Effects Of Postextrasystolic Potentiation Research Articles

Intracellular calcium transients underlying interval-force relationship in whole rat hearts: effects of calcium antagonists

Much of the understanding about the cardiac interval-force relationship of the whole heart, including mechanical restitution and postextrasystolic potentiation (PESP), has been inferred from isolated muscle studies. We tested whether results from isolated muscles about intracellular Ca2+([Ca2+]i) transients underlying the interval-force relationship can be substantiated in whole hearts. Additionally, we investigated whether Ca2+ antagonists could alter [Ca2+]i transients underlying mechanical restitution and postextrasystolic potentiation. [Ca2+]i transients were studied in isolated perfused rat hearts by surface fluorometry and Indo-1. Using computer-controlled pacing protocols, we performed restitution curves for left ventricular developed pressure and [Ca2+]i (developed pressure and [Ca2+]i plotted as a function of extrasystolic intervals). To quantify restitution curves, we fitted monoexponential functions to plots and analyzed their shift and slope. Then, we used Ca2+ antagonists, low extracellular Ca2+([Ca2+]o) and PESP to modify restitution curves. [Ca2+]i transients in isolated rat hearts were interpreted as Ca2+ released from the sarcoplasmic reticulum. Interval-dependent changes in developed pressure were strongly correlated to interval-dependent changes in the amplitude of [Ca2+]i transients in isolated whole rat hearts. Additionally, nifedipine and low [Ca2+]o led to similar downward shifts but not to a changed slope of restitution curves for [Ca2+]i. On the other hand, PESP increased the slope of restitution curves for [Ca2+]i. Furthermore, the effect of PESP on developed pressure was blunted by high concentrations of Ca2+ antagonists. The results from isolated muscles about [Ca2+]i transients underlying the interval-force relationship could be substantiated in whole hearts. Additionally, low [Ca2+]i (induced by nifedipine or low [Ca2+]o) decreased the maximal Ca2+ release of the sarcoplasmic reticulum but did not change the release kinetics. On the other hand, PESP presumably accelerated Ca2+ release kinetics of the sarcoplasmic reticulum.

Effects of positive inotropic stimulation (post-extrasystolic potentiation) on non-uniformity of left ventricular contraction in patients with coronary artery disease.

In patients with chronic coronary artery disease, post-extrasystolic potentiation (PESP) slightly worsens relaxation, increasing the constant tau of ventricular pressure decay. However, it does not negatively influence left ventricular (LV) diastolic filling. To our knowledge, no data are available on the effects of PESP on segmental relaxation in chronic coronary artery disease. The effects of PESP on the LV pressure-volume (P/V) relationship and on segmental pressure-length loops (P/L) were studied in eight patients with coronary artery disease submitted to LV angiography. P/V loops were constructed by means of frame-to-frame analysis of ventriculograms and simultaneous high-fidelity LV pressure tracings; P/L loops were calculated by the endocardial movement of 45 chords intersecting the LV outline (centreline method). PESP was produced by programmed stimulation during ventriculography. P/V and P/L loops were studied in basal conditions and after PESP.(ABSTRACT TRUNCATED AT 250 WORDS)

Biventricular Function During Postextrasystolic Potentiation in Man A Study Using List-Mode Radionuclide Ventriculography

The effects of postextrasystolic potentiation during spontaneous ventricular ectopy on both left and right ventricular function were studied in 12 patients with the aid of list-mode radionuclide ventriculography. The left ventricular ejection fraction showed a significant increase (+ 11.0 +/- 5.0%; p less than .001) with associated mild increases in end-diastolic volumes (+ 4.9 +/- 4.6; p less than .01) and significant decreases in end-systolic volumes (-13.4% +/- 7.3%; p less than .001). A more heterogeneous response was seen for the right ventricle. Right ventricular ejection increased significantly in 8/12 patients (+ 3.3 +/- 3.0%; p less than .02). Despite a large increase in end-diastolic volumes (+ 10 +/- 7.9%; p less than .001), there were only mild changes in end-systolic volumes (+ 2.2 +/- 9.0; p = NS). It is concluded that, for spontaneous ventricular ectopy in man, the increase in right ventricular ejection fraction reflects improved ventricular filling whereas the increase in left ventricular ejection fraction is linked to improved emptying.

High-energy phosphates, myocardial contractile function and material properties after short periods of oxygen deficiency.

