivists emphasise the role of language in the construction of social realities, enacted through controlling the message agenda; material determinists assert that economic and social structural factors are more constitutive of reality as seen in strategies emphasising structural and resource interventions. Here we define a third view of language and materiality - one that leads to the potential for a reflexive, experimental approach to change based on the view that organisations are complex evolving systems.

Notch and NOXA-related pathways in melanoma cells

Notch receptor-mediated intracellular events represent an ancient cell signaling system, and alterations in Notch expression are associated with various malignancies in which Notch may function as an oncogene or less commonly as a tumor suppressor. Notch signaling regulates cell fate decisions in the epidermis, including influencing stem cell dynamics and growth/differentiation control of cells in skin. Because of increasing evidence that the Notch signaling network is deregulated in human malignancies, Notch receptors have become attractive targets for selective killing of malignant cells. Compared with proliferating normal human melanocytes, melanoma cell lines are characterized by markedly enhanced levels of activated Notch-1 receptor. By using a small molecule gamma-secretase inhibitor (GSI) consisting of a tripeptide aldehyde, N-benzyloxycarbonyl-Leu-Leu-Nle-CHO, which can block processing and activation of all four different Notch receptors, we identified a specific apoptotic vulnerability in melanoma cells. GSI triggers apoptosis in melanoma cells, but only G2/M growth arrest in melanocytes without subsequent cell death. Moreover, GSI treatment induced a pro-apoptotic BH3-only protein, NOXA, in melanoma cells but not in normal melanocytes. The use of GSI to induce NOXA induction overcomes the apoptotic resistance of melanoma cells, which commonly express numerous cell survival proteins such as Mcl-1, Bcl-2, and survivin. Taken together, these results highlight the concept of synthetic lethality in which exposure to GSI, in combination with melanoma cells overexpressing activated Notch receptors, has lethal consequences, producing selective killing of melanoma cells, while sparing normal melanocytes. By identifying signaling pathways that contribute to the transformation of melanoma cells (e.g. Notch signaling), and anti-cancer agents that achieve tumor selectivity (e.g., GSI-induced NOXA), this experimental approach provides a useful framework for future therapeutic strategies in cutaneous oncology.

Exploring the role of gender and risk perceptions in people’s decisions to register as a bone marrow donor

Increasing the number of bone marrow (BM) donors is important to ensure sufficient diversity on BM registries to meet the needs of patients. This study used an experimental approach to test the hypothesis that providing information about the risks of BM donation to allay unsubstantiated fears would reduce male and female participants’ perceptions of risk for donation and joining the Australian BM Donor Registry (ABMDR). Males’ and females’ intentions to register on the ABMDR, their attitudes, norms, and perceived behavioural control (efficacy) in relation to registering were explored also. Participants were allocated randomly to either a risk (exposed to risk information about BM donation) or no risk(not exposed to risk information) condition. In partial support of hypotheses, exposure to risk information did reduce perceived risk for registering on the ABMDR for males only. Participants in the risk condition also demonstrated lower scores on attitude (males only) and intention compared to participants in the no risk condition. These findings highlight the complex role of risk perceptions and gender differences in understanding people’s decisions to join a BM registry.

System level tests of transformer differential protection using an IEC 61850 process bus

The IEC 61850 family of standards for substation communication systems were released in the early 2000s, and include IEC 61850-8-1 and IEC 61850-9-2 that enable Ethernet to be used for process-level connections between transmission substation switchyards and control rooms. This paper presents an investigation of process bus protection performance, as the in-service behavior of multi-function process buses is largely unknown. An experimental approach was adopted that used a Real Time Digital Simulator and 'live' substation automation devices. The effect of sampling synchronization error and network traffic on transformer differential protection performance was assessed and compared to conventional hard-wired connections. Ethernet was used for all sampled value measurements, circuit breaker tripping, transformer tap-changer position reports and Precision Time Protocol synchronization of sampled value merging unit sampling. Test results showed that the protection relay under investigation operated correctly with process bus network traffic approaching 100% capacity. The protection system was not adversely affected by synchronizing errors significantly larger than the standards permit, suggesting these requirements may be overly conservative. This 'closed loop' approach, using substation automation hardware, validated the operation of protection relays under extreme conditions. Digital connections using a single shared Ethernet network outperformed conventional hard-wired solutions.

