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Finite element (FE) modeling is becoming increasingly prevalent in the world of cardiac mechanics; however, many existing FE models are phenomenological and thus do not capture cellular-level mechanics. This work implements a cellular-level contraction scheme into an existing nonlinear FE code to model ventricular contraction. Specifically, this contraction model incorporates three myosin states: OFF-, ON-, and an attached force-generating state. It has been speculated that force-dependent transitions from the OFF- to ON-state may contribute to length-dependent activation at the cellular level. The current work investigates the contribution of force-dependent recruitment out of the OFF-state to ventricular-level function, specifically the Frank-Starling relationship, as seen through the end-systolic pressure-volume relationship (ESPVR). Five FE models were constructed using geometries of rat left ventricles obtained via cardiac magnetic resonance imaging. FE simulations were conducted to optimize parameters for the cellular contraction model such that the differences between FE predicted ventricular pressures for the models and experimentally measured pressures were minimized. The models were further validated by comparing FE predicted end-systolic strain to experimentally measured strain. Simulations mimicking vena cava occlusion generated descending pressure volume loops from which ESPVRs were calculated. In simulations with the inclusion of the OFF-state, using a force-dependent transition to the ON-state, the ESPVR calculated was steeper than in simulations excluding the OFF-state. Furthermore, the ESPVR was also steeper when compared to models that included the OFF-state without a force-dependent transition. This suggests that the force-dependent recruitment of thick filament heads from the OFF-state at the cellular level contributes to the Frank-Starling relationship observed at the organ level.

Functional adaptation of the right ventricle (RV) to its afterload plays an important prognostic role in pulmonary hypertension (PH) [1]. The preferred “multibeat” (MB) method for assessing RV–pulmonary vascular interaction involves the measurement of end-systolic elastance (Ees), the slope of the end-systolic pressure (ESP) to end-systolic volume over sequential heart beats with varying preload. The Ees value is then matched to simultaneous pulmonary arterial (PA) elastance at end systole (Ea), calculated as ESP pressure divided by stroke volume (SV). The ratio of Ees to Ea (Ees/Ea) is termed RV–PA coupling, preservation of which indicates maintenance RV functioning in the face of increasing afterload [1]. However, while the MB method is generally regarded as the reference standard, it requires continuous, accurate measurement of RV volume and is therefore not readily applicable in most clinical settings., Surrogates of right ventricle (RV) end-systolic pressure (ESP) used to determine RV–pulmonary artery coupling vary across studies. ESP using point of maximal time varying elastance provides most accurate estimate of actual ESP. https://bit.ly/3xuqX3B

The left ventricular (LV) end-systolic (ES) pressure volume relationship (ESPVR) is the cornerstone of systolic LV function analysis. We describe a 2D real-time (RT) MRI-based method (RTPVR) with separate software tools for 1) semi-automatic level set-based shape prior method (LSSPM) of the LV, 2) generation of synchronized pressure area loops and 3) calculation of the ESPVR. We used the RTPVR method to measure ventricular geometry, ES pressure area relationship (ESPAR) and ESPVR during vena cava occlusion (VCO) in normal sheep. 14 adult sheep were anesthetized and underwent measurement of LV systolic function. Ten of the 14 sheep underwent RTMRI and eight of the 14 underwent measurement with conductance catheter; 4 had both RTMRI and conductance measurements. 2D cross sectional RTMRI were performed at apex, mid-ventricle and base levels during separate VCOs. The Dice similarity coefficient was used to compare LSSPM and manual image segmentation and thus determine LSSPM accuracy. LV cross-sectional area, major and minor axis length, axis ratio, major axis orientation angle and ESPAR were measured at each LV level. ESPVR was calculated with a trapezoidal rule. The Dice similarity coefficient between LSSPM and manual segmentation by two readers was 87.31±2.51% and 88.13±3.43%. All cross sections became more elliptical during VCO. The major axis orientation shifted during VCO but remained in the septo-lateral direction. LV chamber obliteration at the apical level occurred during VCO in 7 of 10 sheep that underwent RTMRI. ESPAR was non-linear at all levels. Finally, ESPVR was non-linear because of apical collapse. ESPVR measured by conductance catheter (EES,Index = 2.23±0.66 mmHg/ml/m2) and RT (EES,Index = 2.31±0.31 mmHg/ml/m2) was not significantly different. LSSPM segmentation of 2D RT MRI images is accurate and allows calculation of LV geometry, ESPAR and ESPVR during VCO. In the future, RTPVR will facilitate determination of regional systolic material parameters underlying ESPVR.

