Left ventricular and myocardial perfusion responses to volume unloading and afterload reduction in a computer simulation

Ventricular assist devices (VADs) have been used successfully as a bridge to transplant in heart failure patients by unloading ventricular volume and restoring the circulation. In a few cases, patients have been successfully weaned from these devices after myocardial recovery. To promote myocardial recovery and alleviate the demand for donor organs, we are developing an artificial vasculature device (AVD) that is designed to allow the heart to fill to its normal volume but eject against a lower afterload. Using this approach, the heart ejects its stroke volume (SV) into an AVD anastomosed to the aortic arch, which has been programmed to produce any desired afterload condition defined by an input impedance profile. During diastole, the AVD returns this SV to the aorta, providing counterpulsation. Dynamic computer models of each of the assist devices (AVD, continuous, and pulsatile flow pumps) were developed and coupled to a model of the cardiovascular system. Computer simulations of these assist techniques were conducted to predict physiologic responses. Hemodynamic parameters, ventricular pressure-volume loops, and vascular impedance characteristics were calculated with AVD, continuous VAD, and asynchronous pulsatile VAD support for a range of clinical cardiac conditions (normal, failing, and recovering left ventricle). These simulation results indicate that the AVD may provide better coronary perfusion, as well as lower vascular resistance and elastance seen by the native heart during ejection compared with continuous and pulsatile VAD. Our working hypothesis is that by controlling afterload using the AVD approach, ventricular cannulation can be eliminated, myocardial perfusion improved, myocardial compliance and resistance restored, and effective weaning protocols developed that promote myocardial recovery.     

Biventricular support with the Jarvik 2000 ventricular assist device in a calf model of pulmonary hypertension

The Jarvik 2000 ventricular assist device (VAD) is clinically efficacious for treating end-stage left ventricular failure. Because simultaneous right ventricular support is also occasionally necessary, we developed a biventricular Jarvik 2000 technique and tested it in a calf model. One VAD was implanted in the left ventricle with outflow-graft anastomosis to the descending aorta. The other VAD was implanted in the right ventricle with outflow-graft anastomosis to the pulmonary artery. Throughout the 30 day study, hemodynamic values were continuously monitored. On day 30, both pumps were evaluated at different speeds, under various hemodynamic conditions. By gradually occluding the pulmonary artery proximally or distally, we simulated varying degrees of high pulmonary vascular resistance, right ventricular hypertension, global heart failure, or ventricular fibrillation. The two VADs maintained biventricular support even during pulmonary artery occlusion and ventricular fibrillation, yielding a cardiac output of 3-11 L/min, left ventricular end-diastolic pressure of 11-24 mm Hg, and central venous pressure of 9-25 mm Hg. End-organ function was unimpaired, and no major adverse events occurred. The dual VADs offered safe, effective biventricular assistance in the calf. Additional studies are needed to assess the effects of lowered pulse pressure upon the pulmonary circulation and to develop a single pump speed controller.     

Evaluation of recovery directed left ventricular assist device using isolated perfused rabbit hearts

We have developed a recovery directed left ventricular assist device (RDLVAD) that can promote cardiac recovery by achieving very low ventricular work and ensuring full ventricular relaxation and filling. It consists of a valved apical conduit, an afterload controlling chamber, and a centrifugal pump. To test the previously described effects of RDLVAD on the left ventricle, we made an RDLVAD suitable for isolated perfused rabbit hearts. The control LVAD was of a continuous flow type (CLVAD). Thirty-two rabbits were used. The working left heart model proved inappropriate for evaluation of LVAD. In the isolated heart-lung preparation (n = 4), the CLVAD showed a substantial backward flow and a severe negative pressure during diastole. This negative pressure may have resulted in severe restriction of ventricular relaxation and filling. In contrast, in the RDLVAD with the afterload controlling chamber pressure kept as low as possible, the pump flow was stable and increased by 86% (NS), and the peak left ventricular pressure, max dP/dt, and systolic pressure time index decreased by 22.3% (p = 0.022), 29.4% (p = 0.017), and 42% (p = 0.022), respectively. In conclusion, these results indicate that the RDLVAD does not restrict ventricular relaxation or filling and greatly reduces ventricular workload. The RDLVAD, therefore, can promote cardiac recovery.     

