迷走神经和肺静脉刺激对心房肌动作电位和乙酰胆碱激活钾电流的影响

目的研究迷走神经和肺静脉快速刺激对心房肌动作电位和乙酰胆碱激活钾电流的影响。方法24只犬随机分为3组,每组8只犬。对照组：采用20Hz频率和0．2ms波宽刺激迷走神经,观察诱发心房颤动（房颤）情况。左上肺静脉（LSPV）刺激组：快速刺激LSPV4h,观察刺激前后左有心房和LSPV动作电位时限（APD）的变化,随后行迷走神经刺激,观察诱发房颤情况。迷走神经干预组：先采用5Hz频率、0．2ms波宽和5～10V电压刺激迷走神经30min,然后快速刺激LSPV4h,观察刺激前后APD的变化,冉迷走神经刺激观察诱发房颤情况。所有犬在电生理检测后开胸取心脏,分离LSPV和左右心房肌细胞,采用膜片钳技术观察乙酰胆碱激活钾电流（IK,ACh）变化。结果LSPV刺激组,APD。明显缩短,动作电位时限高散度（dAPD90）明显增加[（5±3）msVS（14±5）ms,P〈0．05]。迷走神经干预组,APD。无明显变化,但APD90-d明显增加[（6±3）mvs vs（12±5）ms,P〈0．05]。与对照组相比,LSPV刺激组细胞Ik、ACh明显增加,但对照组与迷走神经干预组相比,IK．ACh差异无统计学意义。结论APD缩短是胆碱能房颤诱发的基础,肺静脉快速刺激可增加IK．ACh密度,快速刺激前行迷走神经能阻止电重构的发生。     

Electrical remodeling in fibrillating canine atrium: action potential alternans during rapid atrial pacing and late phase 3 early afterdepolarization after cessation of rapid atrial pacing

Sustained atrial fibrillation (AF) was induced by atrial burst pacing, and monophasic action potentials (MAPs) were recorded. MAP alternans was observed at a cycle length (CL) of 167.5 ± 28.2 msec before burst pacing and 201.3 ± 40.2 msec after burst pacing. AF > 5 minutes duration was induced in 1 dog in the control condition but in all 8 dogs after burst pacing. The difference in RA MAPD(80) of the first spontaneous beat and steady-state sinus rhythm was significantly larger after atrial burst pacing than before atrial burst pacing (31.5 ± 15.9 msec versus 8.2 ± 9.0 msec) In 4 dogs, late phase 3 early after depolarization was observed after rapid atrial pacing. Rapid atrial pacing-induced electrical remodeling includes APD alternans during rapid atrial pacing and also causes an increase in the MAPD of the initial several beats and the development of late phase 3 early afterdepolarizations after a sudden increase in CL.     

Rate-dependent prolongation of action potential duration in isolated rat ventricular myocytes

Rate-dependent alterations of action potential duration (APD) in rat ventricular myocytes were investigated. Action potentials of the isolated myocytes were recorded with patch electrodes containing EGTA (11 mM), and showed a marked rate-dependent prolongation in the APD (0.2–5 Hz). This prolongation was significantly inhibited in the presence of 4-aminopyridine (4-AP), a blocker of the transient outward K⁺ current (I_to). Thus, the rate-dependent decrease in I_to may underlie the change in APD. In contrast, the action potentials recorded from rat ventricular papillary muscles with conventional microelectrodes did not show rate-dependent alterations in the APD, i.e., the APD remained practically unaltered at the frequency range of 0.2–5 Hz. These results suggest that the rate-dependent prolongation of APD (due to rate-dependent blockade of I_to) becomes evident when the intracellular Ca²⁺ was chelated by the internal application of EGTA via patch pipette. We speculate that the rate-dependent prolongation of APD (via decreases in I_to) is masked in the ventricular papillary muscles, probably due to rate-dependent decreases in the inward current (e.g., electrogenic Na⁺–Ca²⁺ exchange current) that is regulated by the intracellular calcium.     

