Sinus Node Recovery Time Research Articles

Acute effects of zatebradine on cardiac conduction and repolarization.

Zatebradine, a potent bradycardic agent, is believed to act selectively at the sinoatrial node. The selectivity of such a property relative to various electrophysiologic classes of action is not well defined. To characterize the electrophysiologic properties of zatebradine, the corrected sinus node recovery time, sinoatrial conduction time, conduction intervals, atrial effective refractory period and monophasic action potential duration in the ventricle were measured before and after incremental doses of zatebradine (0.1-1.5 mg/kg) in 15 anesthetized dogs. The electrophysiologic effects of zatebradine developed immediately after a single i.v. bolus dose, reaching steady-steady-state at 15 minutes with the maximum effect evident at 0.75 mg/kg. The IC(50) was 0.23 mg/kg. There was no significant effect on the sinus node recovery time. The PR interval on the electrocardiogram was significantly increased when the dose was higher than 0.25 mg/kg. The duration of the P wave and the PA interval were not changed. Zatebridine greatly increased the AH (from 135 to 178 milliseconds) without changing the HH and HV intervals in His bundle recordings. The EC(50) of this effect was 0.58 mg/kg. The QRS interval was not changed. The QTc was significantly increased from 0.43 to 0.56 s(1/2) (P < 0.05). The action potential duration was significantly increased by high dose zatebradine (> 0.5 mg/kg), the EC(50) for this effect was 0.76 mg/kg. The atrium effective refractory period was significantly increased (31%) with an EC(50) 0.69 mg/kg. These results indicate that zatebradine selectively inhibits sinus node automaticity at low doses. The inhibition of the AV nodal conduction and the lengthening of the refractory period and repolarization in the atria and the ventricles occur at higher dose.

Impaired parasympathetic heart rate control in mice with a reduction of functional G protein betagamma-subunits.

Acetylcholine released on parasympathetic stimulation slows heart rate through activation of muscarinic receptors on the sinus nodal cells and subsequent opening of the atrial muscarinic potassium channel (K(ACh)). K(ACh) is directly activated by G protein betagamma-subunits. To elucidate the physiological role of Gbetagamma for the regulation of heart rate and electrophysiological function in vivo, we created transgenic mice with a reduced amount of membrane-bound Gbeta protein by overexpressing nonprenylated Ggamma(2)-subunits in their hearts using the alpha-myosin heavy chain promoter. At baseline and after muscarinic stimulation with carbachol, heart rate and heart rate variability were determined with electrocardiogram telemetry in conscious mice and in vivo intracardiac electrophysiological studies in anesthetized mice. Reduction of the amount of functional Gbetagamma protein by >50% caused a pronounced blunting of the carbachol-induced bradycardia as well as the increases in time- and frequency-domain indexes of heart rate variability and baroreflex sensitivity that were observed in wild types. In addition, sinus node recovery time and inducibility of atrial arrhythmias were reduced in transgenic mice. Our data demonstrate in vivo that Gbetagamma plays a crucial role for parasympathetic heart rate control, sinus node automaticity, and atrial arrhythmia vulnerability.

Gender differences in arrhythmias

Electrocardiographic and electrophysiologic differences between men and women have long been noted. Women have a higher intrinsic heart rate than men, along with a longer corrected QT interval and a shorter sinus nodal recovery time. The incidence of and risk factors for a variety of arrhythmias differ between men and women. Atrioventricular nodal reentry tachycardia has a 2:1 female-to-male predominance, while accessory pathways are twice as frequent in men. Although atrial fibrillation is more prevalent in men of all age groups, the absolute numbers of men and women with atrial fibrillation are equal, and the associated morbidity and mortality experienced by women with atrial fibrillation appear to be worse. Women have a lower incidence of sudden cardiac death, and female survivors of sudden cardiac death have a lower frequency of spontaneous or inducible ventricular tachycardia. On the other hand, drug-induced torsade de pointes and symptomatic long QT syndrome have a female predominance. Therefore, greater caution should be used when prescribing QT-prolonging drugs in women. The incidence of arrhythmias is increased during pregnancy, and management of pregnant patients poses a significant challenge. The mechanisms of these gender differences are unclear but may be related to hormonal effects and the shorter QT interval in adult males. Pharmacologic and nonpharmacologic therapies are usually equally efficacious, but the risks of pharmacologic therapy are different in men and women. Atrial fibrillation may be more difficult to treat in women.

