Creating a new education paradigm to prepare nurses for the 21st Century

Nurse educators are accountable to keep baccalaureate education responsive to the ever changing healthcare delivery environment. The changing context of healthcare delivery requires focusing on population health and social determinants, providing interprofessional, team-based care, advancing innovation, and preparing practice ready baccalaureate nursing graduates. To be practice ready, nursing graduates must be agile and think and reason on their feet due to increasing care complexity beyond the hospital walls, changing care needs of individuals and families, advancing technology, shifting settings of care delivery, and managing multiple transitions. The purpose of this paper is to consider these healthcare changes and share a new baccalaureate nursing curriculum that radically shifts the paradigm from caring for patients to caring for people, and transforms from a diseased-based, acute care focused curriculum to one promoting a culture of health and multiple new and emerging roles of registered nurses

Effect of Exercise on Right Ventricle Inflammation in a Rat Model of Severe Monocrotaline-Induced Pulmonary Arterial Hypertension

poster abstractPulmonary arterial hypertension (PAH) is a devastating disease of progressive remodeling of small and mid-size pulmonary arteries that leads to elevated pulmonary pressure. The work of the right heart is increased due to the elevated pulmonary pressures and can lead to maladaptive cardiac wall hypertrophy, right heart failure and then eventually death. Whether exercise-induced cardiac stress also promotes detrimental right ventricle (RV) inflammation in PAH has not been thoroughly examined. The purpose of this study is to determine if treadmill exercise at low relative intensity in a rat model of severe PAH without promoting greater RV inflammation. Adult male Sprague- Dawley rats were injected with monocrotaline (60mg/kg, subcutaneously, n=14) or saline (healthy controls, n=4). RV tissue was obtained from these rats following a 6 week, 5 times/week treadmill training program at a low intensity of 50% of measured aerobic capacity (VO2max) and compared to tissue obtained from sedentary counterparts. RV immunofluorescent staining for CD45, a lymphocyte marker, was performed to evaluate the inflammatory response due to chronic exercise training. The experiment is still underway and the expected result is that there is no greater exercised induced RV inflammation in PAH rats compared to healthy rats

Cardiac and Skeletal Muscle Lipotoxicity in a Rat Model of Pulmonary Arterial Hypertension

poster abstractPatients with Pulmonary Arterial Hypertension (PAH)experience shift from aerobic to anaerobic respiration in cardiac and skeletal muscle myocytes. This shift can be identified histologically by an increased presence of the glucose transporter Glut 1 in the tissue, indicating increased reliance on cytoplasmic glycolysis. Previous studies have demonstrated that in patients with diabetes, an increase in Glut 1 is accompanied by an increase in fat storage in the cell. Excessive myocyte fat storage may contribute to tissue and systemic inflammation and has therefore been termed ‘lipotoxicity’. This study tested the hypothesis in a PAH rat model that an increase in cardiac and skeletal muscle Glut 1 abundance would be associated with an increase in fat storage in the cell. Oil Red O staining was performed to assay for lipotoxicity in cryosections of right ventricle and soleus muscle tissue, imaged using brightfield microscopy. The experiment was conducted using tissue from a moderately severe PAH phenotype produced by monocrotaline(60 mg/kg) injection, as well as from saline injected control animals. Lipids have been observed in the first few samples tested with Oil Red O staining, and results are still pending as a larger sample size is currently being collected

Overwintering Locations, Migrations, and Fidelity of Radio-Tagged Dolly Varden in the Hulahula River, Arctic National Wildlife Refuge, 2007–09