Chronic activation of the low affinity site of β1-adrenoceptors stimulates haemodynamics but exacerbates pressure-overload cardiac remodelling

Background and Purpose The β1-adrenoceptor has at least two binding sites, high and low affinity sites (β1H and β1L, respectively), which mediate cardiostimulation. While β1H-adrenoceptor can be blocked by all clinically used β-blockers, β1L-adrenoceptor is relatively resistant to blockade. Thus, chronic β1L-adrenoceptor activation may mediate persistent cardiostimulation, despite the concurrent blockade of β1H-adrenoceptors. Hence, it is important to determine the potential significance of β1L-adrenoceptors in vivo, particularly in pathological situations. Experimental Approach C57Bl/6 male mice were used. Chronic (4 or 8 weeks) β1L-adrenoceptor activation was achieved by treatment, via osmotic mini pumps, with (-)-CGP12177 (10 mg·kg−1·day−1). Cardiac function was assessed by echocardiography and micromanometry. Key Results (-)-CGP12177 treatment of healthy mice increased heart rate and left ventricular (LV) contractility. (-)-CGP12177 treatment of mice subjected to transverse aorta constriction (TAC), during weeks 4–8 or 4–12 after TAC, led to a positive inotropic effect and exacerbated fibrogenic signalling while cardiac hypertrophy tended to be more severe. (-)-CGP12177 treatment of mice with TAC also exacerbated the myocardial expression of hypertrophic, fibrogenic and inflammatory genes compared to untreated TAC mice. Washout of (-)-CGP12177 revealed a more pronounced cardiac dysfunction after 12 weeks of TAC. Conclusions and Implications β1L-adrenoceptor activation provides functional support to the heart, in both normal and pathological (pressure overload) situations. Sustained β1L-adrenoceptor activation in the diseased heart exacerbates LV remodelling and therefore may promote disease progression from compensatory hypertrophy to heart failure.

Phosphodiesterase PDE3, but not PDE4, reduces β1- and β2-adrenoceptor-mediated inotropic and lusitropic effects in failing ventricle from metoprolol-treated patients

Background and purpose Phosphodiesterases PDE3 and/or PDE4 control ventricular effects of catecholamines in several species but their relative effects in failing human ventricle are unknown. We investigated whether the PDE3-selective inhibitor cilostamide (0.3-1μM) or PDE4 inhibitor rolipram (1-10μM) modified the positive inotropic and lusitropic effects of catecholamines in human failing myocardium. Experimental approach Right and left ventricular trabeculae from freshly explanted hearts of 5 non-β-blocker-treated and 15 metoprolol-treated patients with terminal heart failure were paced to contract at 1Hz. The effects of (-)-noradrenaline, mediated through β1-adrenoceptors (β2-adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through β2-adrenoceptors (β1-adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of PDE inhibitors. Catecholamine potencies were estimated from –logEC50s. Key results Cilostamide did not significantly potentiate the inotropic effects of the catecholamines in non-β-blocker-treated patients. Cilostamide caused greater potentiation (P=0.037) of the positive inotropic effects of (-)-adrenaline (0.78±0.12 log units) than (-)-noradrenaline (0.47±0.12 log units) in metoprolol-treated patients. Lusitropic effects of the catecholamines were also potentiated by cilostamide. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline on right and left ventricular trabeculae from metoprolol-treated patients. Conclusions and implications Metoprolol induces a control by PDE3 of ventricular effects mediated through both β1- and β2-adrenoceptors, thereby further reducing sympathetic cardiostimulation in patients with terminal heart failure. Concurrent therapy with a PDE3 blocker and metoprolol could conceivably facilitate cardiostimulation evoked by adrenaline through β2-adrenoceptors. PDE4 does not appear to reduce inotropic and lusitropic effects of catecholamines in failing human ventricle.