The role of climate change in a developing threat: the case of bluetongue in Europe.

There is a solid theoretical basis for expecting climate change to have a considerable effect on the infectious diseases of humans, animals and plants. Vector-borne diseases are the most likely to be affected. It is, however, rare to observe such impacts, as diseases are also influenced by many other drivers, some of which may have stronger effects over shorter time scales than climate change. Nevertheless, there is evidence that our warming climate has already influenced some animal diseases, of which bluetongue is considered a prime example. Bluetongue emerged dramatically in southern Europe after 1998 and in northern Europe from 2006. While the speed and scale of this emergence is a challenge to explain, there is evidence, principally from the development of climate-driven models, that recent climate change has played a significant role. Climate-driven models point to an increase in the risk of bluetongue transmission in Europe in recent decades, caused by an increased suitability of parts of southern Europe for the Afro-tropical biting midge, Culicoides imicola, as well as an increase in the vectorial capacity of indigenous Culicoides vectors in northern Europe. Farm-to-farm transmission models of bluetongue in England and Wales under predicted climatic conditions further suggest that, under high-emission scenarios, the scale of future outbreaks could far exceed those experienced to date. The role of climate change in the developing threat of animal disease is, therefore, likely to be economically and socially costly, unless lower emission targets can be set and followed.

Nombre d'arguments théoriques sérieux confirment l'ampleur des effets du changement climatique sur les maladies infectieuses affectant l'être humain, les animaux et les végétaux. Les maladies à transmission vectorielle sont probablement les plus sujettes à cette influence. Toutefois, il est très rare de pouvoir observer ces effets directement, dans la mesure où d'autres facteurs exercent également une influence sur les maladies, dont certains ont des effets plus marquants et plus rapides que le changement climatique. L'influence du réchauffement climatique sur certaines maladies animales a néanmoins été prouvée ; à ce titre, le cas de la fièvre catarrhale ovine est considéré comme exemplaire. La fièvre catarrhale ovine a fait son apparition en Europe méridionale après 1998, puis en Europe du Nord à partir de 2006. Si la rapidité et l'envergure de cette émergence sont difficiles à expliquer, plusieurs démonstrations, recourant pour la plupart à des modèles axés sur le climat font état du rôle important joué par le changement climatique. Les modèles axés sur le climat font ressortir un risque accru de transmission de la fièvre catarrhale ovine en Europe au cours des dernières décennies, associé, d'une part, à l'adéquation croissante de régions entières de l'Europe méridionale vis-à-vis du moucheron afro-tropical Culicoides imicola et, d'autre part, à l'accroissement de la capacité vectorielle des vecteurs Culicoides autochtones dans le nord de l'Europe. D'après les études basées sur des modèles de transmission de la fièvre catarrhale ovine entre exploitations en Angleterre et au Pays de Galles, dans les conditions climatiques prévisibles, il apparaît qu'en cas de fortes émissions, l'ordre de grandeur des foyers futurs serait considérablement plus élevé que dans les épisodes que nous avons connus jusqu'à présent. Par conséquent, le rôle du changement climatique dans les menaces évolutives de santé animale risque d'avoir un coût économique et social élevé, à moins que des objectifs de réduction de l'émission soient mis en place et fassent l'objet d'un suivi approprié.

Existen sólidas bases teóricas para prever que el cambio climático tendrá efectos considerables en las enfermedades infecciosas que afectan al hombre, los animales o las plantas. Las que más probablemente se verán afectadas son las enfermedades transmitidas por vectores. Sin embargo, rara vez pueden observarse tales efectos, pues hay otros muchos factores que influyen en las enfermedades, algunos de los cuales, a una escala temporal más breve, pueden tener una influencia más marcada que el cambio climático. Aun así, hay pruebas de que el clima, en pleno proceso de calentamiento, ya ha incidido en algunas enfermedades animales, de las que la lengua azul se considera un perfecto ejemplo. La lengua azul hizo una espectacular aparición en el sur de Europa a partir de 1998, y en la Europa septentrional a partir de 2006. Aunque resulta difícil explicar la velocidad y las proporciones de tal aparición, existen sólidos indicios, obtenidos principalmente de la elaboración de modelos regidos por variantes climáticas, de que el reciente cambio climático ha cumplido una función importante. Estos modelos apuntan a un incremento del riesgo de transmisión de la lengua azul en Europa en los últimos decenios, lo que se explica por las condiciones más propicias al jején afrotropical, Culicoides imicola, que ofrecen ciertas partes de Europa meridional y por un aumento de la capacidad vectorial de los Culicoides autóctonos del norte de Europa. Los modelos de transmisión de la lengua azul entre explotaciones agropecuarias de Inglaterra y Gales en las condiciones climáticas predichas indican además que, en la hipótesis de un elevado volumen de emisiones, los futuros brotes pueden revestir una escala muy superior a cuanto hemos conocido hasta ahora. Por consiguiente, a menos que se logre establecer y cumplir objetivos de emisiones menos cuantiosas, es probable que el cambio climático resulte económica y socialmente gravoso por su incidencia en la creciente amenaza que plantean las enfermedades animales.