Essential overwintering habitats for anadromous Dolly Varden Salvelinus malma on Alaska’s North Slope appear to be limited to a small number of perennial springs, primarily in eastern Brooks Range drainages. Because future petrochemical development in the region continues to be a possibility, and development would require large quantities of freshwater, we sought to identify and document the overwintering areas used by Dolly Varden in the Hulahula River, eastern Brooks Range. In August 2007, we implanted 52 Dolly Varden with multi-year radio transmitters at a known overwintering area in the lower Hulahula River. Other wintering areas were located during 11 aerial surveys conducted over the next 2.5 years. A stationary receiver located in the lower Hulahula River provided migration timing information. Radio-tagged Dolly Varden used four discrete areas with perennial springs for overwintering in the Hulahula River drainage. The springs, totaling approximately 12 km in stream length, were located between river km 40 and 105. Radio-tagged Dolly Varden migrated downstream on their way to the Beaufort Sea in early June. Most tagged fish known to have survived the summer at sea returned to the Hulahula River during late July and August, but seven fish overwintered in other North Slope drainages. Within the Hulahula River drainage, 15 fish overwintered in more than one area during the three winters of the project, but only the four identified perennial spring areas were used. These data clearly indicate that the perennial springs in the Hulahula River are essential overwintering habitats for Dolly Varden.Les aires de concentration hivernales essentielles du Dolly Varden Salvelinus malma anadrome sur la North Slope de l’Alaska semblent limitées à un petit nombre de sources pérennes, principalement dans les bassins hydrographiques de l’est de la chaîne de Brooks. Puisqu’il est toujours possible qu’il y ait des aménagements pétrochimiques dans la région et que ceux-ci demanderaient de grandes quantités d’eau douce, nous avons tâché de déterminer les aires de concentration hivernales du Dolly Varden dans la rivière Hulahula faisant partie de l’est de la chaîne de Brooks, et nous les avons répertoriées. En août 2007, nous avons installé des émetteurs radio pluriannuels sur 52 poissons Dolly Varden dans une aire de concentration hivernale connue faisant partie de la rivière Hulahula inférieure. D’autres aires de concentration hivernales ont été repérées grâce à 11 levés aériens effectués au cours des 2,5 années qui ont suivi. Un récepteur fixe situé dans la rivière Hulahula inférieure nous a permis de relever des données sur le moment de la migration. Les Dolly Varden dotés d’émetteurs radio ont utilisé quatre sources discrètes où se trouvent des sources pérennes pour passer l’hiver, dans le bassin versant de la rivière Hulahula. Les sources, qui s’étendent sur une douzaine de kilomètres de longueur, étaient situées entre les kilomètres 40 et 105 de la rivière. Les Dolly Varden munis d’émetteurs radio ont migré en aval, en route vers la mer de Beaufort au début juin. La plupart des poissons avec émetteur ont survécu l’été à la mer et ont regagné la rivière Hulahula vers la fin de juillet et en août, mais sept poissons ont passé l’hiver dans d’autres bassins versants de la North Slope. Dans le bassin versant de la rivière Hulahula, 15 poissons ont passé l’hiver dans plus d’une aire au cours des trois hivers visés par le projet, mais seules les quatre sources pérennes déterminées ont été utilisées. Ces données indiquent clairement que les sources pérennes de la rivière Hulahula sont des aires de concentration hivernales essentielles pour le Dolly Varden

Investigating Skeletal Muscle Metabolic Adaptations underlying Aerobic Fitness Gains Following High Intensity Interval Training in a Rat Model of Pulmonary Arterial Hypertension

poster abstractRationale: In patients with pulmonary arterial hypertension (PAH) a shift from oxidative to a less efficient non-oxidative (glycolytic) metabolism in skeletal muscle is believed to contribute to the reduced exercise tolerance hallmark of the disease. As seen for other cardiopulmonary diseases, exercise training (ExT) may ameliorate this “glycolytic switch” in PAH and improve exercise capacity. Previous studies in this lab showed an improved metabolic profile of skeletal muscle in PAH rats following an ExT protocol of continuous running at moderate relative intensity, 60 minutes at 75% of maximal aerobic capacity (VO2Max). High intensity interval training (HIIT) has been shown in healthy individuals as well as in patients with cardiovascular disease to promote favorable cardiac and skeletal muscle adaptations and greater improvements in aerobic capacity versus customary continuous training. This study tests the hypothesis in a PAH rat model that HIIT will result in preserved aerobic capacity and a greater attenuation of skeletal muscle glycolytic shift than that observed with continuous moderate intensity exercise. Methods: Male Sprague-Dawley rats received either monocrotaline (MCT, 40 mg/kg, s.q.) to induce PAH (n= 8), or saline, for healthy controls (n=4). After 2 wks, with MCT-induced PAH wellestablished, 6 wks of treadmill HIIT was initiated for a subset of PAH animals (PAH-ExT, n= 6) and healthy controls (CON-ExT, n=2). The HIIT runs were alternated between 2 to 3 minutes of high intensity exercise (85% VO2max reserve) and active recovery intervals between 2 to 3 minutes (10 m/min, 0 incline) VO2max was assessed at baseline, and in pre-training and post-training via analysis of expired gases during incremental treadmill running. Preliminary results: MCT-induced decrement in VO2max was attenuated by HIIT. Abundance of membrane glucose transporter Glut-1, a marker of glycolytic metabolism, is currently being evaluated in soleus cryosections with immunofluorescent staining. Findings are being compared to historical data for PAH and healthy rats from a study protocol that differed only by training approach-continuous instead of HIIT