The left ventricular (LV) end-systolic pressure volume relationship (ES; ESPVR) is the cornerstone of systolic LV function analysis. Recently, it became possible to measure 2D LV chamber shape during vena cava occlusion (VCO) with MRI. We used an improved level-set semi-automatic segmentation method (LSSM) to determine the effect of VCO on LV geometry, ES pressure area (PA) and ESPVR.10 healthy adult sheep were anesthetized. LV pressure transducer and inferior vena cava (IVC) balloon catheter were percutaneously inserted. Ferumoxytol (0.125 ml/kg iv; AMAG Pharmaceuticals, Waltham, MA) was given to enhance blood pool contrast. LV pressure and 2D retrospectively-gated cine MRI of LV cross sections 25 (Apex), 50 (Mid) and 75% (Base) of the distance from the apex to the base of the LV were obtained during separate IVC balloon inflations (VCO). LV pressure was digitally filtered and LV chamber segmented with the LSSM. Cross sectional area, major and minor axes, major axis orientation, ESPAR and ESPVR were calculated.The LSSM had excellent reliability. All cross sections became more elliptical during VCO. The orientation (angle) of each major axis relative to the anterior RV insertion shifted during VCO. However, the orientation remained toward the septum. There was chamber collapse (LV area < 0.25 cm2) at the apical level during VCO (7 cases). ESPAR was non-linear at all levels. ESPVR was non-linear because of apical collapse.In conclusion, MRI-based measurement of LV geometry, ESPAR and ESPVR during VCO is a valuable method that may lead to improved understanding of systolic LV function.New and NoteworthyReal-time MRI was used to continuously measure the LV PA relationship as loading conditions were transiently varied in anesthetized sheep. All three examined cross-sections became more elliptical during VCO. The ESPAR were non-linear at all three cross-sections. Chamber collapse at the apical level during VCO resulted in a non-linear ESPVR. The heart contracted in a non-concentric manner during VCO which could inform modeling studies and elucidate mechanisms underlying LV adaptations to sudden load changes.

Cardiac driver functions, used to model elastance changes that drive heart contraction, have significance both in the context of larger models and independently as a means of deriving important metrics such as the End Systolic Pressure Volume Relationship (ESPVR). This paper describes an approach for deriving the driver function on a beat-to-beat basis using a combination of strong correlations (R > 0.97) to readily measured aortic pressure waveform features and population constants assessed across a development cohort of 3 porcine specimens (62350 heartbeats). This approach was then validated over an independent test cohort of 4 porcine specimens (54410 heartbeats) and found to decrease the normalised area-under-the-curve error to a median of 18.0% compared to 41.0% when using only population constant values. This approach has the potential to provide further, real-time, patient specific information about the internal dynamics of the heart without requiring additional, invasive instrumentation of patients.

Objective The end-systolic pressure–dimension relationship (ESPDR) and the preload recruitable stroke work (PRSW) relationship are load-insensitive measures of contractility, but their clinical application has been limited by the need to record multiple beats over a wide volume range. In this study, we therefore sought to validate a new method to concomitantly determine the ESPDR and the PRSW relationship from a single beat. Methods Pressure–dimension loops were recorded in 14 conscious dogs under various haemodynamic and pathological conditions. Multiple-beat PRSW relationship was determined for its slope (Mw) and for a dimension-axis intercept (Dw). The ESPDR represented by the formula , was estimated from a steady-state, single-beat late-systolic pressure–dimension relationship. The single-beat Mw was determined as an end-systolic pressure when the end-systolic dimension was equal to Dw. Results A strong correlation was observed between multiple-beat and single-beat ESPDRs (zero-stress dimension; r=0.98, p