Combined effects of matrix stiffness and obesity-associated signaling directs progressive phenotype in PANC-1 pancreatic cancer cells in vitro.

Obesity is a leading risk factor of pancreatic ductal adenocarcinoma (PDAC) that contributes to poor disease prognosis and outcomes. Retrospective studies have identified this link, but interactions surrounding obesity and PDAC are still unclear. Research has shifted to contributions of fibrosis (desmoplasia) on malignancy, which involves increased deposition of collagens and other extracellular matrix (ECM) molecules and increased ECM crosslinking, all of which contribute to increased tissue stiffening. However, fibrotic stiffening is underrepresented as a model feature in current PDAC models. Fibrosis is shared between PDAC and obesity, and can be leveraged for in vitro model design, as current animal obesity models of PDAC are limited in their ability to isolate individual components of fibrosis to study cell behavior. In the current study, methacrylated type I collagen (PhotoCol®) was photo-crosslinked to pathological stiffness levels to recapitulate fibrotic ECM stiffening. PANC-1 cells were encapsulated within PhotoCol®, and the tumor-tissue constructs were prepared to represent normal (healthy) (~600 Pa) and pathological (~2000 Pa) tissues. Separately, human mesenchymal stem cells were differentiated into adipocytes representing lean (2D differentiation) and obese fat tissue (3D collagen matrix differentiation), and conditioned media was applied to PANC-1 tumor-tissue constructs. Conditioned media from obese adipocytes showed increased vimentin expression, a hallmark of invasiveness and progression, that was not seen after exposure to media from lean adipocytes or control media. Characterization of the obese adipocyte secretome suggested that some PANC-1 differences may arise from increased interleukin-8 and -10 compared to lean adipocytes. Additionally, high matrix stiffness associated induced an amoeboid morphology in PANC-1 cells that was not present at low stiffness. Amoeboid morphology is an accessory to epithelial-to-mesenchymal transition and is used to navigate complex ECM environments. This plasticity has greater implications for treatment efficacy of metastatic cancers. Overall, this work 1) highlights the importance of investigating PDAC-obesity interactions to study the effects on disease progression and persistence, 2) establishes PhotoCol® as a matrix material that can be leveraged to study amoeboid morphology and invasion in PDAC, and 3) emphasizes the importance of integrating both biophysical and biochemical interactions associated within both pathologies for in vitro PDAC models.

The role of CO2 in the genesis of Dabie-type porphyry molybdenum deposits.

Porphyry-type molybdenum deposits, many of which are in China, supply most of the World's molybdenum. Of particular importance are the molybdenum deposits located in the Qinling-Dabie region that are responsible for more than half of China's molybdenum production. A feature that distinguishes this suite of deposits from the better-known Climax and Endako sub-types of porphyry molybdenum deposits is their formation from CO2-rich magmatic-hydrothermal fluids. The role of CO2, if any, in the transport of molybdenum by these fluids, however, is poorly understood. We conducted experiments on the partitioning of molybdenum between H2O-CO2, H2O-NaCl, and H2O-NaCl-CO2 fluids and a felsic melt at 850 °C and 100 and 200 MPa. Here we show that the exsolution of separate (immiscible) brine and vapor leads to the very high brine DMo values needed for efficient extraction of Mo from the magmas forming Dabie-type porphyry molybdenum deposits.

Outcome of infection of C57BL/6 IL-10(-/-) mice with Campylobacter jejuni strains is correlated with genome content of open reading frames up- and down-regulated in vivo.