Modeling and control of a brushless DC axial flow ventricular assist device

This article presents an integrated model of the human circulatory system that incorporates circulatory support by a brushless DC axial flow ventricular assist device (VAD), and a feedback VAD controller designed to maintain physiologically sufficient perfusion. The developed integrated model combines a network type model of the circulatory system with a nonlinear dynamic model of the brushless DC pump We show that maintaining a reference differential pressure between the left ventricle and aorta leads to adequate perfusion for different pathologic cases, ranging from normal heart to left heart asystole, and widely varying physical activity scenarios from rest to exercise.     

人工心脏泵辅助对左心室血流动力学影响的数值研究

目的采用数值模拟方法研究人工心脏辅助装置植入对左心室内血流动力学的影响。方法首先利用心血管集中参数模型获取了健康状态、心衰状态以及人工心脏泵辅助状态下收缩末期左心室三维几何模型,其中选取超弹性材料Ogden为心肌材料,以左心房压力,主动脉压力以及通过左心室容积计算获取的左心室壁面位移作为边界条件,利用CFD方法对上述三种情况进行左心室的数值模拟。同时对比了健康时的模拟结果和生理状态下的左心室压力,以及心衰和人工心脏泵辅助两种状态下的血流动力学指标的差别。通过左心室压力和流速等评价灌注和负荷的情况,通过壁面切应力和涡流,评价人工心脏泵辅助后的左心室血流动力学变化规律。结果健康状态下模拟的左心室压力与生理指标相符合。在心衰和人工心脏泵辅助状态下,收缩期内左心室压力与健康状态比分别降低了1718 Pa和8455 Pa,辅助后左心室最大压力下降速度高于心衰时。人工心脏泵辅助后,舒张期壁面切应力峰值由4.3 Pa降低至3.8 Pa,收缩期壁面切应力峰值由4.1 Pa降低至1.3 Pa,射血速度峰值由1.61 m/s降低至0.68 m/s,主动脉瓣开放时间由0.25 s增加至0.65 s,左室射血分数由43.6%增加至52.7%,心室底端漩涡持续时间由0.35 s增加至0.51 s,顶端漩涡出现血流分离。结论左心室压力对比表明本研究方法可以用来模拟左心室的行为。人工心脏泵辅助能够快速降低心室内压力和心室负荷,增加灌注时间,提高器官灌注,降低左心室壁面切应力以及提高左心室内血液流场的涡流强度,延长涡流持续时间。     

Norepinephrine-induced cardiac hypertrophy of the cat heart

Norepinephrine administration causes progressive hypertrophy of the mammalian heart as measured by myocardial mass. The purpose of this study was to determine the growth response of the myocardial tissue components as well as the myocardial cell itself to norepinephrine. Young, adult cats were given low doses of norepinephrine in dextrose or dextrose alone twice daily for 15 days. On day 16, there were no changes in the animals body weight, right ventricular systolic pressure, right ventricular end-diastolic pressure, heart rate, cardiac index, or blood pressure. However, the right ventricle/body weight, the left ventricle/body weight and the total heart weight/body weight were increased significantly in the norepinephrine treated animals. The increase was on the order of 40%. The cardiac muscle cell was also significantly increased in size and both the right and left ventricular cardiac muscle cells exhibited a dramatic increase in size as measured by cross sectional area. Upon stereological examination it was found that the amount of hypertrophy as seen in the cardiac muscle cells was paralleled by the hypertrophy seen in the other tissue components of the myocardium. The volume density of the muscle cells, the interstitial components, as well as the blood vessel compartment were identical in the control and in the norepinephrine-treated groups. In conclusion, this study demonstrates that the response of the myocardium to norepinephrine is similar to that seen in response to a volume overload rather than that seen in response to pressure overload.     

