End Of Pacing Research Articles

Reliable pace termination of postoperative atrial fibrillation in the canine sterile pericarditis model: Implications for atypical atrial flutter.

BackgroundWe have identified a reentrant circuit in the pulmonary vein region, which drives the atria, producing fibrillatory conduction, as one mechanism of postoperative atrial fibrillation (POAF) in the canine sterile pericarditis model.ObjectiveIn this model, we tested the hypothesis that overdrive pacing from a site at or near such a reentrant circuit would interrupt it and thereby terminate POAF.MethodsWe studied 11 sterile pericarditis dogs on postoperative days 1–4. Atrial electrograms (AEGs) were recorded during POAF, overdrive pacing, and pace termination from 3 sites simultaneously: Bachmann's bundle, posterior left atrium, and right atrial appendage. When recorded AEGs demonstrated regular activation, pace termination was attempted at that site by delivering a drive train starting with 4 consecutive beats at a cycle length (CL) of 2–5 ms shorter than that of the intrinsic CL.ResultsSixteen episodes of sustained POAF (>5 minutes) diagnosed by electrocardiogram were induced. During all episodes of POAF, AEGs recorded from the left atrium exhibited regular activation, ie, constant AEG morphology and CL. When capture of the reentrant circuit by overdrive pacing occurred (mean 13 ± 5, range 5–23 beats), all 16 POAF episodes were successfully terminated. In all termination episodes, at the end of pacing but prior to the return of sinus rhythm, there was disorganized atrial activation in the previously organized sites (mean 2 seconds, range 0.1–8 seconds). However, these beats did not sustain POAF in the absence of a reentrant circuit (“driver”).ConclusionOverdrive pacing from a site demonstrating regular activation during sustained POAF terminated the POAF by interrupting the reentrant circuit.

Short-term memory in the heart: A road map for channel trafficking required

Short-term memory in the heart: A road map for channel trafficking required

Feasibility of Using an Implantable System to Measure Thoracic Congestion in an Ambulatory Chronic Heart Failure Canine Model

Noninvasive measures of impedance reflect alterations in thoracic fluid and pulmonary edema in acute animal and human studies. We evaluated the feasibility of using an implantable impedance measuring device and cardiac lead system to monitor intrathoracic congestion in a pacing-induced heart failure canine model. Three devices were implanted in each of five dogs: a modified pacemaker to measure impedance from a defibrillation lead implanted in the right ventricle; an implantable hemodynamic monitoring device to measure left ventricular end diastolic pressure (LVEDP) and a second pacemaker to deliver rapid (240 pulses per minute) ventricular pacing to induce heart failure. All five dogs developed severe heart failure after 3-4 weeks of rapid pacing and recovered following pacing termination. The LVEDP increased and impedance decreased during pacing-induced heart failure and recovered after pacing cessation. At the end of pacing, there was a mean impedance reduction of 10.6 +/- 8.3% and a mean LVEDP increase of 18.1 +/- 4.5 mmHg compared to baseline. The impedance and LVEDP were inversely correlated (r =-0.41 to -0.85, all P < 0.05). In the canine model, measurement of chronic intrathoracic impedance with an implantable system effectively revealed changes in thoracic congestion due to heart failure reflected by LVEDP. These data suggest that implantable device-based impedance measurement merits further investigation as a tool to monitor the fluid status of heart failure patients.

