Ex vivo experiments

Our solutions for Ex vivo experiments includes analysis modules for isolated heart and tissue/organ baths methods.

The Langendorff-perfused isolated heart model allows to observe the effect of a drug on the heart without the complications involved with in vivo experimentation, such as neuronal and hormonal effects from the living animal.

By using advanced high resolution data acquisition devices such as TMSi PORTI or REFA, NOTOCORD-hem™ combines monophasic action potential, ECG, flow, pressures and video to perform state of the art ex vivo cardiovascular assays.

Example analysis - Isolated heart with atrial stimulation

When the isolated heart is stimulated on the atrial level, stimulation artifact is followed by atrial depolarization signal (P wave). In the example below, ECG is acquired on a rabbit isolated heart. The signal is filtered out with TAR10s to remove the stimulation artifact.
 

LVP and ECG analysis in Langendorff-perfused rabbit heart with atrial stimulation

The ECG signal is analyzed with ECG51a and shows PQRST detections. Analysis of the left ventricular pressure signal is carried out with LVP30a and shows dP/dtmax (blue marks).


Example analysis - Isolated heart with ventricular stimulation

In the following example, ECG and monophasic action potentials (MAP) are acquired in the Langendorff-rabbit heart model, stimulated at the ventricular level. Acquisition of ECG is performed by two electrodes placed on the surface of the heart, in a position similar to lead II. Ventricular stimulation artifact is closely followed by ventricular depolarization signal.

Our ECG analyzer for isolated heart ISO10r detects the Q peak (yellow) and R peak (red) and S peak (purple), the J point (black), T peak (light blue) and T end (dark blue). Spontaneous beat is indicated by a green marker.

ECG & MAP analysis in Langendorff-perfused rabbit heart with ventricular stimulation

Monophasic action potentials are measured on different locations on the heart surface and analyzed with MAP30a. The following parameters are evaluated: action potential duration (APD), conduction, instability (indicative of beat to beat APD variability), triangulation (indicative of changes of Phase 3 repolarization), and reverse-use dependency (indicating that the APD is more prolonged at slow heart rates).


Example analysis - Transmural repolarization index (TRI)

The Transmural Repolarization Index (TRI) allows to identify a relation between prepolarization dispersion (apico-basal and transmural) and proarrhythmic risk in the whole isolated heart.

TRI is acquired using three needles, placed in the base, in the apex and in the middle of the heart and each containing 8 electrodes evenly spaced on needles in the ventricle wall’s width.

Our dedicated module TRI10a analyzes transmural repolarization heterogeneity in rabbit isolated perfused heart preparations.

TRI analysis in rabbit's heart.

In the example above, acquired on a rabbit, TRI10a's detection of depolarization onset (green cross), peak (blue cross) and end (red cross) of repolarization are shown on the TRI signal. "End repol: Duration" is the time difference between repolarization peak and repolarization end.

Tissue or organ bath assays are mostly used for cardiovascular research, using isolated aortic rings, heart tissue (papillary muscle, left ventricles) or arteries. They also find applications in the respiratory field, using isolated tracheal rings for example, and for studying responses of urinary bladder or penile muscle strips. This experimental setup allows to monitor dose-responses in drug research while keeping flexibility in the experimental protocol.

Collecting organ’s tension signals from 8, 16 or more channels is easy as NOTOCORD-hem™ can be interfaced with most organ baths systems using general purpose glassware to small form factors systems produced by DMT (Denmark).

Example analysis - Pulsatile tissue

The figure below shows an example of analysis with NOTOCORD®'s contraction analyzer PUL30a.

 Pulsatile tissue analysis

PUL30a detects the characteristic values of pulsatile tissue contractions: start of contraction, minimum, maximum, maximum and minimum derivations, frequency, rise time, recover time and area under the curve.
The stimulation tissue contraction analyzer STT30a is also available.

ECG51a Semi-automated electrocardiogram analyzer
ISO10r Rabbit isolated heart electrocardiogram analyzer
LVP31a Left ventricular pressure analyzer
MAP30a Monophasic action potential analyzer
PUL30a Pulsatile tissue contraction analyzer
STT30a Stimulated tissue contraction analyzer
TAR10s Triggered Artifact Remover
TRI10a Analysis of transmural repolarization index

 

Keywords

  • Isolated heart
  • Atrial stimulation
  • Ventricular stimulation
  • TRI
  • Tissue bath
  • Pulsatile tissue