Refractory Period Of Atrioventricular Node Research Articles

A clue to the triples from an echo.

A clue to the triples from an echo.

ECG based assessment of circadian variation in AV-nodal conduction during AF-Influence of rate control drugs.

The heart rate during atrial fibrillation (AF) is highly dependent on the conduction properties of the atrioventricular (AV) node. These properties can be affected using β-blockers or calcium channel blockers, mainly chosen empirically. Characterization of individual AV-nodal conduction could assist in personalized treatment selection during AF. Individual AV nodal refractory periods and conduction delays were characterized based on 24-hour ambulatory ECGs from 60 patients with permanent AF. This was done by estimating model parameters from a previously created mathematical network model of the AV node using a problem-specific genetic algorithm. Based on the estimated model parameters, the circadian variation and its drug-dependent difference between treatment with two β-blockers and two calcium channel blockers were quantified on a population level by means of cosinor analysis using a linear mixed-effect approach. The mixed-effects analysis indicated increased refractoriness relative to baseline for all drugs. An additional decrease in circadian variation for parameters representing conduction delay was observed for the β-blockers. This indicates that the two drug types have quantifiable differences in their effects on AV-nodal conduction properties. These differences could be important in treatment outcome, and thus quantifying them could assist in treatment selection.

Characterization of the HCN Interaction Partner TRIP8b/PEX5R in the Intracardiac Nervous System of TRIP8b-Deficient and Wild-Type Mice.

The tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b/PEX5R) is an interaction partner and auxiliary subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are key for rhythm generation in the brain and in the heart. Since TRIP8b is expressed in central neurons but not in cardiomyocytes, the TRIP8b-HCN interaction has been studied intensely in the brain, but is deemed irrelevant in the cardiac conduction system. Still, to date, TRIP8b has not been studied in the intrinsic cardiac nervous system (ICNS), a neuronal network located within epicardial fat pads. In vitro electrophysiological studies revealed that TRIP8b-deficient mouse hearts exhibit increased atrial refractory and atrioventricular nodal refractory periods, compared to hearts of wild-type littermates. Meanwhile, heart rate, sino-nodal recovery time, and ventricular refractory period did not differ between genotypes. Trip8b mRNA was detected in the ICNS by quantitative polymerase chain reaction. RNAscope in situ hybridization confirmed Trip8b localization in neuronal somata and nerve fibers. Additionally, we found a very low amount of mRNAs in the sinus node and atrioventricular node, most likely attributable to the delicate fibers innervating the conduction system. In contrast, TRIP8b protein was not detectable. Our data suggest that TRIP8b in the ICNS may play a role in the modulation of atrial electrophysiology beyond HCN-mediated sino-nodal control of the heart.

Intrinsic Electrical Remodeling Underlies Atrioventricular Block in Athletes.

[Figure: see text].

Effect of Antazoline on Electrophysiological Properties of Atrial Muscle and Conduction System of the Heart

PurposeAntazoline is a first-generation antihistaminic agent with additional anticholinergic properties and antiarrhythmic potential. Recent data shows its high effectiveness in sinus rhythm restoration among patients with paroxysmal atrial fibrillation. The effect of antazoline on electrophysiological parameters of the heart in vivo has not yet been examined. The aim of this study was to evaluate changes in electrophysiological parameters of the heart muscle and conduction system as a response to increasing doses of antazoline.MethodsAfter successful ablation of supraventricular arrhythmias, the electrophysiological parameters: sinus rhythm cycle length (SRCL), AH, HV, QRS, QT, QTc intervals, Wenckebach point (WP), sinus node recovery period (SNRT), intra- (hRA-CSos) and interatrial conduction time (hRA-CSd), right and left atrium refractory period (RA-; LA-ERP), and atrioventricular node refractory period (AVN-ERP) were assessed initially and after 100, 200, and 300 mg of antazoline given intravenously.ResultsFifteen patients (8 males, 19–72 years old) undergoing EPS and RF ablation were enrolled. After 100 mg bolus, a significant reduction in SRCL was noticed. After antazoline administration, significant prolongation of HV, QRS, QTc, hRA-CSos, hRA-CSd intervals, RA– and LA-ERP and reduction of SRCL were observed. After a total dose of 300 mg, QT interval prolonged significantly. Increasing the dose of antazoline had no impact on AH, Wenckebach point, AVN-ERP, and SNRT.ConclusionAntazoline has an effect on electrophysiological parameters of the atrial muscle and has rapid onset of action. No negative effect on sinus node function and atrioventricular conduction in a unique property among antiarrhythmic drugs.

