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CardioRespiratory

The cardiovascular platform is designed to detect major cardiac phenotypes and indicators of cardiac diseases. Through in vivo evaluation of cardiovascular function we are able to detect congenital heart disease, systolic and diastolic dysfunctions, myocardial infarction, intracardiac shunting, valvular disease, cardiac hypertrophy and dilatation, aberrant conduction, arrhythmias, hypertension and hypotension. We can also propose sensitized pathological models to help reveal pathological phenotypes or for preclinical compound testing.

The lung function analysis platform provides evaluation of strain-, sex-, and gene-specific differences in breathing patterns. Using normal developmental conditions as well as different inflammatory stresses, we can use the lung as an organ system for first-line study of inflammatory sensitization or resistance.

Cardio_Titre_Cardiac system

  • Non invasive blood pressure
  • Electrocardiography
  • Echocardiography
  • Telemetry

Cardio_Titre_Vascular system

  • Vascular exploration

Cardio_Titre_Lung function

  • Spontaneous breathing
  • Airway responsiveness
  • Bronchoalveolar lavage fluid

Cardio_Titre_Models challenges

  • Hypertension
  • Cardiac hypertrophy
  • Thrombosis
  • Atherosclerosis

Cardio_Titre_Inflammatory disease models

  • Ovalbumin-induced asthma model
  • HDM-induced lung inflammation
  • LPS-induced lung inflammation

Have a look at our listing of prestations

Purpose

Bleomycin-induced pulmonary fibrosis requires 14 days after a single administration to see significant airway fibrosis as well as associated inflammation. Effects are monitored by whole body plethysmography.  

Purpose

Exploration of lung inflammatory cells and mediators, e.g. cytokines, contained in bronchoalveolar lavage fluid (BAL). The service includes either the use of standard cytokines and chemokines techniques (Luminex, Elisa) or application of specific protocols provided by users.

Sample test results

Respi_BALF graph

Lung inflammatory cell content in bronchoalveolar lavages (BAL) in House Dust Mite (HDM) model: WT/KO study (C57BL/6 background)

Equipment

Advia 120 (Siemens AG, Erlangen, Germany)
Cytospin 4

Recommendations

Number of animals: 8 mice/gender/genotype

Purpose

The intranasal instillation of 3U of elastase is sufficient to establish a meaningful multifocal emphysema in the lungs of mice C57BL6/N after 14 days. This can currently be evaluated by flexiVent™, microCT, and histology.  

Purpose

Non-invasive tracking of emphysema or tumor growth using computed tomographyic X-ray imaging.

Purpose

Assessment of airway responsiveness to metacholine-induced brochoconstriction challenge in conscious mice by whole-body barometric plethysmography.

Purpose

Plethysmography (Penh) allows determination of airway volumes, breath frequency and assessment of airway obstruction in non-restrained mice. This test allows evaluation of fibrosis, as well as physiological and anatomical defects of lungs (e.g. emphysema).

Cardiac

Purpose

Echocardiography is considered the first-line diagnostic test, from which subsequent imaging or interventions can be recommended.

The Vevo 2100 High-Frequency Ultrasound Systems have been developed specifically for use in small animal imaging and are ideally suited for mouse or rat echocardiography. With center operating frequencies ranging from 15MHz to 50MHz one imaging system can be used to assess cardiac function from embryo to adult in many commonly used small animal models. 

Strain background references

Cardio_Echocardiography left ventricular weight graph Cardio_Echocardiography ejection fraction graph

Cardio_Echocardiography cardiac output graph Cardio_Echocardiography E/A ratio graph

Equipment

Vevo imaging System (VISUALSONICS, Amsterdam, The Netherlands).

Recommendations

Number of animals: 7-9 mice/gender/genotype

Purpose

Evaluation of the electrical activity of the heart in anesthetized mice.

Purpose

Experimental reproduction of a cardiac infarction by reversible suturing.

Purpose

Implantation of a cannula probe to directly measure arterial of ventricular blood pressure in an anesthetized mouse.

Purpose

Pathological model resulting in average 10% increase in blood pressure but with major fibrosis and left ventricle thickening.

Purpose

We perform multi-derivation ECG heart in anesthetized mice with 8 probes to generate information about how the electrical activity propagates in 3 dimensions and to determine the electrical axis of the heart.  Axis deviations may result from cardiac injury or from a congenital defect. 

Sample results

Cardio_Multiderivational ECG image

Electrical heart axis difference and specific electrical transmission issues are determined by multiderivational ECG.  Multiderivational ECG profiles of a wild-type mouse (left) and mutant mouse (right).  Deviated profiles in the mutant animal suggest a left-heart contraction deficiency as well as rotation of the electrical axis to 90-120⁰ from the normal 30-60⁰. 