Measurement of nitrate and nitrite in biopsy-sized muscle samples using HPLC

Studies of rats have indicated that skeletal muscle plays a central role in whole-body nitrate ( NO−3 )/nitrite ( NO−2 )/nitric oxide (NO) metabolism. Extending these results to humans, however, is challenging due to the small size of needle biopsy samples. We therefore developed a method to precisely and accurately quantify NO−3 and NO−2 in biopsy-sized muscle samples. NO−3 and NO−2 were extracted from rat soleus samples using methanol combined with mechanical homogenization + ultrasound, bead beating, pulverization at liquid N2 temperature or pulverization + 0.5% Triton X-100. After centrifugation to remove proteins, NO−3 and NO−2 were measured using HPLC. Mechanical homogenization + ultrasound resulted in the lowest NO−3 content (62 ± 20 pmol/mg), with high variability [coefficient of variation (CV) >50%] across samples from the same muscle. The NO−2 / NO−3 ratio (0.019 ± 0.006) was also elevated, suggestive of NO−3 reduction during tissue processing. Bead beating or pulverization yielded lower NO−2 and slightly higher NO−3 levels, but reproducibility was still poor. Pulverization + 0.5% Triton X-100 provided the highest NO−3 content (124 ± 12 pmol/mg) and lowest NO−2 / NO−3 ratio (0.008 ± 0.001), with the least variability between duplicate samples (CV ~15%). These values are consistent with literature data from larger rat muscle samples analyzed using chemiluminescence. Samples were stable for at least 5 wk at -80°C, provided residual xanthine oxidoreductase activity was blocked using 0.1 mmol/l oxypurinol. We have developed a method capable of measuring NO−3 and NO−2 in <1 mg of muscle. This method should prove highly useful in investigating the role of skeletal muscle in NO−3 / NO−2 /NO metabolism in human health and disease. NEW & NOTEWORTHY Measurement of nitrate and especially nitrite in small, i.e., biopsy-sized, muscle samples is analytically challenging. We have developed a precise, accurate, and convenient method for doing so using an affordable commercial HPLC system

EFFECT OF TREADMILL RUNNING ON CARDIAC AND SKELETAL MUSCLE METABOLISM AND RIGHT VENTRICLE INFLAMMATION IN RATS WITH PULMONARY ARTERIAL HYPERTENSION

poster abstractIt has been suggested that a shift from oxidative to non-oxidative (glycolytic) metabolism promotes a right ventricle (RV) and skeletal muscle dysfunction in patients with pulmonary arterial hypertension (PAH), contributing to their reduced exercise tolerance. Exercise training may ameliorate this glycolytic switch in PAH as it does for other cardiopulmonary diseases. However, whether exercise-induced cardiac stress also promotes detrimental RV inflammation in PAH has not yet been thoroughly examined. We hypothesized that exercise training will promote a shift back towards the more efficient oxidative metabolism in cardiac and skeletal muscle of PAH rats and that 45 minutes of exercise at a prescribed moderate intensity will not promote greater RV inflammation in PAH rats. Tissues were obtained from monocrotaline-induced PAH and healthy control rats immediately following a 45 min treadmill run (75% VO2max) that concluded a 4 week treadmill familiarization/running program (15-45 min, 4x/wk). A group of unexercised PAH and healthy rats served as sedentary controls. Immunofluorescent staining (IF) for inflammatory markers CD45 (lymphocytes) and CD68 (macrophages) in cryofixed RV sections were used to assess the acute inflammatory response to exercise. In fixed soleus and RV sections, IF for the glucose transporter Glut1, and for capillary marker CD31, were used as indicators of glycolytic metabolism and tissue capillarization, respectively. Data thus far indicates no greater acute exercise-induced RV inflammation in PAH rats compared to healthy rats. We observed higher expression of Glut1 and lower capillarization in the RV and soleus of PAH rats, indicative of a shift toward greater dependency on non-oxidative metabolism. However, since Glut1 levels for exercised rats were measured in tissue harvested immediately following a run bout, evaluation of a chronic training effect on Glut1 expression is potentially confounded by the acute exercise effect and therefore remains to be investigated in a follow-up study

Microvascular inflammatory responses to ceramide and cigarette smoke in the intact rat assessed with intravital two-photon microscopy

