Myocardial mechanical restitution and potentiation partly underlie alternans decay of postextrasystolic potentiation: Simulation

Summary We have reported that the postextrasystolic potentiation (PESP) decays in alternans or monotonically, respectively, depending on whether the first postextrasystolic beat interval has a compensatory pause or not, in the canine left ventricle. To get better mechanistic insight into the alternans PESP decay, we hypothesized that the myocardial mechanical restitution and potentiation could partly account for both types of PESP decay. To test this hypothesis, we simulated PESP decay on a computer using a documented equation combining myocardial mechanical restitution and potentiation. We changed the first postextrasystolic beat interval after a fixed extrasystolic beat interval without changing regular and other postextrasystolic beat intervals. The simulated PESP decayed in alternans or monotonically as a function only of the first postextrasystolic beat interval. Thus, the myocardial mechanical restitution and potentiation could partly account for both alternans and monotonic decay of PESP. We conclude that myocardial mechanical restitution and potentiation may partly underlie the initial two alternating beats, the first beat being the most potentiated and the second beat being the most depressed, of alternans PESP decay in the canine heart. This study was partly supported by Grants-in-Aid for Scientific Research (07508003, 09470009, 10558136, 10770307, 10877006) from the Ministry of Education, Science, Sports and Culture, and 1997–1998 Frontier Research Grants for Cardiovascular System Dynamics from the Science and Technology Agency, all of Japan.     

Frequency potentiation and postextrasystolic potentiation in patients with and without coronary arterial disease.

Frequency potentiation and postextrasystolic potentiation of myocardial contractility were induced in 17 patients found not to have cardiac disease (group 1) and in 10 patients with coronary arterial disease (group 2). Atrial stimulation was performed starting at a rate of 110/min and going up to 200/min (frequency potentiation). Single, premature venriculr beats with decreasing coupling intervals were induced every fifteenth beat during basal atrial stimulation at 125/min, after which compensatory pauses were provided (posts used an an idex of contractility. With increasing heart rate dp/dt max was augmented equally, in both groups of patients, by frequency increases and premature beats (the coupling interval of the extrasystole being expressed as heart rate). dp/dt min and left ventrricular systolic pressure remained unchanged while left ventricular end-diastolic pressure decreased in both groups of patients with the two forms of potententiation. It was concluded that both these forms of potentiation have the same augmenting effect on myocardial contractility. Shortening the coupling intervals of premature beats caused a decreased in left ventricular end-diastolic pressure, suggesting that the Frank-Starling mechanism was not involved in postextrasystolic potentiation. Patients with coronary arterial disease had lower values of dp/dt max, dp/dt min, and higher values of left ventricular end-diastolic pressure during rest and stimulation procedures, while the systolic pressures equalled those in the control group. Though individual case values fromthe healthy and diseased hearts might be similar, it was only under the stress of potentiation that the true state of contractility was made apparent. Impairment of dp/dt min was not found without an impairment of dp/dt max in the presence of myocardial ischaemia.     

Frequency potentiation and postextrasystolic potentiation in patients with and without coronary arterial disease.

Frequency potentiation and postextrasystolic potentiation of myocardial contractility were induced in 17 patients found not to have cardiac disease (group 1) and in 10 patients with coronary arterial disease (group 2). Atrial stimulation was performed starting at a rate of 110/min and going up to 200/min (frequency potentiation). Single, premature venriculr beats with decreasing coupling intervals were induced every fifteenth beat during basal atrial stimulation at 125/min, after which compensatory pauses were provided (posts used an an idex of contractility. With increasing heart rate dp/dt max was augmented equally, in both groups of patients, by frequency increases and premature beats (the coupling interval of the extrasystole being expressed as heart rate). dp/dt min and left ventrricular systolic pressure remained unchanged while left ventricular end-diastolic pressure decreased in both groups of patients with the two forms of potententiation. It was concluded that both these forms of potentiation have the same augmenting effect on myocardial contractility. Shortening the coupling intervals of premature beats caused a decreased in left ventricular end-diastolic pressure, suggesting that the Frank-Starling mechanism was not involved in postextrasystolic potentiation. Patients with coronary arterial disease had lower values of dp/dt max, dp/dt min, and higher values of left ventricular end-diastolic pressure during rest and stimulation procedures, while the systolic pressures equalled those in the control group. Though individual case values fromthe healthy and diseased hearts might be similar, it was only under the stress of potentiation that the true state of contractility was made apparent. Impairment of dp/dt min was not found without an impairment of dp/dt max in the presence of myocardial ischaemia.     

