Flow and power output of right ventricle facing load with variable input impedance.

The output from the right ventricle (RV) was studied at different load impedances. Isolated cat hearts were perfused with Tyrode solution with erythrocytes. Coronary perfusion pressure and RV end-diastolic pressure were kept constant. The RV pumped into an artificial hydraulic load with independently variable resistance (R) and compliance (C). Mean RV flow (RVO) decreased after R increase or C reduction. For each heart, RVO and mean RV pressure were linearly related. The slope of the regression line is interpreted as an "apparent source resistance" (Rs). Rs was on average 3.4 X 10(3) (dyn.s.cm-5). The static hydraulic power output was maximum at a certain load R (Rm). Rm was C dependent at an average high C of 5 X 10(-5) dyn-1.cm5, Rm was 9.4 X 10(3) dyn.s.cm-5 on average and shifted to 5.4 X 10(3) at low C (avg 0.8 X 10(-5). Theoretical considerations show that Rm/Rs will be equal to total heart period divided by ejection period in the extreme case C leads to infinity, and Rm/Rs leads to 1 when C leads to 0. Experimentally, Rm/Rs was 2.4 (avg) for high C, and approached 1 for low C, which fits the theoretical predictions. The results indicate that high C facilitates the matching between the right heart and the vascular resistance in the lung.     

Numerical modeling of ventricular filling

The fluid dynamical and physiological assumptions underlying general mathematical modeling of ventricular filling are outlined. We then describe the use of a lumped parameter model and computer simulation to study how the early transmitral velocity profile is affected by isolated changes in ventricular compliance and relaxation, atrial pressure and compliance, and valvular morphology. We show that the transmitral velocity is fundamentally affected by twophysical determinants: the transmitral pressure difference and the net compliance of the atrium and the ventricle. These physical determinants in turn are specified by the variousphysiologic parameters of interest. This approach has shown that peak velocity is most strongly affected by initial left atrial pressure, lowered somewhat by prolonged relaxation, low atrial and ventricular compliance, and systolic dysfunction. Peak acceleration is directly affected by atrial pressure and inversely affected by the time constant of isovolumic relaxation, with little influence of compliance, whereas the deceleration rate is almost purely given by mitral valve area divided by instantaneous atrioventricular compliance at the end of the rapid filling wave.     

Performance of the isolated,ejecting heart: effects of aortic impedance and exogenous substrates

The workload of the isolated, left-ventricular ejecting heart (i.e. working heart) is determined by the left atrial filling pressure and the afterload imposed on the left ventricular outflow tract. In addition to the level of end-diastolic aortic pressure, afterload is highly determined by the aortic impedance. For the isolated, ejecting heart optimum matching of the left ventricle to its afterload requires the highest possible similarity between the impedance of the artificial aortic conduit and the natural aortic impedance. The present study shows that the haemodynamic performance of the ejecting rat heart preparation can be affected by the impedance of the aortic conduit. A proper choice of substrates in the perfusion fluid further improves the performance of the heart in the artificial set-up. The present paper also provides guidelines with respect to the design of the aortic cannula and compliance chamber. The occurrence of turbulence, which is related to the Bernoulli pressure drop, is a major determinant of the impedance of the aortic conduit. This effect is used to simulate the natural resistance component of the aortic impedance. Further, the applicability of the perfusion model can be extended by the so-called assisted-mode perfusion, which allows automatic adjustment from antegrade to retrograde perfusion if the heart is not able to generate sufficient pumping power to provide its own coronary perfusion.Supported by NWO grant 900-516-091     

The effect of an increase in aortic pressure upon the inotropic state of eat and dog left ventricles

