Evaluation of left ventricular function with cardiac magnetic resonance imaging and echocardiography after administration of dobutamine and esmolol in healthy beagle dogs.

Unlike echocardiography, cardiac magnetic resonance imaging (cardiac MRI) results in a near-exact assessment of cardiac structures and function. However, most veterinary studies have focused on dogs with normal cardiac function. We hypothesized that there would be significant differences in cardiac measurements between cardiac MRI and echocardiography when left ventricular (LV) function was abnormal. This study was undertaken to compare measurements of LV function produced by cardiac MRI and echocardiography in dogs whose LV function was altered by pharmacological agents. This study was conducted with six healthy beagle dogs. We increased left ventricular contractility by administration of dobutamine; we decreased cardiac contractility with esmolol. Stroke volume measurements were made by using both cardiac MRI and echocardiography under seven different conditions with general anesthesia: control, three doses of esmolol (100, 200, and 500 µg/kg/min), and three doses of dobutamine (10, 20, and 50 µg/kg/min). Experiments involving each condition were conducted at least 1 week apart. When LV contractility was normal, ejection fraction (EF) and stroke volume (SV), as measured by echocardiography and cardiac MRI, were not significantly different. However, when contractility was changed by pharmacological agents, EF and SV were overestimated by echocardiography, compared to MRI. Evaluation of cardiac function in patients treated with pharmacological agents should be conducted carefully because EF and SV measured by echocardiography can be overestimated, compared with EF and SV obtained by cardiac MRI.

CT and radiographic evaluation of bronchial collapsibility at forced expiration in asymptomatic brachycephalic dogs.

Bronchial collapse due to bronchomalacia is an important cause of chronic coughing in dogs. Radiographic and CT evidence of bronchial collapse has previously been reported in healthy Beagle dogs under forced expiration. However, published studies in brachycephalic dog breeds that are prone to bronchial collapse are currently lacking. In the present prospective analytical experimental study, CT and radiography were used to measure the bronchial diameter and collapsibility of each pulmonary bronchus during end-expiratory, 5 mL/kg forced-expiratory, and 10 mL/kg forced-expiratory phases in 17 asymptomatic brachycephalic dogs and six healthy Beagle dogs. Bronchial collapsibility was significantly greater during forced expiration, than that at the end of expiration in both groups (P < .001). Bronchial collapsibility measurements of the left lung lobes and the right cranial, middle, and accessory lobes were significantly higher in asymptomatic brachycephalic dogs than those in healthy Beagle dogs, during all expiratory phases (P < .05). The higher bronchial collapsibility of brachycephalic dogs was also supported using CT multiplanar reconstruction images and radiography. In conclusion, radiographic and CT measures of bronchial collapsibility in asymptomatic brachycephalic dogs are higher than measures in healthy Beagle dogs. Therefore, measures of bronchial collapse in brachycephalic dogs should not be evaluated using the same baseline measures as those used for healthy Beagle dogs.

Computed tomographic and radiographic bronchial collapse may be a normal characteristic of forced expiration in dogs.

Tracheobronchomalacia has been diagnosed using radiography or bronchoscopy to confirm bronchial changes in luminal diameter during the respiratory cycle. However, studies in healthy humans suggest that some degree of bronchial collapse may be observed during the normal respiratory cycle. In this analytical study, the luminal diameter of the bronchus to each of the six pulmonary lobes and the mean percentage of expiratory collapse from end inspiratory, end expiratory, and two forced expiratory phases (10 and 15 ml/kg) were determined via computed tomography (CT) and radiography in 22 healthy Beagle dogs. The bronchial collapsibility was significantly greater during the forced expiration than the end expiration (P < 0.001); the same results were observed in dorsal and sagittal CT images and radiographs (P < 0.001). Median collapsibility values associated with 15 ml/kg forced expiratory collapse determined via cross-sectional CT images were measured as 16.6-45.5% and differed according to the pulmonary lobe. Median collapsibilities on radiography with 15 ml/kg forced expiration were 57.8% and 62.1% in the right cranial lobe and right caudal lobe, respectively. In conclusion, bronchial diameter may change during the respiratory cycle, and some degree of reduction in bronchial diameter may be an incidental finding in healthy dogs. More rigorous criteria are needed with regards to bronchial collapsibility during normal respiration for the diagnosis of bronchomalacia in order to avoid false-positive diagnoses.