Strain background reference

Any strain background can be used

Equipment

Electrocardiograph ISO DAM8 amplifier (World Precision Instruments, Sarasota, USA) with ECG AUTO v3.3.5.5 (Emka technologies, USA) and 8 lead positions probes.

recommendations:

We recommend 6 mice per group minimum in same anaesthesia conditions and probes positions

Purpose

Regular forced exercise can create a situation of cardiac hypertrophy. We utilize a swimming regimen in a warm pool over several weeks to induce cardiac hypertrophy.

Purpose

Telemetry blood pressure and heart rate: continuous recording of the systolic, diastolic and mean blood pressure and heart rate in conscious mice.

Telemetry EKG: continuous recording of electrocardiogram in conscious mice.

Strain background references

Cardio_Telemetry systolic blood pressure 1 graph Cardio_Telemetry systolic blood pressure 2 graph

Equipment

24 channels Data Sciences International acquisition system with 24 RPC-1 telemetric probe

Cardio_Telemetry acquision system scheme

The radio-telemetry system consists in implants and receiver: telemetry implants for small animals transmit data to receiver via AM radio waves.

The receiver is the RPC-1 receiver - DSI

-The Data Exchange Matrix - DSI
-The Computer (Dell) - DSI
-The Data Acquisition and Analysis System (Dataquest) - DSI

Cardio_Telemetry receiver image

Telemetry blood pressure and heart rate

The implantable telemetry, PA-C10 Device (transmitter), for blood pressure and heart rate - DSI

Cardio_Telemetry blood pressure equipment 1 image

Cardio_Telemetry blood pressure equipment 2 image

Telemetry EKG

The implantable telemetry devices (transmitters) – DSI ETA-F20 Device for Electrocardiogram

Cardio_Telemetry electrocardiogram equipment image

Recommendations

Number of animals: 8-10 mice/gender/genotype

Optimal body weight: 30g

Models

Purpose

Exploration of airway inflammation and/or airway responsiveness in House Dust Mite-induced lung inflammation.

Equipment

Advia120
Cytospin 4
Whole-body barometric plethysmograph (EMKA Technologies, Paris, France)

Recommendations

Number of animals - inflammation: 8 mice/gender/genotype

Number of animals - airway responsiveness: 12 mice/gender/genotype

 

Respi_HDM induced asthma model 1 graph Respi_HDM induced asthma model 2 graph

Respi_HDM induced asthma model 3 graph Respi_HDM induced asthma model 4 graph

Purpose

Exploration of airway inflammation and airway responsiveness in LPS-induced inflammation model.

Strain background references

Respi_LPS induced lung inflammation 1 graph

Respi_LPS induced lung inflammation 2 graph

Equipment

Advia120
Cytospin 4
Whole-body barometric plethysmograph (EMKA Technologies)

Recommendations

Number of animals - inflammation: 8 mice/gender/genotype
Number of animals - airway responsiveness: 12 mice/gender/genotype

Purpose

We are able to induce eosinophilic inflammation of the lung by presensitizing then exposing the lung to ovalbumin. This can be monitored by whole-body plethysmography, and examined terminally by cytology and cytokine analyses of BALF, immunoglobulin levels in blood and histology. 

Use of hypoxia chambers to induce Pulmonary Arterial Hypertension (PAH) for three of four weeks demonstrates significant resemblance to WHO group III categorized PAH, which includes COPD.  

Purpose

Exposure to chronic hypoxia provides a model of COPD and other PAH disorders in mice. For C57BL/6 mice maintained for 21 days at 0% we see highly significant increases in haematocrit, cardiomyocyte surface area, and right ventricular systolic pressure mimicking human PAH. 

Sample test results

Cardio_PAH graph

Exposure of C57BL/6N mice to 10% O2 for extended periods resulted in (A) weight loss; (B) increased hematocrit; (C) increase right-ventricular systolic pressure (RSVP); and (D) increased cardiomyocyte surface area.  

Equipment

  • Custom fabricated hypoxia chambers with feedback sensors.
  • Invasive blood pressure mouse probe throught the implantable telemetry, PA-C10 Device (transmitter), for blood pressure and heart rate - DSI (St. Paul,  U.S.A.) 

Open in full size

  • Advia complete blood counts Advia 120 (Siemens AG, Erlangen, Germany)

Vascular

Purpose

Pathological model resulting in average 37% increase in blood pressure with small decrease of myocardial relaxation.

Purpose

Pathological model resulting in average 18% increase in blood pressure with thinkening of arteries and left ventricle.