Potentiation of atrial contractility by paired pacing augments ventricular preload and systolic performance

BACKGROUND: Paired electrical stimulation and postextrasystolic potentiation (PESP) of contractility has been extensively studied in ventricular myocardium, but less is known about PESP of atrial contractility. Our aim was to determine whether PESP of atrial contractility could augment left ventricular (LV) preload and improve LV systolic performance. METHODS AND RESULTS: A paired electrical stimulus closely following the pacing stimulus was applied to isolated atrial and ventricular myocardium from 4 dog hearts, and the interval dependent force potentiation was examined. In isolated atrial myocardium, paired pacing increased the active tension from a baseline of 1.36 +/- 0.23 to 2.60 +/- 0.57 g/mm(2); in ventricular myocardium active tension increased from 2.58 +/- 0.42 to 3.81 +/- 0.27 g/mm(2) (both P <.01). Then, LV pressure (micromanometer) and segment length (ultrasonic crystals) were measured in the intact hearts of 7 anesthetized dogs in which premature stimuli were applied to the atrium. In intact hearts, paired pacing of the atrium (coupling interval 200 ms) increased LV end-diastolic pressure from 3.8 +/- 1.0 to 6.4 +/- 1.0 mm Hg; systolic pressure increased from 105 +/- 6 to 112 +/- 7 mm Hg (both P <.05). LV pressure-length loop area (regional stroke work) increased 10.5 +/- 0.2%. CONCLUSIONS: Isolated atrial myocardium exhibits substantial PESP of contractility, which is similar to ventricular myocardium. In the intact heart, atrial PESP augments LV systolic performance by effecting an increase in LV preload. This technique may provide a means of improving cardiac performance in patients with heart failure.     

Postextrasystolic potentiation: analysis of methods of induction

Studies were conducted in 15 patients with coronary artery disease to determine if the type of pacing used to induce an extrasystole had a bearing on subsequent postextrasystolic potentiation (PESP) and if the fact that these were evaluated in jeopardized or nonjeopardized portions of the ventricle altered the ability to assess PESP. Two types of pacing were used. In the first group, all beats in the test sequence (basic heart rate, extrasystole, and postextrasystole) were delivered from a programmed external pacemaker. This group was termed the "all-paced" (AP) group, and the postextrasystole was introduced before a compensatory pause could occur, so that loading conditions within the ventricle at the last regular beat and after the extrasystole were not different. In the second group, the extrasystole was coupled to the sensed intrinsic heart rate of the patient, and the postextrasystole was allowed to occur spontaneously. This group was termed the "sensed-paced" (SP) group. Despite differences in basic heart rates and postextrasystolic intervals between the two groups, comparable results were obtained with the two techniques. However, the postextrasystole in the SP group occurred much earlier than expected, probably due to intrinsic cardioacceleration during ventriculography. The net result was that loading conditions in this group before and after the extrasystole were also not different from each other. Results from the pacing techniques were not influenced by whether they were obtained from jeopardized or nonjeopardized segments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of postextrasystolic T wave alterations in identification of patients with coronary artery disease or left ventricular dysfunction

This study was performed (1) to assess the value of postextrasystolic T wave alterations in identification of patients with cardiac disease and (2) to determine if their frequency depends on length of compensatory pause. In 52 patients a pacing catheter was placed in the right ventricular (RV) apex, and premature beats were programmed to occur 30 msec beyond RV refractory period. Postextrasystolic T wave alterations occurred in 32 patients, 13 with an 19 without coronary artery disease (CAD) (NS). Such alterations were also not related to presence of abnormal left ventricular (LV) ejection fraction (less than 0.55) or end-diastolic pressure (greater than 12 mm Hg). In 33 patients, premature beats were also introduced 330 msec beyond the RV refractory period to compare effects of long and short compensatory pauses on frequency of postextrasystolic T wave alterations. When the pause was near maximal, 18 patients had alterations in 60 ECG leads; when it was shorter, seven patients had alterations in 10 leads (p less than 0.001). Thus, judging from provoked postextrasystolic T wave alterations, such spontaneous changes appear neither sensitive nor specific in the identification of patients with cardiac disease. The frequency of postextrasystolic T wave changes depends on the length of the compensatory pause.     

