DSI Monitor - Summer 2015 (Issue 2)

  • Circulatory and Renal Consequences of Pregnancy in Diabetic NOD Mice

    Pregnant women with diabetes have an elevated risk of circulatory complications. However, little is known about the mechanisms that underlie such risks. Previous research suggests that the adaptive physiologic changes required for successful pregnancy may be susceptible to impairment in pregnancy complicated by diabetes. Placental insufficiency occurs more often in pregnant women with diabetes, suggesting the possibility of inadequate uterine spiral artery (SA) remodeling. (SA remodeling occurs during pregnancy to change arteries into the high-flow, low-resistance vessels needed to ensure the fetus and placenta can develop properly.) The presence of diabetes during pregnancy in women can also increase the frequency and severity of preeclampsia (which is characterized by hypertension and often damage to the kidneys), as well as late miscarriage and fetal growth restriction.

    To learn more about the association between diabetes and physiologic impairments in pregnancy, preclinical researchers have begun to evaluate whether pregnant non-obese diabetic (NOD) mice may be an appropriate model for human pregnancy in diabetic women. NOD mice are already a well-established model of autoimmune Type 1 diabetes in humans. Researchers have previously shown that in a comparison with pregnant non-diabetic mice, pregnant diabetic NOD mice had impaired SA remodeling and fewer uterine natural killer (uNK) cells (lymphocytes that should be abundant during early pregnancy, as they play an important role in remodeling the SAs). Pregnant diabetic NOD mice also exhibited dysfunctional interactions in vitro between endothelial cells and lymphocytes (similar to the effect often seen in human Type 1 diabetes). Additionally, many of the NOD fetuses were growth-restricted, suggesting diabetes-induced placental insufficiency.

    Based on these findings, the researchers monitored signs of preeclampsia by measuring cardiovascular parameters and renal function in normoglycemic and overtly diabetic pregnant NOD mice. The researchers hypothesized that overtly diabetic pregnant NOD mice would develop hypertension and renal dysfunction, thus providing evidence for NOD mice as a promising model for future pharmacologic interventions. For the study1, the female mice were implanted with blood pressure transmitters so the researchers could continuously monitor hemodynamic changes. Hemodynamic baseline data were collected and starting at 12 weeks (the typical age at which NOD mice do or do not spontaneously develop diabetes), blood glucose measurements were collected biweekly. The NOD mice that developed diabetes were paired with age-matched non-diabetic pregnant NOD mice for comparison purposes. Then the female mice were mated with normoglycemic males and physiologic data were collected before and during pregnancy. Physiologic data included hemodynamic parameters: mean arterial pressure (MAP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), pulse pressure (PP), heart rate (HR), activity; and renal parameters: urinalysis, serum biochemistry, renal histopathology.

    Results showed that before mating, normoglycemic and diabetic female NODs had similar hemodynamic profiles. During pregnancy, normoglycemic mice showed hemodynamic profiles similar to other inbred strains: an early decline in arterial pressure until mid-pregnancy, and no difference throughout pregnancy on assessments of MAP, SAP, DAP, HR, PP, or activity levels. Renal parameters were also normal in normoglycemic mice. Diabetic NODs had normal BP until mid-pregnancy then became mildly hypotensive and severely bradycardic. They also showed signs of acute kidney injury. The health of the diabetic NODs did not rebound post-partum and offspring were growth restricted.

    As expected, diabetic NOD mice did exhibit signs of cardiovascular and renal dysfunction. However, impairment did not present as expected. Instead of displaying the obvious preeclamptic signs that typically occur in human pregnancy, the main cardiovascular dysfunctions were low blood pressure and slow heart rate.The authors suggested that further studies will be needed to identify the mechanisms behind these findings, but pointed out that the study provided evidence that impaired cardiovascular adaptation may go beyond hypertension and that the lingering post-partum abnormalities do suggest that vascular dysfunction occurred, as in preeclampsia studies. The authors concluded by asserting “While understanding of the full scope of the alterations occurring in maternal circulatory mechanisms and required for preservation of fetal circulation remain to be achieved, the findings from the study of this animal model provide new insights into cardiovascular complications in diabetic pregnancy.”