As a well-known property of the heart, many studies has reported that the left ventricular end-systolic pressure-volume relationship (ESPVR) is linear. However, the reason of the linearity is poorly understood. This article presents a multiscale circulation model to be a tool for theoretical analyses on the mechanism of the linearity of ESPVR. The model is composed of three sub-models; a detailed closed-loop lumped-parameter model for cardiovascular system, geometric left ventricle model, a comprehensive ventricular myocyte model. Although the present model integrates nonlinear sub-models, the model can successfully reproduce highly linear ESPVR without any arbitrary modifications.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:40:07Z No. of bitstreams: 1 S0066-782X2000000700003.pdf: 275689 bytes, checksum: 666888ff118721d9a482a1c5ce890b1b (MD5) Made available in DSpace on 2013-08-22T18:40:07Z (GMT). No. of bitstreams: 1 S0066-782X2000000700003.pdf: 275689 bytes, checksum: 666888ff118721d9a482a1c5ce890b1b (MD5) Previous issue date: 2000-07-01 Made available in DSpace on 2013-09-30T19:25:18Z (GMT). No. of bitstreams: 2 S0066-782X2000000700003.pdf: 275689 bytes, checksum: 666888ff118721d9a482a1c5ce890b1b (MD5) S0066-782X2000000700003.pdf.txt: 39324 bytes, checksum: 7e854408e6ae64f3617cb5263a0df495 (MD5) Previous issue date: 2000-07-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:07:13Z No. of bitstreams: 2 S0066-782X2000000700003.pdf: 275689 bytes, checksum: 666888ff118721d9a482a1c5ce890b1b (MD5) S0066-782X2000000700003.pdf.txt: 39324 bytes, checksum: 7e854408e6ae64f3617cb5263a0df495 (MD5) Made available in DSpace on 2014-05-20T15:07:13Z (GMT). No. of bitstreams: 2 S0066-782X2000000700003.pdf: 275689 bytes, checksum: 666888ff118721d9a482a1c5ce890b1b (MD5) S0066-782X2000000700003.pdf.txt: 39324 bytes, checksum: 7e854408e6ae64f3617cb5263a0df495 (MD5) Previous issue date: 2000-07-01 OBJECTIVE: To assess the effect of transient and sustained variations in cardiac load on the values of the end-systolic pressure-diameter relation (ESPDR) of the left ventricle. METHODS: We studied 13 dogs under general anesthesia and autonomic blockade. Variations of cardiac loads were done by elevation of blood pressure by mechanical constriction of the aorta. Two protocols were used in each animal: gradual peaking and decreasing pressure variation, the transient arterial hypertension protocol (TAH), and a quick and 10 min sustained elevation, the sustained arterial hypertension protocol(SAH). Then, we compared the ESDR in these two situations. RESULTS: Acute elevation of arterial pressure, being it transitory or sustained, did not alter the heart frequency and increased similarly the preload and after load. However, they acted differently in end systolic pressure-diameter relation. It was greater in the SAH than TAH protocol, 21.0±7.3mmHg/mm vs. 9.2±1.2mmHg/mm (p

Background On-line determination of right ventricular (RV) volume to assess its function is clinically difficult. Echocardiographic automated border detection measures of left ventricular (LV) cavity area have been shown to reflect changes in volume, and pressure-area relations have been used to estimate LV contractility. The potential for RV cavity area to estimate changes in volume and to assess RV function, however, has not been evaluated. Accordingly, the objective of this study was to determine the relation between echocardiographic automated border-detected RV cross-sectional area and true volume and to assess the potential for end-systolic pressure-area relations to estimate RV function in an isovolumically contracting isolated canine heart preparation. Methods and Results Eight excised dog hearts with both right and left intraventricular balloons were perfused in an ex vivo apparatus in which both ventricular volumes were controlled independently. RV area data from the level of the left midventricular short-axis plane and pressure data were recorded on a computer through a customized hardware and software interface with the ultrasound system. RV volumes were varied from 9.4±3.9 to 43.8±6.9 mL at each of three different LV volume ranges (low range, 12.5±3.8 mL; medium range, 23.9±5.6 mL; and high range, 37.5±5.4 mL). The variation of RV area during isovolumic contraction, which we called deformational area change, was considerable (1.49±0.68 cm 2 mean±SD) but did not change significantly with changing RV and LV volumes. Linear regression analysis correlated the maximum, minimum, and mean automated border-detected RV area during isovolumic contraction with absolute volume. A predominantly linear relation was observed, with the group mean r =.98 ( y =0.16 x +0.97; SEE=0.21 cm 2 ). The effect of LV volume on RV area-volume relation was a significant parallel downward shift ( P Conclusions Echocardiographic automated border-detected RV area reflects changes in RV volume under a constant LV volume, and the derived end-systolic pressure-area relation has potential for on-line assessment of RV function.

Left ventricular end systolic pressure (LV ESP) is important in assessing left ventricular performance and is usually derived from prediction equations. It is unknown whether these equations are accurate at rest or following exercise in a young, healthy population.Measured LV ESP vs. LV ESP values from the prediction equations were compared at rest, 15 min and 30 min following peak aerobic exercise in 60 participants.LV ESP was obtained by applanation tonometry at rest, 15 min post and 30 min post peak cycle exercise.Measured LV ESP was significantly lower (p0.05) at all time points in comparison to the two calculated values. Measured LV ESP decreased significantly from rest at both the post15 and post30 time points (p0.05) and changed differently in comparison to the calculated values (significant interaction; p0.05). The two LV ESP equations were also significantly different from each other (p0.05) and changed differently over time (significant interaction; p0.05).The two commonly used prediction equations did not accurately predict either resting or post exercise LV ESP in a young, healthy population. Thus, LV ESP needs to be individually determined in young, healthy participants. Non-invasive measurement through applanation tonometry appears to allow for a more accurate determination of LV ESP.