Norepinephrine-induced cardiac hypertrophy of the cat heart.

Norepinephrine administration causes progressive hypertrophy of the mammalian heart as measured by myocardial mass. The purpose of this study was to determine the growth response of the myocardial tissue components as well as the myocardial cell itself to norepinephrine. Young, adult cats were given low doses of norepinephrine in dextrose or dextrose alone twice daily for 15 days. On day 16, there were no changes in the animals body weight, right ventricular systolic pressure, right ventricular end-diastolic pressure, heart rate, cardiac index, or blood pressure. However, the right ventricle/body weight, the left ventricle/body weight and the total heart weight/body weight were increased significantly in the norepinephrine treated animals. The increase was on the order of 40%. The cardiac muscle cell was also significantly increased in size and both the right and left ventricular cardiac muscle cells exhibited a dramatic increase in size as measured by cross sectional area. Upon stereological examination it was found that the amount of hypertrophy as seen in the cardiac muscle cells was paralleled by the hypertrophy seen in the other tissue components of the myocardium. The volume density of the muscle cells, the interstitial components, as well as the blood vessel compartment were identical in the control and in the norepinephrine-treated groups. In conclusion, this study demonstrates that the response of the myocardium to norepinephrine is similar to that seen in response to a volume overload rather than that seen in response to pressure overload.     

Left heart bypass support with the Rotaflow Centrifugal Pump? as a bridge to decision and recovery in an adult

Since left heart bypass or biventricular circulatory assist with an extracorporeal centrifugal pump as a bridge to decision or recovery sometimes requires long-time support, the long-term durability of extracorporeal centrifugal pumps is crucial. The Rotaflow Centrifugal Pump(?) (MAQUET Cardiopulmonary AG, Hirrlingen, Germany) is one of the centrifugal pumps available for long-term use in Japan. However, there have been few reports of left heart bypass or biventricular circulatory support over the mid-term. This is a case report of left heart bypass support with the Rotaflow Centrifugal Pump(?) as a bridge to decision and recovery for an adult patient who could not be weaned from cardiopulmonary bypass and percutaneous cardiopulmonary support after cardiac surgery. We could confirm that the patient's consciousness level was normal; however, the patient could not be weaned from the left heart bypass support lasting 1 month. Therefore, the circulatory assist device was switched to the extracorporeal Nipro ventricular assist device (VAD). This time, left heart bypass support could be maintained for 30 days using a single Rotaflow Centrifugal Pump(?). There were no signs of hemolysis during left heart bypass support. The Rotaflow Centrifugal Pump(?) itself may be used as a device for a bridge to decision or recovery before using a VAD in cardiogenic shock patients.     

Direct cardiac potential trigger for chronic control of a ventricular assist device

As a new trigger method for chronic drive control of a ventricular assist device (VAD), a direct cardiac potential trigger was assessed under various conditions in a chronic experimental model. A pneumatic pulsatile VAD was implanted as circulatory support between the left ventricular apex and the ascending aorta in 12 adult pigs. Hemodynamic parameters and pump output were continuously monitored. Two tips of a bipolar electrode were set on the RV anterior wall and the LV posterior wall for recording direct cardiac potential. Counterpulsation drive of the VAD was applied by using the R wave in a standard electrocardiogram (ECG) or the direct cardiac potential as an ECG trigger. As special conditions, various artifacts on ECG, electromusculogram, arrhythmia, irregular ventilation, and passive vibration (simulation of exercise) were set for assessing the ECG trigger modes. Artifacts of irregular ventilation and passive vibration made the drive control poor using a standard ECG trigger. In contrast, the direct cardiac potential trigger maintained the counterpulsation control of the VAD well in all conditions of this study, and was a safe and reliable support for the native heart. It also supported animals for up to 48 hours after operation. The above results suggested that the direct cardiac potential trigger might be useful for monitoring native heart beats and adjusting the support cycle to the native heart cycle as a chronic control method for various VADs.     

