Cessation Of Pacing Research Articles

284 The combination of BNP and diastolic filling pattern reflects exercise respiratory abnormalities in patients with chronic heart failure

nary heart disease death. The multivariate adjusted risks lor luture atrial fibrillation were 1.464old (p<O.O01) and 1.72-fold (p<O.O01) lot each SD increment in NT- proANP and NT-proBNP. respectively. NT-proANP was associated with LV ejection lraclion (15=-0.237. p<O.O01 ). LV mass (15=0.143. p=O.OOG) and lelt atrium diameter ((5=0.166. p<O.O01), whereas NT-proBNP was related to LV ejection lraction (15=- 0.242. p<O.O01). LV mass (15=0.148. p=O.O01) and left atrium diameter (15=0.133. p=O.O02), respectively. Conclusions: The present study shows that NT-proANP and NT-proBNP are strong predictors of death lrom any and cardiovascular causes and atrial fibrilla- lion. NT-proANP and NT-proBNP provide additional prognostic value for identilying men with high risk of death and its co-morbidities. Background: Brain natriurelic peplide (BNP) can be used to monitor cardiac func- lion in patients with ventricular dyslunction. While conventional asynchronous right ventricular pacing (VVI) has been lound to increase the BNP levels in patients with normal lelt ventricular systolic function (LVSF), it is not known whether VVI ~0(erts similar BNP responses in patients with decreased LVSF. Methods: To examine the BNP responses after short-term VVI pacing we stud- ied 58 clinically stable patients (mean age 66±8 years) who had been implanted with a dual-chamber automatic defibrillator. There were 48 patients with ischemic and 10 patients with dilated cardiomyopathy. After the baseline echocardiographic standard, color M-Mode and tissue Doppler (TD) evaluation during atrioventricu- lar rhythm (64±9 bpm) devices were programmed to continuous VVI pacing for 30 minutes individually adjusted slightly above the baseline rhythm (73±11). The BNP levels were measured at baseline, immediately alter pacing termination (Time O). and 30 and 60 minutes thereafter. Results: Patients had mean lelt venlricular ejection fraction 38±11%. The baseline BNP levels were 166 (89-364)pg/ml and rose to 218 (106-387) pg/ml at Time 0 (p<O.O01). In multivariate analysis the baseline BNP correlated wit the TD-Ea (15=- O.43,p<O.OO1)and the ratio ENp (15=0.38,p<0.005). The transient post-VVI pacing BNP increases were characterized by a peak value immediately alter VVI pacing cessation and a slow decreasing trend. The median incremental rise ol BNP at Time 0 (BNP at Time 0 minus BNP at BL, 33 (8-68) pg/ml) showed independent posilive association with the ratio E/Ea (p<0.001). Conclusions: BNP increases following WI pacing in asymptomatic patients with decreased LVSF are mainly related to diastolic abnormalities and elevated filling pressures.

Effects of Cardiac Resynchronization Therapy on Myocardial Perfusion Reserve

Cardiac resynchronization therapy (CRT) is a relatively new treatment strategy for patients with heart failure and mechanical asynchrony. Reported effects of CRT on regional myocardial blood flow (MBF) are conflicting, and effects on hyperemic MBF are scarce. The aim of the present study was to assess serial changes of MBF and MBF reserve in patients receiving a biventricular pacemaker. Fourteen patients with heart failure (NYHA class III or IV; left ventricular ejection fraction <35%), QRS width >120 ms, and sinus rhythm were studied (mean age, 58+/-10 years; 8 men). MBF and hyperemic MBF were measured at baseline, 3 months after biventricular pacing (CRT on), and after cessation of pacing (CRT off) with PET and H2(15)O. CRT had no significant effect on resting MBF (baseline versus CRT on versus CRT off: 0.82+/-0.25 versus 0.69+/-0.24 versus 0.74+/-0.24 mL x min(-1) x mL(-1); P=NS). Hyperemic MBF increased during CRT (1.91+/-1.03 versus 2.66+/-1.66 versus 1.92+/-1.06 mL x min(-1) x mL(-1); P=0.01 by MANOVA), as did MBF reserve (2.25+/-1.00 versus 3.76+/-2.38 versus 2.49+/-0.94 mL x min(-1) x mL(-1); P=0.023). CRT (reversibly) resulted in a more homogeneous distribution of regional resting MBF as demonstrated by the septal-to-lateral ratio. The decrease in the ratio of left ventricular end-diastolic volume to left ventricular mass, as a reflection of wall stress, was related to the increase in hyperemic MBF (r=0.53, P<0.05). Left ventricular ejection fraction increased from 25+/-7% to 37+/-9% (P<0.01). Resting MBF is unaltered by CRT despite an increase in left ventricular function. However, the distribution pattern of resting MBF becomes more homogeneous. Hyperemic MBF and consequently MBF reserve are enhanced by CRT.

