Cardiovascular

Safety

The right data the first time. Every time. With highly predictive assays, profound analysis, and expert interpretation IPST maximizes the scientific and strategic value of the safety data generated for our clients.

hERG Inhibition assays (screens or GLP-compliant, pre-IND assays) offer extraordinary sensitivity, much greater than whole-organ assays, or whole-animal assays. Of course, proper study design and data interpretation decreases the risk of false positives resulting from this immense sensitivity. It is therefore imperative, when considering hERG inhibition patch-clamp data, to obtain expert interpretation, usually from the study director who oversaw the study.

Ionic Currents assays are generally conducted using patch-clamp, a versatile, high-resolution and low-throughput method which measures the currents generated by a single cell upon stimulation. Patch-clamp, albeit technically difficult, remains the most reliable and resolutive method to study ionic channels.Thanks to the flexibility of the patch-clamp technique, virtually all ionic channels in the body – ligand-gated, voltage-gated, calcium-gated, fast/slow activating and deactivating – can be studied with unmatched resolution using well-designed electrophysiology protocols.

The Action Potential Kinetics (APD) aka Purkinje Repolarisation assay can be conducted in cardiac Purkinke fibres, ventricular strips, or ventricular papillary muscles. The shape of the action potentials and the complement of ionic currents which underline the action potentials is different in the various tissues, and proper selection of the tissues exposed ensures the best sensitivity for the assay.

The potential to prolong the QT interval has a major impact on drug development programs. The Isolated Heart Preparation (Langendorff) preparation allows the assessment of the effects of a drug on electrophysiological (ECG,MAP) and mechanical parameters of cardiac function, yielding a variety of safety or toxicity indicators in a single study.

Indeed, whereas the above-described ionic current assays (conducted using isolated cells) benefit from incredible resolution, they lack the integrated nature of a spontaneously-beating heart. With less resolution, but greater physiological context, the isolated heart assay uncovers the impact of the compound on the ionic currents and mechanical phenomena which underlie the heart’s functions: electrical conduction and mechanical contraction.

Insist on best-in-protocol-customization to get the most out of all of your electrophysiological studies.