Estimation of left ventricular diastolic characteristics in patients with myocardial ischemia by pulsed Doppler echocardiography: transmitral blood flow velocity in postextrasystolic beats]

To investigate diastolic dynamics of the left ventricle in postextrasystolic (PES) beats during myocardial ischemia induced by rapid atrial pacing (RAP), transmitral blood flow velocity was evaluated using pulsed Doppler echocardiography in 13 subjects. The subjects consisted of eight patients with ischemic heart disease and five healthy subjects. An atrial extrasystole was artificially induced before and immediately after RAP, while the transmitral flow velocity was recorded continuously. The ratio of the early peak diastolic velocity to the peak atrial velocity (A/E) on PES beat was less than that in a basic beat without an extrasystole. The A/E increased in the PES beat in four patients who experienced myocardial ischemia; whereas, other patients and the normals showed a decrease in the A/E in the PES beat even after RAP. These findings indicated that left ventricular dynamics coupled with left atrial contraction are quite different in myocardial ischemic and nonischemic situations, and that postextrasystolic potentiation may be a useful means of detecting the ventricular diastolic dysfunction.     

Ventricular Extrasystoles with Interpolation or Postponed Compensatory Pause during Atrial Fibrillation: Fact or Fiction?

A Holter recording obtained from a patient with atrial fibrillation showed ventricular extrasystoles often in bigeminal rhythm. Most extrasystoles were followed by a long return cycle, and only in a few instances the postextrasystolic interval was short. The latter phenomenon was interpreted as a manifestation of poor retrograde concealed penetration of the ventricular impulse into the atrioventricular (A‐V) junction: accordingly, an ensuing relatively early fibrillation impulse reached the ventricular chamber, since it did not find the A‐V node refractory. These events are similar to what happens in interpolated ventricular extrasystoles occurring during sinus rhythm, the absent or minimal concealed retrograde penetration of the ectopic impulse into the A‐V node being necessary to permit anterograde conduction of the ensuing sinus impulse. Analysis of the recording also revealed that a very long (>2 second) interval between two consecutive narrow beats only occurred after an “interpolated” extrasystole. This was interpreted with the same mechanism underlying the “postponed compensatory pause” observed at times after interpolated ventricular extrasystoles during sinus rhythm: the minimal or nil penetration of the ventricular ectopic impulse into the A‐V junction, followed by conduction of an ensuing early atrial impulse, “shifts to the right” the A‐V nodal refractory period, preventing conduction of several further supraventricular impulses and generating a pause. Both interpolated ventricular extrasystoles and the phenomenon of “postponed compensatory pause” are, thus, conceivable during atrial fibrillation, although no definite demonstration is possible.     

Calcium equally increases the internal calcium recirculation fraction before and after β-blockade in canine left ventricles

Summary We studied whether intracoronary Ca administration after β-blockade would increase the internal Ca recirculation fraction (RF) analogously to the Ca administration before β-blockade. This was performed in excised cross-circulated canine hearts. We analyzed the exponential decay component of the postextrasystolic potentiation (PESP) following a spontaneous extrasystole. All the PESPs decayed in alternans with atrial pacing at a constant rate. We obtained the time constant (τ_e) of the monoexponential decay component of the alternans PESP. An increment of intracoronary Ca by 1.5mmol/1 enhanced the left ventricular contractility indexE _max (end-systolic maximum elastance) by 2.5 times before and after β-blockade with propranolol. The intracoronary Ca after β-blockade slightly but significantly increased τ_e, and hence increased RF calculated from τ_e by RF=exp(−1/τ_e). This was analogous to the slightly increased τ_c and RF with Ca before β-blockade. We speculate that the myocardial cyclic AMP-dependent phosphorylation level would not significantly alter the effect of intracoronarily administered Ca on myocardial Ca handling, in terms of τ_e and RF. This study was partly supported by Grants-in-Aid for Scientific Research (07508003, 09470009, 10770307, 10558136, 10877006) from the Ministry of Education, Science, Sports and Culture, a Research Grant for Cardiovascular Diseases (7C-2) from the Ministry of Health and Welfare, 1997 and 1998 Frontier Research Grants for Cardiovascular System Dynamics from the Science and Technology Agency, and research grants from the Ryobi Teien Foundation, the Mochida Memorial Foundation, and the Nakatani Electronic Measuring Technology Association, all of Japan.     