To investigate myocardial performance and diastolic properties after repeated periods of oxygen deficiency auxotonic and isovolumic measurements were performed after three periods (4 min) of asphyxia in Wistar rats (n = 19). Additionally, the response of the peak isovolumic left ventricular pressure to postextrasystolic potentiation was measured. The hemodynamic results were compared to the levels of high-energy phosphates. Already after 15 min of recovery from asphyxia auxotonic measures of systolic function were completely normal compared to the control group (n = 19). Isovolumic measurements after 20 min of postasphyctic recovery, however, demonstrated a considerable reduction of the peak left ventricular pressure (226.5 +/- 7.5 mm Hg vs. 262.6 +/- 3.4 mm Hg in controls, mean +/- SEM (p less than 0.01) indicating persistence of decreased postischemic contractile performance. The relative effect of postextrasystolic potentiation was similar in both groups, but could not compensate for the reduced performance of the postasphyctic hearts: the absolute postextrasystolic peak isovolumic pressure of the postasphyctic hearts was lower than the value of the regular isovolumic peak pressure in the controls. Diastolic properties (pressure/volume and stress/strain relationships) of the postasphyctic myocardium remained unchanged. The total sum of the adenine-nucleotides decreased from 7.2 +/- 0.2 to 5.6 +/- 0.3 mumol/gww (p less than 0.01). ATP was reduced from 4.8 +/- 0.2 to 3.9 +/- 0.3 mumol/gww (p less than 0.01). Phosphocreatine was elevated to 7.0 +/- 0.6 mumol/gww, x +/- SEM (p less than 0.01). Our results demonstrated normal postasphyctic basal hemodynamics and material properties. Thus, the energy supply was sufficient to maintain steady state conditions - in spite of decreased overall adenine-nucleotide levels. Isovolumic measurements and postextrasystolic potentation tests, however, indicated that the contractile performance of the postischemic myocardium was still reduced. This functional limitation cannot be explained by altered material properties and is probably not causally related to the decreased overall ATP content.

Diverging effects of postextrasystolic potentiation on left ventricular segmental wall motion in coronary heart disease

The effects of postextrasystolic potentiation (PESP) on regional left ventricular (LV) wall motion were evaluated in 40 coronary artery disease (CAD) patients. Of the 40 CAD patients, 20 had a prior myocardial infarction and 20 had a history of angina pectoris. PESP was obtained by applying programmed atrial stimulation during LV angiography, in a way that basal cycle length, premature beat, and postextrasystolic pause were almost identical in all patients. Segmental wall motion was evaluated by calculating regional ejection fraction (EF) of 5 different areas with a computerized method before and after the premature beat. The results were compared to those obtained in a group of 8 normal subjects. LV areas were classified as normokinetic, mildly hypokinetic, severely hypokinetic, and hyperkinetic, on the basis of their regional EF in respect to normals, and classified as "responder" (R) and "nonresponder" on the basis of the magnitude of the increase of regional EF with PESP. Of a total of 200 areas 129 were normokinetic (68% R), 45 were mildly hypokinetic (78% R), 17 severely hypokinetic (76% R), and 9 were hyperkinetic (78% R). Infarcted patients had a higher percentage of hypokinetic areas in basal conditions (p less than 0.001), however, the percentage of hypokinetic areas that responded to PESP was not significantly different from noninfarcted patients. In CAD patients, as a whole, a significant direct correlation was found between basal regional EF and regional EF after PESP (r = 0.88, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Force-interval relationship in heart muscle of mammals. A calcium compartment model

A mathematical model was derived that describes peak force of contraction as a function of stimulus interval and stimulus number in terms of Ca2+ transport between three hypothetical Ca2+ compartments. It includes the conventional uptake and release compartments and recirculation of a fraction r of the activator Ca2+. Peak force is assumed to be proportional to the amount of activator Ca2+ released from the release compartment into the sarcoplasm. A new extension is a slow exchange of Ca2+ with the extracellular space via an exchange compartment. Six independent parameters were necessary to reproduce the different effects of postextrasystolic potentiation, frequency potentiation, and post-rest potentiation in isolated heart muscle from the rat. The normalized steady state peak force (F/Fmax) under standard conditions varied by a factor of ten between preparations from rat heart. Analysis with the model indicated that most of this variation was caused by two variables: the Ca2+ influx per excitation and the recirculating fraction of activator Ca2+. The influence of the Ca2+ antagonist nifedipine of the force-interval relationship was reproduced by the model. It is concluded that the model may serve to analyze the variability of contractile force and the mode of actions of drugs in heart muscle.

