Postextrasystolic Research Articles

Arterial and Left Ventricular Pressures Illude Transient Alternans of Contractility during Postextrasystolic Potentiation

We have previously found that the postextrasystolic (PES) potentiation (PESP) of the left ventricular (LV) contractility (Emax) decays typically in transient alternans even in the normally ejecting canine heart. This contradicted the general expectation that arterial pressure (AP) and LV pressure (LVP) usually decay exponentially during PESP. We hypothesized this contradiction to be due to the different cardiodynamic behaviors of AP and LVP from LV Emax during PESP. We tested this hypothesis by measuring AP, LVP, LV volume, Emax, effective arterial elastance (Ea) as an index of afterload, and pulse pressure (PP) during PESP in eight anesthetized open-chest dogs by using the conductance catheter system. We changed Ea by changing the total peripheral resistance (TPR) with methoxamine hydrochloride (iv) and repeated the measurements. Although the Emax alternans patterns during PESP were comparable between the normal and high afterloads, LVP and PP were slightly potentiated and alternated under the normal afterload, whereas LVP and PP were obviously potentiated and alternated under the high afterload. We also simulated the effects of Ea/Emax on the transient alternans of AP and LVP on a computer. Despite the same alternans pattern of Emax, a higher Ea/Emax, which is typical in heart failure, caused a larger PP alternans, whereas a lower Ea/Emax, which is typical in normal hearts, almost eliminated it. These results suggest that a transient alternans of LV contractility during PESP could be overlooked when AP and LVP are monitored in in situ normal hearts.

Postextrasystolic contractility normally decays in alternans in canine in situ heart.

We have reported that the postextrasystolic (PES) potentiation of left ventricular (LV) contractility usually decays in alternans at heart rates above 80-100 beats/min in the canine excised, cross-circulated heart. We examined whether the PES contractility would also decay in alternans even in the canine in situ heart presumably more physiological than the excised heart. In anesthetized, ventilated, and open-chest mongrel dogs, we measured LV pressure and volume with a micromanometer and a conductance catheter cannulated into the LV and obtained LV end-systolic maximum elastance (E(max)) as the reasonably load-independent contractility index. We inserted an extrasystole followed by a compensatory pause into steady-state regular beats at heart rates above 90 beats/min and analyzed the PES decay pattern of E(max). We found that E(max) potentiated in the first PES beat decayed in alternans within 5-6 PES beats. This indicates that PES contractility also decays in alternans in the normal canine in situ heart.

New calculation of internal Ca(2+) recirculation fraction from alternans decay of postextrasystolic potentiation.

In our previous studies, we calculated the internal Ca(2+) recirculation fraction (RF) after obtaining the beat decay constant (tau(e)) of the monoexponential component in the postextrasystolic potentiation (PESP) of the alternans decay by curve fitting. However, this method sometimes suffers from the sensitive variation of tau(e) with small noises in the measured contractilities of the 5th and 6th postextrasystolic (PES) beats in the tail of the exponential component. We now succeeded in preventing this problem by a new method to calculate RF without obtaining tau(e). The equation for the calculation in the new method expresses an alternans decay of PESP as a recurrence formula of PESP. It can calculate RF directly from the contractilities of the 1st through the 4th PES beats without any fitting procedure. To evaluate the reliability of the new method, we calculated RF from the alternans decay of PESP of the left ventricle (LV) of the canine excised cross-circulated heart preparation by both the original fitting and the new method. Although there was no significant difference in the mean value of the obtained RF between these two methods, the variance of RF was smaller with the new method than with the original method. Thus the new method proved useful and more reliable than the original fitting method.

The heart extrasystole: an energetic approach.

The consequences of an extrasystole (ES) on cardiac muscle's energetics and Ca2+ homeostasis were investigated in the beating heart. The fraction of heat release related to pressure development (pressure dependent) and pressure-independent heat release were measured during isovolumic contractions in arterially perfused rat ventricle. The heat release by a contraction showed two pressure-independent components (H1 and H2) of short evolution and a pressure-dependent component (H3). The additional heat released by ES was decomposed into one pressure-independent (H'2) and one pressure-dependent (H'3) component with time courses similar to those of control components H2 and H3. ES also induced the potentiation of pressure development (P) and heat release during the postextrasystolic (PES) beat. The slope of the linear relationship between pressure-dependent heat and pressure maintenance was similar in control, ES, and PES contractions (0.08 +/- 0.01, 0.10 +/- 0.02, and 0.08 +/- 0.01 mJ. g-1. mmHg-1. s-1, respectively). The potentiation of H2 (heat component related with Ca2+ removal processes) in PES was equal to H'2 at 0.3, 0.5, 1, and 2 mM Ca2+, suggesting that the extra amount of Ca2+ mobilized during ES was recycled in PES. Pretreatment with 1 mM caffeine to deplete sarcoplasmic reticulum Ca2+ content inhibited both the mechanical and energetic potentiation of PES. However, the heat released and the pressure developed during ES were not changed by sarcoplasmic reticulum depletion. The results suggest that 1) the source of Ca2+ for ES would be entirely extracellular, 2) the Ca2+ entered during ES is accumulated in the sarcoplasmic reticulum, and 3) the Ca2+ stored by the sarcoplasmic reticulum during ES induces an increased contribution of this organelle during PES compared with the normal contraction.

