title: Adult human heart slices are a multicellular system suitable for electrophysiological and pharmacological studies.
abstract: Electrophysiological and pharmacological data from the human heart are limited due to the absence of simple but representative experimental model systems of human myocardium. The aim of this study was to establish and characterise adult human myocardial slices from small patients' heart biopsies as a simple, reproducible and relevant preparation suitable for the study of human cardiac tissue at the multicellular level. Vibratome-cut myocardial slices were prepared from left ventricular biopsies obtained from end-stage heart failure patients undergoing heart transplant or ventricular assist device implantation, and from hearts of normal dogs. Multiple slices were prepared from each biopsy. Regular contractility was observed at a range of stimulation frequencies (0.1-2 Hz), and stable electrical activity, monitored using multi-electrode arrays (MEA), was maintained for at least 8 h from slice preparation. ATP/ADP and phosphocreatine/creatine ratios were comparable to intact organ values, and morphology and gap junction distribution were representative of native myocardium. MEA recordings showed that field potential duration (FPD) and conduction velocity (CV) in human and dog slices were similar to the values previously reported for papillary muscles, ventricular wedges and whole hearts. Longitudinal CV was significantly faster than transversal CV, with an anisotropic ratio of 3:1 for human and 2.3:1 for dog slices. Importantly, slices responded to the application of E-4031, chromanol and 4-aminopyridine, three potassium channel blockers known to affect action potential duration, with an increase in FPD. We conclude that viable myocardial slices with preserved structural, biochemical and electrophysiological properties can be prepared from adult human and canine heart biopsies and offer a novel preparation suitable for the study of heart failure and drug screening.
authors: Heart Science Centre, National Heart & Lung Institute, Imperial College London, UK. p.camelliti@imperial.ac.uk
authors: Patrizia
authors: P
authors: Camelliti
authors: Sara Abou
authors: SA
authors: Al-Saud
authors: Ryszard T
authors: RT
authors: Smolenski
authors: Samha
authors: S
authors: Al-Ayoubi
authors: Alexandra
authors: A
authors: Bussek
authors: Erich
authors: E
authors: Wettwer
authors: Nicholas R
authors: NR
authors: Banner
authors: Christopher T
authors: CT
authors: Bowles
authors: Magdi H
authors: MH
authors: Yacoub
authors: Cesare M
authors: CM
authors: Terracciano
mesh_terms: D000328:Adult; D000818:Animals; D004285:Dogs; D055724:Electrophysiological Phenomena / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D014022:Tissue Survival / Q000502:physiology
chemical_list: D026902:Potassium Channel Blockers