Isolated organ bath
Isolated organ bath

Cardiac contractility studies using the isolated organ baths set-up

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.

Inotropic effects using the isolated organ baths 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
  • 5 preparations tested and 5 control preparations (as basic design protocol but can be adapted)

Measured parameters

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

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 compounds

Reference compoundsConcentration

Isoprenaline 0.03 µmol/L

Isolated organ bath

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
  • 5 preparations tested and 5 control preparations (as basic design protocol but can be adapted)

Measured parameters

  • Spontaneous atrial beating rate
  • Frequency recordings

Protocol

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

Ref­er­ence compounds

Reference CompoundsConcentration

Isoprenaline4.77 nM

Forskolin0.08 µM

IBMX7.48 µM

Typical cumulative effects of isoprenaline on spontaneous atrial beating rate

Typical cumulative effects of isoprenaline on spontaneous atrial beating rate.

Concentration-effect curve of isoprenaline

Concentration-effect curve of isoprenaline.

Additional tests according to PhysioStim scientist’s expertise

Humans cardiomyocites

Human Cardiomyocytes

PhysioStim Isolated Perfused Heart

Isolated perfused heart

hERG assays

PhysioStim Sodium Channel assays

Sodium channel assays

Calcium channel

Calcium channel assays

PhysioStim Potassium Channel assays

Other Potassium channel assays

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