title: A device for rapid and quantitative measurement of cardiac myocyte contractility.
abstract: Cardiac contractility is the hallmark of cardiac function and is a predictor of healthy or diseased cardiac muscle. Despite advancements over the last two decades, the techniques and tools available to cardiovascular scientists are limited in their utility to accurately and reliably measure the amplitude and frequency of cardiomyocyte contractions. Isometric force measurements in the past have entailed cumbersome attachment of isolated and permeabilized cardiomyocytes to a force transducer followed by measurements of sarcomere lengths under conditions of submaximal and maximal Ca(2+) activation. These techniques have the inherent disadvantages of being labor intensive and costly. We have engineered a micro-machined cantilever sensor with an embedded deflection-sensing element that, in preliminary experiments, has demonstrated to reliably measure cardiac cell contractions in real-time. Here, we describe this new bioengineering tool with applicability in the cardiovascular research field to effectively and reliably measure cardiac cell contractility in a quantitative manner. We measured contractility in both primary neonatal rat heart cardiomyocyte monolayers that demonstrated a beat frequency of 3 Hz as well as human embryonic stem cell-derived cardiomyocytes with a contractile frequency of about 1 Hz. We also employed the β-adrenergic agonist isoproterenol (100 nmol l(-1)) and observed that our cantilever demonstrated high sensitivity in detecting subtle changes in both chronotropic and inotropic responses of monolayers. This report describes the utility of our micro-device in both basic cardiovascular research as well as in small molecule drug discovery to monitor cardiac cell contractions.
authors.affiliation: Kytaro, Inc., 11200 SW 8th Street, MARC 430, Miami, Florida 33199, USA.
authors.forename: Angelo
authors.initials: A
authors.lastname: Gaitas
authors.affiliation: Kytaro, Inc., 11200 SW 8th Street, MARC 430, Miami, Florida 33199, USA.
authors.forename: Ricky
authors.initials: R
authors.lastname: Malhotra
authors.affiliation: Electrical Engineering and Computer Science, University of Michigan, 1301 Beal Ave., Ann Arbor, Michigan 48109, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Center for Arrhythmia Research, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Herron
authors.affiliation: Center for Arrhythmia Research, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: José
authors.initials: J
authors.lastname: Jalife
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004867:Equipment Design; D000066449:Human Embryonic Stem Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D055616:Microtechnology / Q000295:instrumentation*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D051381:Rats
chemical_list: D000318:Adrenergic beta-Agonists; D007545:Isoproterenol
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