Sinus Node Dysfunction and Impairment of Global Atrial Conduction Time After High Rate Atrial and Ventricular Pacing in Dogs

ZUPAN, I., et al .: Sinus Node Dysfunction and Impairment of Global Atrial Conduction Time After High Rate Atrial and Ventricular Pacing in Dogs. It has been shown in animals and humans that AF shortens the atrial refractory period and impairs its rate adaptation. The aim of the study was to evaluate the effects of high rate pacing on sinus node function and intraatrial conduction. Eight dogs were subjected to rapid atrial pacing (AP) at a rate of 400 beats/min for 16 days. After a complete recovery of left ventricular function, they underwent rapid ventricular pacing (VP) at 240 beats/min of equal duration. Sinus node recovery time (SNRT) was measured after pacing at 150, 160, and 170 beats/min. P wave duration was measured on a surface ECG recorded at a paper speed of 200 mm/s. Measurements were performed at baseline, immediately after AP or VP, and four weeks after termination of AP or VP. SNRT immediately after AP and VP was significantly prolonged at all three pacing rates   (P < 0.03)   . P wave duration increased significantly after either type of pacing   (AP: 74.3 ± 6.4 ms, VP: 70.0 ± 3.8 ms)   compared with baseline values   (60.6 ± 6.2 ms, P < 0.05)   . Rapid AP and VP induces sinus node dysfunction and prolongs intraatrial conduction time. The effects of sustained AP and VP on sinus node function and atrial myocardium returned toward control values 4 weeks after cessation of pacing. The authors hypothesize that reversible electrical remodeling occurs both in the sinus node and in the atrial myocardium. (PACE 2003; 26[Pt. II]:507–510)     

Failure of Plasma Atrial Natriuretic Peptide Levels to Increase During Exercise in Patients with Chronic Atrial Fibrillation

It is generally accepted that plasma atrial natriuretic peptide release occurs secondary to atrial stretch. The influence of coordinated atrial contraction (AC) upon this process is not fully appreciated. The aim of the study was to determine the importance of coordinated AC upon peripheral atrial natriuretic peptide levels (α-hANP) during exercise. Peripheral α-hANP levels were measured at rest and during exercise in 12 patients with complete heart block (CHB) and permanent rate responsive pacemakers. Seven patients had coordinated AC and five had chronic atrial fibrillation (AE). Each patient performed three treadmill exercise tests. Maximal inspired oxygen volume (VO₂ max) was determined during test 1. Tests 2 and 3 were performed to 70% VO₂ max, the pacemaker being programmed to either VVI or VVIR mode. Plasma α-hANP was measured using a two-site immunoradiometric assay. At rest there was a small but significant difference between the two patient groups: AF 60.2 pg/mL versus AC 97.6 pg/mL; P = 0.03. During exercise in the AC patients, there was a significant increase in α-hANP levels, in VVIR mode, to 238.4 pg/mL, and in VVI mode, to 207.9 pg/mL, P = 0.002 and 0.003, respectively. In those patients with chronic AF, there was no significant rise or fall in α-hANP levels in either pacing mode, VVIR 65.2 pg/mL, VVI 46.6 pg/mL. Previous workers have suggested that α-hANP release by nonfunctioning atria is normal. We have shown that the presence of coordinated AC is required for the release of α-hANP during exercise in patients with CHB, and that this appears to be independent of ventricular rate.     

No Correlation Between Atrial Natriuretic Peptide Concentrations and Echocardiographic Measurements of Left Atrial Size or Left Ventricular Size and Function in Patients with Persistent Atrial Fibrillation

