Submitted by James Wagner, President, CVTSS
In collaboration with Battelle, the Cardiovascular Toxicology Specialty Section (CVTSS) Executive Committee is pleased to present a webinar entitled “Insidious Cardiotoxicity: Ubiquitous and Important, but Difficult and Expensive to Predict!” that may be of interest to you.
Date: Friday, February 16, 2018
Time: 12:00 Noon to 1:00 PM
Speaker: Dr. Robert Hamlin, Ohio State University
Cardiovascular (CV) functions may be affected adversely by drugs within seconds of exposure or insidiously requiring weeks to decades during or after exposure (e.g., doxorubicin, trastuzumab, sunitinib, digitalis, fenfluramine). Insidious toxicity occurs when a sublethal set of signs results from lengthy exposures to a chemical. It is simple to predict acute deaths to strychnine, but it is infinitely more challenging to identify potential for risk of death a decade after children have been treated successfully with doxorubicin, or months after persons were treated successfully with fen-phen for obesity! Many devastating myocardial toxicities stem from acute, direct, specific, destructive, cytotoxic actions (e.g., apoptosis, lysis, coagulation necrosis, changes in ion channel numbers or physiology), however, a number of drug-induced toxicities may result insidiously either after long-term exposures to therapy or possibly months or decades after cessation of therapy that might have affected genetic factors or might have produced energetic imbalance due to an apparent trivial mismatch between ATP production and demand. Whether energetic imbalance becomes toxic and for how long and to what degree the imbalance must exist before toxicity develops, may be expressed in a paradigm used by neurophysiologists to express the magnitude and duration of a stimulus required to produce a response. Beneficial effects may produce adverse long-term outcome even though they may be life-saving and improve quality of life over the short-term. Under certain conditions, a patient having symptomatic heart failure (aggravated by energetic imbalance) with low cardiac output and systemic arterial pressure, may actually benefit from that heart failure because the failing heart generates less tension, consumes less oxygen, and has decreased energetic imbalance thus preserving survival of myocardium. In fact, many drugs (e.g., milrinone) may improve quality of life, but abbreviate survival, while other drugs (e.g., beta blockers) that may decrease short-term quality of life, actually prolong life in the long-term. Drug regulatory agencies and deliverers of health care (quite wisely) recognize this paradox, but (sometimes) appear to be more interested in long-term survival than in short-term quality of life. This session discusses properties of CV for which insidious toxicities have proven important, methods for how those functions may be interrogated to predict insidious toxicity, what changes in function may predict morbidity and/or mortality, and what are relative times and costs to predict insidious toxicity? This webinar will focus on insidious toxicities of doxorubicin and catechol amines and on chronic but subtle energetic imbalance as one putative mechanism for insidious toxicity.
We look forward to your participation.