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Related Concept Videos

Imaging Studies for Cardiovascular System V: CT01:28

Imaging Studies for Cardiovascular System V: CT

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Cardiac computed tomography (CT) scanning is an advanced cardiac imaging technique that utilizes CT technology, with or without intravenous (IV) contrast, to produce accurate cross-sectional virtual slices of specific areas of the heart, coronary circulation, and major blood vessels such as the aorta, pulmonary veins, and arteries. The computer processes these slices to generate three-dimensional images. Multidetector CT (MDCT) is a rapid form of CT scanning that captures multiple slices...
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Automated Contraction Analysis of Human Engineered Heart Tissue for Cardiac Drug Safety Screening
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Technological Advances in Cardiovascular Safety Assessment Decrease Preclinical Animal Use and Improve Clinical

Brian R Berridge1, A Eric Schultze1, Jon R Heyen1

  • 1Brian R. Berridge, DVM, PhD, is a Senior GSK Fellow and Head of Worldwide Animal Research Strategy at GlaxoSmithKline in King of Prussia, Pennsylvania. A. Eric Schultze, DVM, PhD, is a Senior Research Advisor-Pathologist at Lilly Research Laboratories in Indianapolis, Indiana. Jon R. Heyen, MS, is a Senior Principal Scientist at Pfizer in La Jolla, California. George H. Searfoss, MS, is a Consultant Toxicologist at Lilly Research Laboratories in Indianapolis, Indiana. R. Dustan Sarazan, DVM, PhD, is a cardiovascular consultant currently residing in Rhinelander, Wisconsin.

ILAR Journal
|January 6, 2017
PubMed
Summary
This summary is machine-generated.

Advancements in preclinical cardiovascular safety assessments improve drug development by refining animal study techniques and introducing novel in vitro models. These innovations enhance early detection of drug liabilities and reduce animal use.

Keywords:
3Rsbiomarkerscardiovascularsafety assessment

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Area of Science:

  • Pharmacology and Toxicology
  • Cardiovascular Research
  • Preclinical Drug Development

Background:

  • Cardiovascular safety liabilities are critical concerns in drug development.
  • Preclinical animal studies are the primary method for characterizing these liabilities before human exposure.
  • Traditional methods often involved anesthetized or restrained animals, limiting data quality.

Purpose of the Study:

  • To highlight technological advancements in preclinical cardiovascular safety assessment.
  • To discuss the integration of improved animal models and in vitro systems.
  • To emphasize the goal of reducing animal use and enhancing translational relevance.

Main Methods:

  • Utilizing surgically implantable, telemetered instrumentation for acute cardiovascular assessments.
  • Employing chronically instrumented animals with clinical imaging (echocardiography, MRI) for repeat-dose studies.
  • Developing advanced in vitro modeling systems, including stem cell technology.
  • Measuring circulating cardiovascular biomarkers for longitudinal injury assessment.

Main Results:

  • Improved accuracy and informativeness of preclinical cardiovascular safety studies.
  • Enhanced ability to assess functional and structural cardiovascular effects in repeat-dose settings.
  • Earlier detection of undesirable cardiovascular effects through biomarker analysis.
  • Increased biological relevance of in vitro models compared to historical systems.

Conclusions:

  • Technological progress enables more refined and informative preclinical cardiovascular safety evaluations.
  • Advanced in vitro systems offer potential to replace some animal testing.
  • Continued improvements in both animal and non-animal modeling will decrease animal use and optimize translational relevance.