小檗碱对快速心房起搏兔心房肌场电位时程及兴奋传导速度的影响

目的应用微电极阵(MEA)技术研究小檗碱对快速心房起搏(RAP)兔心房肌场电位时程(fAPD)及兴奋传导速度(ECV)的影响,探讨其抗心房颤动(简称房颤)的作用机制。方法新西兰兔40只,随机分成5组,对照组(n=8),起搏组(n=8),起搏+小檗碱A组(5μmol/L,n=8),起搏+小檗碱B组(10μmol/L,n=8),起搏+小檗碱C组(20μmol/L,n=8)。RAP 24h后,对照组于相应时间,迅速开胸取出心脏,分别灌流改良台氏液或含5、10、20μmol/L小檗碱的改良台氏液行Langendroff灌流,用柔性电极贴附右房,分别记录各组fAPD和ECV的变化。结果相较对照组,起搏组心房肌fAPD缩短,传导速度减慢(P0.05)。相较起搏组,小檗碱A、B、C组心房肌fAPD逐渐延长,ECV逐渐加快(P0.05)。结论在RAP兔模型中,小檗碱不仅能有效延长心房肌fAPD,还能加快ECV,显示出可能具有较好的抗房颤作用。     

Significant prolongation of atrial monophasic action potential duration: short-term reverse electrophysiological changes after internal cardioversion of atrial fibrillation

OBJECTIVE: Since short action potentials and short refractory periods facilitate the induction of atrial reentry, this maladaptation has been proposed as the pathophysiological basis of the frequent immediate recurrences of atrial fibrillation (IRAF) after internal cardioversion. However, short-term reverse electrophysiological changes of the atria after cardioversion have not been studied in humans. METHODS: Thirty-seven patients with chronic atrial fibrillation of 16+/-19 months and ten patients with an atrial fibrillation duration < or =48 h underwent internal cardioversion. Antiarrhythmic medication was only continued in 10 patients (21%), who were on amiodarone before cardioversion. Atrial monophasic action potential duration at 90% repolarization (APD(90)), sinus rate, P wave duration and interatrial conduction times between high right atrium and coronary sinus were recorded at min 0, 1, 3, 5, 10, 15 and 20 after cardioversion. RESULTS: Internal cardioversion was successful in all patients, but twelve of the patients with chronic AF (32%) and three of the patients with intermittent AF (30%) had one to four episodes of IRAF after 16+/-28 s. There was a significant 52+/-30 ms APD(90) prolongation, 83% of which occurred in min 0-3 (P<0.0001) and 17% in min 3-20 (P<0.05) after internal cardioversion. There was no significant temporal change in sinus rate, P-wave and interatrial conduction time during the time studied. APD(90) prolongation and its time dependence did not show a detectable difference in subgroups with chronic AF, IRAF, left atrial size >40 mm and treatment with amiodarone. CONCLUSIONS: There is a significant prolongation of action potential duration in min 0-3 after internal cardioversion of atrial fibrillation, whereas sinus rate and intra- and interatrial conduction time remain unchanged. APD(90) prolongation in min 0-3 shows a temporal relationship to the high rate of immediate recurrences of atrial fibrillation during this time interval. The data imply that there is a transient recovery of atrial refractoriness after cardioversion and suggest a mechanism of the high rate of early recurrences of atrial fibrillation.     

Hemodynamic changes during increasingly rapid atrial pacing]

The cardiac output (Qc), indices of left ventricular function in the isovolumic period (dp/dt/Pt), max, and during the ejection period (EF, VCF), the end diastolic and end systolic ventricular volumes, the speed of ventricular filing, the module of elasticity of the ventricular chamber (kp) and the end systolic pressure-volume relationships were measured in 20 patients (11 normal in group I and 9 with and apparently primary cardiomyopathy in group II) at rest and during progressively rapid atrial pacing. The Qc was lower and the indices of left ventricular function in the isovolumic and ejectional phases, the end systolic pressure-volume relationship and speeds of ventricular filling were decreased in group II: kp was the same in both groups of patients. At progressively higher heart rates the cardiac output slightly in both groups, the systolic volume decreased, (dp/dt/Pt) max increased, the ejection fraction and VCF were unaltered. The speeds of filling and kp were unchanged. The end systolic pressure-volume relationship increased. In group I the reduction in systolic volume seemed to be related to a greater reduction in the end diastolic volume than in the end systolic volume. In group II, the reduction of the systolic volume was related only to a reduction of the end diastolic volume.     

