We are excited to see the vast number of scientific sessions, courses and posters presented this year!
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Preclinical drug-induced cardiotoxicity
Cardiovascular toxicity is an important cause of drug attrition, particularly for small molecule projects administered chronically. Electrocardiography (ECG) analysis can provide deep insights into drug-induced myocardial pathology and help mitigate safety liabilities.
While implanted telemetry remains the gold standard for cardiovascular electrophysiology studies, alternative methods have emerged to provide detailed ECG recordings without the use of anesthesia or surgery. For example, repeat-dose toxicity studies can be carried out in large animals with external (jacketed) telemeters to provide a functional assessment of heart rhythm, conduction, repolarization and morphology, without the need for surgery. Jacketed telemetry is often considered more sensitive and reproducible than traditional “snapshot” recordings in restrained animals, which are the mainstay of cardiovascular toxicity studies owing to their cost-effectiveness and highly valuable reference data.
While rats are generally deemed unsuitable for QT interval assessments due to small ventricular hERG-like current, other ECG parameters such as heart rate, PR and QRS intervals can help uncover clinically relevant drug-induced cardiovascular effects. The advent of restrained ECG research platforms suitable for mice, hamsters and rats, coupled with advanced post-processing software, can provide powerful insights into cardiac rhythm abnormalities associated with chronic exposure to drugs. Non-invasive ECG measurements can also reveal effects that intensify on repeated dosing and can therefore replace or complement implanted telemetry studies in exploratory toxicology and repeat-dose toxicity studies.
Inhaled particulate matter
Inhaled particulate matter (PM) has recently been linked to a staggering 20% of mortality worldwide.
Studies show chronic inhalation of particulate matter causes alterations in cardiac electrophysiology, and can lead to arrhythmias, oxidative stress, inflammation, vascular dysfunction, atherosclerosis and heart failure. Preexisting cardiovascular disease further increases the risk of adverse cardiac events following chronic PM exposure.
When studying adverse effects of inhaled cardiotoxicants in vivo, incorporating functional cardiovascular outcomes such as electrocardiograms (ECGs) acquired via invasive or non-invasive measurement strategies can offer additional insight.
While implanted telemetry studies remain widely regarded as the gold standard in terms of signal quality, alternative methods have emerged to permit detailed ECG recording without the use of anesthesia or telemetry.
For instance, the ecgTUNNEL, a restrained ECG research platform suitable for mice, hamsters and rats, can record 65% of beats for detailed studies of heart rates, R-R intervals, and QT prolongation. Non-invasive ECG measurements can therefore replace or complement implanted telemetry studies, especially for research involving young mice or fragile knockout models.