Intrinsic changes on automatism, conduction, and refractoriness by exercise in isolated rabbit heart.

We have studied the intrinsic modifications on myocardial automatism, conduction, and refractoriness produced by chronic exercise. Experiments were performed on isolated rabbit hearts. Trained animals were submitted to exercise on a treadmill. The parameters investigated were 1) R-R interval, noncorrected and corrected sinus node recovery time (SNRT) as automatism index; 2) sinoatrial conduction time; 3) Wenckebach cycle length (WCL) and retrograde WCL, as atrioventricular (A-V) and ventriculoatrial conduction index; and 4) effective and functional refractory periods of left ventricle, A-V node, and ventriculoatrial retrograde conduction system. Measurements were also performed on coronary flow, weight of the hearts, and thiobarbituric acid reagent substances and glutathione in myocardium, quadriceps femoris muscle, liver, and kidney, to analyze whether these substances related to oxidative stress were modified by training. The following parameters were larger (P < 0.05) in trained vs. untrained animals: R-R interval (365 +/- 49 vs. 286 +/- 60 ms), WCL (177 +/- 20 vs. 146 +/- 32 ms), and functional refractory period of the left ventricle (172 +/- 27 vs. 141 +/- 5 ms). Corrected SNRT was not different between groups despite the larger noncorrected SNRT obtained in trained animals. Thus training depresses sinus chronotropism, A-V nodal conduction, and increases ventricular refractoriness by intrinsic mechanisms, which do not involve changes in myocardial mass and/or coronary flow.

Evaluation of the role of IKAChin atrial fibrillation using a mouse knockout model

OBJECTIVESWe sought to study the role of IKAChin atrial fibrillation (AF) and the potential electrophysiologic effects of a specific IKAChantagonist.BACKGROUNDIKAChmediates much of the cardiac responses to vagal stimulation. Vagal stimulation predisposes to AF, but the specific role of IKAChin the generation of AF and the electrophysiologic effects of specific IKAChblockade have not been studied.METHODSAdult wild-type (WT) and IKACh-deficient knockout (KO) mice were studied in the absence and presence of the muscarinic receptor agonist carbachol. The electrophysiologic features of KO mice were compared with those of WT mice to assess the potential effects of a specific IKAChantagonist.RESULTSAtrial fibrillation lasting for a mean of 5.7 ± 11 min was initiated in 10 of 14 WT mice in the presence of carbachol, but not in the absence of carbachol. Atrial arrhythmia could not be induced in KO mice. Ventricular tachyarrhythmia could not be induced in either type of mouse. Sinus node recovery times after carbachol and sinus cycle lengths were shorter and ventricular effective refractory periods were greater in KO mice than in WT mice. There was no significant difference between KO and WT mice in AV node function.CONCLUSIONSActivation of IKAChpredisposed to AF and lack of IKAChprevented AF. It is likely that IKAChplays a crucial role in the generation of AF in mice. Specific IKAChblockers might be useful for the treatment of AF without significant adverse effects on the atrioventricular node or the ventricles.

Sinus node function after mitral valve surgery using the superior septal approach

Background. Sinus node function after the superior septal approach (SSA) in mitral valve surgery is controversial. We assessed sinus node function after this approach based on electrophysiological examinations and electrocardiographic change. Methods. Forty-six patients underwent successful mitral valve surgery via the SSA. Preoperatively, 25 patients were in atrial fibrillation (AF), 20 were in normal sinus rhythm (SR), and 1 patient was paced. Thirteen patients who demonstrated no sinus node dysfunction preoperatively underwent postoperative electrophysiological studies. Peripostoperative cardiac rhythm was monitored using a portable four-lead electrocardiograph, and late cardiac rhythm was examined using standard 12-lead electrocardiography in the outpatient clinic. Results. Twelve of 20 patients with preoperative SR experienced early postoperative supraventricular arrhythmias, but all spontaneously recovered SR. Electrophysiological studies revealed a basic cycle length of 767 ± 74 ms, sinoatrial conduction time of 72 ± 34 ms, sinus node recovery time of 1,119 ± 139 ms, and corrected sinus node recovery time of 349 ± 114 ms, thus demonstrating a lack of sinus node dysfunction. During the postoperative period (34 ± 24 months), 2 of the 20 patients with preoperative SR developed persistent AF, and 3 of the 25 patients with preoperative AF achieved normal SR. Conclusions. The SSA does not appear to cause long-term adverse effects on sinus node function, although temporary effects may occur.