Because of the strong dependency of the end-systolic pressure-volume relation on the type of transient loading intervention in the in situ left ventricle (LV), experiments in the basal inotropic state in 16 open-chest anesthetized dogs were reanalyzed to find additional variables to model and predict end-systolic pressure (ESP) of both afterloading and preloading interventions by a single equation. Random-coefficients regression analysis was performed on 22 experiments in the basal inotropic state simultaneously, yielding an overall R2 of 0.97. The major part of total variance of ESP was due to linear terms of end-systolic volume (ESV) (74%) and stroke volume (SV) (19%). The SV effect was consistently negative and quantitatively quite important. An average load-independent end-systolic elastance of 6.7 mmHg/ml and an average SV effect of -5.7 mmHg/ml ejected were estimated, separating the “force-length” property from shortening effects in the in situ LV. History-related effects appeared to be only minor.

Over the past two decades, the end-systolic pressure-volume relationship (ESPVR) has undergone intensive investigation assessing its role as an index of ventricular contractile function and performance. From this investigation, we have learned that the ESPVR accurately assesses acute changes in contractility and is especially useful in the research setting where cardiac load can be controlled and altered. However, the need to alter load to develop the relationship and the dependence of ESPVR on cardiac mass limits broad clinical usage of the tool.

We investigated the effect of contractile state (CS) on the curvilinearity of the left ventricular (LV) end-systolic pressure-volume (Pes-Ves) and the dP/dtmax-end-diastolic volume (dP/dtmax-Ved) relations in eight anesthetized open-chest dogs. LV volume was determined from three orthogonal diameters measured by sonomicrometry. The Pes-Ves relation and dP/dtmax-Ved relation were assessed during transient vena caval occlusion and aortic constriction, while CS was altered with dobutamine. At all CS, both relations were linear when volumes were decreased by caval occlusion. However, at higher volumes obtained by aortic constriction, the relations became nonlinear. At enhanced CS, the nonlinearity of both the Pes-Ves relation and the dP/dtmax-Ved relation increased. The dP/dtmax-Ved relation began to deviate from linearity at larger volumes, but closer to baseline operating volume, than the Pes-Ves relation. The relation between end-systolic mean circumference stress and wall strain (sigma es-epsilon es) was linear at control CS when the Pes-Ves relation was nonlinear but became nonlinear with enhanced CS. We conclude that both the Pes-Ves relation and the dP/dtmax-Ved relation are nonlinear, saturating at higher volumes. With increased CS, the nonlinearity of both relations increases. This CS-dependent curvilinearity of the Pes-Ves relation is due to both CS-dependent nonlinearity of the sigma es-epsilon es relation (consistent with length-dependent activation) and geometric factors that alter the relation between Pes and sigma es.

This study presents new mathematical relations to link oxygen consumption to different areas under the end-systolic pressure-volume relation (ESPVR). The approach consists of approximating the relation between oxygen consumption and left ventricular pressure by a quadratic polynomial, and then relating the coefficients of the quadratic polynomial to different areas under the ESPVR. The procedure applies to both ejecting contraction and isovolumic contraction. The concept of external energy reserve, EER, is introduced and experimental data that corroborate the derived theoretical results are discussed. The clinical significance of the results obtained enhances the potential possibility of using ESPVR in clinical work.

This study compared end-systolic pressure-volume relationship (P/V) versus wall stress index (WS) as a tool for the evaluation of ventricular contractile state during upright isometric exercise. Both indices of contractility exhibit significant (p < 0.001) increase during exercise compared to resting values. The correlation coefficients for the two indices of contractility were r = -0.45 for exercise and r = -0.70 for rest. Both were significant at the p < 0.01 level. The correlation of the difference scores between rest and exercise as computed by both indices was low (-0.20) and insignificant. These data suggest that changes in contractility from rest to exercise as measured by one index do not reflect the pattern of individual differences that are measured by means of the other index. However, from a reliability point of view, it seems appropriate to prefer the use of P/V index over the WS index in order to determine contractile state.