Temporal patterns of progression and regression of electrical and mechanical remodeling of the atrium

Objectives: We evaluated serial changes of electrical and mechanical parameters of atrial remodeling in dogs subjected to rapid atrial pacing. Background: Prolonged rapid atrial excitation causes electrical and mechanical remodeling, which contributes to persistence of atrial fibrillation and clot formation. However, the temporal relationship between these two types of atrial remodeling remains unknown. Methods: In 8 dogs, rapid pacing at 400 ppm was continued for 14 days. The electrophysiologic and transesophageal echocardiographic studies were performed on the day before and after 2, 7, and 14 days of rapid pacing, then 1 and 7 days after the cessation of pacing. These were compared with sham-operated dogs (instrumented but not paced, n=6). Results: With rapid pacing, there was an immediate shortening of the effective refractory period (ERP) and decreases in the transmitral atrial wave velocity (MAV) and the left atrial appendage emptying velocity (LAAV). In contrast, conduction velocity (CV) decreased and the left atrial appendage area (LAAA) increased progressively over 14 days. During the recovery, ERP, MAV, and LAAV returned to the baseline in 1 day, whereas CV and LAAA did in 7 days. ERP was highly positively correlated with LAAV ( r=0.78, p<0.001) and MAV ( r=0.73, p<0.001), while CV was negatively correlated only with LAAA ( r=−0.58, p<0.001). Conclusions: Pacing-induced electrical and mechanical remodeling of the atrium exhibits divergent patterns of progression and regression such that changes of ERP and contractile function take place more rapidly than those of CV and atrial size.

Autonomic responses to single- and dual-chamber pacing

We investigated the autonomic effects of short-term, single- and dual-chamber pacing by evaluating frequency-domain indexes of heart rate variability (HRV). The study group comprised 25 patients (mean age 62 ± 7 years) without organic heart disease and with normal sinus node function who were implanted with a permanent dual-chamber DDD (n = 16) or VDD (n = 9) pacing system for transient high-degree atrioventricular block. Continuous overdrive pacing for 15 minutes slightly above the intrinsic rhythm was programmed to ensure complete capture in AAI, DDD, and VVI modes, and the atrioventricular delays were set to ensure permanent ventricular pacing in DDD and VDD modes. Components of frequency-domain measures of HRV (low frequency [LF], high-frequency [HF], and LF/HF ratio) were calculated in 5-minute intervals over a 30-minute period after cessation of each pacing mode. AAI pacing did not significantly affect LF and LF/HF measures, and presented the highest HF power. DDD and VDD modes led to similar responses with slightly increased fluctuations of LF and LF/HF power. VVI pacing triggered an acceleration in heart rate (p <0.05), the most significant increases in LF power and in the LF/HF ratio, and the lowest HF power. Autonomic effects of pacing did not resolve with cessation of pacing. Atrial AAI pacing appears to have lesser effect on sympathovagal balance. Synchronous VDD and DDD stimulation favor a shift in autonomic balance toward sympathetic predominance. Asynchronous VVI pacing triggers both sympathetic overactivity and vagal withdrawal.

Left atrial pacing induces memory and is associated with atrial tachyarrhythmias.

