title: Organotypic slice culture from human adult ventricular myocardium.
abstract: OBJECTIVE
  Cardiovascular research requires complex and functionally intact experimental models. Due to major differences in the cellular and subcellular composition of the myocardium between species, the use of human heart tissue is highly desirable. To enhance the experimental use of the human myocardium, we established methods for the preparation of vital tissue slices from the adult ventricular myocardium as well as conditions for their long-term preservation in organotypic culture.
  
  
  RESULTS
  Human ventricular heart samples were derived from surgical specimens excised during a therapeutic Morrow myectomy and cut into 300 μm thick slices. Slices were either characterized in acute experiments or cultured at a liquid-air interface. Viability and functionality were proven by viability staining, enzyme activity tests, intracellular potential recordings, and force measurements. Precision-cut slices showed high viability throughout 28 days in culture and displayed typical cardiomyocyte action potential characteristics, which enabled pharmacological safety testing on the rapid component of the delayed rectifier potassium current (I(Kr)) and ATP-dependent potassium channels throughout the whole culture period. Constant expression of major ion channels was confirmed by quantitative PCR. Acute slices developed excitation-dependent contractions with a clear preload dependency and a β-adrenergic response. Contractility and myosin light chain expression decreased during the first days in culture but reached a steady state with reactivity upon β-adrenergic stimulation being preserved.
  
  
  CONCLUSIONS
  Organotypic heart slices represent a multicellular model of the human myocardium and a novel platform for studies ranging from the investigation of molecular interactions to tissue engineering.
authors.affiliation: Department of Experimental and Clinical Pharmacology and Toxicology, Medical University of Lübeck, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Brandenburger
authors.forename: Jan
authors.initials: J
authors.lastname: Wenzel
authors.forename: Roman
authors.initials: R
authors.lastname: Bogdan
authors.forename: Doreen
authors.initials: D
authors.lastname: Richardt
authors.forename: Filomain
authors.initials: F
authors.lastname: Nguemo
authors.forename: Michael
authors.initials: M
authors.lastname: Reppel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Heinrich
authors.initials: H
authors.lastname: Terlau
authors.forename: Andreas
authors.initials: A
authors.lastname: Dendorfer
mesh_terms: D000328:Adult; D002320:Cardiovascular Physiological Phenomena; D055724:Electrophysiological Phenomena; D006352:Heart Ventricles / Q000033:anatomy & histology* / Q000601:surgery; D006801:Humans; D008955:Models, Cardiovascular; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009924:Organ Culture Techniques / Q000379:methods*