The purpose of this study was to evaluate the usefulness of the end-systolic pressure-volume relationship, the end-systolic pressure-dimension relationship and the end-systolic wall stress-mean rate corrected velocity of circumferential fiber shortening relationship in patients with severe congestive heart failure due to a dilated cardiomyopathy

An elastance-based control (EBC) algorithm has been developed to produce a Frank-Starling response in a mockloop used for evaluation of ventricular assist devices. In this paper, the EBC has been tested for changes in contractility and afterload in order to evaluate its capabilities of mimicking the natural heart response. The results have shown that the end-systolic pressure-volume relationship remains fixed despite changes in afterload and reduction in end systolic pressure with decreasing contractility changes. The EBC algorithm has shown performance similar to the natural heart in response to afterload and contractility changes.

Background The end-systolic pressure-volume relationship is often considered as a load-independent property of the heart and, for this reason, is widely used as an index of ventricular contractility. However, many criticisms have been expressed against this index and the underlying time-varying elastance theory: first, it does not consider the phenomena underlying contraction and second, the end-systolic pressure volume relationship has been experimentally shown to be load-dependent. Methods In place of the time-varying elastance theory, a microscopic model of sarcomere contraction is used to infer the pressure generated by the contraction of the left ventricle, considered as a spherical assembling of sarcomere units. The left ventricle model is inserted into a closed-loop model of the cardiovascular system. Finally, parameters of the modified cardiovascular system model are identified to reproduce the hemodynamics of a normal dog. Results Experiments that have proven the limitations of the time-varying elastance theory are reproduced with our model: (1) preload reductions, (2) afterload increases, (3) the same experiments with increased ventricular contractility, (4) isovolumic contractions and (5) flow-clamps. All experiments simulated with the model generate different end-systolic pressure-volume relationships, showing that this relationship is actually load-dependent. Furthermore, we show that the results of our simulations are in good agreement with experiments. Conclusions We implemented a multi-scale model of the cardiovascular system, in which ventricular contraction is described by a detailed sarcomere model. Using this model, we successfully reproduced a number of experiments that have shown the failing points of the time-varying elastance theory. In particular, the developed multi-scale model of the cardiovascular system can capture the load-dependence of the end-systolic pressure-volume relationship.

The chronic changes of the end-systolic pressure-volume relationship (ESPVR) after regional myocardial infarction were evaluated in a sheep model. Pressure-volume area (PVA) obtained from the pressure-volume diagram and left ventricular oxygen consumption (LVO2) were studied. The regional myocardial infarction was created by ligating distal branches of the left coronary artery. ESPVR was obtained using a conductance catheter during transient inferior vena cava occlusion. Measurements were performed at baseline (n = 13), 1 hour (n = 8), 3 months (n = 9), and 6 months (n = 4) after infarction. Ees, the slope of the ESPVR did not change at 1 hour after infarction and remained the same at 3-month and 6-month measurements (baseline 2.26 +/- 1.24 mmHg/mL, 1 hour 2.71 +/- 1.06, 3 months 3.46 +/- 1.51, 6 months 2.45 +/- 0.64, NS). Because of the ventricular dilatation, which was demonstrated as an increase in changes of end-systolic volume (Ves) correlating with the time course after infarction (y = -3.21 + 0.12x, r = 0.454, p < 0.05), V0, the volume intercept of the ESPVR increased at 1 hour after the infarction, and showed a tendency to increase at 3 months and 6 months after the infarction (baseline -18.0 +/- 22.5 mL; 1 hour -0.9 +/- 11.6; 3 months 5.4 +/- 10.9, 6 months 9.2 +/- 23.1, baseline vs 3 months p < 0.05, baseline vs 6 months p < 0.05). PVA and LVO2 were unchanged over time after infarction (PVA: baseline 2097 +/- 1526 mmHg/mL per 100 g-1; 1 hour 1771 +/- 699; 3 months 2483 +/- 1086; 6 months 1,608 +/- 1,010, NS), (LVO2: baseline 40.6 +/- 13.1 x 10(-3) mL/100 g-1 per beat-1; 1 hour 42.9 +/- 9.7; 3 months 35.0 +/- 8.6; 6 months 31.2 +/- 18.1, NS). Chronic regional infarction in the sheep model did not affect Ees over 6 months, but significantly increased V0 after the increase in the acute phase. PVA and LVO2 were not affected by this regional infarction either acutely or over 6 months.