Transiently altering the atrial activation sequence induces atrial memory, manifested as an altered atrial gradient as measured in electrocardiographic XYZ leads. We hypothesized that protracted periods of left atrial impulse initiation alter the atrial gradient in a manner predictive of arrhythmias. A total of 12 chronically instrumented mongrel dogs in complete heart block were paced AV sequentially from the left or right atrium for 7-28 days, and then recovered in normal sinus rhythm for 21 days. Rate histograms were recorded during the entire period, and electrophysiological studies were conducted to note changes in the atrial gradient, effective refractory period and atrial rhythm. No atrial arrhythmias were seen in eight control animals that were instrumented but not paced. Left atrial pacing was associated with a decreased atrial gradient and occurrence of atrial tachycardias that appeared during pacing and persisted during recovery from pacing. In contrast, right atrial pacing did not alter the atrial gradient significantly. Atrial tachycardias occurring during right atrial pacing disappeared after cessation of pacing, when dogs recovered in sinus rhythm. The effective refractory period did not change in either group. Pacing-induced impulse initiation from the left atrium alters the atrial gradient and is associated with atrial tachycardias. These changes in atrial gradient occur in the absence of ERP changes and may be early predictors of an arrhythmogenic substrate.

Experimental study of the effect of the vagus nerve on atrial electrical remodeling

Recent studies have shown that rapid atrial activation causes atrial electrical remodeling (AER), which recovers quickly following withdrawal of stimulation. The underlying mechanisms, however, are incompletely understood. The purpose of the present study, therefore, was to characterize the effect of the vagus on AER as well as define possible mechanisms of the phenomenon. Eight dogs were used in the study for 3 consecutive protocols. In the first, the dogs were subjected to atrial pacing at 800 ppm for 7 hours. Every hour, pacing was interrupted for a short time and atrial effective refractory period (AERP) was measured at 6 sites. The rapid atrial pacing was then discontinued and the electrophysiological study was repeated every hour for another 7 hours. Time-domain parameters of heart rate variability (HRV) were also computed 1 hour before pacing as well as each of 7 hours after the rapid atrial pacing protocol. The second program was performed two weeks after the first; 0.04 mg/kg of atropine was administered intravenously 30 min before pacing, and then 0.007 mg/kg was added at each hour. Parameters of HRV were not evaluated. Finally, the 8 dogs were subjected to the third protocol 2 weeks after completion of the second; 0.2 mg/kg of propranolol was given intravenously 30 min before pacing, and 0.04mg/kg was added at each hour. The dispersion of AERP (dAERP) was calculated as, maximum AERP minus minimum AERP. There was a prompt decrease in AERP as the result of pacing ( P<.05), but dAERP did not change significantly. The AERP recovered quickly, and dAERP increased from 21 ±5.3ms to 40 ± 7.4ms ( P<.05) after cessation of pacing. At the same time, the parameters of HRV increased ( P<.05) after cessation of pacing. The AERP increased from 128 ± 12 ms to 135 ± 12 ms and from 127 ± 12 ms to 142 ± 14 ms ( P<.05) after vagal and autonomic blockade. However, AERP decreased during pacing ( P<.05) with vagal or autonomic blockade, but dAERP did not change significantly during or after pacing. These results suggest that vagal and autonomic blockade can not prevent AER, but a high vagal tone is associated with a high dAERP during recovery from AER, indicating that the vagus and sympathetic have a synergistic effect on the refractory period.

An evaluation of the use of new doppler methods for detecting longitudinal function abnormalities in a pacing-induced heart failure model

Background Doppler tissue echocardiography and color M-mode Doppler flow propagation velocity have proven useful in evaluating cross-sections of patients with left ventricular (LV) dysfunction, but experience with serial changes is limited. Purpose and methods We tested their use by evaluating the temporal changes of LV function in a pacing-induced congestive heart failure model. Rapid ventricular pacing was initiated and maintained in 20 dogs for 4 weeks. Echocardiography was performed at baseline and weekly during brief pacing cessation. Results With rapid pacing, LV volume significantly increased and ejection fraction (57%-28%), stroke volume (37-18 mL), and mitral annulus systolic velocity (16.1-6.6 cm/s) by Doppler tissue echocardiography significantly decreased, with ejection fraction and mitral annulus systolic velocity closely correlated ( r = 0.706, P < .0001). In contrast to the mitral inflow velocities, mitral annulus early diastolic velocity decreased steadily (12.3-7.3 cm/s) resulting in a dramatic decrease in mitral annulus early/late (1.22-0.57) diastolic velocity with no tendency toward pseudonormalization. The color M-mode Doppler flow propagation velocity also showed significant steady decrease (57-24 cm/s) throughout the pacing period. Multiple regression analysis chose mitral annulus systolic velocity ( r = 0.895, P < .0001) and propagation velocity ( r = 0.782, P < .0001) for the most important factor predicting LV systolic and diastolic function, respectively. Conclusions Doppler tissue echocardiography and color M-mode Doppler flow could evaluate the serial deterioration in LV dysfunction throughout the pacing period. These were more useful in quantifying progressive LV dysfunction than conventional ehocardiographic techniques, and were probably relatively independent of preload. These techniques could be suitable for longitudinal evaluation in addition to the cross-sectional study.