Effects of Regulatory Peptides on Electrophysiological Properties of the Human Heart

During transesophageal electrical stimulation of the left atria in patients with heart diseases, an intravenous administration of Sandostatin prolonged the cardiac cycle and the effective refractory period of the atrioventricular junction, slowed down the sinoatrial conduction and the sinus node recovery time, and shifted the Wenckebach's point downwards. Neurotensin produced effects opposite to those of Sandostatin. During the Valsalva maneuver, Sandostatin strengthened bradycardia and broadened the range of heart rate changes associated with the vagal tone variations. The latter effect was also observed after the administration of neurotensin. Met-enkephalin and dalargin shortened the cardiac cycle, increased the corrected time of sinus node recovery time, but did not affect the cardiac rhythm dynamics during the Valsalva maneuver. These findings suggest that the regulatory peptides can be involved in control mechanisms determining the electrophysiological parameters of the human heart.

Diagnosis of sick sinus syndrome with intravenous adenosine injection

Background：The most widely utilized indexes of sinus node dysfunction are the sinus node recovery time (SNRT and the corrected sinus node recovery time (CSNRT, both of which generally require catheterization. Adenosine exhibits negative chronotropic effects on the sinoatrial node. The use/accuracy of the Nnon-invasive and reliable sinus node function test with intravenous adenosine was investigated. Methods and Results： The clinical value of rapid intravenous injection of adenosine for the assessment of sinus node dysfunction was examined in 14 patients with sick sinus syndrome (SSS and 31 controls. After prophylactic insertion of a temporary pacemaker in the right ventricle, overdrive suppression test was conducted according to the standard technique. CSNRT was first measured to evaluate the sinus node function, and then measured again, after administration of an intravenous bolus of adenosine (6 mg and 12 mg. Post-adenosine corrected sinus node recovery time (ADO：CSNRT was calculated by subtracting the basal sinus cycle length from the longest sinus cycle length. When it was assumed that an ADO：CSNRT reading of over 550 msec indicated sinus node dysfunction, intravenous injection of 6 mg of adenosine exhibited a sensitivity of 85% and a specificity of 100% for the detection of sick sinus syndrome, while 12 mg had a sensitivity of 100% and a specificity of 90%. There were significant differences in ADO：CSNRT between the patient and control groups (6 mg 1501±1081 msec vs 64±109 msec；12 mg 4005±2055 msec vs 216±315 msec, respectively. Conclusion： ADO：CSNRT was found to be a highly sensitive and specific index for the diagnosis of sick sinus syndrome, and should be considered as an alternative to invasive testing in patients with suspected sick sinus syndrome. ( ( ( (Korean Circulation J 2001;31(8 :788-793

Disfunción sinusal atípica. Utilidad del Holter implantable. A propósito de un caso

We present an 84 year-old female patient with repeated syncopes/presyncopes in the last nine years. All diagnosis tests were negative, including ECG, 24-hour Holter, tilt table test and EP study. Therefore, a subcutaneous insertable loop recorder was implanted (Reveal). The recording of three episodes showed the association of presyncope with the onset of atrial fibrilation and, in two syncopes, with an atrial pause between AF episodes. Probably an abnormal prolonged sinus node recovery time (more than 6 s) allowed AF to restart before the sinus rhythm.

Electrical remodeling of the atria associated with paroxysmal and chronic atrial flutter.