1. The effect of increased aortic pressure on the inotropic state of the left ventricle was studied in isolated cat hearts, perfused with bovine red cells in Tyrode solution, ejecting into a hydraulic model with the same input impedance as that of the cat aorta.2. Inotropic state was assessed at a controlled left ventricular end-diastolic pressure by interpolating single isovolumic beats by means of an occluder in the aortic cannula.3. When such isovolumic beats during periods of raised aortic pressure were compared with those during control periods, the difference in peak isovolumic pressure ranged from -0.3 to +0.5 kPa indicating differences in inotropic state which were small and inconsistent in direction.4. The maximum rate of rise of left ventricular pressure (dP/dt(max).) of ejecting beats was little affected by a rise of aortic pressure and the direction of changes was inconsistent.5. The effect of increased aortic pressure was studied in intact dogs after cardiac denervation; left ventricular end-diastolic pressure was uncontrolled and therefore rose to a higher steady level.6. No consistent change of dP/dt(max). was found during the period of increased aortic pressure.7. All flow and pressure variables remained steady during the period of increased aortic pressure after the higher level of left ventricular end-diastolic pressure had been established.8. These results demonstrate that neither the positive inotropic effect nor the negative inotropic effect of increased load dominates in these preparations. This may be the result of a balance between the two effects, or they may be of unimportant magnitude under physiological conditions.     

The arterial Windkessel

Frank’s Windkessel model described the hemodynamics of the arterial system in terms of resistance and compliance. It explained aortic pressure decay in diastole, but fell short in systole. Therefore characteristic impedance was introduced as a third element of the Windkessel model. Characteristic impedance links the lumped Windkessel to transmission phenomena (e.g., wave travel). Windkessels are used as hydraulic load for isolated hearts and in studies of the entire circulation. Furthermore, they are used to estimate total arterial compliance from pressure and flow; several of these methods are reviewed. Windkessels describe the general features of the input impedance, with physiologically interpretable parameters. Since it is a lumped model it is not suitable for the assessment of spatially distributed phenomena and aspects of wave travel, but it is a simple and fairly accurate approximation of ventricular afterload. J.-W. Lankhaar is supported by a grant from the Netherlands Heart Foundation, the Hague, the Netherlands (NHS2003B274).     

Consequences of myocardial structural adaptation on left ventricular compliance and the Frank-Starling relationship in spontaneously hypertensive rats.

The Frank-Starling relationship of hearts from adult spontaneously hypertensive rats (SHR, Okamoto 1969), representing the established phase of hypertension, and of young SHR, representing the initial phase of hypertension, was investigated by using the isolated working heart preparation. In the "normal" diastolic pressure range (5 to 10 cm H2O), the left ventricle of both SHR groups displayed significantly reduced stroke volumes compared with hearts of normotensive controls (NCR); the degree of reduction being proportional to the left ventricular hypertrophy. This is suggested to be due to a reduced left ventricular diastolic compliance in SHR, as indicated by direct measurements of ventricular wall thickness and end-diastolic volumes in arrested hearts exposed to different end-diastolic filling pressures. Such a progressive shift of the Frank-Starling relationship to the right with duration of hypertension could, in combination with the gradual development of "structural autoregulation" of the precapillary resistance vessels, constitute dominating factors in shifting the hemodynamic situation in labile hypertension into that characterizing the established, or "fixed", state of hypertension.     

Left ventricle load impedance control by apical VAD can help heart recovery and patient perfusion: a numerical study

The aim of this work is to investigate the dependence between left ventricular load impedance control by an apical ventricular assist device (VAD) and the consequent benefits for pathological heart recovery. A pathological left ventricle with 34% contractility has been simulated in the assisted and nonassisted conditions. By means of an extended Kalman filter, left ventricular pressure-volume loops have been partially estimated and ventricular as well as circulatory quantities inferred. The heart operation mode, based on cardiac energetic criteria, is imposed by controlling the VAD filling phase. In the assisted condition, results show that the left ventricle end-diastolic volume, left atrial pressure, and wall stress all decrease; stroke volume, ejection fraction, ventricular efficiency, aortic pressure, and cardiac output all increase. Benefits are also evident for the right ventricle and systemic and pulmonary circulation. The strategy outlined in this work also shows that good results for heart recovery are achievable and a possible way to improve the functional properties of commercial pulsatile VADs.     

