Cardiovascular Safety Pharmacology Studies in Anesthetized Dogs and Other Species

Cardiovascular Safety Pharmacology Studies in Anesthetized Dogs and Other Species 

Measurements possible in this model include end-diastolic and systolic pressure of the left ventricle, contractility of the heart (usually using peak positive LVdP/dt or LVdP/dt at a developed pressure of 40mmHg), heart rate, cardiac output and arterial blood flow in a given local perfusion bed. Test 

In summary, despite the preference for studies in conscious animals stated in the ICHS7A guideline, the use of anesthetized animals for assessing cardiovascular effects of drags is a valid and useful approach with a variety of practical advantages in comparison to conscious animals. 

Cardiac output can be measured using dye- or thermal-dilution techniques or by placement of an electromagnetic flow probe around the pulmonary artery. Insertion of a pressure transducer or fluid-filled catheter into the pulmonary artery and pulmonary vein allows for the calculation of pulmonary vascular resistance. The measurement of flow through the proximal aorta may also be useful but does not include coronary blood flow and as such is not equivalent to 

The electrocardiogram can be obtaining using standard limb leads and/or precordial leads. A lead should be selected that is stable over time and that has a sharp demarcation at the end of the T wave to facilitate the measurement of the QT interval duration. One can also position a monophasic action potential electrode catheter through the femoral or carotid artery to obtain endocardial monophasic action potentials (see below Modification of the Method). 

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