Atrial electrical remodeling may be important for the initiation and perpetuation of atrial arrhythmias. Whether paroxysmal atrial flutter (AFL) and chronic AFL cause electrical remodeling of the atria has not been conclusively determined. Before radiofrequency ablation of paroxysmal AFL, 15 patients in sinus rhythm were evaluated under autonomic blockade. Lateral right atrial (LRA) effective refractory periods (ERPs) at 600 and 450 ms were measured before and at 1-minute intervals for 10 minutes after spontaneous or pace termination of a 5- to 10-minute period of induced AFL. In 10 patients with chronic AFL, LRA, septal, and coronary sinus (CS) ERPs and corrected sinus node recovery times (cSNRTs) at 600 and 450 ms were measured under autonomic blockade 15 minutes, 30 minutes, and 3 weeks after termination of chronic AFL by ablation. In the paroxysmal AFL group, LRA ERPs decreased by 18% at 600 ms and 12% at 450 ms (P:<0.01) after induced AFL and recovered to baseline over approximately 5 minutes. Atrial fibrillation developed during AFL in 3 patients and during ERP testing in 3 patients when refractoriness was at its nadir. In the chronic AFL group, LRA, septal, and CS ERPs at 3 weeks were significantly greater than at 15 and 30 minutes after termination of chronic AFL at both cycle lengths (P:<0.01). Three weeks after ablation, cSNRT decreased 35% at 600 ms (P:<0.05) and decreased 44% at 450 ms (P:<0. 05). Both ERPs and cSNRTs measured 15 and 30 minutes after ablation of chronic AFL were not significantly different. Both paroxysmal AFL and chronic AFL cause reversible electrical remodeling of the atria but demonstrate different time courses of recovery.

Atrial automaticity and atrioventricular conduction in athletes: contribution of autonomic regulation.

Little is known about the sinoatrial automatism and atrioventricular conduction of trained individuals who present a normal resting electrocardiogram. We used transesophageal atrial stimulation, a minimally invasive technique, to evaluate aerobically trained athletes (n = 10) and sedentary individuals (n = 10) with normal resting electrocardiograms, to test the hypothesis that parasympathetic tone, as detected by heart rate variability, could be associated with changes in sinoatrial automatism and atrioventricular conduction. Corrected sinus node recovery time tended to be longer in athletes than in sedentary individuals, but this difference did not reach statistical significance. The Wenckebach point occurred at a lower rate in athletes than in the controls. Over a 24-h period of measurement, the mean RR interval was longer in the athletes than in the sedentary individuals. The mean square root of successive differences (rMSSD) tended to be higher in athletes than in controls, but this difference did not reach statistical significance. There was a moderate correlation (r = 0.48, P < 0.05) between the index of atrioventricular conduction, the rate at the Wenckebach point, and the logarithmically transformed rMSSD. Thus, as a corollary to its effects on the sinus node, where increased parasympathetic tone, decreased sympathetic tone, and non-autonomic components may contribute to sinus bradycardia, it is possible that athletic training may also induce intrinsic adaptations in the conduction system, which could contribute to the higher prevalence of atrioventricular conduction abnormalities observed in athletes.

Progressive atrioventricular conduction block in a mouse myotonic dystrophy model.

Myotonic dystrophy is caused by expansion of a CTG trinucleotide repeat on human chromosome 19, and leads to progressive skeletal myopathy and atrioventricular conduction disturbances. A murine model of myotonic dystrophy has been designed by targeted disruption of the myotonic dystrophy protein kinase (DMPK) gene. The DMPK-deficient mice display abnormalities in A-V conduction characteristics, similar to the human cardiac phenotype. The purpose of this study was to determine whether age-related progression of A-V block occurs in a mouse model of DMPK-deficiency. Surface ECGs and intracardiac electrophysiology (EP) studies were performed in 60 immature and 90 adult homozygous (DMPK-/-), heterozygous (DMPK+/-), and wild-type (WT) DMPK+/+ control mice. Complete studies were obtained on 141 of 150 mice. The RR, PR, QRS, and QT intervals were measured on ECG. Sinus node recovery time, AV refractory periods, paced AV Wenckebach and 2:1 block cycle lengths, atrial and ventricular effective refractory periods were compared between genotypes and age groups. There were no differences in ECG intervals or EP findings in the young mutant mice, but progressive PR prolongation in older mice. The A-V conduction defects are also sensitive to DMPK gene dosage. Adult DMPK-/- mice develop 1 degrees, 2 degrees and 3 degrees A-V block, whereas DMPK+/- mice develop only 1 degrees heart block. These data demonstrate that both age and DMPK dose are important factors regulating cardiac conduction in myotonic dystrophy. This mouse model of DM is remarkably similar to the human phenotype, with age-related progression in atrioventricular conduction defects.