Dependence of Doppler echocardiographic transmitral early peak velocity on left ventricular systolic function in coronary artery disease

The influence of systolic function on pulsed Doppler echocardiographic transmitral flow velocity patterns was assessed before and after postextrasystolic (PES) potentiation in 12 normal subjects (control group) and in 25 patients with previous healed myocardial infarction (MI) group. Simultaneous high-fidelity left ventricular pressure measurements were performed in all patients. A programmed single-coupled right ventricular extrasystole was induced during echocardiographic and subsequent cineangiocardiographic recordings. Adequate angiograms for volumetric analysis in both baseline and PES beats were obtained in 23 patients (7 in the control group and 16 in the MI group). PES potentiation of contraction was more pronounced in the MI group than in the control group. PES changes in ejection fraction, stroke volume and end-systolic volume were significantly greater in the MI group than in the control group (11 vs 5%, p < 0.005; 15 vs 5 ml/m 2, p < 0.005; and -13 vs -4 ml/m 2, p < 0.01, respectively). In contrast, PES potentiation prolonged the time constants of left ventricular pressure decline derived from exponential curve fits with a zero (Tw) and non-zero (Tb) asymptote pressure in the MI group to the same extent as in the control group (4 vs 5 ms, difference not significant [NS], and 9 vs 11 ms, NS, respectively). In the PES beat, peak E velocity remained unaltered (48 vs 49 cm/s, NS) in the control group, whereas it increased significantly (p < 0.0001) from 47 to 51 cm/s in the MI group. In contrast, peak E velocity normalized to time velocity integral during diastole, which is equivalent to volumetric peak filling rate normalized to stroke volume (SV), decreased after PES potentiation in both control and MI groups (from 5.2 to 4.7 SV/s, p < 0.005 and from 5.5 to 5.2 SV/s, p < 0.005, respectively). In conclusion, despite a prolonged relaxation, PES potentiation of contraction maintained peak E-wave velocity in the control subjects and enhanced H in patients with Ml. Early diastolic filling is strongly affected by systolic function. Thus, the influence of the preceding contraction should be accounted for in the Doppler echocardiographic assessment of early diastolic filling dynamics.

Influence of pacing site on canine left ventricular force-interval relationship

We tested the hypothesis that while absolute extrasystolic (ES) and postextrasystolic (PES) dP/dtmax would be influenced by pacing site, if these values were normalized by the steady-state dP/dtmax obtained with the same pacing site, they would be independent of pacing site. We employed an isovolumetrically contracting isolated heart preparation with a balloon placed in the left ventricle. Pacing electrodes were placed on the atrium and four different epicardial ventricular sites. While pacing from each site separately, a steady mechanical state was established at a constant rate, and the interval between beats was then perturbed. The same pacing sequence was used while pacing from each of the five sites. On each ES and PES beat, dP/dtmax was expressed as a percentage of the steady-state dP/dtmax. The normalized responses measured with each ventricular pacing site (DPventr) were plotted as a function of the normalized responses obtained with atrial pacing (DPatr). On average, DPventr = 1.02 DPatr - 3.2% (n = 6, with r2 = 0.989), indicating that pacing site did not significantly influence the "normalized" force-interval relationship. Thus the basic information retrievable from measurements of the ventricular force-interval relationship is independent of the site from which the heart is paced.