Relationships between beat-to-beat interval and the strength of contraction in the healthy and diseased human heart

Twenty-six adult patients, classified by clinical and catheter criteria into groups of those with normal and abnormal left ventricular function, were studied during cardiac catheterization. Right heart pacing was established, and left ventricular dP/dt was measured with end-catheter manometers. By varying the interval preceding a test beat after periods of steady pacing it was confirmed that recovery of left ventricular mechanical function (maximum dP/dt) occurs approximately 800 msec (optimum interval) after a beat. The augmentation of maximum dP/dt of the first 2 beats after an extrasystole, each spaced at the optimum interval, was also studied; the amount of potentiation was varied by alterations in extrasystolic interval. Potentiation decayed from the first to the second postextrasystolic beat with a ratio that was fixed in each individual patient. The ratio (recirculation fraction) was higher in patients with normal than in those with abnormal left ventricular function (mean +/- SD 0.52 +/- 0.10 vs 0.37 +/- 0.11, p less than .005). There was an inverse relationship between this ratio and the degree of potentiation of the first postextrasystolic beat (r = .80, p less than .001). We postulate a disturbance of excitation-contraction coupling mechanisms to explain these effects.     

Influence of left ventricular dysfunction on the role of atrial contraction: an echocardiographic-hemodynamic study in dogs

OBJECTIVES: The purpose of this study was to understand the significance of an effective atrial systole and the interactions between atrial and ventricular function. BACKGROUND: The significance of atrial function is controversial, particularly in the setting of left ventricular (LV) dysfunction. METHODS: Serial, rapid pacing in five dogs that had undergone radiofrequency ablation and implantation of right atrial and ventricular pacemakers produced reversible atrial and ventricular dysfunction (alone and in combination). Atrial function (echocardiograph-determined transmitral diastolic flow, left atrial appendage emptying, and pulmonary venous flow), cardiac output, and right heart pressures were measured at matched paced heart rates of 80 beats/min. RESULTS: Isolated rapid atrial pacing (LV ejection fraction approximately 60%) decreased atrial booster pump in the body and appendage of the left atrium, but increased the conduit function of the left atrium. Isolated LV dysfunction (LV ejection fraction approximately 34%) increased atrial booster pump function. The decreased atrial booster pump function in animals with combined atrial and ventricular dysfunction was incompletely compensated by the redistribution of the reservoir and conduit functions of the left atrium. As a result, cardiac output decreased and right heart pressures increased only after superimposed pacing. CONCLUSIONS: In the presence of a normal left ventricle (LV), atrial failure has little effect on cardiac output and right heart pressures because of compensatory conduit function, but when early LV dysfunction coexists, changes in reservoir and conduit functions are insufficient to compensate for an impairment of atrial contraction.     

Atrial alternans: Experimental echocardiographic and hemodynamic demonstration during programmed pacing

Simultaneous hemodynamic and echocardiographic recordings were used to demonstrate mechanical atrial alternans during programmed atrioventricular (A-V) pacing in five open chest dogs. Each animal was studied in two stages, first with the A-V conduction system intact (phase I) and later after the experimental induction of complete A-V block (phase II). Atrial alternans was demonstrated during rapid atrial stimulation at cycle lengths ranging from 250 to 120 ms. During phase I, rapid atrial pacing resulted in complex combinations of variable A-V conduction disturbances with superimposed atrial and ventricular alternans. During phase II, atrial alternans could be observed during a programmed prolonged pause in ventricular activity. It is anticipated that this method will facilitate recognition of atrial alternans in various clinical situations and shed further light on its possible hemodynamic significance.     