Human Campylobacter jejuni infection can result in an asymptomatic carrier state, watery or bloody diarrhea, bacteremia, meningitis, or autoimmune neurological sequelae. Infection outcomes of C57BL/6 IL-10(-/-) mice orally infected with twenty-two phylogenetically diverse C. jejuni strains were evaluated to correlate colonization and disease phenotypes with genetic composition of the strains. Variation between strains was observed in colonization, timing of development of clinical signs, and occurrence of enteric lesions. Five pathotypes of C. jejuni in C57BL/6 IL-10(-/-) mice were delineated: little or no colonization, colonization without disease, colonization with enteritis, colonization with hemorrhagic enteritis, and colonization with neurological signs with or without enteritis. Virulence gene content of ten sequenced strains was compared in silico; virulence gene content of twelve additional strains was compared using a C. jejuni pan-genome microarray. Neither total nor virulence gene content predicted pathotype; nor was pathotype correlated with multilocus sequence type. Each strain was unique with regard to absences of known virulence-related loci and/or possession of point mutations and indels, including phase variation, in virulence-related genes. An experiment in C. jejuni 11168-infected germ-free mice showed that expression levels of ninety open reading frames (ORFs) were significantly up- or down-regulated in the mouse cecum at least two-fold compared to in vitro growth. Genomic content of these ninety C. jejuni 11168 ORFs was significantly correlated with the capacity to colonize and cause enteritis in C57BL/6 IL-10(-/-) mice. Differences in gene expression levels and patterns are thus an important determinant of pathotype in C. jejuni strains in this mouse model.

The effect of temperature on di(2-ethylhexyl) phthalate leaching from PVC infusion sets exposed to lipid emulsions.

Poly vinyl chloride (PVC) infusion equipment contains substantial amounts of the plasticiser di(2-ethylhexyl) phthalate (DEHP). We determined the amount of DEHP leached from Mediplus Dual TIVA(®) Infusion sets, into lipid and non-lipid infusates. Two propofol admixtures (Diprivan(®) 1%, Propoven(®) 1%), Intralipid(®) 10% and 0.9% saline were evaluated as infusates. Solutions were infused through TIVA sets at 12 ml.h(-1) for 6 h at 24, 32 and 37 °C. In addition, TIVA sets were filled with 2 ml infusates, sealed and incubated at 24 and 37 °C for 6 h. Di(2-ethylhexyl) phthalate was detected in all lipid infusates after dynamic infusion and static contact, and in 0.9% saline after dynamic infusion at 37 °C. At 32 and 37 °C, the quantity of di(2-ethylhexyl) phthalate leaching into the lipid infusates may exceed the recommended maximum exposure amount set by the European Union for DEHP of 20-48 µg.kg(-1) day(-1) if lipid based infusates are used for sedation or intravenous feeding of infants or neonates.

Biodiversity of air-borne microorganisms at Halley Station, Antarctica.

A study of air-borne microbial biodiversity over an isolated scientific research station on an ice-shelf in continental Antarctica was undertaken to establish the potential source of microbial colonists. The study aimed to assess: (1) whether microorganisms were likely to have a local (research station) or distant (marine or terrestrial) origin, (2) the effect of changes in sea ice extent on microbial biodiversity and (3) the potential human impact on the environment. Air samples were taken above Halley Research Station during the austral summer and austral winter over a 2-week period. Overall, a low microbial biodiversity was detected, which included many sequence replicates. No significant patterns were detected in the aerial biodiversity between the austral summer and the austral winter. In common with other environmental studies, particularly in the polar regions, many of the sequences obtained were from as yet uncultivated organisms. Very few marine sequences were detected irrespective of the distance to open water, and around one-third of sequences detected were similar to those identified in human studies, though both of these might reflect prevailing wind conditions. The detected aerial microorganisms were markedly different from those obtained in earlier studies over the Antarctic Peninsula in the maritime Antarctic.

New drugs and technologies, intravenous anaesthesia is on the move (again).

Although well established in clinical practice, both propofol and midazolam have limitations. New hypnotics with different and potentially superior pharmacokinetics and pharmacodynamics are under development. These include the benzodiazepine receptor agonists CNS7056 and JM-1232 (-), the etomidate-based methoxycarbonyl-etomidate and carboetomidate, the propofol-related structures PF0713 and fospropofol, and THRX-918661/AZD3043. The basic pharmacology and the initial anaesthesia studies for each of these agents are reviewed. Several of the agents (CNS7056, THRX-918661/AZD3043, and fospropofol) have reached the stage of clinical trials. To be successful, novel compounds need to establish clear clinical advantages over existing agents and where possible the new agents are discussed in this context. Computer-controlled drug administration offers the ability to automatically implement infusion schemes too complex for manual use and the possibility of linking patient monitoring to administration to enhance patient safety.

Stent angioplasty for treatment of canine valvular pulmonic stenosis.