Assessment of potentially salvageable myocardium during acute myocardial infarction: Use of postextrasystolic potentiation

Twenty-three patients with evolving acute myocardial infarction (AMI) undergoing catheterization for thrombolytic therapy had interventional contrast ventriculography using programmed atrial stimulation. Postextrasystolic (PES) potentiation was present in 67% of infarct-related segments up to 9 hours after the onset of AMI. The presence of segmental potentiation was not related to time from onset of pain to ventriculography, initial ejection fraction, presence of collaterals, left ventricular end-diastolic pressure or the PES delay. In 18 patients reperfusion was successful using intracoronary streptokinase an average of 6.2 hours after the onset of AMI; in these patients repeat contrast ventriculography was performed an average of 11 days after AMI. Improved chronic segmental ventricular function was predicted by the presence of collaterals to the infarct-related artery at the time of acute catheterization (p = 0.02), but was best predicted by analysis of acute PES potentiation (p less than 0.0001). The predictive value of PES analysis was highest in segments without collaterals. Thus, atrial stimulation is safe during AMI and analysis of segmental ventricular function shows potentially viable myocardium up to 9 hours after the onset of AMI. In addition, analysis of PES segmental function can predict chronic function if reperfusion is successful, especially in segments without collaterals. PES ventriculographic analysis may allow prospective determination of which patients during AMI are most likely to benefit from acute thrombolytic therapy.

Postextrasystolic pulsus alternans and heart rate.

Postextrasystolic (PES) pulsus alternans, an alternation in systolic blood pressure above and then below base line for several beats after a premature ventricular depolarization was noted many years ago in patients with heart failure. We noted in acute animals studies that the occurrence of PES alternans was related to heart rate. We studied five open-chest dogs suppressing intrinsic heart rate by vagal stimulation and pacing the right ventricle over a range of 100-200 beats/min introducing an extrastimulus at 50% of the paced rate. We found that the pressure of the second PES beat was augmented up to 120 beats/min and then began to decrease approximately 10 Torr for each 10-beats/min increase in rate. The physiological variables most closely related to the occurrence of PES alternans were the duration of systole of the first PES (strong) beat and the rate of rapid diastolic filling of the second PES (weak) beat. Postextrasystolic and possibly sustained pulsus alternans is an inevitable consequence of heart rate and of the relationship between ejection and diastolic filling. The details of that relationship and the effects of various diseases determine whether alternans is observed or not.

Myocardial relaxation. V. Postextrasystolic contraction-relaxation in the intact dog heart.

Postextrasystolic (PES) relaxation of the left ventricle was studied in 24 anesthetized dogs using the time constant (tau) of the left ventricular isovolumic pressure decline as an index of global relaxation velocity. Using programmed atrial stimulation and a control RR interval of 500 msec, the "coupling interval/compensatory pause" was varied from 400/600 msec to 250/750 msec, and left ventricular pressure-segment length data from control beats were compared with data from PES beats. Contractile state and fractional shortening increased in the PES beat, but the relaxation time constant remained unchanged (control, 35 +/- 3 msec; PES at 250/750 msec, 36 +/- 3 msec) (p = NS). Pretreatment with propranolol did not qualitatively influence these results. Isoproterenol and calcium were given in doses sufficient to increase the time derivative of isovolumic pressure (maximal positive dP/dt) by an amount equal to that obtained with PES potentiation (approximately 50%); isoproterenol produced a substantial decrease in the relaxation time constant (38 +/- 4 to 30 +/- 6 msec, p less than 0.01), whereas calcium administration produced only a small decrease in the time constant (30 +/- 5 to 27 +/- 5 msec, p less than 0.05). Thus, in the intact dog heart, some positive inotropic interventions augment contraction and speed relaxation, but PES potentiation of contraction is not associated with a change in relaxation velocity.

Influence of timing of the extrasystolic beat on the extent of postextrasystolic potentiation in the intact human left ventricle.

The analysis of the post-extrasystolic (PES) beat, which follows an at random elicited extrasystole, has been used frequently in clinical studies for the evaluation of the functional reserve of the left ventricle. Therefore, the relation between the PES potentiation and the normalized coupling interval (RR'/RR) and the normalized length of the PES pause (R'R/RR) were investigated in patients with and without coronary heart disease by means of programmed extrasystoles. The PES increase of the maximal rate of left ventricular (LV) pressure rise (max dP/dt) showed a good exponential correlation with the coupling interval in the individual patients (r=0.87–0.99) and with length of the PES pause (r=0.87–0.99), as interpolated extrasystoles were excluded. With interpolated extrasystoles the correlation between the max dP/dt-increase and the length of the PES pause became much weaker (r=0.24 resp. 0.33 in two patients). As an angiographic ejection phase parameter of LV function the ejection fraction was analyzed. The change of EF in the PES beat was completely independent (r=0.05) from the coupling interval of tje preceding extrasystole and showed an only moderate correlation to the length of the PES pause (r=0.67), which became weaker when the interpolated extrasystoles were excluded (r=0.46).

Action potential configuration and contractile response during paired stimulation

Action potential configuration and contractile response during paired stimulation