Effects of the T-type calcium channel blockade with oral mibefradil on the electrophysiologic properties of the human heart.
BACKGROUND
As the calcium T-channel blockade is a new pharmacological category with presumably unique electrophysiological effects, the influence of its only representative yet mibefradil was tested after the single oral dose.


METHODS
10 patients underwent the electrophysiologic examination. Normal baseline values in sinus node cycle length (SNCL), sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), PA interval, atrial effective refractory period, AH interval, Wenckebach point (WP), atrioventricular nodal refractory period, and HV interval were measured using standard techniques. After that a single dose of 100 mg mibefradil was given and the testing repeated in 90 minutes.


RESULTS
Though non-significantly in a study-group limited in size due to global withdrawal of mibefradil, sinus node automaticity was suppressed (prolongation of SNRT by 5.1% and CSNRT by 11.5%) and heart rate lowered (SNCL prolonged by 2.8%) comparatively more than was the negative dromotropic effect on the atrioventricular node (negligible prolongation of AH interval by 1.1% and WP cycle by 0.4%).


CONCLUSIONS
Demonstrated electrophysiological effects of oral mibefradil with more pronounced influence on the automaticity of the sinus node seem to be in agreement with the preclinical data on the predominant role of T-channels in the pacemaker activity of the sinus node. According to the Framingham data on the risk of heart rate for the cardiovascular as well as all-cause mortality, calcium T-channel blockade offers a desirable profile for antihypertensive treatment. From this point of view development of new representatives of calcium T-channel blockers could be a useful contribution to clinical practice.
Mádle
A
A
2nd Department of Medicine, University Hospital, 30599 Pizen, Czech Republic.
Linhartová
K
K
Koza
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001283:Atrioventricular Node / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008297:Male; D020748:Mibefradil / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D012849:Sinoatrial Node / Q000187:drug effects; D013575:Syncope / Q000503:physiopathology*
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D020748:Mibefradil