poster abstractsmoke, characterized by alterations of the alveolar barrier function. We investigated this hypothesis by utilizing a novel application of intravital two-photon excitation microscopy (TPM) of the lung in a living, breathing animal. Methods: We first developed a technique of TPM to permit imaging of the lung maintained within the thoracic cavity of an intact rat. To accomplish this, we optimized the lung-microscope interface with an imaging window uniquely designed to minimize cardiac and respiratory motion during TPM acquisitions. To investigate alveolar barrier disruption in real time, we utilized intravenous (i.v.) fluorescent probes to examine changes in alveolar leukocyte trafficking and microvascular barrier function in response to i.v. ceramide (C16:0 PEG, 10 mg/kg), and to cigarette smoke extract (CSE) delivered i.v. (1ml/kg) or intratracheally via a nebulizer (2mL/kg). Results: We performed intravital TPM monitoring of the lung microcirculation of a living rat with maintained physiological cardio-pulmonary parameters for up to 3h. Time-lapse and 3-D reconstruction images revealed heterogeneous extravasation of FITC-labeled serum albumin from the alveolar microcirculation into the alveolar airspaces in response to ceramide, in a dose-dependent manner. Further, we noted that in response to both ceramide and to CSE, leukocytes accumulated in the lung parenchyma and demonstrated reduced mobility through the microcirculation, suggesting increased adhesion to the endothelium. Intratracheal administration of CSE caused increased extravasation of leukocytes into alveolar spaces within 10 minutes. Conclusions: We developed approaches that permit the application of intravital TPM to lung with no motion artifacts from the breathing and cardiac cycles. This approach permits visualization of the lung subpleural parenchyma with a high resolution. Both gross and subtle inflammatory changes that reflect alveolar epithelial and/or endothelial barrier dysfunction can be assessed with this methodology

Acute Exercise Activates Pulmonary eNOS and Lowers Pulmonary Pressure in Rats with Pulmonary Arterial Hypertension

poster abstractNO-dependent arterial relaxation is impaired in pulmonary arterial hypertension (PAH). Exercise may be beneficial in PAH, just as it is for systemic vascular disease, via upregulation of endothelial nitric oxide synthase (eNOS) expression and activity. However, exercise-induced cardiac stress in PAH could also promote detrimental RV inflammation. We investigated pulmonary pressure and eNOS, as well inflammatory indicators in the RV, following a single 45 min run bout at moderate intensity in a rat model of PAH. Male Sprague-Dawley rats received either monocrotaline to induce PAH, or saline, for healthy controls. A subset of PAH and healthy controls performed 4 wks of progressive TM familiarization (15-30min, 8-20 m/min) in preparation for their final 45 min run @ 75% of VO2max. Immediately following the run, RV systolic pressure was measured and RV and lung tissues were harvested and cryofixed. eNOS and phosphorylated (at Ser1177) eNOS (p-eNOS) was measured via immunoblotting in lung homogenates and expressed normalized to vinculin. Immunofluorescence for inflammatory markers CD45/68 in cryofixed RV sections evaluated the acute inflammatory response to exercise. MCT reduced VO2max and caused RV hypertrophy (expressed as RV/LV+septum) as consistent with this model. RVSP (normalized by systemic BP) was lower in PAH-Ex vs. unexercised PAH with no difference between exercised and unexercised controls. Greater p-eNOS was measured in PAH-Ex lung compared to unexercised PAH, with no difference between exercised and unexercised controls. PAH-Ex also tended to have greater pulmonary eNOS than their unexercised counterparts. No greater exercise-induced CD45/68 infiltration was observed in RV of PAH compared to that of controls. In rats with moderate MCT-induced PAH, a single exercise bout does not increase acute RV inflammation but lowers pulmonary pressure, possibly mediated in part via pulmonary eNOS activation

Disinhibiting neurons in the dorsomedial hypothalamus delays the onset of exertional fatigue and exhaustion in rats exercising in a warm environment

Stimulants cause hyperthermia, in part, by increasing heat generation through exercise. Stimulants also delay the onset of fatigue and exhaustion allowing animals to exercise longer. If used in a warm environment, this combination (increased exercise and decreased fatigue) can cause heat stroke. The dorsomedial hypothalamus (DMH) is involved in mediating locomotion from stimulants. Furthermore, inhibiting the DMH decreases locomotion and prevents hyperthermia in rats given stimulants in a warm environment. Whether the DMH is involved in mediating exercise-induced fatigue and exhaustion is not known. We hypothesized that disinhibiting neurons in the dorsomedial hypothalamus (DMH) would delay the onset of fatigue and exhaustion in animals exercising in a warm environment. To test this hypothesis, we used automated video tracking software to measure fatigue and exhaustion. In rats, using wearable mini-pumps, we demonstrated that disinhibiting the DMH, via bicuculline perfusion (5 µM), increased the duration of exercise in a warm environment as compared to control animals (25 ± 3 min vs 15 ± 2 min). Bicuculline-perfused animals also had higher temperatures at exhaustion (41.4 ± 0.2 °C vs 40.0 ± 0.4 °C). Disinhibiting neurons in the DMH also increased the time to fatigue. Our data show that the same region of the hypothalamus that is involved in mediating locomotion to stimulants, is also involved in controlling exhaustion and fatigue. These findings have implications for understanding the cause and treatment of stimulant-induced-hyperthermia