维拉帕米对快速心房起搏家兔心房有效不应期和单相动作电位的影响

目的研究维拉帕米对快速心房起搏家兔心房有效不应期(AERP)和单相动作电位(MAP)的影响,探讨其抗心律失常的机制。方法 24只家兔分为对照组、快速起搏组和维拉帕米组,每组各8只。经颈内静脉将电极置入右心房。分别测定各组基础状态,以600次/min行快速心房起搏和快速起搏同时给予药物维拉帕米后测定2、4、6、8 h的心房有效不应期(AERP_(200)和AERP_(150))和MAP_(90)。结果快速心房起搏组在不同基础刺激周长作用下的AERP缩短,AERP_(200-150)的频率适应性不良,P_8与起搏前P_0比较差异有统计学意义(P<0.05),同时MAP_(90)相应缩短。维拉帕米组AERP基本无改变,AERP_(200-150)频率适应性维持,MAP_(90)无明显改变(P>0.05)。结论维拉帕米可能因减轻钙超载而抑制快速心房起搏所致电重构,即同时延长AERP和MAP,发挥其抗心律失常作用。     

快速心房刺激对P波时限及离散度的影响

目的分析快速心房刺激对P波时限及离散度的影响.方法在74例射频消融术及82例经食管心房调搏检查中,用180ppm的S1S1刺激心房3min,在刺激前后立刻记录12导联同步心电图,通过心电图测出刺激前后的最大P波时限、最小P波时限及P波离散度,然后进行比较.结果射频消融组最大P波时限在心房刺激后比刺激前有显著性延长（p=0.002）,最小P波时限及P波离散度无显著性差异,食管心房调搏组最大P波时限及P波离散度在心房刺激后比刺激前有显著性增加（p=0.001）,最小P波时限无显著性差异.结论快速心房刺激能引起心房传导时间延长,非均质电活动的离散程度增加.最大P波时限及P波离散度是可以用来评价心房电重构的简便而无创的指标.     

Electrophysiological effect of adenosine triphosphate and adenosine on atrial and ventricular action potential duration in humans

Bolus injection of adenosine triphosphate (ATP) or adenosine is widely used clinically for terminating supraventricular tachycardia. However, bolus injection of these drugs has been reported to provoke atrial fibrillation (Afib). The effects of ATP and adenosine on the monophasic action potential duration (MAPD) of atrial and ventricular muscle was investigated, as well as the changes in the spatial distribution of atrial functional refractoriness caused by adenosine. Bolus injection of ATP and adenosine shortened atrial MAPD; no change was observed in the ventricle. Because local f-f intervals during atrial fibrillation correlate with the atrial refractory period, changes in mean f-f intervals in the right atrial appendage, His bundle region, coronary sinus ostium and distal coronary sinus were compared before and after injection of adenosine during induced Afib. Maximal shortening of f-f intervals was observed in the right atrial appendage. Inhomogeneous shortening of atrial refractoriness may account for the Afib following bolus injection of ATP or adenosine.     

快速起搏左房后部分心房电生理参数的变化

目的探讨采用快速起搏左房构建心房颤动(简称房颤)模型的可行性以及快速起搏心房后心房部分电生理特性的变化。方法新西兰兔,分为假手术组(n=11只)和起搏组(n=15只),起搏组中成功诱发房颤的动物为房颤亚组,不能诱发房颤的为非房颤亚组。起搏组以1 500次/分持续起搏左房8周。描记起搏前;起搏2,4,6,8周后体表心电图,测量相应时间点P波时限,予基础心率周期-程序刺激(S1-S2)刺激,检测左房有效不应期(AERP)。结果起搏8周后起搏组成功诱发房颤7只,其中房颤持续时间最长为24 h、最短为6.5 h。起搏8周P波时限较基础值延长(P=0.015)。起搏2,4,6,8周后,AERP较基础值缩短(P<0.05),并随着起搏时间的延长,AERP进行性缩短(P<0.05);起搏组中房颤亚组在起搏4,6,8周后P波时限延长较非房颤亚组明显(P<0.05),起搏8周后左房AERP缩短较非房颤亚组明显(P<0.05)。结论持续快速起搏左房是构建房颤模型的有效方法。快速起搏左房导致P波时限延长,AERP缩短。     

Short-term rapid atrial pacing produces electrical remodeling of sinus node function in humans