Purpose

Pathological model resulting in average 17% increase in blood pressure and some left ventricular hypertrophy.

Purpose

Determination of systolic blood pressure and heart rate in conscious mice by tail-cuff method.

Strain background reference

Cardio_Non invasive blood pressure graph

Equipment

Two apparatus of BP-2000 seriesII 6 channels (Visitech Systems, Apex, North Carolina, USA)

Recommendations

Number of animals: 9 mice/gender/genotype . Maximum age : 8 weeks

Purpose

Scan arteries and veins with ultrasound to :

  • Investigate the progression of disease processes. Ultrasound can provide data on anatomical changes, such as plaque formation, plaque size and composition as well as blood velocity
  • Determine the flow volume in a particular artery
  • Determine physical changes in artery walls
  • Determination of intravascular thrombus location.
  • Determine the health and nature of tissues supplied by that artery

Equipment:

The Vevo 2100 High-Frequency Ultrasound System from Vevo Imaging Systems (VISUALSONICS, Amsterdam, The Netherlands).

Recommendations

Number of animals: 7 mice/gender/genotype/experimental group

Models and Challenges

Purpose

Pathological model resulting in average 37% increase in blood pressure with small decrease of myocardial relaxation.

Purpose

Bleomycin-induced pulmonary fibrosis requires 14 days after a single administration to see significant airway fibrosis as well as associated inflammation. Effects are monitored by whole body plethysmography.  

Purpose

Pathological model resulting in average 18% increase in blood pressure with thinkening of arteries and left ventricle.

Purpose

The intranasal instillation of 3U of elastase is sufficient to establish a meaningful multifocal emphysema in the lungs of mice C57BL6/N after 14 days. This can currently be evaluated by flexiVent™, microCT, and histology.

Purpose

Exploration of airway inflammation and/or airway responsiveness in House Dust Mite-induced lung inflammation.

Equipment

Advia120
Cytospin 4
Whole-body barometric plethysmograph (EMKA Technologies, Paris, France)

Recommendations

Number of animals - inflammation: 8 mice/gender/genotype

Number of animals - airway responsiveness: 12 mice/gender/genotype

 

Respi_HDM induced asthma model 1 graph Respi_HDM induced asthma model 2 graph

Respi_HDM induced asthma model 3 graph Respi_HDM induced asthma model 4 graph

Purpose

Experimental reproduction of a cardiac infarction by reversible suturing.

Purpose

Pathological model resulting in average 10% increase in blood pressure but with major fibrosis and left ventricle thickening.

Purpose

Pathological model resulting in average 17% increase in blood pressure and some left ventricular hypertrophy.

Purpose

Exploration of airway inflammation and airway responsiveness in LPS-induced inflammation model.

Strain background references

Respi_LPS induced lung inflammation 1 graph

Respi_LPS induced lung inflammation 2 graph

Equipment

Advia120
Cytospin 4
Whole-body barometric plethysmograph (EMKA Technologies)

Recommendations

Number of animals - inflammation: 8 mice/gender/genotype
Number of animals - airway responsiveness: 12 mice/gender/genotype

Purpose

We are able to induce eosinophilic inflammation of the lung by presensitizing then exposing the lung to ovalbumin. This can be monitored by whole-body plethysmography, and examined terminally by cytology and cytokine analyses of BALF, immunoglobulin levels in blood and histology. 

Use of hypoxia chambers to induce Pulmonary Arterial Hypertension (PAH) for three of four weeks demonstrates significant resemblance to WHO group III categorized PAH, which includes COPD.  

Purpose

Exposure to chronic hypoxia provides a model of COPD and other PAH disorders in mice. For C57BL/6 mice maintained for 21 days at 0% we see highly significant increases in haematocrit, cardiomyocyte surface area, and right ventricular systolic pressure mimicking human PAH. 

Sample test results

Cardio_PAH graph

Exposure of C57BL/6N mice to 10% O2 for extended periods resulted in (A) weight loss; (B) increased hematocrit; (C) increase right-ventricular systolic pressure (RSVP); and (D) increased cardiomyocyte surface area.  

Equipment

  • Custom fabricated hypoxia chambers with feedback sensors.
  • Invasive blood pressure mouse probe throught the implantable telemetry, PA-C10 Device (transmitter), for blood pressure and heart rate - DSI (St. Paul,  U.S.A.) 

Open in full size

  • Advia complete blood counts Advia 120 (Siemens AG, Erlangen, Germany)

Purpose

Regular forced exercise can create a situation of cardiac hypertrophy. We utilize a swimming regimen in a warm pool over several weeks to induce cardiac hypertrophy.