The step response of left ventricular pressure to ejection flow: A system oriented approach

Left ventricular pressure is dependent on both ventricular volume and ventricular ejection flow. These dependencies are usually expressed byventricular elastance, andresistance, respectively. Resistance is a one-valued effect only, when ejection flow either is constant or increases. Decreasing ejection flow elicits a third effect: a decrease of elastance. The effects of elastance, resistance and elastance depression were modeled in a three-compartment model consisting of a dead-volume compartment, an elastance compartment, and a second series-elastance compartment connected to the elastance compartment by a resistance. This model was identified with the pressure response determined experimentally by imposing pumped constant-flow ejection epochs on isolated rabbit hearts. The experimental flow epochs consisted of two phases of constant flow separated by an increasing or decreasing flow step. It was found that elastance is not changed after the flow step if this is positive or zero. Negative flow steps induced a deactivation of elastance that is linearly dependent on the difference between isovolumic pressure that would be developed at the volume existing at the time of measurement and actual pressure. The parameters found from the identification procedure are ventricular active volume, nondepressed elastance, series-elastance, resistance, and the elastance deactivation factor. The first four parameter values were found in agreement with other results reported in literature. The elastance depression factor is a new parameter that could be of physiological or clinical significance since it may be related to the inability of the force generators in the heart muscle to be restored to their full number, after being inactivated or decoupled by filament sliding associated with ejection. On the basis of the results, an alinear state-model of the ventricle, for arbitrary, including physiological flow patterns is proposed.     

Ischaemic contracture and myocardial perfusion in isolated rat heart

Summary The development of left ventricular contracture and myocardial perfusion defect was studied in isolated rat hearts during global ischaemia of 90 min duration. The left ventricular pressure was measured by a balloon catheter inserted into the ventricle and filled with water. The pressure reached the maximum at 16 min of ischaemia. The left ventricular volume and compliance (passive distensibility) were measured by the same balloon, the former by connecting the balloon to an open catheter and the latter by applying a constant additional volume (0.020 ml) into the balloon. The left ventricular volume and compliance both decreased progressively for 20 min of ischaemia after which they remained low for the rest of the observation period (90 min). The myocardial perfusability was tested by infusing 0.1 per cent sodium fluorescein in isotonic saline into the cannulated aortic root of the isolated heart preparation. The percentage perfused with the fluorescent tracer in horizontal frozen myocardial sections was estimated by point counting from colour photographs taken under ultraviolet light. The proportion of the perfused area decreased gradually from 100% at 0 min of ischaemia to 93, 67, 43 and 37% at 15, 30, 60 and 90 min of ischaemia, respectively. It was concluded that ischaemic contracture of the left ventricle is followed by the development of a myocardial perfusion defect in isolated ischaemic rat heart.     

Remodeling of chick embryonic ventricular myoarchitecture under experimentally changed loading conditions

Adult myocardium adapts to changing functional demands by hyper‐ or hypotrophy while the developing heart reacts by hyper‐ or hypoplasia. How embryonic myocardial architecture adjusts to experimentally altered loading is not known. We subjected the chick embryonic hearts to mechanically altered loading to study its influence upon ventricular myoarchitecture. Chick embryonic hearts were subjected to conotruncal banding (increased afterload model), or left atrial ligation or clipping, creating a combined model of increased preload in right ventricle and decreased preload in left ventricle. Modifications of myocardial architecture were studied by scanning electron microscopy and histology with morphometry. In the conotruncal banded group, there was a mild to moderate ventricular dilatation, thickening of the compact myocardium and trabeculae, and spiraling of trabecular course in the left ventricle. Right atrioventricular valve morphology was altered from normal muscular flap towards a bicuspid structure. Left atrial ligation or clipping resulted in hypoplasia of the left heart structures with compensatory overdevelopment on the right side. Hypoplastic left ventricle had decreased myocardial volume and showed accelerated trabecular compaction. Increased volume load in the right ventricle was compensated primarily by chamber dilatation with altered trabecular pattern, and by trabecular proliferation and thickening of the compact myocardium at the later stages. A ventricular septal defect was noted in all conotruncal banded, and 25% of left atrial ligated hearts. Increasing pressure load is a main stimulus for embryonic myocardial growth, while increased volume load is compensated primarily by dilatation. Adequate loading is important for normal cardiac morphogenesis and the development of typical myocardial patterns. Anat Rec 254:238–252, 1999. © 1999 Wiley‐Liss, Inc.     