Accessory-pathway block on alternate beats in the Wolff-Parkinson-White syndrome: supernormal conduction as the mechanism

The Holter monitor electrocardiograms were taken from 2 patients with intermittent Wolff-Parkinson-White syndrome. In these patients, when the heart rate was increased, accessory-pathway block on alternate beats was found and was maintained for a considerably long period. In one patient, when accessory-pathway block on alternate beats was found, a ventricular extrasystole occurred. After the long compensatory pause after that extrasystole, a sinus impulse was blocked in the accessory pathway, showing that the effective refractory period of the accessory pathway is markedly long. These findings strongly suggest that alternate sinus impulses fell in the supernormal period of the accessory pathway. An attempt was made to explain the mechanism of accessory-pathway block on alternate beats by using the concept of supernormal conduction in the accessory pathway, in the same way as in bundle-branch block on alternate beats.     

Left ventricular inotropic effect of atrial pacing after coronary artery bypass grafting

The effect of atrial pacing on left ventricular (LV) performance was studied in 19 patients, 24 hours after coronary artery bypass grafting (CABG). LV volumes were calculated from simultaneous radionuclide-thermodilution measurements at rest (heart rate 82 +/- 12 beats/min), 10 minutes after the start of atrial pacing (100 beats/min), and with atrial pacing plus volume loading to return preload toward baseline. Atrial pacing reduced preload as reflected by LV end-diastolic volume index (69 +/- 14 vs 60 +/- 14 ml/m2, mean +/- standard deviation) (p less than 0.0001), but returned to baseline with volume loading. Afterload, as reflected by arterial end-systolic pressure, did not change with atrial pacing (63 +/- 9 at baseline vs 64 +/- 8 mm Hg with pacing, difference not significant). Afterload increased with volume loading (68 +/- 10 mm Hg, p less than 0.025 vs baseline and pacing). LV stroke volume decreased with atrial pacing due to reduced preload, but returned to baseline with volume loading. Cardiac index increased with atrial pacing and increased further with volume loading. Compared with baseline, LV end-systolic volume index was reduced during atrial pacing both before and after volume loading, despite unchanged or augmented afterload. The combination of atrial pacing and volume loading resulted in augmentation of LV stroke work, despite no increase in preload compared with baseline. Thus, after CABG, increased (paced) heart rate augments inotropic state, as indicated by reduced LV end-systolic volume under conditions of unchanged or increased afterload, and elevated LV stroke work without an increase in preload or a decrease in afterload.     

Ectopic right atrial rhythms: experimental and clinical data

In 18 out of 25 canine hearts studied with bipolar plunge electrodes, ectopic right atrial (RA) beats were observed occurring (1) spontaneously, (2) during vagal stimulation, (3) after destruction of the sinus node, and (4) during ventricular pacing. In these beats the RA appendage was activated first, followed by Bachmann's bundle, sinus node, left atrial appendage, posterior left atrium, and proximal coronary sinus. This sequence was consistently reproduced by pacing through the RA appendage recording electrode.     

Pressure-dimension analysis of the poststimulation potentiation--influence of heart rate and ventricular function (author's transl)

The mechanism of poststimulation potentiation (PSP) was studied in 17 patients with coronary artery disease by simultaneous pressure-dimension analysis. The left ventricular pressure (LVP) was measured by catheter-tip-micromanometer and LV diameter by M-mode echocardiography. The pressure signals were digitised and analysed on line by 400 Hz. The pressure-dimension tracings were additionally analysed half-automatically. Measurements were done during right atrial pacing at 80, 120, 140 beats/min and during the poststimulation period. 1. Right atrial pacing increased the rate of LV pressure development (dp/dt max), the rate of pressure fall (dp/dt min), the velocity of circumferential fiber shortening (VCF mn), and fiber dilatation (vcf mx) dependent on heart rate and cardiac function. 2. LV enddiastolic diameter (LVEDD) reached during the first poststimulation period the starting point independent on pacing rate and cardiac function. LV enddiastolic pressure (LVEDP) showed a slight overshoot. PSP resulted in an increase of LVP, dp/dt max, VCF mn, and the velocity of posterior wall motion, dp/dt min, VCF mx, and the velocity of posterior wall relaxation decreased, however, with the first post-stimulation beat. 3. The PSP was dependent on atrial pacing rate. The higher the pacing rate the higher the PSP. dp/dt max increased after cessation of 120/min for +29% and after 140/min for +38%. The PSP for the preload independent parameter of contractility, V-40, was, however, equal for both heart rates +25% and +28% respectively. 4. Another determinant of PSP was cardiac function. The PSP was relatively higher in patients with reduced ejection fraction than in patients with a normal ejection fraction: dp/dt max +55% and 25%, VCF mn +18% and +7% respectively. From the derived ventricular function curves, it could be shown, that atrial pacing reflected an increase in LV contractility (Bowditch effect), whereas PSP reflected an increase in LV performance by the Frank-Straub-Starling (Woodworth staircase) effect on a new left ventricular function curve, which was shifted to the left by atrial pacing.     