Overexpression of KCNN3 results in sudden cardiac death

A recent genome-wide association study identified a susceptibility locus for atrial fibrillation at the KCNN3 gene. Since the KCNN3 gene encodes for a small conductance calcium-activated potassium channel, we hypothesized that overexpression of the SK3 channel increases susceptibility to cardiac arrhythmias. We characterized the cardiac electrophysiological phenotype of a mouse line with overexpression of the SK3 channel. We generated homozygote (SK3(T/T)) and heterozygote (SK3(+/T)) mice with overexpression of the channel and compared them with wild-type (WT) controls. We observed a high incidence of sudden death among SK3(T/T) mice (7 of 19 SK3(T/T) mice). Ambulatory monitoring demonstrated that sudden death was due to heart block and bradyarrhythmias. SK3(T/T) mice displayed normal body weight, temperature, and cardiac function on echocardiography; however, histological analysis demonstrated that these mice have abnormal atrioventricular node morphology. Optical mapping demonstrated that SK3(T/T) mice have slower ventricular conduction compared with WT controls (SK3(T/T) vs. WT; 0.45 ± 0.04 vs. 0.60 ± 0.09 mm/ms, P = 0.001). Programmed stimulation in 1-month-old SK3(T/T) mice demonstrated inducible atrial arrhythmias (50% of SK3(T/T) vs. 0% of WT mice) and also a shorter atrioventricular nodal refractory period (SK3(T/T) vs. WT; 43 ± 6 vs. 52 ± 9 ms, P = 0.02). Three-month-old SK3(T/T) mice on the other hand displayed a trend towards a more prolonged atrioventricular nodal refractory period (SK3(T/T) vs. WT; 61 ± 1 vs. 52 ± 6 ms, P = 0.06). Overexpression of the SK3 channel causes an increased risk of sudden death associated with bradyarrhythmias and heart block, possibly due to atrioventricular nodal dysfunction.

Post-ablation prolongation of atrioventricular nodal refractory period is correlated with long-term success of cryoablation for atrioventricular nodal reentrant tachycardia in the case of the persistence of a residual jump.

PurposeA residual slow pathway after successful cryoablation for atrioventricular nodal reentrant tachycardia (AVNRT) is correlated with a higher recurrence rate. We described determinants of recurrence in subjects with a residual jump.MethodsWe analyzed the data of subjects with acute successful slow pathway cryoablation for AVNRT using a 6-mm-tip cryocatheter. Success was defined as AVNRT non-inducibility. Patients with no baseline elicitable jump, no inducible AVNRT, and transient first atrioventricular (AV) block at the last site were excluded.ResultsFrom 371 patients who underwent cryoablation from May 2002 to March 2011, 303 fulfilled the entry criteria (mean age, 41 ± 16; 222 women). Baseline AV nodal effective refractory period (ERP) was 272 ± 57 ms, postprocedural 331 ± 64 (P < 0.001), and the mean of the difference (Δ ERP) 60 ± 41. At the end of the procedure, 64 patients (21 %) had a residual jump, of whom 22 with a single echo. At 12 months follow-up, the actuarial recurrence-free rate was 70.3 % in patients with a residual jump and 86 % in those without (P = 0.01). In patients with a jump, only Δ AV nodal ERP was correlated with recurrence (37 ± 41 vs. 68 ± 47 ms; P < 0.04) while a single echo was not. The actuarial rate of recurrence was 60.8 % in patients with a Δ AV nodal ERP ≤ 30 ms and 18.8 % in those with a Δ AV nodal ERP >30 ms (P < 0.01).ConclusionsSuppression of slow pathway conduction is the optimal endpoint for AVNRT cryoablation. A residual jump can be tolerated if AV nodal ERP postcryoablation is prolonged >30 ms.