Evaluation of left ventricular residual function using postextrasystolic potentiation. Relation between systolic time intervals and angiographic study.

The effects of postextrasystolic potentiation (PESP) on systolic time intervals and left ventricular wall motion were studied during diagnostic cardiac catheterization in 20 patients (4 normal individuals, 11 patients with coronary artery disease and 5 patients with idiopathic dilated cardiomyopathy). Postextrasystolic changes in the aortic pressure and systolic time intervals were measured from the electrocardiogram and aortic pressure tracing. After a micromanometer-tipped catheter was positioned in the ascending aorta just above the aortic valve, a single ventricular premature beat was introduced using an R-wave coupled stimulator. PESP was then studied during left ventriculography which was undertaken simultaneously in the right anterior oblique 30 degrees and left anterior oblique 60 degrees positions. Following two or three normal sinus beats, a right ventricular extrastimulus was delivered again under the same stimulating condition. PESP in all patients caused a decrease in the ratio of the preejection period to the left ventricular ejection time (PEP/ET). The average percent decrease was 21% (from 0.429 +/- 0.162 to 0.339 +/- 0.102, p less than 0.001). The left ventricular ejection fraction (EF) increased in all patients with PESP from 0.52 +/- 0.20 to 0.61 +/- 0.17 (p less than 0.001). The postextrasystolic changes in the PEP/ET ratio and EF were greater in patients with low cardiac performance. There was a good correlation (r = -0.85, p less than 0.001) between the changes in the EF and those in PEP/ET in PESP. Thus, it is possible to determine left ventricular residual function (the postextrasystolic change in the global EF) using the postextrasystolic change in PEP/ET in patients with coronary artery disease and dilated cardiomyopathy.

Intracellular calcium and myocardial contractility. II. Effects of postextrasystolic potentiation in the isolated rabbit heart.

Postextrasystolic potentiation was studied in the isolated perfused rabbit heart to determine its effect on intracellular calcium, sodium, and potassium concentration, 45 Ca uptake, and calcium distribution in mitochondria and microsomes. Paired stimulation at 80/min augmented myocardial contractility with a gradually developing increase in total intracellular calcium and sodium. A greater 45 Ca uptake was also observed and this was proportionate to the increase of intracellular calcium so that no change in exchangeable calcium occurred. A small but statistically insignificant increment was observed in mitochondrial and microsomal calcium. An increase of the rate of single stimuli to 160/min produced a minimal change in myocardial contractility compared to paired stimulation at 80/min, no change in total intracellular calcium, and a greater calcium uptake so that there was a significant increment in exchangeable calcium. Although these experiments do not identify the cellular processes responsible for the positive inotropic response to paired stimulation, they suggest that an alteration of myocardial calcium metabolism is involved. Furthermore, it is apparent that this alteration is distinct from that occurring during a comparable increase in the rate of delivery of single stimuli to the heart.

A comparison between frequency potentiation and postextrasystolic potentiation in vitro and in situ.

Until now, investigations of the force-frequency relationship and on postextrasystolic potentiation have mainly been performed in isolated heart muscle preparations. The present paper deals with similar studies carried out in situ. 1. Using an especially developed, electronically directed stimulation device the compensatory effects of haemodynamics in intact animals could largely be avoided. Accordingly, the validity of the laws, governing the contractile behaviour of isolated muscle preparations could also be demonstrated in the dog heart in situ.—The experimental arrangement allows the separation of the effects of postextrasystolic potentiation from those provoked by the Starling mechanism. 2. In vitro and in situ, the occurrence of extrasystoles does not only potentiate the contraction following the estrasystole but also the subsequent beats. The earlier the extrasystole occurs, the stronger the potentiating effect is. 3. In contrast to the studies in vitro, frequency potentiation could not be demonstrated satisfactorily in the dog heart in situ, probably as a result of the compensatory influence of the circulation. 4. On the other hand upon transition from a higher to a lower frequency in situ a clear cut potentiation was observed in the poststimulation phase. This potentiation could still be demonstrated when ventricular filling pressure and enddiastolic pressure in the aorta did not change any more. As in the isolated muscle preparation, a larger difference between the frequencies of stimulation provoked a larger degree of increased contractility. 5. The possibility to use frequency and postextrasystolic potentiation for the diagnostic evaluation of myocardial insufficiency in situ is discussed.