Atrial fibrillation (AF) may be associated with activation of atrial natriuretic peptide (ANP). The exact trigger for the release of ANP is still being debated. Atrial volume, pressure, and wall stretch are considered to be the main determinants of ANP activation. The aim of the study was to evaluate plasma ANP concentrations in patients with persistent AF and to analyze the echocardiographic determinants of ANP concentration in this group. The study population included 67 patients, 59 ± 7 years of age, with a median AF duration of 5.5 months (range 0.1–12). The relationship between plasma ANP concentrations and echocardiographic left atrial (LA) diameter and volume, and left ventricular (LV) diameter and ejection fraction (EF) was analyzed by logistic regression analysis. The median baseline plasma ANP concentration was 63 pg/mL (range 21–126) in the study group versus 34 pg/mL (range 16–73) in a control group. The mean left antero-posterior atrial dimension, LA volume, LV enddiastolic diameter, and LVEF were 48 mm, 104 mL, 52 mm, and 54%, respectively. A significant linear positive correlation was found between plasma ANP concentration and maximal LA volume (r = 0.62, P < 0.01). A negative correlation was found between LVEF and plasma ANP concentration (r =−0.42, P = 0.01). However, by multivariate regression analysis, no echocardiographic parameter was an independent predictor of plasma ANP concentration. Plasma ANP concentrations were independent of echocardiographic measurements of LA size or LV size and function in patients with persistent AF.     

Atrial Natriuretic Peptide During Different Pacing Modes in a Comparison with Hemodynamic Changes

The study investigates the response of atrial natriuretic peptide (ANP) to different cardiac pacing modes in comparison with hemodynamic changes. Ten patients underwent Swan-Ganz catheterization during pacemaker implant. Atrioventricular and ventricular pacing were performed consecutively at three pacing rate levels (80, 100, and 110 ppm). Blood samples were taken from the pulmonary artery for ANP determination, both basally and at the end of each pacing period. Concomitantly, mean pulmonary capillary wedge pressure (PCWP) and mean pulmonary artery pressure (PAP) were measured. Cardiac output (CO) was determined by thermodilution both basally and during the 110 ppm steps. During atrioventricular pacing, whereas no significant changes were observed for ANP, PCWP and PAP, CO increased significantly (P less than 0.0005). At the beginning of ventricular pacing hemodynamic parameters and ANP levels were comparable with those of baseline conditions. During subsequent ventricular pacing PCWP and ANP increased significantly at the 110 ppm rate step (P less than 0.05). PAP did not change significantly, whereas CO decreased in all cases (P less than 0.01). A positive correlation was observed between ANP and PCWP during ventricular (P less than 0.001), but not atrioventricular pacing. The results, while confirming the hemodynamic advantages of atrioventricular pacing, point to a major stimulation of ANP secretion during ventricular pacing. This fact, together with the observed drop in CO and the correlation between ANP and PCWP, suggest that the increase of ANP in ventricular pacing may be the expression of a compensatory mechanism to the hemodynamic disadvantages of atrioventricular asynchrony.     

尿激酶对急性心肌梗死血浆心钠素的影响

对40例急性心肌梗死患者血浆的心钠素水平检测结果显示，急性心肌梗死患者各测定时点的血浆心钻素值明显高于正常人水平，差异显著（P＜0．01），并于入院当时（病后5．07±3．08小时）达高峰（0．69±0．54ng／ml），以后逐渐降低．于48小时时再次达高峰（0．69±0．34ng／ml），于72小时时仍未恢复至正常人水平（健康正常人血浆心钠素水平为0．49±0．08ug／ml）。在缺血性心肌损伤早期，血浆心钠素水平即升高，低氧血症可能是刺激心钠素早期释放的原因。尿激酶溶栓治疗20例病人的血浆心钠素水平较非溶栓治疗的20例病人的血浆心钠素水平明显降低，且下降较快，第二峰值降低。各测定时点血浆心钠素水平比较，差异非常显著（P＜0．05，P＜0．01）。溶栓使血浆心钠素降低的原因可能与血液动力学失调有关，或者可能因尿激酶具有纤维蛋白和纤维蛋白原降解产物的血管舒张作用。血浆心钠素浓度的降低可能提示尿激酶具有短暂的有益的血液动力学作用。     

新生儿呼吸衰竭时血浆心房利钠多肽水平的变化

目的 :探讨血浆心房利钠多肽 (ANP)在新生儿呼吸衰竭中的作用及临床意义。方法 :应用放射免疫法分别测定 48例 (新生儿窒息 32例 ,新生儿肺炎 16例 )呼吸衰竭的足月新生儿病后 3d内、10～ 14d的血浆ANP水平 ,并与不伴有呼吸衰竭的 18例 (新生儿窒息 10例 ,新生儿肺炎 8例 )对照     

