Cardiac contractility studies using the isolated organ bath set-up

Why study contractility using isolated organ baths ?

More and more molecules show adverse side effects on cardiac contractility. However, these effects are generally detected in the later stage of drug development. Between early hERG screening assays and high-cost in vivo telemetry studies, the isolated organ bath set-up offers an affordable ex vivo model to detect drug-​induced effects on contractility (inotropism with the papillary muscle model and chronotropism with the spontaneously beating right atrium model). Pre­clinical determination of inotropism or chronotropism modification may provide valuable information for toxicity prediction in man.

Why choose PhysioStim for your contractility study?

The experts at PhysioStim have a profound working knowledge of cardiac electrophysiology and make sure you get the most out of your assay.

Inotropic effects using the isolated organ bath set-up

We study inotropic effects induced by drugs using the isolated organ bath set-up. The tissue, isolated papillary muscle, for example, is fixed in the organ bath chamber and electrically stimulated or not. The evoked twitch force is recorded using a force transducer.

Technique

  • Isolated organ baths

Study model

  • Guinea-pig papillary muscles
  • 6 preparations tested and 6 control preparations (as basic design protocol but can be adapted)

Protocol

  • 3 cumulative increasing concentrations of assay compound
  • Stimulation rate: 2 Hz
  • Washout period or positive control at the end of the experiment
  • Option: other stimulation rates

Reference product

  • Isoprenaline 0.03 µmol/L

Measured parameters

  • Systolic tension (Peak)
  • Diastolic tension (Base)
  • Developed tension (dF)

Results

  • Developed force recordings
Contractility curve in isolated organ bath set-up

Typical effects of isoprenaline on developed force of guinea-pig papillary muscle

Chronotropic effects using the isolated organ bath set-up

We study chronotropic effects induced by drugs using the isolated organ bath set-up. The tissue, spontaneously beating right atria, is mounted in the organ bath chamber. The spontaneous beating frequency of isolated rat right atria is recorded using a force transducer.

Technique

  • Isolated organ baths

Study model

  • Rat right atria
  • 6 preparations tested and 6 control preparations (as basic design protocol but can be adapted)

Protocol

  • Until 5 cumulative increasing concentrations of assay compound
  • Washout period or positive control at the end of the experiment

Ref­er­ence com­pounds

REFERENCE COM­POUNDS EC50
Isoprenaline 4.77 nM
Forskolin 0.08 µM
IBMX 7.48 µM

Measured parameters

  • Spontaneous atrial beating rate

Results

  • Frequency recordings

Typical cumulative effects of isoprenaline on spontaneous atrial beating rate

Physiostim concentration effect curve isoprenaline

Concentration-effect curve of isoprenaline

Advice from our expert scientists

In order to confirm the results obtained during your contractility study and the impact on electrical activity or ECG results, PhysioStim recommends completing your study with additional tests:

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