BACKGROUND Systolic shortening is known to produce muscle deactivation. The present study was designed to analyze whether the velocity and the timing of ejection play a role on end-systolic pressure-volume relations (ESPVR). METHODS AND RESULTS In isolated rabbit hearts, left ventricular pressure and volume were recorded and digitized, and left ventricular volume was controlled by a servosystem (4-millisecond cycles) to alter the timing of ejection. A significant deficit in end-systolic pressure was observed when ejection was late in systole with respect to earlier ejection. This was associated with a significantly reduced end-systolic elastance. End-systolic pressure of beats with slow ejection was intermediate between that of the beats with early ejection and that of beats with late ejection with a significantly increased end-systolic volume compared with beats with early rapid ejection. The same results were obtained with hypertrophied hearts (abdominal aortic stenosis). Pressure-volume loop areas were significantly increased in beats with slow ejections and with rapid delayed ejections versus early rapid ejections. No change in the positive peak of dP/dt was observed when the timing and the velocity of ejection were modified. CONCLUSIONS ESPVR is modified by the ejection profile, with a decreased end-systolic pressure and an increased pressure-volume loop area related to the velocity and the amount of shortening during the end-systolic phase. These indices of ventricular function thus must be used with caution when the timing of ejection is altered, and the end-diastolic volume-peak dP/dt relation may be a better index of ventricular function.

To clarify the difference of negative inotropic effects, we evaluated the effects of 0, 0.5, and 1 MAC halothane and enflurane on systolic performance in anesthetized, mechanically ventilated, vagotomized dogs. Left ventricular myocardial contractility was assessed by the slope of the end-systolic pressure-diameter relationship (Ees), which have been reported to be independent of alterations in preload and afterload but sensitive to changes in myocardial contractility. Both anesthetics decreased heart rate and dose-dependently decreased left ventricular systolic pressure. Enflurane decreased heart rate and left ventricular systolic pressure more than an equivalent MAC of halothane. Both anesthetics increased left ventricular end-diastolic diameter without any change in % shortening of the left ventricular internal diameter. TheEes was decreased to a similar extent at both 0.5 and 1 MAC halothane. TheEes was decreased with increasing concentrations of enflurane. TheEes was significantly larger (P

We predicted the shape of the end-systolic pressure-thickness relationship (ESPTR) by modeling the left ventricle as thick-walled sphere. To test the validity of the predicted relationships, we then measured the ESPTR over wide volume ranges in seven isolated blood-perfused canine hearts. Both simulation and experiments demonstrated that the ESPTR is curvilinear. However, within a physiological left ventricular systolic pressure range (80–150 mmHg), the ESPTR was described reasonably well by a straight line. Within that pressure range, changes in left ventricular contractile state, assessed by slope changes of the end-systolic pressure-volume relationship, were associated with almost parallel shifts in the ESPTR. In contrast, in a low pressure range (less than 80 mmHg), contractility changes were associated with slope changes of the ESPTR. We conclude that, in general, there are limitations in the application of ESPTR for assessing left ventricular contractility, but if the limitations are recognized and accounted for, then the ESPTR may be useful for assessing contractility changes in vivo.

Accurate determination of the transaortic valve gradient has required two catheters, one in the left ventricle and one in the ascending aorta. We now report a new technique for measurement of the transaortic valve gradient from the simultaneous left ventricular (LV) and femoral artery (FA) pressure tracings. This technique was compared with the "true" gradient obtained by measurement of the simultaneous LV and central aortic pressures, and is accurate (R = 0.999) and relatively simple. Other approaches used to determine the mean transaortic valve gradient were less accurate: simultaneous LV-FA (R = 0.991); aligned LV-FA (R = 0.974); averaged simultaneous and aligned LV-FA (R = 0.981); and nonsimultaneous LV-aorta pullback (R = 0.953). Thus, this new technique provides an accurate transaortic valve gradient without requiring the use of two central catheters.

End-systolic pressure (PES), volume (VES), wall tension (TES) and circumference (CES) of the human left ventricle were studied at cardiac catheterization in 24 subjects with varying degrees of left ventricular dysfunction. Acute alterations in systolic load consistently resulted in changes in VES and CES, with a smaller volume and circumference characterizing the lower systolic load in each subject. End systolic pressure-volume lines were constructed by plotting PES against VES at the higher and lower systolic load in each subject. The slope of the resultant lines was considerably steeper for normal than for poorly contractile left ventricles. Vo, the volume axis intercept of the line (i.e., the theoretical VES at PES = O) was significantly smaller for normal than for poorly contractile ventricles. Similar findings were noted for Co, the theoretic end-systolic circumference at zero end-systolic ventricular wall tension. Post-extrasystolic potentiation resulted in decreased VES and CES with no change in PES and only a slight fall in TES. In conclusion, end-systolic pressure-volume and tension-circumference relations reflect the contractile state of left ventricular myocardium. Quantitation of these relationships may provide a useful new approach to the assessment of myocardial function in man.

