A new ECG measure (RSh) for detecting possible sodium channel blockade in vivo in rats.
A new electrocardiographic (ECG) measure for detecting possible sodium channel blocking actions of drugs in anaesthetized rats is described. The conventional measures for sodium channel blockers are increased QRS width and/or P-R prolongation, however, these are limited in their sensitivity. This new measure, RSh, is the height from the peak of the R wave to the bottom of the S wave; it is more sensitive to known sodium channel blocking agents than conventional measures. This was shown by comparing the ECG effects of sodium channel blocking class I antiarrhythmic drugs from the three subclasses lidocaine (Ia), quinidine (Ib), and flecainide (Ic). In each case, RSh increased before changes could be detected in QRS or P-R. With tetrodotoxin and quinacainol, a new class I agent, changes in RSh correlated directly with previously reported changes in dV/dtmax of intracellular potentials recorded in vivo from epicardial cells. Representatives from antiarrhythmic classes II, III, and IV were also tested and only changed RSh when they had known sodium channel blocking properties at high doses. Other physiological maneuvers for altering heart rate, such as changing vagal activity, administration of catecholamines, or direct right atrial pacing, did not alter RSh. Thus RSh is a useful in vivo measure for the detection of possible class I antiarrhythmic actions. It has the advantages of being sensitive, selective, easy to measure, and involving minimal preparation.
Penz
W
W
Department of Pharmacology and Therapeutics, Faculty of Medicine, UBC, Vancouver, Canada.
Pugsley
M
M
Hsieh
M Z
MZ
Walker
M J
MJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001794:Blood Pressure; D004562:Electrocardiography / Q000187:drug effects / Q000379:methods*; D005424:Flecainide / Q000494:pharmacology; D006339:Heart Rate; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D011802:Quinidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*
D000889:Anti-Arrhythmia Agents; D015222:Sodium Channels; D008012:Lidocaine; D012964:Sodium; D011802:Quinidine; D005424:Flecainide