title: Limitations of animal electrical cardiac safety models.
abstract: BACKGROUND
  Human electrical safety standards are based almost exclusively on animal studies and there is an unjustified assumption that ventricular fibrillation (VF) thresholds in animals are the same as those in humans.
  
  
  RESULTS
  We analyzed differences between animals and humans in cardiac stimulation. A broad literature survey revealed that swine are a fragile electrophysiologic research species and have a dense intramural Purkinje fiber network, which is not found in some other species, including humans. Anesthesia agents have to be chosen carefully as swine are prone to malignant hyperthermia. Cardiac stimulation thresholds depend on weight and capture rates. Thus, the animal weight has to be representative of the weight of human subjects. Studies have shown significant ECG differences between humans and other species, including swine and canine. At least one study suggested that rabbit hearts tend to develop VF in a manner more similar to that seen in humans.
  
  
  CONCLUSIONS
  Animal studies can play a role in conservatively evaluating cardiac safety. However, while still abiding by the precautionary principle, animal study design has to take into account the significant anatomical and electrophysiological differences between humans and other mammals. Data from multiple animal models may offer broader perspectives. If attempts are made to extrapolate animal results to humans then appropriate numerical correction factors should be applied, such as some of those discussed in this article.
authors.forename: Dorin
authors.initials: D
authors.lastname: Panescu
authors.forename: Mark
authors.initials: M
authors.lastname: Kroll
authors.forename: Michael
authors.initials: M
authors.lastname: Brave
mesh_terms: D000777:Anesthetics / Q000009:adverse effects; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D004594:Electrophysiology / Q000379:methods; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D023421:Models, Animal; D011690:Purkinje Fibers / Q000502:physiology*; D011817:Rabbits; D012449:Safety; D013045:Species Specificity; D013552:Swine; D014693:Ventricular Fibrillation / Q000503:physiopathology*
chemical_list: D000777:Anesthetics