title: Technological Advances in Cardiovascular Safety Assessment Decrease Preclinical Animal Use and Improve Clinical Relevance.
abstract: Cardiovascular (CV) safety liabilities are significant concerns for drug developers and preclinical animal studies are predominately where those liabilities are characterized before patient exposures. Steady progress in technology and laboratory capabilities is enabling a more refined and informative use of animals in those studies. The application of surgically implantable and telemetered instrumentation in the acute assessment of drug effects on CV function has significantly improved historical approaches that involved anesthetized or restrained animals. More chronically instrumented animals and application of common clinical imaging assessments like echocardiography and MRI extend functional and in-life structural assessments into the repeat-dose setting. A growing portfolio of circulating CV biomarkers is allowing longitudinal and repeated measures of cardiac and vascular injury and dysfunction better informing an understanding of temporal pathogenesis and allowing earlier detection of undesirable effects. In vitro modeling systems of the past were limited by their lack of biological relevance to the in vivo human condition. Advances in stem cell technology and more complex in vitro modeling platforms are quickly creating more opportunity to supplant animals in our earliest assessments for liabilities. Continuing improvement in our capabilities in both animal and nonanimal modeling should support a steady decrease in animal use for primary liability identification and optimize the translational relevance of the animal studies we continue to do.
authors.affiliation: Brian 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.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Berridge
authors.affiliation: Brian 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.
authors.forename: A Eric
authors.initials: AE
authors.lastname: Schultze
authors.affiliation: Brian 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.
authors.forename: Jon R
authors.initials: JR
authors.lastname: Heyen
authors.affiliation: Brian 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.
authors.forename: George H
authors.initials: GH
authors.lastname: Searfoss
authors.affiliation: Brian 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.
authors.forename: R Dustan
authors.initials: RD
authors.lastname: Sarazan
mesh_terms: D032761:Animal Experimentation; D000818:Animals; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D004195:Disease Models, Animal; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D006801:Humans
keywords: 3Rs; biomarkers; cardiovascular; safety assessment