A CANINE MODEL OF CHRONIC MITRAL VALVE REGURGITATION WITH PRESERVATION OF RESTING CARDIAC FUNCTION

Background: The purpose of this study was to develop a canine model of chronic dilated cardiomyopathy with preservation of resting cardiac function. Methods: The baseline cardiac geometry and function of eight mongrel dogs (20–22 kg) were evaluated using transthoracic echocardiography (TTE). A right atrial pacer lead was implanted, and mild MR was produced through a fixed lesion to the mitral valve apparatus. Incremental pacing induced LV dilation over an eight-month period. The pacer was deactivated and the dogs followed for an additional six weeks. The heart was arrested in diastole and myocytes were examined histo-logically. All animals were evaluated in-vivo at baseline, following acute MR, at the end of pacing and at explant. TTE evaluations were performed hi-weekly. Similar studies were performed in six control dogs. Results: TTE data demonstrated significant changes in LV and LA geometry, which were sustained following pacing deactivation. MR severity increased significantly, whereas baseline cardiac function was preserved. There was preservation of stroke volume and systemic pressures with a significant increase in pulmonary capillary wedge pressure. Cardiac function decreased significantly at increased pacing rates. Isolated myocytes demonstrated significant cellular enlargement from control studies with increased cell area and volumes. Conclusion: The methodology presented represents a novel model of chronic MR with preservation of baseline cardiac function. Our results demonstrate progressive cardiac remodelling and worsening MR without significant changes in EF or stroke volume.

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)

Modified Rapid Ventricular Pacing

Rapid ventricular pacing (RVP) in dogs creates a well characterized model of dilated cardiomyopathy. Standard pacing protocols use RVP at 240-260 beats/min for 2-4 weeks, and result in high mortality rates if continued longer. The authors describe a modification of RVP that results in significant heart failure by 4 weeks, but can be continued for up to 10 weeks with low mortality. Nineteen mongrels underwent RVP at 215 beats/min for 10 weeks. Serial pressure-volume analysis and echocardiography were performed in this model to assess longitudinally changes in left ventricular (LV) function and volumes. The mortality rate was 10%. Significant progressive LV dysfunction with concomitant LV enlargement was observed throughout the pacing period. Finally, norepinephrine levels were elevated at the end of pacing, consistent with an activated sympathetic system. This modified RVP protocol permits long-term pacing with a low mortality rate and results in progressive heart failure throughout the pacing period. This model would be useful in the long-term evaluation of newer surgical and medical therapies of the failing heart.

915-81 Release of Endothelin After Severe Short Lasting Myocardial Ischemia

Endothelin (ET) is an endothelium-derived vasoactive peptide, its possible contribution to myocardial ischemia and infarction is not yet well understood. was to elucidate whether a brief period of myocardial ischemia (CI) not leading to myocardial infarction may increase plasma ET levels and to determine the kinetics of a possible ET release. A coronary sinus lactate study with incremental atrial pacing was performed in 16 patients (pts) with obstructive coronary artery multivessel disease (CAD). A Zucker-catheter was positioned in the distal coronary sinus for incremental atrial pacing (100–160 bpm) and lactate sampling. ET was measured by a radio-immuno-assay 1100% ET-1, 52% ET-2, 96% ET-3, 7% Big-ET, Nichols Institute). ET, cardiac troponin-T (TnT, Boehringer Mannheim) and creatine phosphokinase (CPK) samples were withdrawn from the coronary sinus (CS) and a peripheral vein (PV) before and at time 1, 5, 10, 30, 45 min, 1, 2, 3, 6 h after pacing. Significant ST depressions in the 12-lead ECG after pacing was a further criterion for CI. A comparison to the results of a control group (CG, n = 13) without heart disease and statistical analysis was done. In CAD pacing stress induced a CI in all pts (duration 6.1 ± 1.2 min). The mean cardiac lactate production was 143.9 ± 19.3% compared with the arterial lactate concentration, all pts suffered from typical angina pectoris, significant ST depressions of 0.32 ± 0.11 mV were found in 14/16 pts. All pts developed pathological elevated ET concentration, whereas the levels in the CG were within the limits of normal (p &lt; 0.003). The mean ET concentrations increased from 5.0 pg/ml in CS and PV before pacing to 10.9 pg/ml in CS and 8.9 pg/ml in PV at 1 min after the end of pacing. The concentrations further remained elevated within 1 h after pacing with higher levels in CS than in PV due to a persisting cardiac release of ET, ET concentrations dropped to the limits of normal (2.3–5.3 pg/ml) after 1 h with identical levels in CS and PV In both groups TnT and CPK were not elevated, no signs of CI were detected in the CG. A short lasting severe myocardial ischemia without myocardial infarction was followed by a significant ET release for 1 h reaching 218% of the base line concentration in CS and 178% in PV respectively. The higher ET levels in CS compared to PV indicate, that the ET release is of cardiac origin.