左室收缩功能正常的心房颤动患者血清NT-pro-BNP水平的变化及影响因素探讨

目的:观察左室收缩功能正常的心房颤动(房颤)患者氨基末端-脑钠肽前体(NT-pro-BNP)的变化并探讨其影响因素。方法:对116例左室射血分数正常(LVEF>50％)患者测定血清NT-pro-BNP水平,行经胸超声心动图检查,并调查人口学特征、心血管病主要危险因素情况、合并症、用药情况、血生化学检查。除外既往心功能不全、肝肾功能不全、甲状腺疾病或肿瘤病史患者。结果:持续性房颤血清NT-pro-BNP水平的中位值显著升高(1018．0ng／L比137．9 ng／L,P<0．001),多因素分析发现房颤类型(P<0．0001)、年龄(P=0．0004)、LAD(P<0．0001)是影响NT-pro-BNP的因素,而性别、体重指数、LVEF,房颤的病程和伴随疾病与NT-pro-BNP水平无关。结论:房颤类型,患者年龄和左房内径是房颤患者NT-proBNP升高的独立预测因素。     

Hemodynamic Recovery, Atrial Natriuretic Peptide, and Catecholamines During Simulated Ventricular Tachycardia: Effects of Ventriculoatrial Conduction

Ventriculoatrial (VA) sequence and neurohumoral responses may be important modulators of hemodynamic recovery during VT. We studied the effects of VA conduction on blood pressure recovery, and levels of atrial natriuretic peptide (ANP), epinephrine, and norepinephrine during simulated VT. After diagnostic coronary angiography, VT was simulated by rapid right ventricular pacing (150 beats/min, 3 mins) in a consecutive series of patients. Whenever the patients demonstrated VA dissociation during ventricular pacing, they were included in the study. After 10 minutes of recovery, a group of nine patients then underwent an additional VA pacing (150 beats/min, 3 mins, VA delay of 150 msec). Intra-arterial blood pressure was continuously monitored, and plasma ANP and catecholamine levels were measured before, during, and after both pacing protocols. The mean arterial pressures declined rapidly by 26% and 30% after initiation of ventricular and VA pacing, respectively. The blood pressure then gradually recovered, the hemodynamic recovery being better during VA pacing. Plasma ANP and catecholamine levels increased toward the end of both pacing periods. The observed increase in ANP concentration was more prominent during VA pacing than ventricular pacing (P < 0.001), whereas catecholamine levels increased similarly. The results show that during simulated VT hemodynamic recovery is partially dependent on VA sequence. The increases in circulating ANP and Catecholamines occur too slowly to account for the rapid changes in blood pressures observed after initiation of simulated VT. Therefore, other mechanisms, such as reflex stimulation of the sympathoadrenergic nervous system, must be involved, too. ANP release increases when atrial contraction frequency increases, but the exact determinants for this release remain unknown.     

Plasma Levels of Natriuretic Peptides During Ventricular Pacing in Patients with a Dual Chamber Pacemaker

The mechanism(s) responsible for the release of brain natriuretic peptide (BNP), a cardiac hormone of ventricular origin, are still not completely understood. We measured plasma atrial natriuretic peptide (ANP) and BNP in 15 subjects (10 men, mean age 67 ± 3 years) with a dual chamber pacemaker and unimpaired heart function during ventricular pacing, which is known to induce an increase in atrial pressure and plasma ANP concentration. Under ECC monitoring, all subjects received sequential atrioventricular pacing for 30 minutes and ventricular pacing for 30 minutes, at the same rate of 80 beats/min. Arterial pressure and plasma BNP and ANP levels were measured every 10 minutes throughout the study. Ventricular pacing led to atrioventricular dissociation in eight subjects and to retrograde ventriculo-atrial conduction in seven. Arterial pressure remained unchanged in all subjects. In the group with atrioventricular dissociation, plasma ANP increased from 10.14 ± 0.58 to 16.72 ± 0.92 fmol/mL at the 60th minute (P < 0.0001), whereas plasma BNP did not change at all (fiom 1.26 ± 0.07 to 1.16 ± 0.09 fmol/mL). In the group with retrograde conduction, plasma ANP concentration doubled (fiom 10.95 ± 1.66 to 21.40 ± 1.51 fmol/mL, P < 0.0001), BNP increased 1.5-fold (from 1.16 ± 0.06 to 1.64 ± 0.14 fmol/mL, P < 0.001), and the ANP: BNP ratio augmented fiom 10:1 to 13.4:1. These results indicate that the release of ANP and BNP is regulated by different mechanisms, supporting the view that there is a dual natriuretic peptide system, comprising ANP fiom the atria and BNP fiom the ventricles.     