Effects of inadvertent atrioventricular block on clinical outcomes during cryoablation of the slow pathway in the treatment of atrioventricular nodal re-entrant tachycardia

The study aimed at evaluating the long-term effects of transient atrioventricular (AV) block on clinical outcomes during atrioventricular nodal re-entrant tachycardia (AVNRT) cryoablation. In 150 consecutive patients (39 +/- 14 years, ineffective anti-arrhythmic drugs 1.9 +/- 1.3), slow-pathway cryoablation for AVNRT was performed. A 7 Fr 6 mm-tip cryocatheter was used. After successful cryomapping (-30 degrees C), defined as jump abolition or AV nodal refractory period prolongation, cryoablation (-80 degrees C for 4 min) was applied if no AV block occurred. Atrioventricular nodal re-entrant tachycardia inducibility was checked after 30 min. Acute success (AVNRT non-inducibility) was achieved in 142 patients (95%). Overall, after a follow-up of 18 +/- 10 months, 118 of 150 patients (79%) were recurrence-free (including 2 patients for whom the procedure was unsuccessful). Among successful procedures, 116 of 142 (82%) patients were recurrence-free. During cryoablation, inadvertent transient AV block of varying degrees occurred in 34 patients (22.7%), namely, increased PR in 17 patients and a 2nd-3rd AV block in the remaining 17. In 24 patients, AV block occurred at the last effective site (increased PR in 13 patients and a 2nd-3rd AV block in 11). In the study population as a whole, univariate predictors of recurrence in the follow-up were AVNRT inducibility (P < 0.001), increased PR at the last effective site (P < 0.001), residual jump (P < 0.02), and small Koch's triangle (X-ray distance < 11 mm between the His and coronary sinus ostium catheters; P < 0.02). Atrioventricular nodal re-entrant tachycardia inducibility (P < 0.03), increased PR (P < 0.01), and small Koch's triangle (P< 0.04) were independently significant. For attempts at the last effective site, 3 groups of patients were compared: 13 patients with increased PR duration (Group A), 11 with a 2nd-3rd AV block (Group B), and 126 without AV block (Group C). Cryo-application time was 277 +/- 203 s in Group A, 75 +/- 87 s in Group B, and 253 +/- 135 s in Group C (A vs. B, P < 0.01; B vs. C, P < 0.001; and C vs. A, P= NS). There was no statistical difference among groups in the atriogram/ventriculogram amplitude ratio at the site of the last attempt, unsuccessful acute procedure, small Koch's triangle, and residual jump. Actuarial incidence of recurrence-free status at 12 months was 38% in A, 82% in B, and 82% in C (A vs. B, P < 0.05; B vs. C, P = NS; and C vs. A, P < 0.001). All AV blocks occurring during cryoablation were transient, confirming the safety of this method. An increased PR duration at the last effective site is associated with a higher recurrence rate, whereas a 2nd-3rd degree AV block has a recurrence rate similar to that of patients without AV block despite a shorter cryo-application time at the last site.

Influence of Cheyne-Stokes respiration on ventricular response to atrial fibrillation in heart failure

In subjects with sinus rhythm, respiration has a profound effect on heart rate variability (HRV) at high frequencies (HF). Because this HF respiratory arrhythmia is lost in atrial fibrillation (AF), it has been assumed that respiration does not influence the ventricular response. However, previous investigations have not considered the possibility that respiration might influence HRV at lower frequencies. We hypothesized that Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) would entrain HRV at very low frequency (VLF) in AF by modulating atrioventricular (AV) nodal refractory period and concealed conduction. Power spectral analysis of R-wave-to-R-wave (R-R) intervals and respiration during sleep were performed in 13 subjects with AF and CSR-CSA. As anticipated, no modulation of HRV was detected at HF during regular breathing. In contrast, VLF HRV was entrained by CSR-CSA [coherence between respiration and HRV of 0.69 (SD 0.22) at VLF during CSR-CSA vs. 0.20 (SD 0.19) at HF during regular breathing, P < 0.001]. Comparison of R-R intervals during CSR-CSA demonstrated a shorter AV node refractory period during hyperpnea than apnea [minimum R-R of 684 (SD 126) vs. 735 ms (SD 147), P < 0.001] and a lesser degree of concealed conduction [scatter of 178 (SD 56) vs. 246 ms (SD 72), P = 0.001]. We conclude that CSR-CSA entrains the ventricular response to AF, even in the absence of HF respiratory arrhythmia, by inducing rhythmic oscillations in AV node refractoriness and the degree of concealed conduction that may be a function of autonomic modulation of the AV node.