Prevention of torsade de pointes in the congenital long QT syndrome: use of a pause prevention pacing algorithm

Torsade de pointes in the congenital long QT syndrome (LQTS) is often pause dependent. Thus, the main goal of pacemaker treatment in the LQTS may be the prevention of pauses that facilitate the onset of torsade de pointes. A pause prevention pacing algorithm (rate smoothing) was used for arrhythmia prevention in a 14 year old girl with congenital LQTS. By temporarily increasing the pacing rate after spontaneous premature beats, rate smoothing down of 18% prevented postextrasystolic pauses, pause related T-U changes, and recurrence of pause induced torsade de pointes. Rate smoothing is a potentially useful tool that ought to be evaluated for the prevention of torsade de pointes in the LQTS.

Keywords: long QT syndrome; torsade de pointes; ventricular fibrillation; ventricular tachycardia; pacing     

Clinical and hemodynamic characteristics of patients with inducible pulsus alternans

Pulsus alternans can be found in some patients with abnormal left ventricular function and also can develop after spontaneous premature beats. The purposes of this study were to: (1) determine the inducibility of pulsus alternans in a series of patients referred for routine cardiac catheterization and (2) define the clinical and hemodynamic characteristics of those who develop pulsus alternans. In 104 patients referred for right and left heart catheterization, atrial premature beats and rapid atrial pacing were used to try to provoke pulsus alternans. The 29 patients who developed pulsus alternans in response to these maneuvers were older (63 +/- 6 vs 59 +/- 10 years, p less than 0.01) and had a greater incidence of valvular heart disease (45% vs 23%, p less than 0.01) and congestive heart failure (38% vs 17%, p less than 0.05). Aortic stenosis was the most prevalent valve lesion found. Those who developed pulsus alternans in response to pacing were further characterized by higher left ventricular systolic (143 +/- 42 vs 121 +/- 23 mm Hg, p less than 0.02) and end-diastolic pressures (17 +/- 9 vs 13 +/- 6 mm Hg, p less than 0.05), higher pulmonary artery systolic pressure (35 +/- 14 vs 29 +/- 11 mm Hg, p less than 0.04), and lower left ventricular ejection fractions (0.42 +/- 0.13 vs 0.53 +/- 0.14, p less than 0.001). Eight patients (28%) with inducible pulsus alternans had a normal left ventricular ejection fraction (greater than 0.50) and left ventricular end-diastolic pressure (less than 13 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Dynamic ventriculography in patients with ischaemic heart disease. II. Influence of postextrasystolic potentiation on left ventricular function.

The effect of postextrasystolic potentiation [PESP] on left ventricular [LV] function was assessed by means of left ventricular cineangiography in 26 patients with ischaemic heart disease. Ventricular extrasystoles were induced by a catheter inserted into the LV during injection of the contrast agent. The values of parameters of segmental and global function of LV, found in potentiated and nonpotentiated sinus contractions, were compared. Segmental disturbances present at rest in 13 patients improved or disappeared after extrasystole in 8 patients. Improvements in contraction also took place in segments with normal resting contraction. Global LV function improved significantly; an improvement was observed even without an increase in the LV end-diastolic volume in the postextrasystolic beat. The advantages and limitations of the method for preoperative estimation of the effect of intended myocardial revascularization on the LV function are discussed.     

Localized and dynamic repolarization alternans in Ajmaline accentuated Brugada syndrome

We performed incremental atrial pacing immediately after Ajmaline infusion in an asyntomatic female patient whose basal ECG was suggestive of Brugada Syndrome. Ajmaline accentuated the BS ECG pattern. Incremental Atrial pacing induced localized and dynamic repolarization alternans and unequal diastolic intervals (TQ intervals). No ventricular rhythms were elicited (other than short-coupled, monomorphic, low-density ventricular beats.