Electrospun Silk Fibroin Nanofibrous Scaffolds with Two-Stage Hydroxyapatite Functionalization for Enhancing the Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells.

The development of functional scaffolds with improved osteogenic potential is important for successful bone formation and mineralization in bone tissue engineering. In this study, we developed a functional electrospun silk fibroin (SF) nanofibrous scaffold functionalized with two-stage hydroxyapatite (HAp) particles, using mussel adhesive-inspired polydopamine (PDA) chemistry. HAp particles were first incorporated into SF scaffolds during the electrospinning process, and then immobilized onto the electrospun SF nanofibrous scaffolds containing HAp via PDA-mediated adhesive chemistry. We obtained two-stage HAp-functionalized SF nanofibrous scaffolds with improved mechanical properties and capable of providing a bone-specific physiological microenvironment. The developed scaffolds were tested for their ability to enhance the osteogenic differentiation of human adipose-derived mesenchymal stem cells (hADMSCs) in vitro and repair bone defect in vivo. To boost their ability for bone repair, we genetically modified hADMSCs with the transcriptional coactivator with PDZ-binding motif (TAZ) via polymer nanoparticle-mediated gene delivery. TAZ is a well-known transcriptional modulator that activates the osteogenic differentiation of mesenchymal stem cells (MSCs). Two-stage HAp-functionalized SF scaffolds significantly promoted the osteogenic differentiation of TAZ-transfected hADMSCs in vitro and enhanced mineralized bone formation in a critical-sized calvarial bone defect model. Our study shows the potential utility of SF scaffolds with nanofibrous structures and enriched inorganic components in bone tissue engineering.

Biodegradation-tunable mesoporous silica nanorods for controlled drug delivery.

Mesoporous silica in the forms of micro- or nanoparticles showed great potentials in the field of controlled drug delivery. However, for precision control of drug release from mesoporous silica-based delivery systems, it is critical to control the rate of biodegradation. Thus, in this study, we demonstrate a simple and robust method to fabricate "biodegradation-tunable" mesoporous silica nanorods based on capillary wetting of anodic aluminum oxide (AAO) template with an aqueous alkoxide precursor solution. The porosity and nanostructure of silica nanorods were conveniently controlled by adjusting the water/alkoxide molar ratio of precursor solutions, heat-treatment temperature, and Na addition. The porosity and biodegradation kinetics of the fabricated mesoporous nanorods were analyzed using N2 adsorption/desorption isotherm, TGA, DTA, and XRD. Finally, the performance of the mesoporous silica nanorods as drug delivery carrier was demonstrated with initial burst and subsequent "zero-order" release of anti-cancer drug, doxorubicin.

Mechanically-reinforced electrospun composite silk fibroin nanofibers containing hydroxyapatite nanoparticles.

Electrospun silk fibroin (SF) scaffolds provide large surface area, high porosity, and interconnection for cell adhesion and proliferation and they may replace collagen for many tissue engineering applications. Despite such advantages, electrospun SF scaffolds are still limited as bone tissue replacement due to their low mechanical strengths. While enhancement of mechanical strengths by incorporating inorganic ceramics into polymers has been demonstrated, electrospinning of a mixture of SF and inorganic ceramics such as hydroxyapatite is challenging and less studied due to the aggregation of ceramic particles within SF. In this study, we aimed to enhance the mechanical properties of electrospun SF scaffolds by uniformly dispersing hydroxyapatite (HAp) nanoparticles within SF nanofibers. HAp nanoaprticles were modified by γ-glycidoxypropyltrimethoxysilane (GPTMS) for uniform dispersion and enhanced interfacial bonding between HAp and SF fibers. Optimal conditions for electrospinning of SF and GPTMS-modified HAp nanoparticles were identified to achieve beadless nanofibers without any aggregation of HAp nanoparticles. The MTT and SEM analysis of the osteoblasts-cultured scaffolds confirmed the biocompatibility of the composite scaffolds. The mechanical properties of the composite scaffolds were analyzed by tensile tests for the scaffolds with varying contents of HAp within SF fibers. The mechanical testing showed the peak strengths at the HAp content of 20 wt.%. The increase of HAp content up to 20 wt.% increased the mechanical properties of the composite scaffolds, while further increase above 20 wt.% disrupted the polymer chain networks within SF nanofibers and weakened the mechanical strengths.