Impaired early and intact late diastolic function in stunned myocardium induced by demand ischemia.

Changes in left ventricular diastolic properties of pacing-induced stunned myocardium were examined in 10 anesthetized dogs instrumented with a micromanometer for left ventricular pressure and sonomicrometers for left ventricular short axis, anterior and posterior segment lengths, and posterior wall thickness. After the creation of a critical stenosis on a carotid-circumflex coronary artery bypass, left ventricular pressure and dimensions were recorded simultaneously during temporary superior and inferior vena caval occlusion to allow for the construction of end-diastolic pressure-segment length curves. After 15 min of high-frequency pacing (190-220 beats/min), measurements were repeated and compared with those before pacing. The mean lengthening rate of each dimension during the first half of diastole was calculated as an index of early diastolic function. Three minutes after the end of pacing, coronary blood flow and perfusion pressure were unchanged, whereas systolic function of the posterior wall was depressed, indicating stunning of the posterior myocardium. The time constant of left ventricular pressure decay was prolonged by 14%. The mean lengthening rate during the first half of diastole decreased by 50% in the left ventricular internal short axis and by 119% in the posterior segment. Despite the significant impairment of early diastolic function, the regional end-diastolic pressure-segment length relation of the posterior wall was unchanged. Thus, in contrast to the results reported for pacing-induced ischemia that were measured immediately after pacing, the distensibility of the left ventricular wall in stunned myocardium induced by pacing was unchanged despite depressed early diastolic function.

Haemodynamic and neurohumoral response in heart failure produced by rapid ventricular pacing.

The aim was to determine the exact sequence of hormone changes during the progression of fluid retention in a canine model of "congestive cardiac failure" induced by rapid right ventricular pacing, and during recovery when pacing is stopped. Rapid ventricular pacing at a rate of 250 pulses.min-1 was used in six mongrel dogs with implanted right ventricular pacemakers. Right heart haemodynamics were measured by means of Swan Ganz catheterisation, allowing flow measurement by thermodilution and pressure measurement by external manometry. Plasma renin activity, arginine vasopressin, and atrial natriuretic factor were assayed on venous blood samples by radioimmunoassay. Noradrenaline was assayed by high pressure liquid chromatography. The onset of rapid pacing was accompanied by a fall in cardiac output and a rise in pulmonary arterial, pulmonary capillary wedge, and right atrial pressures. Noradrenaline and atrial natriuretic factor rose. Plasma renin activity showed an initial fall followed by a rise, and arginine vasopressin was unchanged in the first 8 h. When rapid pacing was continued for a further 35 d, clinical signs of fluid retention appeared by day 28, by which time cardiac output had fallen, and central pressures risen further. Atrial natriuretic factor peaked at around 14 d whereas plasma renin activity, arginine vasopressin, and noradrenaline tended to reach a plateau at about d 20 and then to show further increases as clinical signs of fluid retention appeared; this was most marked with plasma renin activity. Cessation of pacing at d 35 caused a rapid reversal (increase) of cardiac output but a more gradual reversal (decrease) of right heart pressures over 5 d; only wedge pressure returned to base line. Arginine vasopressin and plasma renin activity fell rapidly to around 40% of the final pacing levels and reached basal values after 8 h and 48 h respectively. Noradrenaline fell after 8 h and reached basal levels in 5 d. Atrial natriuretic factor fell quickly by 60% after 8 h but remained above basal levels for 5 d. At the end of pacing, body weight fell rapidly in conjunction with a large diuresis. These findings are compatible with a major role of one or more of renin, vasopressin, and noradrenaline in the pathophysiology of the fluid retention of heart failure; the manifestations are not counteracted by the rise in atrial natriuretic factor.