INTRODUCTION: Depression of sinus node function occurs in dogs and in patients after cessation of atrial flutter and fibrillation. We tested whether transient atrial pacing might produce similar changes in humans. METHODS AND RESULTS: We studied the impact of short-term rapid atrial pacing, simulating atrial tachyarrhythmias, on sinoatrial conduction time (SACT) and corrected sinus node recovery time (CS-NRT) in 10 patients undergoing electrophysiologic study. None had recognizable structural heart disease, history of atrial fibrillation or flutter, autonomic dysfunction, or any tachycardia for at least 24 hours before study. All cardiac drugs were discontinued >5 half-lives prior to study. No patient had significant hypotension during atrial stimulation. SACT and CSNRT were measured at baseline, and sinus node reset zone was determined. Right atrial pacing was performed for 10 to 15 minutes, after which SACT and CSNRT were measured again. Both parameters increased significantly, from 423+/-208 msec to 491+/-214 msec and from 80+/-50 msec to 96+/-53 msec, respectively (P = 0.02 and P < 0.001, respectively). CONCLUSION: Rapid atrial pacing for only 10 to 15 minutes, simulating transient atrial tachyarrhythmias, alters sinus node function in humans. Additional studies are needed to evaluate the mechanism, but the clinical implication is that even transient episodes of atrial tachyarrhythmias can cause sinus node remodeling in patients.     

Evaluation of rapid atrial pacing in diagnosis of coronary artery disease. Evaluation of atrial pacing test.

Seventeen patients presenting with anginal-type pain were studied by bicycle exercise testing, rapid atrial pacing, and coronary angiography. Ten patients with angina and abnormal pacing tests at rates less than 180/minute were found to have significant coronary artery disease as demonstrated by coronary angiography. Seven patients with pacing-induced chest pain only at rates of 180 and above had normal coronary angiogram. This suggests that patients requiring rates of 180 or more to produce a positive atrial pacing test, following our protocol, do not usually have significant coronary artery disease though confirmation requires a larger study.     

经心内和食管快速心房刺激对P波时限及离散度的影响

目的分析快速心房刺激对P波时限及离散度的影响。方法在74例射频消融术经电极导管起搏高位右房及82例经食管心房调搏检查者中,用180次/分的S1S1刺激心房3min,在刺激前后立刻记录12导同步心电图,通过心电图测出刺激前后的最大P波时限(Pmax)、最小P波时限(Pmin)及P波离散度(Pd),然后进行比较。结果:射频消融组Pmax在心房刺激后比刺激前有显著性延长(P<0.01),Pmin及Pd无显著性差异。食管心房调搏组Pmax及Pd在心房刺激后显著性增加(P<0.01),Pmin无显著性差异。结论:快速心房刺激能引起心房传导时间延长,非均质电活动的离散程度增加。     

Dispersion of monophasic action potential duration: demonstrable in humans after premature ventricular extrastimulation but not in steady state.

Abnormal dispersion of repolarization may contribute to the arrhythmogenic physiologic substrate of ventricular arrhythmia. Geographic dispersion of monophasic action potential duration was determined in steady state (drive cycle lengths 600 and 430 ms) between widely spaced right ventricular endocardial sites (geographic dispersion) in 10 control patients with right ventricular disease and complicating ventricular tachycardia (n = 9), 6 patients with right and left ventricular disease and complicating ventricular tachycardia and 7 patients with ischemic heart disease and complicating ventricular tachycardia. No significant difference in geographic dispersion could be demonstrated among the groups. Difference of monophasic action potential duration at adjacent right ventricular endocardial sites (adjacent dispersion) was determined after ventricular extrastimulation during construction of simultaneous electrical restitution curves in the same patient groups. Maximal adjacent dispersion over the electrical restitution curve was compared between disease and control groups. There was a significant difference in observations of maximal adjacent dispersion in patients with right ventricular disease and complicating ventricular tachycardia (range 5 to 85 ms, median 22.5; 14 pairs of sites; p less than 0.05) and patients with right and left ventricular disease and complicating ventricular tachycardia (range 5 to 50 ms, median 17.5; 14 pairs of sites; p less than 0.05) compared with control patients (range 5 to 20 ms, median 10; 15 pairs of sites). This difference was not evident when patients with ischemic heart disease and complicating ventricular tachycardia (range 5 to 25 ms, median 12.5; 12 pairs of sites) were compared with control patients. Maximal percent monophasic action potential shortening from steady state was significantly greater (p less than 0.001) in both groups with greater adjacent dispersions, and prolongation of activation time at monophasic action potential recording sites after premature extrastimulation tended to be greater in patients with right or right and left ventricular disease and complicating ventricular tachycardia. It is concluded that in disease, exaggeration of monophasic action potential shortening after premature ventricular extrastimulation may contribute to the electrophysiologic arrhythmogenic substrate.     