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.

Effect of atrial overdrive pacing on pulmonary vein focal discharge in patients with atrial fibrillation.

Recently, it has been shown that atrial fibrillation may be caused by spontaneously discharging foci located predominantly in the pulmonary veins. However, the effect of atrial overdrive pacing on these pulmonary vein foci has not been studied. In 58 patients with drug refractory paroxysmal or persistent atrial fibrillation we performed radiofrequency catheter ablation of arrhythmogenic triggers inside the pulmonary veins and/or an ostial pulmonary vein isolation with conventional mapping and ablation technology. Continuous bigeminal pattern of discharge from one or more arrhythmogenic pulmonary veins was recorded in 14 patients. Atrial overdrive pacing resulted in suppression of pulmonary vein 'focus' activity in all patients. The longest mean atrial pacing cycle length resulting in overdrive suppression was 587+/-114 ms. Independent of pacing rate and duration, bigeminal pulmonary vein focus activity reemerged 2.5+/-3.7s after cessation of pacing. Overdrive suppression of the pulmonary vein focus was incomplete in 9 pacing attempts, and resulted in induction of atrial fibrillation from the same vein in 3 of 31 pacing manoeuvres. At 2 years follow-up 79% of these patients were free of atrial fibrillation, 55% without antiarrhythmic drugs, 24% on previously ineffective antiarrhythmic drug therapy. Stable pulmonary vein 'focus' activity in patients with atrial fibrillation can be suppressed by atrial overdrive pacing. However, 'proarrhythmic' effects of atrial overdrive pacing, such as induction of atrial fibrillation, were also seen.

Discordant temporal changes in electrophysiological properties during electrical remodeling and its recovery in the canine atrium.

Prolonged rapid atrial excitation gives rise to atrial electrical remodeling, which perpetuates atrial fibrillation (AF). However, there has been controversy regarding the nature of temporal changes in conduction characteristics during the development and recovery of electrical remodeling. This study was designed to clarify the nature of the development and recovery of electrical remodeling in relation to AF inducibility in dogs subjected to rapid atrial pacing. Eleven dogs underwent rapid atrial pacing (400/min) for 28 days. The electrophysiological study was performed on the day just prior to the commencement of pacing, on days 2, 7, 14, and 28 of rapid pacing, as well as 1 and 7 days after the cessation of pacing. In response to rapid atrial pacing, atrial effective refractory period (ERP), conduction velocity and wavelength decreased significantly (p < 0.05). ERP had shortened significantly and rapidly within 2 days of pacing, while conduction velocity decreased more gradually. During the recovery, ERP returned to almost baseline levels within a day, whereas conduction velocity returned to baseline by day 7. Sustained AF became inducible in 37% of the dogs from 7 days of pacing until 1 day after the cessation, when wavelength fell below 8.7 cm. In conclusion, rapid atrial excitation causes a progressive but discordant temporal pattern of a decrease in ERP and conduction velocity. The resultant shortening of the wavelength determines the inducibility and maintenance of AF. The electrophysiological changes produced by one month of rapid atrial pacing can be fully reversed within a week, although in a discordant temporal pattern.

Cardiac memory in canine atrium : identification and implications.