Four dogs presented for evaluation and treatment of severe pulmonic valve stenosis and underwent stenting of the pulmonic valve annulus using bare-metal balloon-expandable stents. All dogs survived the procedure with immediate reduction of the transpulmonary valve pressure gradient and increase in activity levels. One dog had a stent fracture and migration 1 month after the intervention. This dog underwent a second procedure, in which multiple stents were used to alleviate the obstruction. The stents that were placed at the level of the right ventricular outflow tract fractured within 1 month of the procedure, and the patient died when a third (surgical) approach was attempted. The other three dogs remain alive 54, 42, and 29 months after the procedure. Stent angioplasty may be a viable option for dogs with valvular pulmonic stenosis in which routine balloon valvuloplasty does not provide a successful outcome. Aggressive attempts to diminish RVOT dynamic obstruction with high-dose beta blockade and avoiding deployment of the stent within the RVOT are recommended to prevent stent fracture and migration.

The UK's suitability for Aedes albopictus in current and future climates.

The Asian tiger mosquito Aedes albopictus is able to transmit various pathogens to humans and animals and it has already caused minor outbreaks of dengue and chikungunya in southern Europe. Alarmingly, it is spreading northwards and its eggs have been found in the UK in 2016 and 2017. Climate-driven models can help to analyse whether this originally subtropical species could become established in northern Europe. But so far, these models have not considered the impact of the diurnal temperature range (DTR) experienced by mosquitoes in the field. Here, we describe a dynamical model for the life cycle of Ae. albopictus, taking into account the DTR, rainfall, photoperiod and human population density. We develop a new metric for habitat suitability and drive our model with different climate data sets to analyse the UK's suitability for this species. For now, most of the UK seems to be rather unsuitable, except for some densely populated and high importation risk areas in southeast England. But this picture changes in the next 50 years: future scenarios suggest that Ae. albopictus could become established over almost all of England and Wales, indicating the need for continued mosquito surveillance.

Transvenous pacing implantation: techniques, tips, and lessons learned along the way.

The right ventricular apex has been the traditional site for lead placement in veterinary patients who require permanent cardiac pacing therapy for atrioventricular block and sick sinus syndrome. Implantation of leads in this location is a straightforward procedure that most veterinary cardiologists perform routinely. Pacing at the right ventricular apex, however, has been demonstrated to have long-term deleterious effects on the left ventricular function in numerous patient populations and animal models. Alternative lead placement sites and pacing system configurations have been developed, and the purpose of this review article is not to review the literature or the decision-making process in selecting a specific pacing system but rather to share the experiences of our group with the use of alternative pacing implantation techniques for veterinary patients in need of permanent cardiac pacing.

The effect of temperature, farm density and foot-and-mouth disease restrictions on the 2007 UK bluetongue outbreak.

In 2006, bluetongue (BT), a disease of ruminants, was introduced into northern Europe for the first time and more than two thousand farms across five countries were affected. In 2007, BT affected more than 35,000 farms in France and Germany alone. By contrast, the UK outbreak beginning in 2007 was relatively small, with only 135 farms in southeast England affected. We use a model to investigate the effects of three factors on the scale of BT outbreaks in the UK: (1) place of introduction; (2) temperature; and (3) animal movement restrictions. Our results suggest that the UK outbreak could have been much larger had the infection been introduced into the west of England either directly or as a result of the movement of infected animals from southeast England before the first case was detected. The fact that air temperatures in the UK in 2007 were marginally lower than average probably contributed to the UK outbreak being relatively small. Finally, our results indicate that BT movement restrictions are effective at controlling the spread of infection. However, foot-and-mouth disease restrictions in place before the detection and control of BT in 2007 almost certainly helped to limit BT spread prior to its detection.

The contact structure of Great Britain's salmon and trout aquaculture industry.

We analyse the network structure of the British salmonid aquaculture industry from the perspective of infectious disease control. We combine for the first time live fish transport (or movement) data covering England and Wales with data covering Scotland and include network layers representing potential transmission by rivers, sea water and local transmission via human or animal vectors in the immediate vicinity of each farm or fishery site. We find that 7.2% of all live fish transports cross the England-Scotland border and network analysis shows that 87% of English and Welsh nodes and 72% of Scottish nodes are reachable from cross-border connections via live fish transports alone. Consequently, from a disease-control perspective, the contact structures of England and Wales and of Scotland should not be considered in isolation. We also show that large epidemics require the live fish movement network and so control strategies targeting movements can be very effective. While there is relatively low risk of widespread epidemics on the live fish transport network alone, the potential risk is substantially amplified by the combined interaction of multiple network layers.