Intrinsic sinus and atrioventricular node electrophysiologic adaptations in endurance athletes

ObjectivesIn the present study, we evaluated sinus and atrioventricular (AV) node electrophysiology of endurance athletes and untrained individuals before and after autonomic pharmacologic blockade. BackgroundEndurance athletes present a higher prevalence of sinus bradycardia and AV conduction abnormalities, as compared with untrained individuals. Previous data from our laboratory suggest that nonautonomic factors may be responsible for the longer AV node refractory period found in well-trained athletes. MethodsSix aerobically trained male athletes and six healthy male individuals with similar ages and normal rest electrocardiograms were studied. Maximal oxygen uptake (o2max) was measured by cardiopulmonary testing. The sinus cycle length (SCL), AV conduction intervals, sinus node recovery time (SNRT), Wenckebach cycle (WC) and anterograde effective refractory period (ERP) of the AV node were evaluated by invasive electrophysiologic studies at baseline, after intravenous atropine (0.04 mg/kg) and after addition of intravenous propranolol (0.2 mg/kg). ResultsAthletes had a significantly higher o2max as compared with untrained individuals. The SCL was longer in athletes at baseline, after atropine and after the addition of propranolol for double-autonomic blockade. The mean maximal SNRT/SCL was longer in athletes after atropine and after propranolol. The WC and anterograde ERP of the AV node were longer in athletes at baseline, after atropine and after propranolol. ConclusionsUnder double-pharmacologic blockade, we demonstrated that sinus automaticity and AV node conduction changes of endurance athletes are related to intrinsic physiology and not to autonomic influences.

Gender Differences in the Electrophysiological Characteristics of Atrioventricular Conduction System and their Clinical Implications

Objective - The underlying mechanisms of the differences in sex distribution of patients with atrioventricular (AV) nodal re-entrant tachycardia and Wolff-Parkinson-White syndrome are poorly understood. The objective of this study was to determine potential gender differences in the electrophysiological properties of the normal AV conduction system that may be attributable to differences in sex distribution. Design - The AV conduction properties were studied in 96 patients (52 men and 44 women) who underwent electrophysiological testing, 32 patients with atrial tachycardia, 39 with idiopathic ventricular tachycardia and 25 with unexplained palpitations or syncope. Results - The AH (83 - 15 ms) and His-ventricular intervals in men (42 - 6 ms) were significantly longer than in women (78 - 14, 38 - 6 ms, p < 0.05, respectively), as was the PR interval (160 - 17 vs 152 - 13 ms, p = 0.02). The effective refractory period of AV node in men (349 - 75 ms) was longer than in women (297 - 45 ms, p = 0.03). However, no significant difference was observed between men and women with respect to the incidence of AV nodal dual pathway and the maximum AH interval achieved during premature stimulation or incremental pacing. The AV block cycle length was significantly longer in men (371 - 76 ms) than in women (330 - 52 ms, p = 0.02). A longer ventriculoatrial block cycle length was also found in men than in women although not at a significant level (436 - 107 vs 384 - 90 ms, p = 0.08). In addition, men (23%) were twice as likely to have ventriculoatrial dissociation during ventricular pacing as women were (11%, p = 0.2). Conclusion - The data show that gender-related differences in AV conduction properties may be responsible for the differences in sex distribution observed in patients with AV nodal re-entrant tachycardia and those with ventricular pre-excitation.

Safety of Slow Pathway Ablation in Patients With Atrioventricular Node Reentrant Tachycardia and a Long Fast Pathway Effective Refractory Period

Radiofrequency catheter ablation is an accepted primary therapy for atrioventricular (AV) node reentrant tachycardia (AVNRT). There is concern that slow pathway ablation in patients with a long anterograde fast pathway effective refractory period (ERP) may potentially impair subsequent node conduction. Eighteen patients (14 women; age 53 ± 20 years) with symptomatic AVNRT, whose fast pathway ERP at baseline was ≥500 ms, underwent slow pathway ablation. Their outcome was compared with 24 consecutive control patients (17 women; age 42 ± 17 years) who underwent ablation for AVNRT whose fast pathway ERP at baseline was <500 ms (controls). Slow pathway ablation was successful in 16 patients (90%). One patient had inadvertent fast pathway ablation. In a second patient the slow pathway could not be ablated because of recurrent transient AV block. Ablation was successful in all patients in the control group. Transient AV block related to current application occurred in 4 patients (22%) versus 1 control (4%) (p = 0.07). After ablation, the AV node refractory period increased in patients (368 ± 68 to 428 ± 92 ms, p = 0.02) and in controls (282 ± 35 to 336 ± 55 ms, p <0.0001), but the fast pathway ERP shortened in both groups (patients: 558 ± 63 to 428 ± 92 ms, p = 0.003; controls: 356 ± 53 to 336 ± 55 ms, p = 0.05). Furthermore, the slope of the regression line relating to shortening of the fast pathway ERP to the baseline ERP was markedly steeper in patients compared with controls (1.9 vs 0.4, p <0.0001). The shortening of the fast pathway ERP was greater in patients compared with controls (122 ± 130 vs 21 ± 50 ms, p = 0.001). During a mean follow-up of 18 ± 11 months, 1 patient with severe coronary artery disease died suddenly 2 years after ablation. There was no recurrence of clinical tachycardia, and none of the patients developed symptoms of bradycardia or required permanent pacing. Thus, slow pathway ablation in patients with AVNRT and a long fast pathway ERP is safe and effective.