Heart transplantation: Influence of the surgical technique on sinus function

This study analyzes the influence of the surgical technique on the development of sinus dysfunction. Cycle length, corrected sinus node recovery time, and sinoatrial conduction time were determined in 4 groups of dogs under the following conditions: group 1, controls; group 2, subjected to heterotopic heart transplantation with conservation of atrial anatomy; group 3, subjected to orthotopic heart transplantation by using a standard technique; and group 4, treated as in group3, but with an ischemic time of 24 hours. The cycle length was prolonged in all the treated groups when compared with the controls ( P < .01), an effect attributed to the disconnection of the autonomic nervous system during the transplantation procedure. The corrected sinus node recovery time and sinoatrial conduction time were significantly longer in all the animals in groups 3 and 4 when compared with those of groups 1 and 2 ( P < .01); however, there were no significant differences between groups 3 and 4 or between groups 1 and 2. These results suggest that the atrial anatomy play a more relevant role than the ischemic time in the origin of sinus dysfunction occurring after orthotopic heart transplantation.

Electrophysiologic Properties of the Atrium in Patients with Chronic and Paroxysmal Atrial Fibrillation

Background:Atrial fibrillation (AF) causes electrical remodeling of the atrium that plays an important role in increasing atrial vulnerability and the perpetuation of AF. The regional variation and heterogeneities of AFinduced electrical remodeling in patients with AF remain unclear. The purpose of present study was to test the hypothesis that regional heterogeneity of the atrial electrical properties including sinus node dysfunction is more apparent in patients with chronic AF than in patients with paroxysmal AF. Methods:The study group consisted of chronic AF (CAF, n=19), paroxysmal AF (PAF, n=19) and control group (CON, n=13). Monophasic action potential duration 90% (MAPD90) and atrial effective refractory period (AERP) were measured at 9 different sites in the right atrium using MAP catheter. Dispersion of MAPD90 and AERP were calculated from the difference between the maximum and minimum value at 9 sites, respectively. Intra-atrial conduction time (IACT) was calculated from the distance between the earliest activation and the latest one of the electrograms by 20-pole steerable catheter with 2-mm interelectrode distance which was positioned along the tricuspid annulus anterior to the crista terminalis. To evaluate sinus node function, post shock sinus node recovery time (PSRT) was measured. A rate corrected PSRT (PSRTc) was calculated from the difference between PSRT and basic sinus cycle length. Results:MAPD90 significantly shortened in patients with CAF (227.0±32.6 ms) compared with PAF (246.8±38.3 ms, p<0.05) and CON (239.1±39.3 ms, p<0.05), but AERP was not significantly different among 3 groups. The regional changes and dispersion of MAPD90 and AERP in patients with CAF did not differ from those of PAF and CON. IACT was prolonged in CAF group (73.8±22.5 ms) compared with PAF (58.2±8.0 ms, p<0.05) and CON groups (51.6±12.3 ms, p<0.05). IACT in CAF group (73.8±22.5 ms) was significantly prolonged compared with CON groups (51.6±12.3 ms, p<0.05) and was longer than that of PAF groups (58.2±8.0 ms) without statistical significance. PSRTc was longer in CAF group (758.3±525.8 ms) than in PAF group (209.5±125.0 ms, p<0.05). Conclusion: Electrical changes defined as shortened MAPD 90, prolonged IACT and PSRTc were more apparent in 논문접수일:1999년 11월 22일 심사완료일:2000년 2월 17일 교신저자:김영훈, 136-705 서울 성북구 안암동 5가 126-1 고려대학교 의과대학 내과학교실 전화:(02) 920-5445·전송:(02) 927-1478 E-mail:yhkmd@unitel.co.kr