We studied the effects of regional ischemia on the left ventricular isovolumic end-systolic pressure-volume relationship (ESPVR) in six excised, blood-perfused canine ventricles. We created different extents of regional ischemia by ligating various branches of the coronary arteries while keeping the coronary arterial pressure constant (80 mm Hg). The extent of regional ischemia (Rm) relative to the total mass of the left ventricular myocardium was determined by regional myocardial blood flow measured by the radioactive microsphere technique. With regional ischemia, the ESPVR shifted rightward without significant change in slope in the physiologic end-systolic pressure range. In the subphysiological end-systolic pressure range, however, its slope became lower than control. In order to quantify the degree of the rightward shift, we measured the extrapolated volume axis intercept (Vo) by fitting a straight line to the ESPVR in the physiological range under control and ischemic conditions. The shift in Vo (delta Vo) associated with ischemia was linearly correlated with Rm (delta Vo = 50.7Rm-0.6, n = 28, r = 0.944, P less than 0.001). We conclude that the major effect of acute regional ischemia on the ESPVR in the physiological pressure range is a parallel rightward shift. This forms a striking contrast to the effect of global ischemia (under which only the slope is affected without a substantial change in Vo).

Myocardial contractility was measured using the end-systolic pressure-length (ESPL) relationship in dogs subjected to increasing concentrations of halothane (0.5-2 per cent), enflurane (0.77-2.6 per cent) or isoflurane (0.70-2.13 per cent), combined with an infusion 7 micrograms X kg-1 X min-1 of fentanyl, after induction of anaesthesia with 15 mg X kg-1 thiopentone. The relationship between the concentrations of the different drugs and contractility (ESPL) can best be described by ESPL = a + b/(MAC fraction) where "a" is a constant and "b" is the slope of the curve relating ESPL to MAC. At 1.0 MAC values, the ESPL for halothane (69.04 +/- 25.83 mmHg X mm-1) did not differ from that of isoflurane (63.19 +/- 17.36 mmHg X mm-1). However, the myocardial contractility during 1.0 MAC halothane and isoflurane anaesthesia was better preserved than that of enflurane (38.66 +/- 9.73 mmHg X mm-1: p less than 0.01, p less than 0.05 respectively).

SUMMARY Transfusion-dependent patients withthalassemia major(TM) are at an extremely highriskforcardiomyopathy. Traditional tests ofleft ventricular (LV)systolic function performed inthese patientsdo not distinguishderangements in loading conditionsfromabnormalitiesincontractilestate. Inthis study, we used the LV end-systolic pressure dimension (PES-DEs) relation, which is independent of preload,incorporatesafterloadandis highlysensitive to contractile state, to assess LV performancein20 asympto- matic, chronically transfusedpatients, ages 7-25 years, withTM.All patients had normalrestingsystolictimeintervalsand exerciseduration on treadmill. Baseline resting percentfractional shortening(%AD) on M-modeechocardiography(echo) was normalin 14 patients(group1) andabnormalinsix patients(group2). Echoandcarotidpulserecordings were made atrest andduringi.v. infusion of methoxamine to alter LV afterload. DE was measureddirectly fromecho; PES was estimatedfrom a calibratedcarotid pulsetracing.Thevalue for the slope ofthe

The mechanism of coupling in adrenaline-induced ventricular bigeminy in sensitized hearts has been investigated in intact animals, isolated preparations, and single cardiac fibers. The electrophysiological and cardiovascular dynamic changes during the development of fixed interval coupling strongly indicate that the coupled beats result from stretch of subsidiary pacemaker fibers in the specialized ventricular conduction system, induced by the mechanical response to the normally conducted sinus impulse. The resulting intraventricular pressure elicits an extrasystole, when a certain critical end systolic pressure for a particular animal is reached. The interval between the normal and premature ventricular beat decreases progressively as the intraventricular pressure rises, as a result of the combined action of adrenaline and postextrasystolic potentiation. The onset of ventricular bigeminy is preceded by a shift in the pacemaker site to the A–V junctional area, due to a differential effect of the anesthetic–adrenaline combination on fibers of the S–A node and those in the junctional area. The degree of prematurity of the coupled beat shows an inverse linear relationship to the intraventricular pressure of the initiating beat at the end of systole. The premature QRS complex occurs after a period of mechano–electrical latency, the duration of which is directly related to this pressure.

