The cardiac work-loop technique: An in vitro model for identifying and profiling drug-induced changes in inotropy using rat papillary muscles

Sophie Fletcher, Helen Maddock, Rob S. James, Rob Wallis, Mayel Gharanei

Research output: Contribution to journalArticle

Abstract

The cardiac work-loop technique closely mimics the intrinsic in vivo movement and characteristics of cardiac muscle function. In this study, six known inotropes were profiled using the work-loop technique to evaluate the potential of this method to predict inotropy.

Papillary muscles from male Sprague-Dawley rats were mounted onto an organ bath perfused with KrebsHenseleit buffer. Following optimisation, work-loop contractions were perfomed that included an initial stabilisation period followed by vehicle control or drug administration. Six known inotropes were tested:
digoxin, dobutamine, isoprenaline, flecainide, verapamil and atenolol. Muscle performance was evaluated by calculating power output during work-loop contraction.

Digoxin, dobutamine and isoprenaline caused a significant increase in power output of muscles when compared
to vehicle control. Flecainide, verapamil and atenolol significantly reduced power output of muscle. These changes in power output were reflected in alterations in work loop shapes.

This is the first study in which changes in work-loop shape detailing for example the activation, shortening or passive re-lengthening have been linked to the mechanism of action of a compound. This study has demonstrated that the work-loop technique can provide an important novel method with which to assess detailed mechanisms of drug-induced effects on cardiac muscle contractility.
Original languageEnglish
Pages (from-to)(In-press)
JournalScientific Reports
Volume(In-press)
Publication statusAccepted/In press - 26 Nov 2019

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Bibliographical note

To be published in DOAJ listed journal

Keywords

  • Cardiac contractility
  • inotropes
  • work-loop
  • rat papillary muscles

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