    The researchers used DSI solutions to acquire and analyze the physiologic parameters at the core of this study. PhysioTel PA-C10 implants were used to simultaneously detect arterial pressures, PP, HR, and activity and the Dataquest A.R.T.™ acquisition system was used to monitor and analyze the data, resulting in a detailed hemodynamic profile.

    Burke, S. D., Barrette, V. F., David, S, Khankin, E. V., Adams, M. A., & Croy, B. A. (2011). Circulatory and Renal Consequences of Pregnancy in Diabetic NOD Mice. Placenta, 32 (4): 949-955. Doi: 10.1016/j.placenta.2011.09.018

    To read the complete article, visit:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230635/

     
  • Implantable Glucose Telemetry Article

    DSI is excited to share a new publication highlighting our continuous glucose monitoring device. Our thanks to the team at Lilly Research Laboratories for helping to develop this article.
     
    Fully Implantable Arterial Blood Glucose Device for Metabolic Research Applications in Rats for Two Months
     
    Summary of findings: This device provides significant advantages in the quality and quantity of data that can be obtained relative to existing alternatives such as intermittent blood sampling. These devices provide the opportunity to expand the understanding of both glucose metabolism and homeostasis and to work toward improved therapies and cures for diabetes. For more information, the abstract for this publication is available here.
  • Ask Scientific Services: Maximizing the Life of your Telemetry Implants

    There is a right way to perform any task. DSI telemetry implants are sophisticated devices that, if handled properly, will provide your laboratory with highly accurate and reliable data. Here is a little refresher course on the proper care and handling of your DSI implants.

    General Information

    • When you receive a new shipment of implants, always monitor your shipment with a radio to verify that the devices have not been inadvertently switched “ON” in transit.  If the implant is found to be “ON,” immediately turn it “OFF.”  Short transit times, along with an incorporated battery buffer time, ensure that the implant battery life will not be adversely affected.  Test the functionality of each device before implanting it into an animal. Use a magnet and a radio to toggle through the operational modes. 
      • Note: PhysioTel Digital implants cannot be checked with a radio, however, these devices will automatically turn off when they’re out of contact with the computer system. Thus, they do not need to be checked upon arrival.   
    • Ensure the implants are well protected when shipping them back to DSI.  This will help prevent in-transit damage. It may be helpful to keep the original packaging that the implants arrived in.

    Handling

    • Always handle the implant and catheter with care. Pressure implants are sensitive to being dropped and the catheters should not be handled excessively.
    • Rodent pressure catheters should only be handled with Vessel Cannulation Forceps. This is a specially designed instrument with a precise groove in the tips to preserve the integrity of the delicate catheter tip. Handling the catheter with normal dissecting tools can lead to gel loss, incorporation of air bubbles, blown pressure sensors, and damage to the proprietary catheter coatings. These forceps can be purchased from Fine Science Tools (PN 00608-11).

    Cleaning and Resterilizing

    • Use only DSI recommended products to clean and sterilize the implants. A complete listing of these products, along with directions on how to use them, can be found on our website at http://www.datasci.com/resources/technical-notes. Non DSI-approved methods of cleaning or sterilization may void the implant warranty.
    • Anything returned to DSI must be cleaned and sterilized per DSI requirements prior to shipping.
  • Featured Technical Note: Tips on Maintaining Animal Comfort

    Help reduce animal-chewed transmitters with these helpful ideas.

  • Ask DSI Technical Support

    Q: Why did my telemetry blood pressure signal morphology suddenly change? Is my implant broken?

    A: There are several reasons why a systemic blood pressure signal may suddenly change morphology, depending on what the new waveform looks like and how long after surgery the change took place. Such changes are often misattributed to a malfunctioning implant, when they are actually related to the surgery. 

    The explanations and suggestions below assume that you have verified that the correct calibration values are entered into the software (if using non-HD/PTD telemetry).

    Situation: The signal looks like a blood pressure waveform, has a good mean pressure but low pulse pressure (potentially low systolic or high diastolic).