Right ventricular function in rats with hypoxic pulmonary hypertension

The function of the hypertrophic right ventricle (RV) was studied in adult rats with hypoxic pulmonary hypertension induced by intermittent high-altitude (IHA) exposure. The isolated RV working heart preparation that was employed enabled us to estimate ventricular contractile and pump performance under controlled loading conditions. In rats exposed to IHA hypoxia the elevated RV systolic pressure and maximum rate of pressure development were observed at various levels of preload or afterload. The peak indices of mechanical performance were almost doubled in these animals when compared with the normoxic group, while the index of contractility remained unchanged. Maximum ventricular performance was found to be a linear function of the relative RV weight. No evidence of RV pump dysfunction was detected in rats exposed to IHA; moreover, the ability of the ventricle to maintain cardiac output against increased pulmonary resistance was markedly improved. The prevention of tricuspid regurgitation by using an artificial valve did not influence the functional curves and the peak ventricular performance. The regression of hypertrophy was accompanied by a reversal of ventricular function to control values, except for the persisting slight increase of peak RV pressure. It may be concluded that the increase of the RV mass in IHA-exposed rats serves to improve maximum ventricular performance, which aids in overcoming an elevated pulmonary resistance without disturbing the pump function.     

The Influence of Pulmonary Blood Flow Rate on Vascular Input Impedance and Hydraulic Power in the Sympathetically and Noradrenaline Stimulated Cat Lung

This study was designed to evaluate the influence of sympathetic nerve stimulation (NS) and α-adrenergic receptor stimulation (αS) on the pulmonary vascular input impedance and hydraulic power output of the right heart during variations of cardiac output (CO). An open chest cat preparation was used and pulsatile pressure and flow in the pulmonary artery were measured by high frequency response transducers. Calculations showed that vascular resistance (VR) was inversely dependent on CO, hut input impedance of the unstimulated lung was not influenced by CO variations. NS or αS increased VR and input impedance significantly, and the relation pulsatile hydraulic power/total hydraulic power (W_p/W_t) increased 40%, indicating that such stimulation has larger relative influence on impedance than on resistance. The reduction of arterial compliance during NS (maximal stimulus) was calculated to be 60%, independent of CO. Input impedance during NS or αS was reduced by CO elevations, probably because the concomitant distension of the arterial bed reduced arterial resistance and inertance. The ratio W_p/CO, which expresses the fraction of pulsatile hydraulic power lost per ml mean arterial flow, was found to be flow dependent both in control and stimulated conditions: W_p/CO was positively correlated to CO in control condition and weakly negatively correlated to CO during stimulation. At high CO the arterial vessels could he stimulated and stiffened without much extra load on the right heart.     

急性肺栓塞时左右心室压力容量关系变化的实验研究

目的: 建立急性肺栓塞（APE）动物模型，探讨急性肺栓塞时左右心室压力容量关系变化。方法: 成年杂种犬7只，依据动物模型建立过程中不同时段和压力负荷程度分为肺栓塞前组、中度肺栓塞和重度肺栓塞3组，采用漂浮导管经肺动脉内注射缝线线段的方法建立中度APE和重度APE动物模型，并测量心导管压力指标；使用超声心动图声学定量技术获得同步容量指标；两者结合建立左右心室简易压力容量关系。结果: 中度APE时，右室压力容量关系图明显向右上移位，面积扩大明显，环的形态由近似三角形向矩型转变；左室压力容量关系图则小幅度左下移位，形态无明显变化；重度APE时，右室压力容量关系图右上移位且面积缩小，形态不规则。左室压力容量关系图则较大幅度左下移位，面积缩小，形态不规则。结论： 急性肺栓塞时左右心室压力容量关系变化是APE血流动力学变化和临床预后的理论基础，是探讨APE血流动力学变化的实用、简便、直观方法。     

Consequences of Myocardial Structural Adaptation on Left Ventricular Compliance and the Frank-Starling Relationship in Spontaneously Hypertensive Rats