Memory is a diverse biological phenomenon whose importance in the ventricle has been demonstrated. We hypothesized its occurrence in the atrium, contributing to the modulation of cardiac rhythm. We analyzed P and Ta waves in conscious chronically instrumented dogs with complete heart block. Animals were atrioventricularly sequentially paced at 5% greater than the sinus rate from the lateral right atrium (RA) during control, followed by 2 periods of 1-hour test pacing at 50% greater than the sinus rate, or by equivalent test pacing from the left atrial appendage (LAA) at 5% or 50% greater than the sinus rate. Recovery RA pacing periods of 20- and 30-minute duration, respectively, succeeded each test pacing period. RA test pacing at either rate did not affect the variables measured, but changing the pacing site from RA to LAA altered the P and Ta waves. Displacement of the spatial atrial gradient vector occurred during recovery from LAA pacing, was more marked at rapid pacing rates, and manifested accumulation and resolution consistent with cardiac memory. Concurrently, the right effective refractory period decreased. Memory is demonstrable in canine atrium, showing rapid onset, accumulation during successive pacing periods, and resolution on cessation of pacing. Given its association with a reduced effective refractory period, it may contribute to the substrate for atrial arrhythmias.

Alterations in cardiac adrenergic terminal function and β-adrenoceptor density in pacing-induced heart failure

Congestive heart failure is associated with cardiac adrenergic nerve terminal changes and beta-adrenoceptor density downregulation. To study the temporal sequence of these changes, we performed studies in rabbits at 2, 4, and 8 wk of cardiac pacing (360 beats/min) and at 1, 2, and 4 wk after cessation of pacing. Rapid pacing produced left ventricular (LV) dysfunction and an increase in plasma norepinephrine (NE) in 1-2 wk. At week 2, NE uptake activity, NE uptake-1 density, and adenylyl cyclase responses to isoproterenol, 5'-guanylyl imidodiphosphate [Gpp(NH)p], and forskolin reduced. However, immunostained tyrosine hydroxylase profile, beta-adrenoceptor density, and NE histofluorescence did not reduce until 4-8 wk of pacing. After cessation of cardiac pacing, LV function normalized quickly, followed by return of tyrosine hydroxylase and NE profiles in 1 wk and adenylyl cyclase responses to agonists and NE uptake activity in 2 wk. Myocardial beta-adrenoceptor density returned to normal by 4 wk after cessation of pacing. Our results suggest that there is no permanent structural neuronal damage in the myocardium within the first 8 wk of rapid cardiac pacing. Abnormal myocardial NE reuptake mechanism may play an important pathophysiological role in heart failure.

Ten weeks of rapid ventricular pacing creates a long-term model of left ventricular dysfunction

Objective: Rapid ventricular pacing produces a reliable model of heart failure. Cessation after 4 weeks of rapid ventricular pacing results in rapid normalization of left ventricular function, but the left ventricle remains persistently dilated. We present novel data that show that prolonged rapid ventricular pacing (10 weeks) creates a model of chronic left ventricular dysfunction. Methods: In 9 dogs undergoing 10 weeks of rapid ventricular pacing, left ventricular function and volumes were serially assessed by using 2-dimensional echocardiography and pressure-volume analysis for 12 weeks after cessation of pacing. Results: Increased end-diastolic volume and decreased systolic and diastolic function were seen at the end of pacing. By 2 weeks of recovery from rapid ventricular pacing, end-diastolic volume and ejection fraction were partially recovered but did not improve further thereafter. Load-independent and load-sensitive indices of function obtained by pressure-volume analysis at 8 and 12 weeks of recovery confirmed a persistence of both systolic and diastolic dysfunction. In addition, left ventricular mass increased with pacing and remained elevated at 8 and 12 weeks of recovery. Four of these dogs studied at 6 months of recovery showed similar left ventricular abnormalities. Conclusion: Ten weeks of rapid ventricular pacing creates a long-term model of left ventricular dysfunction. (J Thorac Cardiovasc Surg 2000;119:834-41)

Tachycardia induced electrical remodeling of the atria and the autonomic nervous system in goats.