    • These symptoms are usually indicative of a blockage forming at the tip of the implant’s catheter. The blockage allows for the average pressure to be accurately measured, but dampens the implant’s ability to detect small and quick changes in the pressure, which is why the difference between systolic and diastolic (pulse pressure) drops. The effect will slowly take place over time and may not be immediately apparent. The most common cause of this type of blockage is that the catheter tip was not advanced far enough and is not in free-flowing blood. Alternatively, there may have been a bubble in the blood at the catheter tip during implantation, which is subsequently replaced by a clot and fibrosis. To avoid these problems in the future, take extra care that the catheter is advanced far enough and the catheter is hydrated prior to surgery, as described in the appropriate implant’s surgical manual. Also, if it is kinked while trying to insert, remove it and re-gel.

    Situation: The waveform does not look like blood pressure, has low mean pressure, a wandering baseline (possible), and derived parameters are only updating sporadically.

    • This list of symptoms indicates that the pressure catheter has likely pulled out of the blood vessel. The baseline and mean pressure may wander anywhere from -50 to 50 mmHg but will usually not resemble a classic blood pressure waveform. Few, if any, of the cycles will trigger in the software, so the derived parameters will not update as usual. 
    • The most common cause of the catheter pulling out of the blood vessel is use of an inadequate catheter anchoring technique. If this occurs often, please contact DSI Technical Support to be put into contact with one of our surgical specialists.

    Situation: The waveform is a relatively flat line with very large positive or negative values and no derived parameters are updating.

    • In this circumstance it is possible that the pressure sensor has been damaged or the telemetry unit is malfunctioning. Contacting DSI Technical Support is the best course of action, as they may be able to offer additional troubleshooting options to find a root cause. If the cause seems to be a malfunctioning implant, Technical Support may ask that you return the implant for Product Analysis, and will provide you with the appropriate documentation. If the cause is found to be the implant and it is still under warranty, DSI will provide a warranty replacement. 
  • Measure mouse pressure, temperature and activity with the HD-X10--available now!

    The HD-X10 offers these benefits:

    • Auto-loading of calibration data reduces configuration time and eliminates data entry error
    • Battery ON-time counter helps track study duration and remaining battery life
    • Animal ID ensures data collection is from the intended animal 

    View products specifications here.

  • Continuous Glucose Research Award

    DSI, PreClinOmics (PCO), and Research Diets, Inc. are teaming up to recognize a researcher pursuing in vivo physiological research focusing on diabetes or other metabolic diseases. One researcher will receive the supplies and equipment needed to conduct a preclinical study, including:

    • A 4-animal implantable glucose telemetry system (DSI)
    • Up to 8 Zucker diabetic Sprague-Dawley rats (PCO)
    • Specialized animal diets (Research Diets) 

    Visit the award page for more details and to apply!

  • Coming soon!

     
    -Ponemah 6.10 will continue to build upon the Ponemah platform, integrating PhysioTel Digital, glucose monitoring, and remote notification.
     
    -Data Insights software will allow you to quickly detect arrhythmias, data patterns, and anomalies. 
  • Upcoming Events

    SSIB 2015, July 7-11

    The Society for the Study of Ingestive Behavior (SSIB) is committed to advancing scientific research on food and fluid intake and its associated biological, psychological and social processes. The Society provides a multidisciplinary environment for the free exchange of ideas and information, and serves as a resource for scientific expertise and education on topics related to the study of ingestive behavior. Stop by and visit the DSI booth at this year’s annual SSIB meeting!

    SPS 2015, September 28 – October 1

    The Safety Pharmacology Society (SPS) annual meeting is the leading scientific forum bringing together basic and industrial scientists with the goal of optimizing the way this important work is done. Effective early safety testing is imperative for bringing new treatments to market that are not only effective but safe in a wide, diverse patient population. Stop by and visit DSI booth #43 at the meeting!

    United States East Coast User Group Meeting, Fall 2015

    DSI will host a user group meeting in the fall of 2015. The purpose of the meeting is to facilitate the exchange of scientific information among DSI users in the research community. The meeting will include 1-2 days of research presentations, hands-on demonstrations and networking opportunities. Stay tuned for additional details.