The Frank-Starling relationship of hearts from adult spontaneously hypertensive rats (SHR, Okamoto 1969), representing the established phase of hypertension, and of young SHR, representing the initial phase of hypertension, was investigated by using the isoloated working heart preparation. In the “normal” diastolic pressure range (5 to 10 cm H₂O), the left ventricle of both SHR groups displayed significantly reduced stroke volumes compared with hearts of normotensive controls (NCR); the degree of reduction being proportional to the left ventricular hypertophy. This is suggested to be due to a reduced left ventricular diastolic compliance in SHR, as indicated by direct measurements of ventricular wall thickness and end-diastolic volumes in arrested hearts exposed to different end-diastolic filling pressures. Such a progressive shift of the Frank-Starling relationship to the right with duration of hypertension could, in combination with the gradual development of “Structural autoregulation” of the precapillary resistance vessels, constitute dominating factors in shifting the hemodynamic situation in labile hypetension into that characterizing the established, or “fixed”, State of hypertension.     

Predictive changes in ventricular interdependence

Based on the balance of forces across the interventricular septum, we developed a theoretical analysis to explain how one ventricle can directly influence the filling characteristics of the other ventricle. The analysis indicated that the pressure and volume transfer were related to the relative compliances of the interventricular septum and ventricular free walls. The present study examined whether the theoretical analysis could be used to predict changes in ventricular interdependence caused by altering regional compliance. To examine this hypothesis, hearts were removed from 18 dogs and placed in cool cardioplegic solution. Balloons were inserted into each ventricle, and the left and right pressure (δP₁, δP_r) and volume (δV₁, δV_r) changes caused by changing the pressure and volume of the other ventricle were recorded. After the initial measurements, acute changes in left ventricular free wall compliance (n=6), septal compliance (n=6), and right ventricular free wall compliance (n=6) were induced by glutaraldehyde injections. As predicted by the theoretical analysis, decreasing left ventricular free wall compliance increased δP₁/δP_r, δP₁/δV_r, δP_r/δV₁, and δV_r/δV₁ significantly (P<0.05) by 89±15, 155±33, 282±65, and 112±22% (mean±SEM), respectively. Decreasing septal compliance decreases δP₁/δP_r, δV₁/δP_r, δV₁/δV_r, δP_r/δP₁, and δV_r/δV₁ significantly (P<0.05) by 48±7, 71±10, 69±14, 48±7, 62±8, and 57±13%, respectively. Decreasing right ventricular free wall compliance increased δP₁/δV_r, δV₁/δV_r, δP_r/δP₁, and δP_r/δV₁ significantly (P<0.05) by 97±25, 79±20, 57±18, and 59±23%, respectively. Furthermore, these alterations in ventricular coupling were predictable: The actual and predicted percentage changes in the transfer functions were in close agreement. The results of these studies show predictable alterations in the mechanical coupling between the ventricles following changes in right ventricular septal, and left ventricular free wall compliances.     

Circulatory assistance in small infants and neonates with a hydraulically driven system: a viable option?

We have developed a new drive system for a cardiac assist system for use with newborns and infants. This study reports results of animal experiments in which this system was tested using a commercially available 25-ml ventricle. A major property of the device is its hydraulic mode, which allows not only for the conventional full-empty mode (chamber completely filled in diastole) but also for the filled-empty mode, in which the chamber is completely emptied in systole but only partially filled in systole; this mode gives full flexibility to adjust the pump frequency for any given pump flow rate. The assist device was applied in eight pigs (weight 9-14 kg) for left ventricular assistance during normal and impaired cardiac function (pacing-induced cardiac shock, mean arterial blood pressure less than 40 mmHg). Both, full-empty and filled-empty mode during normal cardiac function led to significantly decreased pulmonary capillary wedge pressure, suggesting load reduction of the right ventricle. In impaired cardiac function, circulatory assistance increased the diminished cardiac output and systolic arterial blood pressure, although only the latter was statistically significant. Neither arterial lactate concentration nor oxygen uptake was reduced during circulatory assistance for normal and impaired cardiac function. These results suggest that the cardiac ventricular assist device can be used as an effective circulatory assist device and that the function of the newly introduced filled-empty mode, which allows for a high degree of functional flexibility, is not inferior to that of the classical, but less flexible, full-empty mode.     