Exercise‐Induced Natriuretic Peptide Secretion Predicts Cardioversion Outcome in Patients with Persistent Atrial Fibrillation: Discordant ANP and B‐Type Natriuretic Peptide Response to Exercise Testing

Background: Measurement of natriuretic peptide's (NP) release in response to hemodynamic stress may be complementary to its baseline assessment in individuals. Atrial natriuretic peptide (ANP) and B‐type natriuretic peptide (BNP) increase in patients with atrial fibrillation (AF) and decrease after successful cardioversion, suggesting that AF may stimulate secretion of NPs. However, there are conflicting data on the predictive value of NPs on the cardioversion outcome. Objectives: The purpose of this study was to investigate whether baseline and exercise‐induced NP plasma levels can be useful in predicting successful cardioversion of persistent AF and maintenance of sinus rhythm during 6‐month follow‐up. Methods: A prospective study enrolled 77 consecutive subjects with persistent AF with normal left ventricular function, referred for elective cardioversion. Patients underwent a modified Bruce protocol treadmill exercise test 24 hours before cardioversion. Blood samples for ANP and BNP analyses were obtained at rest and 5 minutes after exercise peak. Results: The group of successful cardioversion and stable sinus rhythm presented higher exercise ANP (110.6 ± 41.2 pg/mL vs 43.8 ± 36.1; pg/mL, P < 0.0001) and lower BNP increase (5.2 ± 5.2 pg/mL vs 40.5 ± 34.2 pg/mL, P < 0.0001) than the group of unsuccessful cardioversion or AF recurrence. Using an optimized cutoff level of ≤12% of relative exercise‐induced increase in BNP concentration, and of >50 pg/mL of ANP increase, successful cardioversion can be predicted with high accuracy. Conclusions: An increase in ANP and stability of BNP plasma concentration during exercise testing are independently associated with successful cardioversion and maintenance of sinus rhythm during 6‐month follow‐up. (PACE 2010; 33:1203–1209)     

Influence of Pacing Mode and Rate on Peripheral Levels of Atrial Natriuretic Peptide (ANP)

The effect of acute modifications of pacing mode and rate on plasma ANP levels was evaluated. ANP was determined in ten resting patients with DDD pacemakers due to binodal disease or intermittent second-and third-degree AV block. At 82/minute pacing rate the ANP plasma levels (normal range 2 to 30 fmol/mL) corresponded to those under AAI (4.05 +/- 2.10 fmol/mL) and DDD (4.18 +/- 2.02 fmol/mL) pacing, but increased significantly (P 0.05) during VVI pacing (6.96 +/- 3.70 fmol/mL). Acceleration of DDD stimulation frequency from 82 to 113/minutes led to significant increase of ANP levels by the factor of three in all chosen AV delays. The lowest ANP plasma levels were measured at 175 msec AV delay under 82/minute pacing rate in DDD mode. Under 113/minutes the differences of ANP concentration after variations of AV delays were less pronounced. The influences of altered atrial pressure and tension on ANP release are discussed to account for changes in ANP plasma levels following different modes and rates of pacemaker stimulation.     

Atrial Natriuretic Factor Release During Exercise in Patients Successively Paced in DDD and Rate Matched Ventricular Pacing

Dual chamber pacemakers were implanted in nine patients with permanent second or third degree AV block feight had complete retrograde block). Two identical exercise tests were performed after at least 1 month after implantation. During the first test (T₁) the pacemaker was programmed to the DDD mode and heart rates were recorded every 15 to 30 seconds during exercise and 30 minutes after exercise. Following 30 minutes of rest, the implanted pacemaker was programmed to the VVT mode and driven by an external pacemaker via a skin electrode. The second exercise test (T₂) was then performed and the rate of the external pacemaker was progressively changed to reproduce exactly the rate observed during T₁ at the same exercise stress. Atrial natriuretic factor (ANF) levels were determined at rest, at regular intervals during exercise, and 30 minutes after exercise. ANF levels and release were statistically higher during rate matched ventricular, than DDD pacing. It is concluded that preservation of AV synchrony reduces ANF release induced by heart rate acceleration during exercise.     