Atrial fibrillation (AF) shortens the atrial effective refractory period (AERP). To investigate the role of the autonomic nervous system during this so-called electrical remodeling of the atria (ERA) and during recovery from ERA we analyzed heart rate variability (HRV). In 12 goats atrioventricular (300:150 beats/min) pacing was performed for 24 hours, interrupted at 4, 8, 16, and 24 hours for recording of 500 atrial (AA) intervals during sinus rhythm and measurement of the AERP(430ms) at 7.4 +/- 0.6 sites. After 24 hours, pacing was stopped and the electrophysiological study and recording of the AA intervals was repeated at 4, 8, 16, and 24 hours after cessation of pacing. Time- and frequency-domain parameters were computed from each 500 AA interval recording. After 24 hours of rapid pacing the AERP had shortened significantly (147 +/- 5.6 to 102+/- 6.4 ms, P < 0.0001). No significant changes in HRV and dispersion of refractoriness (AAERP) (47 +/- 7.1 to 44 +/- 4.2 ms) were observed. After cessation of pacing, the AERP prolonged again (102 +/-6.4 to 135+/-8.8 ms, P < 0.0001) and was paralleled by a significant increase in AAERP (44 +/- 4.2 to 63+/- 7.1 ms, P = 0.01). Furthermore, HRV increased significantly. At each time point an inverse relation between the logarithmically transformed vagal parameter HF (InHF) and AERP was observed. We calculated the mean InHF for each goat using all time points and used the median value to divide the 12 goats into high and low vagal tone groups. We compared the degree of ERA and recovery from ERA for both groups. The AERP shortened 47.4 +/- 6.5 versus 43.0+/-5.0 ms (NS) for goats with high and low vagal tone, respectively. During recovery from ERA the AERP lengthened 23.6 +/- 4.0 versus 42.5 +/- 1.7 ms (P = 0.001) for goats with high and low vagal tone, respectively. Multivariate regression analysis indicated a short AERP as the single independent determinant of the inducibility of AF during ERA and recovery from ERA (P < 0.0001). During recovery from ERA, the AERP prolonged and vagal tone and AAERP increased. A high vagal tone during recovery from ERA was associated with a short AERP and an attenuated recovery of ERA.

Digoxin delays recovery from tachycardia-induced electrical remodeling of the atria.

Atrial fibrillation (AF) induces electrical remodeling, which is thought to be responsible for the low success rate of antiarrhythmic treatment in AF of longer duration. Electrical remodeling seems to be related to tachycardia-induced intracellular calcium overload. Due to its vagomimetic action, digoxin is widely used to control the ventricular rate during AF, but it also increases intracellular calcium. On the basis of these characteristics, we hypothesized that digoxin would aggravate tachycardia-induced electrical remodeling. We analyzed the atrial effective refractory period (AERP) at cycle lengths of 430, 300, and 200 ms during 24 hours of rapid atrio/ventricular (300/150 bpm) pacing in 7 chronically instrumented conscious goats treated with digoxin or saline. Digoxin decreased the spontaneous heart rate but had no other effects on baseline electrophysiological characteristics. In addition to a moderate increase in the rate of electrical remodeling during rapid pacing, digoxin significantly delayed the recovery from electrical remodeling after cessation of pacing (at 430, 300, and 200 ms: P=0. 001, P=0.0015, and P=0.007, respectively). This was paralleled by an increased inducibility and duration of AF during digoxin. Multivariate analysis revealed that both a short AERP and treatment with digoxin were independent predictors of inducibility (P=0.001 and P=0.03, respectively) and duration (P=0.001 for both) of AF. Dioxin aggravates tachycardia-induced atrial electrical remodeling and delays recovery from electrical remodeling in the goat, which increases the inducibility and duration of AF.

Cardiac endothelin release into the coronary sinus in myocardial ischemia and coronary endothelial injury