Anaesthetic effects of propofol polymeric micelle: a novel water soluble propofol formulation.

BACKGROUND: As a result of its very low water solubility, propofol is generally presented as a lipid-based formulation with well-characterized limitations. METHODS: Propofol (99.7%) was added directly to an aqueous solution of poly(N-vinyl-2-pyrrolidone)-block-poly(D,L-lactide)copolymers (PVP-PLA) block copolymers and stirred in order to obtain a clear solution. This formulation was filtered sterile and then lyophilized to its solid form Propofol-PM (propofol polymeric micelle) which reconstitutes to a propofol 1%w/v (10 mg ml(-1)) clear aqueous solution of 30-60 nm propofol-containing micelles. Population pharmacokinetic data from whole blood and plasma were obtained by administering reconstituted Propofol-PM formulations and a 1% oil in water formulation, Diprivan to male Sprague-Dawley rats (n = 40) at a dose of 10 mg kg(-1). Preliminary recovery data were obtained from a further small study. RESULTS: The pharmacokinetics were best described using a two-compartment mamillary population model, which incorporated sample matrix (blood or plasma) and propofol formulation (Diprivan) or Propofol-PM) as covariates. Sample matrix was applied to all structural model parameters as a dichotomous covariate. An influence of propofol formulation was observed for all parameters (excluding distributional clearance) but only when plasma was used for propofol quantification. In this preliminary pharmacodynamic study, there was no statistically significant difference in the timing of the recovery endpoints between the Propofol-PM formulation and Diprivan groups. CONCLUSIONS: Propofol-PM formulations produce anaesthesia in rats. Whole blood pharmacokinetics of Propofol-PM did not differ from those observed with Diprivan.

An approach to determining nickel, vanadium and other metal concentrations in crude oil.

The ability to accurately determine the metal content of crude oils is necessary for reasons ranging from the need to identify the source of the oils (Ni and V) to removing components that might inhibit catalysis during refining or impact negatively on the environment during hydrocarbon combustion. Here we show that ashing followed by chemical oxidation and acid digestion, coupled with ICP-MS analysis, provides an accurate method for determining the concentration of metals in crude oil. Nickel and vanadium concentrations were measured in certified Ni and V oil standards and in various light, intermediate and heavy crude oils after application of a single vessel ashing-chemical oxidation-acid digestion sample preparation and storing technique. Prior to the ashing, chemical oxidation and acid digestion, an aliquot of the crude oil was placed in a 10 ml Pyrex™ culture tube and capped with quartz wool. The capped culture tubes were then subjected to thermal combustion, followed by chemical oxidation and leaching. The leachates and the aqueous standards were diluted and analyzed for their Ni and V contents using inductively coupled plasma mass spectrometry (ICP-MS). The measured concentrations of Ni in oil standards, reported to contain 1, 100, and 1000 mg kg-1 Ni (±2% error), were 1.1 ± 0.01, 99.8 ± 1.46, and 1025 ± 24 mg kg-1 respectively. The corresponding concentrations of V in these standards, reported to contain 2, 100, and 1000 mg kg-1 V, were measured to be 1.93 ± 0.06, 104 ± 1.3, and 1027 ± 7.5 mg kg-1, respectively. Crude oil samples, A, B, C, D and E, that varied significantly in their composition, and ranged from light to heavy, were determined to contain 5.59 ± 0.32, 4.05 ± 0.03, 6.22 ± 0.22, 33.8 ± 0.7 and 41.6 ± 3.5 mg kg-1 Ni, respectively. Their V contents were determined to be 11.98 ± 0.1, 12.2 ± 0.1, 16.5 ± 0.4, 34.7 ± 0.4, and 104 ± 8.9 mg kg-1, respectively. The results were thus repeatable on average to 4.1% and 2.75% for Ni and V, respectively; the repeatability was worst (∼8.5%) for crude oil E, a heavy (viscous) oil with a very high asphaltene content (27.2%). This modified single vessel ashing-digestion technique (combustion, chemical oxidation, acid leaching and storing) minimizes contamination and significantly reduces the loss of ash. Our results are repeatable, comparable to, and in some cases superior to those of other methods. The method is applicable to a wide range of crude oil compositions, is very accessible and robust, easy to use, and does not require costly equipment in preparing the samples for analysis by ICP-MS.

The treatment of stage IIIA Hodgkin's disease.

