By Tao Wang, SOT Continuing Education Committee Member, along with Travis Knuckles and David McGuinn
We had another successful program of Contining Education (CE) courses this year at the 2013 SOT Annual Meeting. I attended the AM03 course entitled “Recent Developments in Cardiovascular Physiology-Based Toxicology.” This course sought to educate researchers about the basic physiology of the cardiovascular system as well as ways to assess toxicity beyond the regulatory standards of the hERG assay and the acute QT interval. Nowadays, we are deep into the molecular toxicology assessment, and for the course attendees, it is great to see that we are reviewing the very important physiology-based toxicology assessment. Travis Knuckles, West Virginia University (WVU), and W. David McGuinn Jr., US Food and Drug Administration, chaired this session. Dr. Knuckles opened the session with an outline of problems inherent in current cardiac toxicity testing and the learning objectives of the course. This introduction began the discussion of the importance of assessing the chronic toxicity of oncology drugs not normally thought of as cardiotoxic. Dr. McGuinn discussed mechanisms of chronic toxicity of drugs like tyrosine kinase inhibitors that are negative in the hERG assay and show no acute ECG changes, but have the potential to cause congestive heart failure after long term exposure.
Mehdi Hazari, of the US Environmental Protection Agency, continued the discussion with a whole-system based approach to measuring the toxicity of environmental chemicals or drugs via electrocardiographic telemetry. Consistent with Dr. McGuinn’s talk, Dr. Hazari stressed the use of repeated radio-telemetric measurements to assess the development of chronic cardiac toxicity. Following a short coffee break, the session picked back up with an overview of the physiology of peripheral circulation control mechanisms and methodological details of microcirculatory measurements Timothy Nurkiewicz, of West Viginia University. Dr. Nurkiewicz demonstrated the usefulness of microscopy techniques for assessing in vivo and in vitro alterations in microvascular function. Following the session, there was an informed discussion about the use of the microcirculation verses the macrocirculation techniques and how these techniques determined various toxicological parameters. Molly Frame, SUNY Stony Brook, further demonstrated the physiomechanical dynamics of the microcirculation by outlining solute extraction from the capillary bed, mechanisms of microvascular toxicity, and angiogenic mechanisms that contribute toxicity. The take home message was that delivery of a given amount of solute is not necessarily tied directly to overall bulk flow.
Lastly, the session was brought to a close with presentation by Vince Castranova, of the National Institue of Occupational Safety and Health, who addressed toxicity measurements in a model system of particle inhalation. Dr. Castranova’s talk brought together all of the aspects of the course in a model system that displays toxicity through direct, inflammatory, and neurogenic mechanisms at cardiac, conduit vessel, and microvascular levels. The attendees commented that the physiology-based risk assessment is so very important, and it is great that the SOT CE Committee offered the course this year.