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Cardiac

 

Research and development

Do you want to know the effects of your molecule, extract or compound on electric or contractile cardiac activity?

Do you want to qualify electrical or contractile cardiac activity of your transgenic animal model ?

We offer completing in vitro, ex vivo and in vivo assays to give you answers. 

 

 

Safety pharmacology

Do you want a preclinical study on the effects of your molecule on cardiac repolarization ?

We offer GLP (Good Laboratory Practice) compliant assay recommended by the International Conference on Harmonisation.

 

 

Technology:

 

  • ECG (6 ou 1 leads)
  • Echocardiography
  • Pressure-volume loops
  • Isolated Working heart
  • Patch-clamp
  • Catheter-mediated intracardiac recording

 

 

 

 

Test 1 : In vivo exploration

 

  • Cardiac electrical function: ECG

 

Standard peripheral six-lead ECG is recorded on anesthetized animals under baseline conditions and after injection of pharmacological compounds.One-lead ECG is recorded by telemetry on conscious animals for continuous recordings on 24 or 48 h, day-night comparisons or the effects evaluation of pharmacological compounds.Measured parameters: RR interval, P wave, PQ interval, QRS complex and QT interval durations. ECG abnormalities (conduction blocks, premature beats, tachycardia…) are documented.

 

 

 

  • Intracardiac recording

This assay combines non-invasive (surface electrocardiogram) and invasive (catheter-mediated intracardiac) recording of spontaneous cardiac electrical activity as well as of cardiac responses to programmed electrical stimulation (PES).

It is designed to explore cardiac electrical activity and to evaluate arrhythmias

This technique can also be used to produce animal models of complete atrioventricular block by radiofrequency-mediated His bundle ablation.

 

 

  • Echocardiography

Anesthetized mice or rats

Assessment of systolic function, diastolic function and anatomical parameters

 

 

  • Cardiac contractile function: pressure-volume loops

Cardiac pump function is evaluated in vivo by measuring left ventricular pressure and volume and constructing left ventricular pressure-volume loops.

Measured parameters: heart rate, end diastolic and systolic left ventricular pressures and volumes. Peak left ventricular pressure (DP), maximum rate of increase in pressure during contraction (dP/dt max), maximum rate of decrease in pressure during relaxation (dP/dt min) are also available.

 

 

 

 

Test 2 : Ex vivo exploration

 

  • Cardiac contractile function: Isolated Working Heart
This assay uses the isolated working heart technique to examine cardiac inotropy, chronotropy and pump function without the complications of an intact animal model but with an intact coronary perfusion system.Measured parameters: heart rate, peak left ventricular pressure (DP), maximum rate of increase in pressure during contraction (dP/dt max), maximum rate of decrease in pressure during relaxation (dP/dt min), cardiac output, cardiac heart cycle period and integrity stress…Those parameters are continuously recorded under vehicle and after increasing concentrations of a test item.

 

 

 

  • Cardiac contractile function: papillary muscles

This assay is designed to assess the direct effects of pharmacological compounds on contractility of isolated cardiac multicellular preparations.

Excised papillary muscles are placed in an experimental chamber, perfused with oxygenated physiological solution and paced at a constant rate. Contractions are recorded with a mechano-electrical force transducer.

Measured parameters: twitch amplitude (developed contractile force), twitch duration, time of half-maximum contraction (contraction velocity) and time of half-maximum relaxation (relaxation velocity).

 

 

 

 

Test 3 : In vitro exploration

 

  • Action potential recording by intracellular microelectrode technique on perfused isolated tissues: auricular and ventricular myocard (mice, rat, guinea pig, rabbit), Purkinje fibers (rabbit)

 

  • Action potential and ionic current recording on isolated cardiomyocytes (mice, rat, guinea pig, rabbit) by patch-clamp

 

  • Functional characterization of ionic channels by patch-clamp on stable or transiently transfected cell lines [Nav1.5, Cav1.2, Kv7.1 (KvLQT1), Kv11.1 (ERG), Kir2.1, Kir6.2, HCN2...]

 

 

 

   

 

 

 

 

Test 4: Cardiac safety: hERG assay

 

This test is designed to measure the inhibitory potency of new compounds on hERG ion channel to evaluate safety margins and potential cardiac repolarization risk.

Recombinant hERG channel tail current are recorded from mammalian expression systems, by means of the whole-cell configuration of the patch-clamp technique.

dfg

 

   

 

 

 

 

 

Animal models:

 

 

  • Septic shock

Animal model: rat

Method: intravenous injection of lipopolysaccharide of Escherichia coli. This model can be studied between 3 pm – 24 hours post-injection.

 

  • Ischemic heart failure

Animal model: rat

Method: left coronary artery ligature with a study during the acute phase of myocardial infarction or later, up to 12 weeks post-ligature, with 2 levels of heart failure, compensated and decompensated.

 

  • Progressive cardiac conduction disease

Animal model: heterozygous knock-out mice for the gene Scn5a which code the sodium channel Nav1.5.

 

  • Dilated cardiomyopathy

Animal model: rat

induced by chronic treatment with Adriamycin