Normal Values for Corrected Sinus Node Recovery Time in Adolescents

Sinus node recovery times have been used to evaluate sinus node function in adults and children. Normal values for corrected sinus node recovery time (CSNRT) are generally accepted as 275 and 500-550 msec in young children and adults, respectively. However, normal CSNRT values have not been determined for adolescent patients. Therefore, we mesured CSNRT in 29 consecutive patients, ages 12-17 years, who underwent electrophysiology testing as part of radiofrequency ablation. CSNRTs were performed by rapid atrial pacing for 30 seconds. Pacing cycle lengths were then shortened in 50-msec decrements to a minimum of 300 msec CSNRTs were determined by subtracting the patients' resting sinus cycle length from the maximal SNRT measured. The mean CSNRT was 323 +/- 61 msec (mean +/- SD, range 186-422 msec). A significant positive correlation between CSNRT and age was found. We conclude that the CSNRT value for the upper limit of normal in adolescents lies between the normal values previously determined for children and adults and is approximately 445 msec (mean + 2 SD). Because sinus node dysfunction is a well-recognized, long-term complication following surgical repair for complex congenital heart disease, this value becomes especially relevant as more children with congenital heart disease survive into adolescence.

Cardiac Conduction Abnormalities in Mice Lacking the Gap Junction Protein Connexin40

The gap junction protein connexin40 (Cx40) normally is expressed in the murine atrial myocardium and ventricular conduction system. In mice lacking Cx40, several changes in the surface ECG have been described. In this study, we analyzed cardiac conduction in more detail. In open chest mice under urethane anesthesia, epicardial electrodes were used to determine a number of atrial and ventricular pacing parameters. The corrected sinus node recovery time was significantly longer in Cx40-/- mice than in Cx40+/+ mice (44.4 +/- 7.2 msec vs 35.5 +/- 8.0 msec). In addition, the Wenckebach period was longer in Cx40-/- mice compared with the wild type (84.6 +/- 5.4 msec vs 78.8 +/- 3.6 msec), with the AV node probably limiting AV conduction in both cases. Whereas arrhythmias could not be induced by ventricular burst pacing in any of the mice, atrial burst pacing induced atrial tachyarrhythmias in 5 of 10 Cx40-/- mice, but not in any of 9 Cx40+/+ mice. Conduction velocities were measured in vivo using an array of unipolar recording electrodes. Ventricular conduction velocity did not differ between the groups, but atrial conduction velocity was reduced by 30% in Cx40-/- mice compared with the wild type. Heterozygous Cx40+/- mice did not differ significantly from the wild type in any respect. These findings indicate that in the atria and the AV conduction system, Cx40 is an important determinant of conduction.

Usefulness of intravenous propofol anesthesia for radiofrequency catheter ablation in patients with tachyarrhythmias: infeasibility for pediatric patients with ectopic atrial tachycardia.

General anesthesia is sometimes required during radiofrequency catheter ablation (RFCA) of various tachyarrhythmias because of an anticipated prolonged procedure and the need to ensure stability during critical ablation. In this study, we examine the feasibility of using propofol anesthesia for RFCA procedure. There were 150 patients (78 male, 72 female; mean age 30 years, range 4-96 years) in the study. Electrophysiologic study was performed before and during propofol infusion in the initial 20 patients and was performed only during propofol infusion in the remaining 130 patients. In the initial 20 patients, propofol infusion increased the sinus rate and facilitated AV nodal conduction. The accessory pathway effective refractory period, as well as the sinus node recovery time, atrial effective refractory period, and ventricular effective refractory period were not significantly changed. There were 152 tachyarrhythmias in 150 patients (24 atrial flutter, 31 AV nodal reentrant tachycardia, 68 AV reciprocating tachycardia, 12 ventricular tachycardia, and 17 atrial tachycardia). Most (148/152) tachycardias remained inducible after anesthesia and RFCA was performed uneventfully. However, in four of the seven pediatric patients with ectopic atrial tachycardia, the tachycardia terminated after propofol infusion and could not be induced by isoproterenol infusion. Consequently, RFCA could not be performed. Intravenous propofol anesthesia is feasible during RFCA for most tachyarrhythmias except for ectopic atrial tachycardia in children.

Effect of ryanodine on sinus node recovery time determined in vitro.