  • Recent Webinars

    Structural and Functional Endpoints in Repeat-Dose Toxicity Cardiovascular Risk Assessments and the Use of In Vivo Physiologic Monitoring. Visit this webpage to watch the recording. (Enter your contact information and hit the Finish button to access.)
     
    Inhalation Exposure Systems for Aerosol Delivery Advancements: Perspective from a Bench Scientist. Visit this webpage to watch the recording. (Enter your contact information and hit the Finish button to access.)
  • Recent User Group Meetings

    2015 European User Group Meeting: “Cheers Mate!
    Eur user group meeting 1

    After Paris in 2011, Berlin in 2013, it was time for the DSI European User Meeting to cross the Channel and meet in the UK. The meeting landed in Leeds, Yorkshire, a region of the UK known for its welcoming folks and its famous pudding! As in Berlin in 2013, a special gift came from the sky this year, as the snow replaced rain and made for “fun & interesting” last minute travel delays. The meeting was held January 29 & 30 2015 at the Weetwood hotel, a very British and delightful facility belonging to the University of Leeds.

    In all, 90 people from 15 different countries joined the meeting to learn from each other, discuss challenges and tips & tricks to address them, and to connect and network.

    The program of the meeting included sessions on the cardiovascular, central nervous and respiratory systems, and on metabolism studies. We got to hear many great talks by some long time but also new DSI users. For the first time ever, two talks presented novel research using the new continuous glucose sensor released in 2014.
    Eur user group 2
    We repeated some of the sessions held in the past. Namely a surgical session hosted by Megan Fine our US based veterinarian, during which the latest surgical tips and tricks for mice to large animals were discussed. We also repeated our now famous “Data Blast” format, where ten people presented a maximum of 3 slides in 3 minutes, optionally holding a pint of the local beverage in one hand--a fun way to present data!

    As requested in 2013, we arranged for delegates to have many opportunities to meet with one another, and to meet with our DSI technical support and technical sales team. A room was set up with most of the DSI systems, implantable telemetry for HD and Physiotel Digital Transmitters, Jacketed External Telemetry (JET) system, and with the most common Buxco systems, Whole Body Plethysmography, Resistance & Compliance and Non-Invasive Airway Mechanics. New this year was also an opportunity to to interface remotely a member from our Data Analysis staff. People brought their data and were discussing and reviewing live over the internet. The interaction with DSI technical support and Data Services was very well received, so we look forward to repeat and expand in the future.

    The social dinner event took place at the Thackray Medical Museum, where one can get a wonderful view into the history of modern medicine, from the early days of human surgeries without anesthetics (ouch!) to the many inventions that took place since then. Not surprisingly, the surgical tools display was particularly well attended.
    Eur user group 3

    We want to address our sincere thanks again to all presenters, session chairs, “Data Blasters”, and to all delegates for their participation. We also thank our US colleagues who provided their help and support to make this event happen, and our partners MedVet, Metris, Noldus and Notocord who joined the 2015 meeting to display their latest respective products.

    Rendezvous in 2017 for the next meeting; we heard your feedback about choosing a city or region where the presence of crystallized water is limited to refrigerators and freezers, in other words, in a warmer location.

    -Your DSI European team

    2015 DSI Australia User Group Meeting

    After several years without a user group meeting, many DSI users shared their desire to meet with their peers and colleagues to discuss telemetry animal models and the use of DSI systems on a scientific and practical level. Thanks to the help of Geoff Head from the Baker IDI Heart and Diabetes Institute in Melbourne, DSI arranged a one-day user group meeting on April 10, 2015.

    Baker logoTwenty-eight of us gathered for this meeting. Eight speakers, some long time users and others new, presented how they use freely moving animal models in their research, in cardiovascular studies and on the CNS control of the cardiovascular system.

    We arranged a remote session with Megan Fine, DVM, and head of the DSI US lab. Megan did a review of the recent surgical advances on rodent models, followed by Q&As. We hope to have Megan live with us next time.

    Lunchtime and breaks allowed for great interactions between users--a good time to (re)connect and share tips and tricks on surgery, system setup and data analysis.

    We would like to thank all presenters, session chairs and all delegates for their participation. Special thanks again to Geoff and the Baker IDI for hosting this event. We look forward to arranging a future DSI user meeting in Australia.