Laser catheter coagulation of atrial myocardium for ablation of atrioventricular nodal reentrant tachycardia. First clinical experience.

A new technique for ablation of atrioventricular nodal reentrant tachycardia, using catheter-directed continuous wave Nd-YAG laser light, 1064 nm, via a novel pin-electrode laser catheter, was applied in 10 patients aged 15-63 years (mean 43 years). A total of 22 laser pulses, 1-5 per patient, at 20 or 30 W, of 10-45 s (mean 27 s) were aimed at the postero-inferior aspect of the tricuspid annulus. In all patients the tachycardia was rendered non-inducible at baseline as well as during orciprenaline administration. The amplitudes of the local atrial potentials diminished from 2.0 +/- 0.5 before to 0.4 +/- 0.4 mV after ablation, atrio-His intervals increased from 73 +/- 7 to 157 +/- 36 ms. Anterograde atrioventricular nodal refractory periods (212 +/- 31 vs 238 +/- 31 ms) and Wenckebach rate (174 +/- 8 vs 167 +/- 8 beats.min-1) did not change significantly (P > 0.05). There were no complications or recurrent arrhythmias in a follow-up of 12-35 (mean 27) months. Anatomically guided laser catheter coagulation of the postero-inferior aspect of the tricuspid valve ring is a safe and effective method for the cure of patients with common atrioventricular reentrant tachycardia.

Normal AV Node Function in Patients with Sinus Node Dysfunction After Cardiac Transplantation

Postoperative atrioventricular nodal (AVN) function was compared in 55 patients with normal and 50 patients with impaired sinus node (SN) function after cardiac transplantation (corrected SN recovery time > 520 msec or sinus arrest +/- escape rhythm). Fifty-two patients had fixed atrial pacing at cycle lengths between 600 and 430 msec, and 53 patients at cycle lengths from 600 to 300 msec between postoperative weeks 1 to 3. Relative (stimulus-R interval; AVNRRP) and effective AVN refractory period (AVNERP) were determined in 53 patients at a cycle length of 500 msec. Only one of 105 recipients had high degree AVN conduction disturbance characterized by a Wenckebach phenomenon at cycle length < 630 msec in the first postoperative week. Three patients with normal and two patients with impaired SN function had Wenckebach cycle lengths > 430 msec while the Wenckebach cycle lengths were < or = 430 msec in the remainder (p = NS). Resting PQ interval (146 +/- 18 vs 162 +/- 32; p = 0.09), Wenckebach cycle length (350 +/- 53 vs 362 +/- 50 msec), AVNRRP (356 +/- 38 vs 367 +/- 37 msec), and AVNERP (217 +/- 48 vs 244 +/- 49 msec) did not differ significantly between patients with normal and impaired SN function. AVN conduction did not deteriorate during 318 +/- 130 days of follow-up (PQ at follow-up 154 +/- 17 and 158 +/- 22 msec, patients with normal and impaired SN function, respectively). One DDD pacemaker was placed for AVN conduction disturbance while 22 pacemakers were implanted for SN deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Extended protocol for demonstration of dual AV nodal physiology.