Estimation of time-varying systolic properties of left ventricular mechanics

A simple model which represents a linear approximation of the pressurel volume/flow relationship extensively used for describing ventricular mechanics, especially in simulation studies, is developed. In this model, the left ventricle is represented by a pressure generator in series with viscous and elastic time-varying elements. Despite its simplicity, the model elucidates the intimate connections between some current approaches for characterising pulsatile ventricular behaviour. A conventional identification scheme was used to estimate viscous and elastic parameters from data measured in both isolated rabbit hearts and open-chest dogs. Their variations with preload and afterload are shown to reflect known local characteristics of the inherently nonlinear cardiac pump, which correspond also to relevant features at muscular level. These results, together with some recent experimental evidence, substantially support the finding that both viscosity and elastance vary with time in linear proportion to the isovolumic pressure.     

Design of an artificial lung compliance chamber for pulmonary replacement

Matching the impedance of an artificial lung for pulmonary replacement to native pulmonary impedance is important in preventing right ventricular dysfunction. A lumped-parameter theoretical model and bench-top experiments were used to investigate the effect of a prototype compliance chamber on input impedance. The bench-top simulation consisted of a pulsatile flow generator, a prototype compliance chamber, and a low resistance artificial lung connected in series. Effective compliance was varied using pneumatic compression. The theoretical model considered a similar circuit with resistors before and after a compliance element. The bundle flow pulsatility (flow amplitude divided by average flow) and input impedance were calculated in the theoretical and experimental models. More compliance and lower upstream resistance result in lower bundle flow pulsatility and reduced first harmonic impedance. Matching the time scale of the circuit to the period of pulsatile flow also reduces impedance. The bench-top circuit demonstrated an optimal chamber pressure at which first harmonic impedance is reduced by 80%. The prototype compliance chamber in series with the artificial lung more closely matches native pulmonary impedance. The lumped-parameter model and the bench-top simulation will aid in the design and testing of compliance chamber modifications to improve its efficiency.     

Analysis of the isovolumic pressure in the canine left ventricle

Summary Some of the factors which influence the shape of left ventricular isometric pressure are discussed. Complete isometric recordings were obtained in dogs by raising the afterload (aortic pressure) with a special blood pump of own design. The effects of ventricular geometry, myocardial wall thickness and finite velocity of the depolarization wave are discussed. The relation between active state of muscle fibers and isometrically developed pressure in the left ventricle is derived analytically. The commonly used velocity of the contractile element was computed in a new way by differentiation of logarithmically transformed pressure data. This derived function is compared with the simple derivative (dp/dt) with regard to their potential value as indices of myocardial contractility. Contractile element velocity as based on a 3-component model was not found sensitive to so-called contractility changes in the intact heart.     

Diastolic properties of the hypertrophied left ventricle in spontaneously hypertensive rats

The influence of myocardial hypertrophy on left ventricular volume compliance was studied in vitro in isolated hearts of 4 and 19 month old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). In both SHR groups diastolic volume compliance was similar to that in the controls, despite the presence of left ventricular hypertrophy. This seems to be mainly due to an altered geometric situation, since with increased wall thickness to internal radius ratio (w/ri), which was at hand, the less are outer myocardial layers stretched at a given increase in ventricular volume. This may imply that these layers will only little interfere with luminal distension (and thereby with diastolic volume compliance) in SHR. It was also observed that the progressive increase of ventricular hypertrophy from 4 to 19 months of age did not further increase w/ri in SHR, indicating an increase in overall ventricular size with age. Left ventricular end diastolic pressure (LVEDP) was also measured in conscious 5 week and 4 month old SHR compared with matched controls. LVEDP increased with the development of hypertension and was significantly elevated in 4 month old SHR. This will increase also the average diastolic pre-stretch of the SHR left ventricle and mobilize the "Starling mechanism" to maintain a normal stroke volume against the increased afterload for the heart in established hypertension. This seems particularly important since the hypertrophic w/ri increase (about 20%) is smaller than the great elevation of mean arterial pressure (40-50%) in SHR.