不同起搏模式对病窦综合征患者血浆脑钠肽的影响

[目的]探讨心脏起搏器不同起搏模式对病态窦房结综合征（病窦综合征）患者血浆脑钠肽（BNP）水平的影响.[方法]常规植入起搏器的病窦综合征患者30例,根据不同起搏模式分为心房起搏组[AAI（R）组] 12例和双腔起搏组[DDD（R）组] 18例;分别于术前、术后3个月、术后6个月测定血浆BNP水平.[结果]术后3个月时两组血浆BNP水平均升高,但差异无显著性[（113.8±31.3） pg/mLvs （95.7±53.2） pg/mL,（92.8±87.2） pg/mL vs （70.1 74.6±69.3） pg/mL;均P〉0.05];6个月时AAI（R）组血浆BNP水平与3个月时[（84.8±73.7）pg/mL vs （113.8±31.3 ）pg/mL]比较无升高,而DDD（R）组血浆BNP水平较3个月时进一步升高[（98.8±61.7）pg/mL vs （92.8±87.2 ）pg/mL],但差异仍无统计学意义（P〉0.05）.[结论]病窦综合征患者采用心房起搏AAI（R）和双腔起搏DDD（R）两种工作模式血浆BNP水平虽无明显改变,但长期双腔起搏模式下的右心室心尖部起搏可能有导致血浆BNP水平增高的趋势.     

Efficacy of Ventricular Rate Stabilization by Right Ventricular Pacing During Atrial Fibrillation

To assess the effect of right ventricular pacing on rate regularity during exercise and daily life activities, 16 patients with sinoatrial disease and chronic atrial fibrillation (AF) were studied. Incremental ventricular pacing was commenced at 40 beats/min until > 95% of ventricular pacing were achieved during supine, sitting, and standing. Thirteen patients also underwent randomized paired submaximal exercise tests in either a fixed rate mode (VVI) or a ventricular rate stabilization (VRS) mode in which the pacingrate was set manually at 10 beats/min above the average AF rate duringthe last minute of each exercise stage. The pacing interval for rate regularization was shortest during standing (692 ± 26 ms) compared with either supine or sitting (757 ± 30 and 705 ± 26 ms, respectively, P < 0.05). During exercise, VRS pacing significantly increased the maximum rate (119 ± 5.2 vs 106 ± 4.2 ms, P < 0.05), percent of ventricular pacing (85%± 5% vs 23%± 7%, P < 0.05), rate regularity index (5.8%± 1.6% vs 13.4%± 1.9%, P < 0.05), and maximum level of oxygen consumption (12.4 ± 0.5 vs 11.3 ± 0.5 ml/kg, P < 0.05) compared with VVI pacing. There was no change in oxygen pulse or difference in symptom scores in this acute study between the two pacing modes. It is concluded that right ventricular pacing may significantly improve rate regularity and cardiopulmonary performance in patients with chronic AF. This may be incorporated in a pacing device for rate regularization of AF using an algorithm that is rate adaptive to postural and exercise stresses.     

超声心动图评价高血压大鼠左室结构变化与血浆及组织心钠素、内皮素变化关系

目的：应用超声心动图评价高血压大鼠心脏结构、功能动态变化,同步监测血浆及心肌组织中心钠素（atrial natriuretic peptide,ANP)、内皮素（cedothelin,ET)含量变化,分析高血压大鼠心脏结构功能变化与血浆及心肌组织中ANP、ET含量变化关系,从而进一步了解高血压心脏病左室结构、功能变化的生物化学基础。方法：SD大鼠左肾动脉狭窄,即二肾一夹型（2K1C）肾血管性高血压大鼠（RHR）。术后每周监测尾动脉压及心脏超声学参数。用放免法测定血浆及心肌组织中ANP、ET含量。结果：1、高血压早期（术后3周左右）血浆及心肌组织（左心室）中ANP、ET含量明显升高;2、高血压左室向心性肥厚组血浆及心肌组织中ANP、ET升高更为显著;3、左室离心性肥厚期血浆ET较向心性肥厚期组更高,但心肌组织中ET含量与其无显著差别,而血浆及心肌组织中ANP含量均较向心性肥厚期组低;4、相关分析：（1）血浆及心肌组织中ANP含量与室间隔厚度（IVST）、左室后壁厚度（PWT）、相对室壁厚度（RWT）呈正相关;（2）血浆及心肌组织中ET含量与LVM／BW（体重）正相关（r=0.682,r=0.557,P＜0．01）,与射血分数（EF）、左室短轴缩短率（FS）均呈负相关;血浆ET、ANP水平分别与心肌组织中ET、ANP正相关（r=0.726,P＜0．01、r=0.57,P＜0．01）。结论：2K1C型RHR血浆及心肌组织中ANP、ET含量均升高,血浆及心肌组织中ET、ANP在2K1C型高血压大鼠左室几何构型中均起着重要作用。     