The incidence of dual atrioventricular (AV) nodal physiology was evaluated in 22 patients (14 males, 8 females, age 52 +/- 18 years) undergoing electrophysiology studies for evaluation of ventricular tachycardia/nonsustained ventricular tachycardia (n = 11), supraventricular tachycardia (n = 5), and syncope (n = 6). Patients with AV node reentrant tachycardia were excluded. Thirteen patients had normal left ventricular function and nine patients (seven with coronary artery disease, two with dilated cardiomyopathy) had depressed left ventricular function. Single atrial extrastimuli (A2) were introduced after eight-beat drives at paced cycle lengths of 550 msec and 400 or 450 msec beginning at coupling intervals of 650 and 500 or 550 msec, respectively. The coupling interval was decreased at 10-msec intervals until AV node or atrial refractoriness. A second atrial extrastimulus (A3) was then added. A2 was fixed at 50 msec greater than the atrial or AV nodal refractory period. A3 was coupled to A2 at 650 and 500 or 550 msec and decremented as with single extrastimulation. Dual AV nodal physiology was defined by a 50-msec increase in A2H2 or A3H3 with a 10-msec decrement in the coupling interval or a discontinuous H1H2 versus A1A2 or H2H3 versus A2A3 curve. Using a single extrastimulus, 1 of 22 patients demonstrated dual AV nodal physiology. Using double extrastimuli, an additional four patients with dual AV nodal physiology were identified. The occurrence of dual AV nodal physiology determined using double extrastimuli is increased compared to using only a single extrastimulus (P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Developmental cellular electrophysiologic effects of propafenone on the rabbit atrioventricular node.

Transmembrane recordings and surface electrograms were used to evaluate the influence of propafenone on the cellular electrophysiology of isolated neonatal and adult rabbit atrioventricular node (AVN) preparations. An automatic interval of 863 +/- 82 ms (mean +/- SEM, n = 14) in neonates was found to be significantly shorter than the 1510- +/- 205-ms (n = 12) automatic interval observed in adults. Propafenone in a concentration of 5 x 10(-6) M significantly increased the automatic interval of neonatal pacemakers but not that of the adult preparations. These changes in automaticity produced by propafenone were not dependent on the adrenergic receptor-blocking action of the drug. The pacemaker escape time after overdrive pacing was also shorter in the neonate than in the adult. Propafenone prolonged the escape time of the neonatal tissues but not those of the adult. AVN refractory period, A-H interval, and antegrade Wenckebach rate were comparably increased in a concentration-dependent manner in both age groups. The maximum diastolic potential was decreased by propafenone in the neonatal atrionodal tissue but not in other regions of the AVN and not in any region of the adult AVN. Action-potential duration was increased in all regions of the AVN in both age groups. Action-potential amplitude and maximum upstroke velocity were decreased by propafenone in both age groups. Unlike other excitable tissues of the heart, the action-potential duration of AVN nodal cells increased with decreasing pacing intervals as the pacing interval approached the Wenckebach interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiologic effects of sotalol on the immature mammalian heart.

Sotalol is a beta-blocker with class III antiarrhythmic properties that has recently been used in children for the treatment of supraventricular and ventricular arrhythmias. However, little is known about its electrophysiologic effects on the immature heart. Using intracardiac electrocardiographic recordings and stimulation techniques, 15 canine neonates (8-15 days) and 15 adult mongrel dogs were studied with cumulative doses of sotalol (0.5, 1, 2, and 4 mg/kg plus an additional dose of 8 mg/kg for neonates). Heart rate decreased significantly in the two groups, but more in adult dogs (-43% in adult dogs versus -25% in neonates, p less than 0.05). There was no significant change for QRS duration and His-Purkinje system conduction time interval. QT and atrioventricular nodal conduction time intervals increased in adult dogs and neonates. Sinus node recovery time increased significantly in the two groups, but more in adult dogs. Refractory periods of the atrioventricular (AV) node increased significantly in neonates. Atrial flutter was no longer inducible in 12 of 15 neonates after the 2 mg/kg dose. Atrial effective refractory period increased significantly more in neonates (96%, p less than 0.001) than in adult dogs (58%, p less than 0.001). Ventricular effective refractory periods increased significantly both in neonates (46%) and adult dogs (50%), in a similar way. In conclusion, sotalol has greater electrophysiologic effects on the immature heart at the atrial level when compared to the adult, and similar effects on the refractory period of AV node and ventricle.

Reflex control of atrioventricular nodal refractory periods by cardiopulmonary receptors in humans.

