Biopta has expertise in the study of both cardiac and vascular tissues.
We can provide information on the potential activity of your compounds in patients. Tests can be designed to investigate the potential efficacy of medicines for cardiovascular disease or we can provide a human cardiovascular risk profile in specific tissues or through CardioForesight, our cardiovascular safety profiling package.
| Tissue Type |
Common Observations |
| Small resistance arteries |
- Vasoconstriction/ vasodilatation
- Changes in peripheral vascular resistance (indicates potential to alter blood pressure)
- Vascular permeability (leakage)
|
| Coronary arteries |
- Vasoconstriction/ vasodilatation
|
| Large conducting arteries |
|
| Muscular arteries |
- Vasoconstriction/ vasodilatation
|
| |
|
| Ventricular muscle |
- Inotropic (contractility) or lusitropic (rate of relaxation) effects
|
| Atrial appendage |
- Inotropic (contractility) or lusitropic (rate of relaxation) effects
|
| hERG cell assay |
- Blockade of hERG channel K+ current (associated with prolongation of Q-T and risk of ventricular arrhythmias)
|
Human cardiovascular tissues can be used to determine the efficacy of treatments for heart failure, angina or hypertension (systemic or pulmonary) but are most commonly used to detect adverse effects.
The ICH S7A guideline proposes a battery of safety studies which are required to be conducted to GLP prior to human exposure. These studies include; cardiovascular assessment, an assessment of central nervous system effects and respiratory function. Routinely, these assessments are carried out in animal in vivo models; however at Biopta we are able to provide powerful supporting data in functional human tissues and cells, entirely to GLP.
The human cardiovascular safety package comprises:
- Human ventricular muscle
Prediction of potential for direct effects on cardiac contractility Ventricular muscle and coronary arteries from the same patient can be investigated
- Human coronary arteries
Prediction of potential for coronary artery vasoconstriction
- Human resistance arteries
Potential to increase or decrease peripheral vascular resistance and hence to alter blood pressure
- hERG assay human cell-based test for IKr blockade
Blockade of IKr, a potassium channel that plays a key role in ventricular repolarisation and which if blocked is associated with an increased risk of Q-T prolongation and torsades be pointes.