Endothelin has both vasoconstrictor and mitogenic properties and might, therefore, play a role in the pathogenesis of acute coronary syndromes and coronary atherosclerosis. The aim of the study was to characterize the mechanisms and kinetics of cardiac endothelin-1 (ET-1) release following a local endothelial injury during PTCA (group A) and after sustained myocardial ischemia (group B). Additionally, the precision of agreement between measurements in coronary sinus and peripheral venous samples should be analyzed. In group A, elective PTCA was performed in 20 patients with stable angina pectoris and a > 70% type A stenosis. Simultaneous determinations of ET-1 from coronary venous and peripheral venous blood were done before balloon inflation and during the several hours following the last dilatation procedure. A coronary sinus study with high rate atrial pacing was performed in 20 group B patients with coronary multivessel disease. ET-1 was determined from coronary sinus and peripheral venous blood samples prior to stimulation and during several hours after cessation of pacing. Control groups were provided for both groups. The control group consisted of 10 patients with coronary angiography without PTCA for group A and 10 patients with angiographic normal coronary arteries for group B.PTCA induced an instantaneous increase of coronary sinus ET levels from 4.1 +/- 1.1 pg/ml to 13.7 +/- 2.3 pg/ml (peripheral venous 7.9 +/- 2.5 pg/ml), which was more pronounced if the target vessel was the left anterior descending artery. This peak was followed by a gradual decrease of ET-1 to the limit of normal within 6 hours. The concentrations of ET, furthermore, remained higher in the coronary sinus compared with the peripheral vein indicating a persisting cardiac release of ET. In group B, incremental atrial pacing resulted in myocardial ischemia, and a significant increase in ET-1 from 4.6 +/- 0.6 pg/ml to 13.1 +/- 2.8 pg/ml was detected in the coronary sinus samples. A persistent cardiac release of ET-1, as reflected by sustained elevated coronary sinus concentrations, was observed for up to one hour after cessation of pacing. The analysis of measurement agreement between coronary venous and peripheral venous samples revealed considerable variations of the differences between the two sampling sites indicating wide limits of agreement. Despite a significant positive correlation, our date reflecting a remarkable lack of agreement. 1) An enhanced release of ET-1 following PTCA is mainly due to the localized endothelial injury, and the ET-1 levels remain elevated for up to hours after the mechanical stimulus. 2) A short-lasting myocardial ischemia is associated with a significant ET-1 increase. 3) For refined evaluations of release kinetics of cardiac ET-1, blood sampling from the coronary sinus seems to be essential.

Change of atrial refractory period after short duration of rapid atrial pacing: regional differences and possible mechanisms.

It is unknown whether there are regional differences in the change of atrial effective refractory period (ERP) after a short duration of rapid atrial pacing. Furthermore, the effects of calcium channel and potassium channel on this phenomenon have not been extensively investigated. In opened-chest dogs, the endocardial monophasic action potential duration at 90% repolarization (APD90) from the right atrial appendage, and ERP from seven atrial sites were measured before and after rapid atrial pacing at 800 beats/min for 30 minutes. Both atrial ERP and APD90 significantly shortened after rapid atrial pacing. The postpacing atrial ERP and APD90 shortening persisted for 119 +/- 3 and 123 +/- 4 seconds after cessation of pacing, respectively. There was no significant difference in the magnitude or recovery course of atrial ERP shortening after pacing among the seven atrial sites. Pretreatment with nicorandil and d-sotalol had no effects on the magnitude or recovery course of atrial ERP shortening after pacing. However, the degree of ERP and APD90 shortening after pacing was significantly attenuated in the verapamil and ryanodine groups; furthermore, the recovery of ERP and APD90 after cessation of pacing was faster in the two groups. In conclusion, shortening of atrial ERP induced by short-duration rapid atrial pacing was uniform in both atria. Both the adenosine triphosphatase (ATP) dependent potassium current and rapid component of the delayed rectifier did not significantly influence this phenomenon, but both the verapamil and ryanodine could significantly attenuate the degree of atrial ERP and APD90 shortening.

Rapid return of left ventricular outflow tract obstruction and symptoms following cessation of long-term atrioventricular synchronous pacing for obstructive hypertrophic cardiomyopathy

Atrioventricular (AV) synchronous pacing reduces left ventricular (LV) outflow tract obstruction and symptoms in patients with obstructive hypertrophic cardiomyopathy (HC). The duration of gradient reduction, if pacing is discontinued for a prolonged period of time, is unknown. This question is addressed in the present randomized double-blind crossover study comparing continued with inactivated pacing. Ten patients, successfully paced for ≥6 months, were randomized to continue pacing or to have their pacemakers inactivated after baseline examinations, including echo-Doppler imaging, exercise testing, and a quality-of-life questionnaire. When entering the study, the patients were in New York Heart Asssosciation functional classes I to II. After pacemaker programming, examinations were repeated at 1, 4, and 12 weeks. At the 12-week follow-up the alternate pacing mode was programmed, and the patient entered the second study arm. Premature pacemaker pacing occurred if severe clinical deterioration or a significant increase of the LV outflow tract obstruction were evident. Three patients started in the inactive mode and 7 patients in the active mode. All patients who started with the pacemaker inactivated required early reprogramming due to return of symptoms after 7, 10, and 13 days, respectively. All 7 patients who started in the active pacing mode completed the first period; however, after reprogramming to the inactive mode they required early activation after 1 to 20 days due to reappearance of intolerable subjective symptoms. The LV outflow tract gradient increased significantly after inactivation of pacing in all patients (22 ± 21 mm Hg to 47 ± 21 mm Hg). Thus, AV synchronous pacing effectively relieves symptoms and reduces the LV outflow tract gradient in patients with obstructive HC. This improvement, which is rapidly established with the initiation of cardiac pacing, is not persistent after cessation of pacing. Reinitialization of pacing promptly reduces the LV outflow tract obstruction and relieves symptoms to a preexisting extent.