Evidence has indicated that the sarcoplasmic reticulum (SR) might be involved in the generation of spontaneous electrical activity in atrial pacemaker cells. We report the effect of disabling the SR with ryanodine (0.1 microM) on the sinus node recovery time (SNRT) measured in isolated right atria from 4-6-month-old male Wistar rats. Electrogram and isometric force were recorded at 36.5 degree C. Two methods for sinus node resetting were used: a) pulse: a single stimulus pulse interpolated at coupling intervals of 50, 65 or 80% of the regular spontaneous cycle length (RCL), and b) train: a 2-min train of pulses at intervals of 50, 65 or 80% of RCL. Corrected SNRT (cSNRT) was calculated as the difference between SNRT (first spontaneous cycle length after stimulation interruption) and RCL. Ryanodine only slightly increased RCL (<10%), but decreased developed force by 90%. When the pulse method was used, cSNRT ( approximately 40 ms), which represents intranodal/atrial conduction time, was independent of the coupling interval and unaffected by ryanodine. However, cSNRT obtained by the train method was significantly higher for shorter intervals between pulses, indicating the occurrence of overdrive suppression. In this case, ryanodine prolonged cSNRT in a rate-dependent fashion, with a greater effect at shorter intervals. These results indicate that: a) a functional SR, albeit important for force development, does not seem to play a major role in atrial automaticity in the rat; b) disruption of cell Ca2+ homeostasis by inhibition of SR function does not appear to affect conduction; however, it enhances overdrive-induced depression of sinusal automaticity.

Conduction disturbances and increased atrial vulnerability in Connexin40-deficient mice analyzed by transesophageal stimulation.

Recently, it has been reported that connexin40 (Cx40) deficiency in targeted mouse mutants is associated with a prolongation of P-wave and QRS complex duration on surface electrograms. The specific effects of Cx40 deficiency on sinus node function, sinoatrial, and atrioventricular conduction properties as well as on atrial vulnerability have not yet been investigated systematically by electrophysiological analysis. Fifty-two mice (18 Cx40(+/+), 15 Cx40(+/-), and 19 Cx40(-/-) mice) were subjected to rapid atrial transesophageal stimulation after anesthesia with avertin. A significant prolongation of sinus node recovery time was noticed in Cx40(-/-) mice compared with Cx40(+/-) and Cx40(+/+) mice (287.8+/-109.0 vs 211.1+/-61.8 vs 204.4+/-60.9 ms; P<0.05). In addition, Wenckebach periodicity occurred at significantly longer atrial pacing cycle lengths in Cx40(-/-) mice than in Cx40(+/-) or Cx40(+/+) mice (93. 3+/-11.8 vs 83.9+/-9.7 vs 82.8+/-8.0 ms, P<0.05). Analysis of 27 Cx40(-/-) mice showed a significant increase in intra-atrial conduction time and atrioventricular conduction time compared with 52 Cx40(+/-) and 31 wild-type (Cx40(+/+)) mice. Furthermore, in Cx40(-/-) mice, atrial tachyarrhythmias could be induced frequently by atrial burst pacing, whereas no atrial arrhythmias were inducible in heterozygous or wild-type mice. This study demonstrates that Cx40 deficiency is associated with sinoatrial, intra-atrial, and atrioventricular conduction disturbances. In atrial myocardium of the mouse, Cx40 deficiency results in increased atrial vulnerability and might contribute to arrhythmogenesis.

Use of intravenous adenosine as a noninvasive diagnostic test for sick sinus syndrome

Background Testing for sick sinus syndrome (SSS) requires invasive stimulation protocols for sinus node recovery time (SNRT) and corrected sinus node recovery time (CSNRT). Methods and Results We compared the CSNRT with the lengthening of the sinus cycle length (ADO:SCL) corrected to the basic cycle length (ADO:CSNRT) after administration of an intravenous bolus of adenosine (0.15 mg/kg) in 10 patients with clinical SSS (group 1) and 67 control patients (group 2). With 550 ms as an abnormal result for the ADO:CSNRT (and for the CSNRT) as an indicator of sinus node dysfunction, the ADO:CSNRT had a sensitivity of 80% and specificity of 97% for detection of SSS compared with sensitivity and specificity of 70% and 95% for invasive CSNRT. When combined, the 2 tests had a sensitivity of 100%. There was significant difference in the CSNRT between group 1 (1848 ± 1825 ms) and group 2 (355 ± 169 ms, P < .0001) and a significant difference in ADO:CSNRT between group 1 (1168 ± 1002 ms) and group 2 (272 ± 592 ms, P < .0001). Conclusions We conclude that the ADO:CSNRT is a sensitive and specific test for SSS that equals invasive testing and should be considered as an alternative to invasive testing in patients with suspected SSS. (Am Heart J 1999;137:435-8.)