The effects of selective cardiopulmonary receptor unloading on atrioventricular (AV) conduction were examined in 7 patients undergoing electrophysiologic testing. During -35 mmHg lower body negative pressure (LBNP) before autonomic blockade with propranolol and atropine, the AV-nodal conduction time (AH interval), the effective and functional refractory periods of AV node decreased at paced cycle length, when systemic arterial and central venous pressures decreased and heart rate increased. These responses to -35 mmHg LBNP except reductions in systemic arterial and central venous pressures disappeared after autonomic blockade. During -10 mmHg LBNP before autonomic blockade, both effective and functional refractory periods of AV node at paced cycle length decreased by 11 +/- 3% (mean +/- SEM) and 6 +/- 1% respectively with the reduction of central venous pressure while AH interval, systemic arterial pressure and heart rate remained unchanged. After autonomic blockade, -10 mmHg LBNP reduced central venous pressure but all the other parameters remained unchanged. These results suggest that cardiopulmonary baroreceptors participate in the reflex control of AV nodal refractoriness in humans.

Antiarrhythmic and proarrhythmic properties of diazepam demonstrated by electrophysiological study in humans

We evaluated the electrophysiological parameters before and after the intravenous infusion of diazepam (0.2 mg/kg) in 20 cardiac patients to investigate the drug's antiarrhythmic effect. Diazepam did not significantly change the arterial pressure. After the intravenous infusion of diazepam, the sinus cycle length significantly shortened from 847 +/- 132 to 747 +/- 155 ms (p less than 0.01). No significant change in the maximal sinus node recovery time was noted. The AH interval at the atrial pacing length of 600 ms shortened significantly from 140 +/- 40 to 127 +/- 39 ms (p less than 0.05). However, there was no significant change after the administration of diazepam in the longest atrial pacing rate associated with Wenckebach conduction in the atrioventricular (AV) node, effective and functional refractory periods of the AV node, HV interval, and QRS width during ventricular pacing at the cycle length of 600 ms. The atrial and ventricular effective refractory periods remained unchanged after the administration of diazepam. Six of the eight patients who showed dual AV nodal refractory period curves in the control study did not demonstrate them after diazepam administration by increasing the atrial or AV node effective refractory period. Thus, diazepam showed significant electrophysiological effects of the heart including shortening of the sinus cycle length, improvement in AV node conduction, and no significant effect on the His-Purkinje or intraventricular conduction and refractoriness of the atrium, AV node and ventricle. On the other hand, diazepam may influence the inducibility of supraventricular reentrant tachycardia incorporating the AV node.

Effects of Milrinone on Atrioventricular Conduction in the Canine Heart Under Normal Conditions, During Atrial Flutter and After Ligation and Reperfusion of the Septal Artery

Milrinone and AV Conduction. Milrinone, in addition to its vasodilatory and inotropic actions, has been shown to enhance or restore electrical activity in depolarized tissues and to improve conduction in isolated cardiac tissues depressed by exposure to an ischemic environment. These electrophysiological actions of the drug are thought to be secondary to milrinone's ability to enhance the transmembrane calcium current (ICa). The present study was designed to evaluate the effectiveness of milrinone (10–100 μg/kg, IV bolus) to modulate atrioventricular (AV) nodal conduction in anesthetized dogs under normal conditions, after ligation and reperfusion of the septal coronary arteries and during atrial flutter. All dosage regimens (10–100 μg/kg milrinone) produced a positive inotropic effect with no significant changes in blood pressure. Under normal conditions, 100 jig/kg of milrinone significantly reduced the PR interval, Wenckebach cycle length and AV nodal refractory period without causing a significant change in heart rate. The improvement in AV conduction and decrease in AV nodal refractoriness led to significant dose‐dependent increases in ventricular rate during atrial flutter. Low doses of milrinone also accelerated the flutter rate. Ligation of the septal coronary arteries for 2 to 6 hours produced stable atrioventricular conduction disturbances in six of the 11 dogs studied: complete AV block (n = 1), second‐degree AV block (n= 2) and first‐degree AV block (n= 3). Milrinone (100 μg/kg) improved AV conduction in five of the six dogs. Reperfusion of the septal arteries following 6 hours of ligation produced a sustained high degree AV block in two out of five dogs. Milrinone promptly restored 1:1 conduction in both cases. Our results suggest that milrinone may be of benefit in the treatment of some cases of AV conduction disturbance and that the drug, through its effects to facilitate AV conduction and abbreviate AV refractoriness, can lead to a significant and perhaps dangerous increase in ventricular rate in patients with atrial flutter or fibrillation. (J Cardiovasc Electrophysiol, Vol 1. pp. 93–102. 1990)