A novel in vivo method using endocardially placed electrodes in rats successfully assessed cardiac electrophysiologic changes in response to various ion channel blocking agents.
Do various ion channel agents alter cardiac refractoriness and conduction in an in vivo rat model?
This study establishes a novel in vivo method to assess cardiac electrophysiology in rats, providing normative data on the effects of various ion channel blockers.
The rat continues to be an important tool to assess cardiac electrophysiologic (EP) effects of test agents and to study the distribution/role of ion channels in cardiovascular diseases. However, no data have been described that accurately measure discrete cardiac EP parameters in rats in vivo. Therefore, we developed a method to assess cardiac EP in rats and then profiled several ion channel agents. Briefly, rats were instrumented with endocardially placed electrodes to assess cardiac refractoriness and conduction. Administration of class I agents resulted in a dose-dependent slowing of ventricular conduction. The potassium channel blocker 4-aminopyridine caused significant increases in atrial and ventricular refractoriness. An IKr blocker had little or no effect on atrial and ventricular refractoriness but significantly increased AV nodal refractoriness. Additionally, an IKs blocker had little effect on rat cardiac EP. The L-type blocker diltiazem caused a dose-dependent delay in AV node conduction and an increase in AV node refractoriness. Overall, this study provides normative data that describe the roles of Na, Ca, and K channels in rat cardiac electrophysiology, in vivo. Furthermore, the model provides a method to assess changes in cardiac electrophysiology in the setting of disease by using well-established rat models of induced or genetic cardiovascular disease.
Regan et al. (2005) studied this question. Ion channel agents was evaluated on Cardiac refractoriness and conduction. A novel in vivo method using endocardially placed electrodes in rats successfully assessed cardiac electrophysiologic changes in response to various ion channel blocking agents.