Cardiac Contractility

Cardiac contractility is of major interest in safety pharmacology, as a number of drugs have been shown to have direct effects on cardiac function that may affect stroke volume and hence cardiac output. Using human isolated fresh cardiac tissues, we can assess your test articles for undesired or off-target effects, or assess their ability to modulate cardiac contractility as potential treatments for heart failure. Our scientists will design studies to answer your specific questions and can provide positive or negative controls to compare your test drug against known modulators of cardiac function.

  1. Heart tissue is dissected to obtain contractile trabeculae muscles
  2. Isolated atrial pectinate muscle or ventricular trabeculae are set up in organ baths
  3. Contractions of the cardiac muscle can be paced with electrical field stimulation. A range of frequencies can be used to mimic the effects of increasing/decreasing heart rate.

human-heart

Image: Example of a human heart used to complete our cardiac studies. 

Ventricular trabeculae muscles

Ventricular muscle functions to control the flow of blood into and out of the ventricles, which are responsible for pumping blood to the lungs and systemic circulation. Any alterations to ventricular contractility can affect cardiac output as well as the workload on the heart.

  • Atrial muscle and coronary arteries from the same donor can also be investigated
  • Inotropic (contractility) or lusitropic (relaxation) effects can be assessed
  • Human healthy or diseased hearts can be sourced 
  • Option for GLP studies
  • Available drug targets include acetylcholine receptors, adrenoceptors, and 5-HT receptors

Ventricular trabeculae and organ bath-1

Image: Left, Trabecular muscles are visible in this human heart. Right, Isolated trabecular muscle suspended in an organ bath.

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Adrenoceptor/isoprenaline model

This model uses ventricular trabeculae muscles to assess the effect of your test article on cardiac contractility on adrenoceptors.

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5-HT receptor/5-HT model

This model uses ventricular trabeculae muscles to assess the effect of your test article on cardiac contractility via 5-HT (serotonin) receptors.

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Acetylcholine receptor/ Acetylcholine model

This model uses atrial pectinate muscles to assess the effect of your test article on cardiac contractility via acetylcholine (ACh) receptors.

Atrial pectinate muscles

Pectinate muscles are mainly located in the right atrium of the heart and can be used as an isolated intact tissue to assess the potential effects of test drugs on atrial contractility.

  • Ventricular muscle and coronary arteries from the same donor can also be investigated
  • Inotropic (contractility) or lusitropic (relaxation) effects can be assessed
  • Human healthy or diseased hearts can be sourced 
  • Option for GLP studies
  • Available drug targets include adrenoceptors, 5-HT receptors, and PDE3 receptors 
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Adrenoceptor/isoprenaline model

This model uses atrial pectinate muscles to assess the effect of your test article on cardiac contractility with isoprenaline as a control.

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5-HT receptor/5-HT model

This model uses atrial pectinate muscles to assess the effect of your test article on cardiac contractility via 5-HT receptors.

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Adrenoceptor/Salbutamol model

This model uses atrial pectinate muscles to assess the effect of your test article on cardiac contractility with salbutamol as a control

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PDE3/Milrinone model

This model uses atrial pectinate muscles to assess the effect of your test article on cardiac contractility via PDE3 receptors.