Comparison of oversensing during bradycardia pacing in two types of implantable cardioverter-defibrillator systems

Background During bradycardia pacing in Ventritex Cadence (Models V-100 and V-110) implantable cardioverter-defibrillators, amplifier gain is maximal and oversensing and false tachyarrhythmia detection have been reported. Newer Ventritex devices (Cadet, Model V-115 and Contour, Model V-145) have a modified automatic gain control that may minimize oversensing. Methods and Results We prospectively studied 50 patients (22 with Cadence, 28 with Cadet or Contour). Electrograms were evaluated for oversensing during bradycardia pacing. The bradycardia pacing refractory period required to prevent oversensing of T waves of paced beats and the time and number of beats required to achieve minimum gain after cessation of pacing were assessed. The bradycardia pacing refractory period could be left at its default setting of 350 ms in only 15 (30%) of 50 patients. The mean bradycardia pacing refractory period required to avoid oversensing of paced T waves was 386 ± 32 ms. During pacing, oversensing of nonpaced T waves was seen in 12 (24%) devices, with similar incidence in Cadence devices (18%) and Cadet and Contour devices (29%, p = not significant). The time and number of beats to achieve minimum gain after pacing were longer in Cadence devices (19.0 ± 4.5 vs 4.6 ± 1.2 sec; 21.3 ± 3.3 vs 5.0 ± 0.4 beats, both p < 0.001). Conclusions The incidence of oversensing at maximum gain is similar in both types of devices, but more rapid changes in autogain levels in the newer devices may reduce the likelihood of false tachyarrhythmia detection. (Am Heart J 1998;136:658-63.)

Time course of sympathovagal imbalance and left ventricular dysfunction in conscious dogs with heart failure.

To elucidate the time course of sympathovagal balance and its relationship to left ventricular function in heart failure, we serially evaluated left ventricular contractility and relaxation and autonomic tone in 11 conscious dogs with tachycardia-induced heart failure. We determined a dynamic map of sympathetic and parasympathetic modulation by power spectral analysis of heart rate variability. The left ventricular peak +dP/dt substantially fell from 3,364 +/- 338 to 1,959 +/- 318 mmHg/s (P < 0.05) on the third day and declined gradually to 1,783 +/- 312 mmHg/s at 2 wk of rapid ventricular pacing. In contrast, the time constant of left ventricular pressure decay and end-diastolic pressure increased gradually from 25 +/- 4 to 47 +/- 5 ms (P < 0.05) and from 10 +/- 2 to 21 +/- 3 mmHg (P < 0.05), respectively, at 2 wk of pacing. The high-frequency component (0.15-1.0 Hz), a marker of parasympathetic modulation, decreased from 1,928 +/- 1,914 to 62 +/- 68 x 10(3) ms2 (P < 0.05) on the third day and further to 9 +/- 12 x 10(3) ms2 (P < 0.05) at 2 wk. Similar to the time course of left ventricular diastolic dysfunction, plasma norepinephrine levels and the ratio of low (0.05- to 0.15-Hz)- to high-frequency component increased progressively from 135 +/- 50 to 532 +/- 186 pg/ml (P < 0.05) and from 0.06 +/- 0.06 to 1.12 +/- 1.01 (P < 0.05), respectively, at 2 wk of pacing. These cardiac and autonomic dysfunctions recovered gradually toward the normal values at 2 wk after cessation of pacing. Thus a parallel decline in left ventricular contractility with parasympathetic influence and a parallel progression in left ventricular diastolic dysfunction with sympathoexcitation suggest a close relationship between cardiac dysfunction and autonomic dysregulation during development of heart failure.