Sixty consecutive previously untreated adults with surgically confirmed stage IIIA Hodgkin's disease (39 stage IIIA1, 21 stage IIIA2) began therapy at St. Bartholomew's Hospital between 1969 and 1981. Prior to 1973, treatment consisted of total nodal irradiation (TNI). From 1973 until 1978 patients were randomly allocated to receive either TNI or cyclic combination chemotherapy of mustine, vinblastine, prednisolone, and procarbazine (MVPP) as part of a Medical Research Council Trial. Since 1978 treatment has been allocated according to substage, those with stage IIIA1 receiving TNI and those with stage IIIA2 receiving MVPP. Seven patients received "non protocol" therapy (extended mantle radiotherapy in three patients, mantle and MVPP in four patients), and have been excluded from the study. Complete remission was achieved in 48 of 53 patients regardless of substage or therapy. Seven have relapsed, one after MVPP and six after TNI. The predicted freedom-from-relapse after MVPP was 96% compared with 60% after TNI, both at 10 years (p less than 0.01). The relapse pattern was the same for both substages in the group receiving TNI. Although overall survival of patients receiving TNI was identical to that of those receiving MVPP, TNI must be considered inappropriate therapy for stage IIIA Hodgkin's disease if permanent freedom-from-recurrence is the goal.

Follicular lymphoma: prognostic factors for response and survival.

One hundred forty-eight patients with newly diagnosed follicular lymphoma were treated over a 12-year period. Twenty-two patients received radiotherapy for stage I and II disease, followed by adjuvant chemotherapy in 14 patients. One hundred thirteen were treated at presentation with short courses of chemotherapy, most often with single-agent chlorambucil for bulky stage II and stages III and IV disease. Thirteen patients were managed expectantly until there was evidence of disease progression. The median survival was 9 years. Patients treated with radiotherapy for stage I and II disease had an 83% relapse-free survival, but those with bulky stage II or stages III and IV disease treated with chemotherapy pursued a remitting and relapsing course with a 70% response rate at initial and subsequent retreatments, but a median duration of remission of 4 years in stage III and 1 year in stage IV disease (P = .041). Patients were observed in relapse and retreatment was administered as appropriate, once every 33 months on average. Poor prognosis patients could be identified by a combination of the presentation characteristics: B symptoms, hepatosplenomegaly, anemia, and abnormal liver function. These factors predicted a poor response to treatment and correlated with a short survival. Histologic subgroups were not associated with differences in survival, but transformation to a diffuse high-grade lymphoma was observed in 23 of the 72 patients (32%) at risk, with a median follow-up of 6 years and 6 months, and was associated with a very poor prognosis. The present treatment strategy has proved successful for most patients with localized disease and those older patients with indolent small volume disseminated follicular lymphoma. New approaches are being investigated for the younger poor prognosis patients.

Reduced cardiac contractile responsiveness to isoproterenol in obese rabbits.

Although obesity is characterized by increased sympathetic nervous system activity, there is often a paradoxical reduction in cardiovascular end-organ response to sympathetic stimulation. Mechanisms involved in reduced sympathetic responsiveness in obesity have not been well characterized. Therefore, we determined cardiac contractile responsiveness to beta-stimulation in the obese rabbit model using both isolated heart (IH) and isolated papillary muscle (IPM) preparations. Female New Zealand White rabbits were fed control (IH: n=9; IPM: n=6) or 10% fat diets (IH: n=9; IPM: n=7) for 12 weeks. Contractile responsiveness in the IH was determined using a modified Langendorff preparation to evaluate the dose-response relationship between isoproterenol and 1) peak developed pressure/g of left ventricular wet weight and 2) maximal rate of pressure development (+dP/dt/P). Contractile responsiveness in the IPM was determined using right ventricular papillary muscles to evaluate the dose-response relationship between isoproterenol and (1) peak developed tension (T)/mm2 cross-sectional area (CSA) and (2) maximal rate of tension development (dT/dt/CSA). In the IH, baseline and maximum developed pressure/g were reduced in obese rabbits by 37% and 31%, respectively (P< or =.05). In the IPM, baseline and maximum T/CSA responses were reduced in obese rabbits by 59% and 33%, respectively (P< or =.05). Potency of isoproterenol as reflected by the EC50 did not differ between lean and obese animals in either preparation. These results demonstrate that left ventricular contractility in obesity is reduced at baseline and in response to stimulation with isoproterenol and suggest that decreased responsiveness to beta-stimulation may be a factor in the obesity-related systolic dysfunction.