Effects of verapamil and procainamide on acute atrial electrical remodeling induced by short-term rapid atrial pacing in humans

Atrial electrical remodeling (ER) after spontaneous or pacing-induced atrial fibrillation has been previously described in humans. We investigated atrial ER induced by a 5-minute period of rapid atrial pacing and the pharmacologic effects of verapamil and procainamide on this atrial ER phenomenon. The atrial effective refractory periods (ERPs) at drive cycle lengths of 400 (ERP 400 ) and 600 (ERP 600 ) ms, at five representative atrial sites (high right atrium [HRA]; proximal, middle and distal coronary sinus; interatrial septum), were determined in 20 patients at baseline and immediately after cessation of a 5-minute period of rapid pacing from the HRA at a rate of 150 bpm. The degrees of atrial ERP 400 and ERP 600 shortening after pacing were calculated as acute atrial ER. The same protocol was repeated in another 15 patients after intravenous administration of verapamil (0.15 mg/kg) and in another 15 patients after intravenous administration of procainamide (15 mg/kg). The results demonstrated that, in the control state acute atrial ER can be significantly demonstrated at each atrial representative site ( p < 0.001). The mean ERP 400 and ERP 600 shortenings were 9 +/- 4% and 8 +/- 4%, respectively. After procainamide infusion, but not after verapamil, baseline ERP 400 and ERP 600 values were significantly prolonged at the five representative atrial sites ( p < 0.01). Acute atrial ER could still be demonstrated at each atrial site after procainamide or verapamil infusion ( p < 0.001). In conclusion, acute atrial ER can be demonstrated after only a 5-minute period of rapid atrial pacing in humans. Intravenous verapamil or procainamide does not abolish this ER process.     

Effect of gender on atrial electrophysiologic changes induced by rapid atrial pacing and elevation of atrial pressure

INTRODUCTION: The incidence of atrial fibrillation is greater in men than in women, but the reasons for this gender difference are unclear. The purpose of this study was to evaluate the effects of gender on the atrial electrophysiologic effects of rapid atrial pacing and an increase in atrial pressure. METHODS AND RESULTS: Right atrial pressure and effective refractory period (ERP) were measured during sinus rhythm and during atrial and simultaneous AV pacing at a cycle length of 300 msec in 10 premenopausal women, 11 postmenopausal women, and 24 men. The postmenopausal women were significantly older than the premenopausal women (61 +/- 8 years vs 34 +/- 10 years; P < 0.01). During sinus rhythm, mean atrial ERP in premenopausal women was shorter (211 +/- 19 msec) than in postmenopausal women and age-matched men (242 +/- 18 msec and 246 +/- 34 msec, respectively; P < 0.05). Atrial ERPs in all patients shortened significantly during atrial and simultaneous AV pacing. However, the degree of shortening during atrial pacing (43 +/- 8 msec vs 70 +/- 20 msec and 74 +/- 21 msec; P < 0.05) and during simultaneous AV pacing (48 +/- 16 msec vs 91 +/- 27 msec and 84 +/- 26 msec; P < 0.05) was significantly less in premenopausal women than in postmenopausal women or age-matched men. CONCLUSION: The results of this study demonstrate a significant gender difference in atrial electrophysiologic changes in response to rapid atrial pacing and an increase in atrial pressure. The effect of menopause on the observed changes suggests that the gender differences may be mediated by the effects of estrogen on atrial electrophysiologic properties.     

Effect of haemodynamic changes during rapid atrial pacing on determination of sinus node recovery time.

Arterial blood pressure was continuously monitored during rapid atrial pacing in 31 patients with different types of heart disease to determine sinus node recovery time and corrected sinus node recovery time. Pacing was initiated at 70 beats/min and increased stepwise to 160 beats/min. One to one atrioventricular conduction was maintained throughout the one minute stimulation period. Blood pressure fell initially during at least one stimulation period in 21 of our patients and at pacing rates up to 130 beats/min in 18. Once blood pressure had fallen during overdrive pacing maximal sinus node recovery time and maximal corrected sinus node recovery time could not be prolonged by increasing the pacing rate. Sinus node recovery time and corrected sinus node recovery time during the pacing induced fall in blood pressure was significantly shorter than those during stimulation runs with constant blood pressure. No pacing induced fall in blood pressure and no relation between changes in blood pressure and sinus node recovery time were evident in 10 of the 31 patients. Sinus node recovery time is therefore influenced by alterations in autonomic tone due to pacing induced haemodynamic changes.