Ejection has previously been thought to exert only negative effects on end-systolic left ventricular pressure, via mechanisms like shortening deactivation and the force-velocity relation. Whether ejection also exerted a positive influence on pressure generation was tested by comparing two successive beats: 1) the last beat of steady-state ejection versus 2) a totally isovolumic contraction at the end-systolic volume. In 12 isolated, blood-perfused canine hearts loaded with a simulated arterial system, ejecting end-systolic pressure exceeded isovolumic pressure by approximately 10 mm Hg when ejection fraction was 0.3. With both higher and lower ejection fractions, the excess of ejecting end-systolic pressure was smaller; beyond an ejection fraction of roughly 0.5, the trend reversed so that ejecting end-systolic pressure fell below isovolumic pressure. The maximum excess in ejecting end-systolic pressure was quite variable (1-17 mm Hg), but the pattern of its variation with ejection fraction was consistent. A correlate of the positive effect of ejection on ventricular pressure was found in the timing of end systole. For an ejection fraction of 0.4, the systolic duration of ejecting beats was approximately 45% longer than in isovolumic beats (range, 23-67%). Potentially, a positive effect of ejection might be due to a residual influence of the stronger activation of cardiac myofilaments early in ejecting systole during which the sarcomeres were at longer lengths than in the isovolumic beat at end-systolic volume (length-dependent activation). A hypothetical model based on this mechanism reproduced both of the positive effects of ejection that were observed: excess end-systolic pressure and prolonged duration of systole. Thus, the approximate load independence of end-systolic pressure could result from the counter balance between opposing influences of ejection.

Although the rate dependence of isolated muscle contractility is well known, the ventricular end-systolic pressure-volume relationship (ESPVR) has been reported to be insensitive to heart rate. To resolve this contradiction, we used an isolated, ejecting canine heart preparation perfused at a constant coronary arterial pressure. Heart rate was changed from 60 to 200 beats/min in steps of 20 beats/min. At least 10 pressure-volume loops under different filling pressures were obtained at each heart rate in each of six hearts. Over a heart rate range from 60 to 120 beats/min, the slope of the ESPVR (Ees) increased significantly from 3.5 +/- 0.4 (SE) to 5.3 +/- 0.6 mm Hg/ml. In the range between 120 and 180 beats/min there was little change in Ees (5.3 +/- 0.6 to 5.4 +/- 0.6 mm Hg/ml), but at 200 beats/min Ees increased slightly to 5.7 +/- 0.5 mm Hg/ml. The volume axis intercept (V0) of the ESPVR changed little over the range of heart rate from 60 to 160 beats/min (10.2 +/- 2 ml to 9.4 +/- 1.3 ml) but increased to 15.2 +/- 1.2 ml at a rate of 200 beats/min. The change in ESPVR with increase in heart rate from 60 to 120 beats/min (i.e., increase in Ees without change in V0) is the same as those seen with a positive inotropic intervention with calcium or cathecholamines, whereas the V0 changes over the range from 160 to 200 beats/min is similar to those seen with regional ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

The left ventricular end-systolic pressure-volume relationship is a load-insensitive measure of left ventricular performance. The relationship at end-systole between left ventricular pressure and dimension is more easily obtained, but the conflicting results of previous studies make it unclear if it has the same properties as the left ventricular end-systolic pressure-volume relationship. To address this issue, 11 dogs were instrumented to measure left ventricular pressure and three orthogonal left ventricular dimensions. Left ventricular pressure and dimensions were varied by use of caval occlusion. Left ventricular volume was calculated as an ellipsoid. The left ventricular end-systolic pressure-volume relationship and each of the three end-systolic pressure-dimension relations were described by straight lines (r = .97 +/- .02, mean +/- SD). In six animals, dobutamine produced similar significant increases (p less than .01) in the slope of the end-systolic pressure-volume relationship (244 +/- 61% of control), the end-systolic pressure-anterior-posterior dimension relationship (248 +/- 89%), the end-systolic pressure--septal-lateral dimension relationship (211 +/- 95%), and the end-systolic pressure-basal-apical dimension relationship (210 +/- 85%). The intercepts at zero pressure were relatively unchanged by dobutamine. In contrast, occlusion of the distal left anterior descending coronary artery in five animals produced a rightward shift of the left ventricular end-systolic pressure-volume relationship and the pressure--basal-apical dimension relationship, while the pressure--anterior-posterior dimension and pressure--septal-lateral dimension relationships were relatively unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

End-systolic length-tension relationships were measured on ultrathin isolated heart preparations of rat (mean diameter ± S. D. = 96 μm ± 45 μm). Independent of contractile state being changed by variation in extracellular Ca + +-concentration no unique end-systolic length-tension relation was found when varying pre-and afterload over a wide range. It is more likely that rectilinear end-systolic curves can be obtained under a low contractile state than under a high one. Thus, the muscle physiological basis is withdrawn from the Emax-concept for which a single end-systolic pressure-volume relation is typical.