PubMed · 5515964
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J C Chignon, R Distel, B Courtois. 1970. [Auricular vectorcardiography].. https://pubmed.ncbi.nlm.nih.gov/5515964/
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Perhexiline maleate is an antianginal drug that has been shown to have antiarrhythmic effects in humans. To examine whether some of these clinical observations could be caused by block of cardiac K+ channels, we examined the effects of perhexiline on a rapidly activating delayed rectifier K+ channel (Kv1.5) cloned from human heart and stably expressed in human embryonic kidney cells as well as a corresponding K+ current (the ultra-rapid delayed rectifier, IKur) in human atrial myocytes. With the use of inside-out macropatches, we found that perhexiline inhibited Kv1.5 current in a time- and voltage-dependent manner with an IC50 value of 1.5 x 10(-6) M at +50 mV. Perhexiline reduced Kv1.5 tail current amplitude and slowed its decay relative to control. These data are consistent with blockade of open channels, probably from the intracellular surface. Perhexiline (3 microM) also blocked IKur in human atrial myocytes. The block that was observed was both time- and voltage-dependent in qualitatively similar ways to block of Kv1.5 channels. However, the time-dependent block of IKur by perhexiline was somewhat slower and its voltage-dependence steeper relative to its effects on Kv1.5. These data indicate that perhexiline blocks both cloned and native human cardiac K+ channels. Blockade of one or more types of voltage-dependent K+ channels may explain some of the electrophysiological effects of perhexiline observed in humans.
The incidence and electrophysiologic characteristics of supernormal atrial conduction (SNC) were examined by cardiac stimulation in 53 control subjects. Their ages ranged from 15 to 71 years (mean age, 50 +/- 21 years) (mean +/- SD). There were 27 women and 26 men in the study. Conduction of premature atrial responses from the sinus node to the atrioventricular node (intraatrial conduction time) was supernormal in 27 (51%) subjects and conduction to the left atrium (interatrial conduction time) was supernormal in 35 (66%) subjects (difference not significant). At coupling intervals ranging between 440 and 240 ms, the conduction time of the premature beats was as much as 25 ms shorter than that of the basic driven beats. The maximum decrease in interatrial conduction time during the period of SNC was 13 +/- 5 ms and the maximum decrease in intraatrial conduction time was 9 +/- 3 ms (P < .001). The supernormal interatrial conduction zone was 71 +/- 29 ms and the supernormal intraatrial conduction zone was 57 +/- 25 ms (P < .05). There was a significant positive correlation between the SNC zone and the maximum decrease in conduction time (r = .82; P < .001). Supernormal atrial conduction was stable, reproducible, and remained constant in individual patients. Supernormal atrial conduction was found to be a relatively frequent phenomenon. There was a significantly greater SNC zone and maximum decrease in conduction time in interartrial conduction than in intraatrial conduction.(ABSTRACT TRUNCATED AT 250 WORDS)
Single chamber rate responsive pacing offers many potential advantages over the more complex dual chamber atrial tracking pacing mode in children, and the preservation of atrioventricular synchrony could be unnecessary in selected groups of pediatric patients. Twenty-two pediatric patients (age range 9 months to 12 years; mean 6.5 years) had implantation of ventricular rate responsive (VVIR) pacemakers over a 2-year period. All patients had chronic third-degree atrioventricular block, and a normal ventricular function at rest. During the follow-up each patient underwent a 24-hour Holter monitoring, and ten performed a graded treadmill test in both ventricular fixed rate (VVI) and rate responsive (VVIR) pacing mode. Paced ventricular rates were found to be normal for age in all 22 patients; maximum rate did not reach the higher programmed rate during daily activities in any patient. Comparing the mean paced ventricular rate to the mean rates of blocked P waves, six patients showed a difference of more than 20 beats/min, which induced the pacemaker parameters to be reprogrammed. In all patients a significant correlation was found between variations of paced ventricular rate and variations of spontaneous blocked atrial rhythm (P < 0.05); this correlation persisted in the subsequent Holter controls in the ten patients with longer follow-up. Exercise tolerance resulted normal in the ten patients who performed a treadmill test either in VVIR or VVI mode, with increased maximal heart rates and maximal systolic blood pressure in VVIR mode (P < 0.0013). Rate responsive ventricular pacemakers seem to adequately respond to the physiological needs of daily life of this selected group of children requiring permanent pacing.