Influence of AV Synchrony on the Plasma Levels of Atrial Natriuretic Peptide (ANP) in Patients with Total AV Block

ANP was determined in 13 patients with DDD pacemakers due to total AV block, at rest and during bicycle ergometry under both pacing modes, DDD and VVI (7O/min). Under DDD pacing, the mean ANP level (normal range 5-95 pg/mL) at rest was 36 +/- 18 pg/mL (mean +/- SD) and increased significantly by the factor of 3.5 to 1 27 pg/mL during exercise (p less than 0.01). By just changing the pacing mode to VVI, the ANP levels rose to 73 +/- 28 pg/mL (p less than O.0 1) at rest (= 203% of DDD resting level) and to 216 +/- 184 pg/mL (= 170% of DDD peak level) during exercise P less than 0.01). These results show that under AV synchronous pacing, the ANP levels we generally lower. A possible explanation for this increased release of ANP during asynchronous VVI pacing is the acute increase of the atrial wall tension which occurs when the atria contacts during the systole against closed AV valves.     

运动对青年血浆内皮素及心钠素的影响

以放射免疫学方法检测了28名青年在Bruce运动试验中血浆ET及ANP的变化，以了解试验中心血管反应的生理机制。方法是将28名（男20名，女8名）学生配对分成4组，每组7名（男5名，女2名），年龄19．6±1．1岁。其中1组不运动作为对照组，其余3组分别作不同水平运动。结果ET及ANP随运动强度增加而增加．运动6min时ANP显著升高（P＜0．05）；运动12min时ANP及ET均显著增加（P＜0．01及0．05），休息8min后ANP明显下降。提示；ET及ANP在运动试验中是影响心血管反应的重要因素之一。     

Rate Stabilization by Right Ventricular Pacing in Patients with Atrial Fibrillation

A recent study of de Jongste has demonstrated the lengthening of short R-R intervals in patients with atrial fibrillation by right ventricular pacing. We have further analyzed the data from this study and specifically looked at the effect of right ventricular pacing on the R-R interval instability and heart rate. At the cost of only a slight increase in mean heart rate, a major reduction of the R-R interval instability can be obtained by right ventricular pacing. Based on these findings, we have developed and evaluated an automatic pacing rate algorithm, which continuously varies the stimulation rate in order to stabilize the otherwise irregular rhythm in patients with atrial fibrillation.     

老年心力衰竭患者心功能对血浆脑钠肽水平的影响

目的探讨血浆脑钠肽（BNP）水平与老年心力衰竭患者心力衰竭严重程度的关系。方法对33例老年心力衰竭患者[观察组,按美国纽约心脏病学会（NYHA）心功能分级：Ⅱ级7例,Ⅲ级20例,Ⅳ级6例]和32例健康老年人（对照组）清晨平卧抽血（患者于入院24h内及出院时）3mL,测定血浆BNP水平;超声心动图测定左室射血分数（LVEF）、左室舒张末期内径值（LVEDD）。比较2组及心功能衰竭各亚组间血浆BNP水平。结果观察组LVEF值低于对照组、LVEDD及血浆BNP水平高于对照组（P〈0．05或P〈O．01）。心力衰竭发作时,观察组中心功能Ⅲ、Ⅳ级组的血浆BNP水平显著高于心功能Ⅱ级组（均P〈0．05）。结论老年心力衰竭患者血浆BNP水平增高程度与心力衰竭的严重程度呈正比．可以作为评定心力衰竭进程和预后的指标。