QA interval as an indirect measure of cardiac contractility in the conscious telemeterised rat: Model optimisation and evaluation

Conscious telemeterised rats are used for early assessment of cardiovascular drug safety. This paper details the surgery required to allow key cardiovascular parameters to be determined and describes how QA interval (QAI), a surrogate measure of cardiac contractility, is related to a more direct measure of cardiac contractility, dP/dtmax (LVdP/dtmax). Experimental studies examining the effect of both positive and negative inotropes are described. Eight rats were surgically implanted with telemetry probes for measuring blood pressure, heart rate, activity, body temperature and ECG parameters. Initial studies focussed on evaluating surgical procedures aimed at improving the ECG signal to allow QAI quantification. Once achieved, experimental studies were undertaken with verapamil, salmeterol, milrinone or vehicle. Following treatment, data was collected for ~20 h from pair-housed animals to establish effects on QAI or LVdP/dtmax, which was measured directly from the left ventricle in a separate group of rats. The modified ECG lead placement produced both a qualitative and quantitative improvement in ECGs. Increases in cardiac contractility (measured directly) were paralleled by a decrease in QAI (measured indirectly). Salmeterol and milrinone increased (all p