Coronary artery contractility

Coronary artery contractility

Using ethically sourced fresh, functional human tissues, Biopta can carry out an array of pharmacological in vitro assays to provide invaluable data on the cardiac safety and vasoactive properties of compounds early in the drug development cycle.  As coronary arteries act as the myocardial blood supply, any changes in blood flow or vascular tone can greatly affect cardiac function. Even a brief reduction in coronary artery blood flow can induce dysfunction of the heart. These assays provide an excellent method for investigating both the efficacy and possible side effects of compounds.

Coronary arteries are isolated and mounted under isometric tension in a wire myograph system.  Arteries are mounted between two stainless steel 'jaws' held in place by two ultra-thin wires. As the tissue contracts or relaxes in response to various compounds, the force is transmitted to a sensitive isometric force transducer, capable of detecting micro-Newton changes in force.

 

5-HT is known to cause vasoconstriction via 5-HT1B/1D receptors and 5-HT2A receptors.  Test compound agonists are often screened for potential coronary artery vasoconstriction with respect to 5-HT receptors.  Figure 1 below shows that both 5-HT and sumatriptan constrict human coronary arteries (n = 5 donors) with pD2 values of 6.5 (5-HT) and 6.6 (sumatriptan), which compares to reported pD2 values of 7.0 for 5-HT (Galzin et al, 2000) and 5.7 (Edvinsson et al, 2005) or 6.33 (Saxena et al, 1997) for sumatriptan.

Key benefits of using Biopta’s in vitro coronary artery assays:

  • Use of fresh, functional human tissue
  • De-risk development and add commercial value by generating human proof of concept data prior to clinic
  • Investigate safety and efficacy of compounds
  • Various endpoints can be investigated
  • Cross species comparisons can be made
  • Blood vessels can be cultured and studied over a period of time
  • Biopta will work with you to design a protocol that meets your requirements

To discuss a coronary artery in vitro pharmacology study at Biopta, please email us at info@biopta.com or contact us via the contact page on the website.

References

Edvinsson, L et al. (2005) ‘Triptan-induced contractile (5-HT1B receptor) responses in human cerebral and coronary arteries: relationship to clinical effect’, Clinical Science, Vol 109, pp. 335 – 342

Glazin, A-M et al. (2000) ‘Effects of SL 65.0472, a novel 5-HT receptor antagonist, on 5-HT receptor mediated vascular contraction’, European Journal of Pharmacology, Vol 404, pp. 361 - 368

Saxena, P.R et al. (1997) ‘Effects of avitriptan, a new 5-HT1B/1D receptor agonist, in experimental models predictive of antimigraine activity and coronary side-effect potential’, Naunyn-Schmiedeberg’s Arch Pharmacol, Vol 355, pp. 295 – 302

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