Increased cyclic GMP in atrial fibrillation

To investigate the role of cyclic nucleotides in the genesis and/or the persistence of atrial fibrillation (AF), plasma levels of cyclic GMP (c-GMP) and cyclic AMP (c-AMP) were measured in dogs with electrically induced AF, and in dogs subjected to high frequency (230 or 410/min) atrial pacing. The atrial fibrillation threshold (AFT) after intravenous administration of a dibutyryl derivative of c-GMP (Dbc-GMP), and the effect of atropine (0.1 mg/kg) on AFT were determined. Plasma levels of c-GMP and c-AMP were also measured in patients during paroxysmal AF and sinus rhythm. The c-GMP level increased significantly 15 min after the onset of artificial AF, and gradually increased during the course of the experiment. The c-GMP level began to increase significantly 15 min after the initiation of pacing at the higher rate (410/min) but not at the lower rate, compared to the prepacing value. The c-GMP level continued to rise until the end of pacing in the animals paced at 410/min. Although Dbc-GMP induced a dose-dependent decrease in AFT, atropine did not prevent the decrease in AFT by Dbc-GMP. In contrast, c-AMP levels were not significantly affected in any of these experiments. Clinical assessment revealed that patients had almost four times higher c-GMP level during AF than during sinus rhythm, though c-AMP levels in these patients did not change significantly during the attack of AF. These results suggest that the increase in c-GMP plays an important role in the maintenance and/or the genesis of AF.

Continuous determination of regional myocardial blood flow with intracoronary Krypton-81m in coronary artery disease

Pacing-induced changes in regional coronary flow were studied continuously with krypton-81m by intracoronary infusion in 25 patients: 21 with 50% or greater diameter narrowing of 1 or more left coronary arteries (group I) and 4 with less than 50% diameter reduction of a left coronary artery (group II). No changes occurred in group II. In group I, krypton-81m perfusion decreased progressively in all areas with more than 70% diameter narrowing, with a simultaneous increase in normal regions. At the end of pacing during angina, krypton-81m perfusion was reduced to 81 ± 4% of control in areas with 71 to 90% diameter reduction (n = 8) and to 69 ± 6% in areas with more than 90% diameter narrowing (n = 15). In contrast, in regions with 50 to 70% diameter reduction changes were variable (decrease in 4 regions, increase in 2 and an unchanged distribution in 1 region). Krypton-81m perfusion decreased early, before general signs of ischemia in areas with more than 90% diameter reduction, whereas this decrease occurred later in regions with 71 to 90% diameter narrowing, concurrently with ST-segment changes but before anginal pain. Although all signs of ischemia had dis-appeared between 2 and 5 minutes after pacing, changes in krypton-81m distribution persisted in most areas for 5 to 15 minutes after pacing. It is concluded that the functional significance of coronary arterial narrowing can be assessed with a continuous intracoronary infusion of krypton-81m. Changes in regional distribution persisted after cessation of pacing-induced ischemia, indicating an ongoing decrease in regional myocardial blood flow.

Continuous coronary sinus and arterial pH monitoring during pacing-induced ischaemia in coronary artery disease.

Catheter tip pH electrodes were used for continuous recording of coronary sinus and arterial pH during atrial pacing in 20 patients undergoing coronary arteriography for chest pain. An ischaemic response to atrial pacing was identified by the onset of angina and/or electrocardiographic abnormalities. Technically satisfactory coronary sinus recordings were obtained in 18 patients. Mean coronary sinus pH at the peak pacing rate fell by 0.021 +/- 0.006 units (n = 9) in the ischaemic group, while there was no significant change in the non-ischaemic group. A larger fall in coronary sinus pH (-0.052 +/- 0.009) was found in the ischaemic group in the 30 seconds after the end of atrial pacing, the maximum change occurring after 16.1 +/- 1.5 seconds. A maximum fall of coronary sinus pH greater then 0.02 units identified patients with an ischaemic response. Changes in arterial pH did not account for these results. The sensitivity of coronary sinus pH recording for the detection of ischaemic heart disease is enhanced by sampling during the "washout" phase after the end of pacing.