Numerical comparison of hemodynamics with atrium to aorta and ventricular apex to aorta VAD support

We report the first attempt to study with numerical methods ventricular assist device (VAD) models and the effects of various inlet VAD cannulations, coupling physical explanations and numerical investigation conclusions with clinical research results. We compared the hemodynamic response with VAD support by using two distinct VAD-inlet cannulation configurations: left atrium to aorta and left ventricular apex to aorta. Impeller pump and displacement pump VADs are considered. Constant VAD flow rate and counterpulsation motion models are simulated. The native cardiovascular system is modeled using the concentrated-parameter method by considering the flow resistance, vessel elasticity, and inertial effect of blood flow in cardiovascular system individual segments. Impeller and displacement pump dynamic models are represented by corresponding inlet and outlet flow rate changes in the VADs. Results show that the two VAD inlet cannulation configurations produce similar cardiac response (flows, pressures, volumes), except that when the VAD flow approaches the 100% assisting condition, the peak left ventricular systolic pressure and diastolic volume increase slightly in the left atrial cannulation, whereas they drop markedly in the left ventricular apex cannulation, suggesting increased ventricular wall tension and ventricular dilatation in the left atrial cannulation and that hemodynamically the left ventricular apex cannulation is more advantageous.     

A two phase harmonic model for left ventricular function

A minimal model for mechanical motion of the left ventricle is proposed. The model assumes the left ventricle to be a harmonic oscillator with two distinct phases, simulating the systolic and diastolic phases, at which both the amplitude and the elastic constant of the oscillator are different. Taking into account the pressure within the left ventricle, the model shows qualitative agreement with functional parameters of the left ventricle. The model allows for a natural explanation of heart failure with preserved systolic left ventricular function, also termed diastolic heart failure. Specifically, the rise in left ventricular filling pressures following increased left-ventricular wall stiffness is attributed to a mechanism aimed at preserving heart rate and cardiac output.     

Heart-rate-proportional oxygen consumption for constant cardiac work in dog heart

We studied whether there is an optimal heart rate (HR) that would minimize myocardial oxygen consumption (MVO2) per min for a constant minute cardiac work. We measured minute MVO2 (ml O2/min) of the left ventricle paced at increasing rates (100-200 beats/min) in 10 right-heart-bypassed dogs. In each experiment, cardiac output was kept constant with a constant-flow bypass pump, and mean aortic pressure was also kept constant by inflation or deflation of an intra-aortic balloon. Minute cardiac work was thus kept constant. Minute MVO2 was obtained as the product of mean coronary arteriovenous O2 difference and mean coronary blood flow drained from the collapsed right ventricle. Both left ventricular Emax (contractility index defined as the slope of the left ventricular end-systolic pressure-volume relation) and PVA (pressure-volume area as a measure of total mechanical energy of contraction) were obtained by an abrupt aortic occlusion method. The obtained-minute MVO2-HR relationship showed a good linear positive correlation (r = 0.824-0.995) in every heart. We accounted for this relationship by the changes in PVA and Emax that we had proposed as primary determinants of MVO2. We conclude that minute MVO2 for a constant minute cardiac work increased monotonically with increases in HR from 100 to 200 beats/min, being minimum at the lowest HR, and that this relation was ascribable to the HR-proportional increase in the MVO2 component for the excitation-contraction coupling.     

Cardiovascular effects of haemorrhagic shock in spleen intact and in splenectomized dogs

Cardiac performance was evaluated during haemorrhagic shock in 27 dogs with spleens intact, 24 splenectomized, and 23 splenectomized transfused dogs that were given a volume of packed red blood cells simulating splenic contraction. Contractile changes were evaluated by calculating dP/dt at 20 mmHg developed pressure (dP/dt DP20), and by relating stroke work to left ventricular end-diastolic volume measured by biplane cinefluorography. Although heart rate increased comparably during early shock, cardiac output, stroke volume, maximal dP/dt, dP/dt DP20, and arterial blood pressure decreased more in splenectomized and splenectomized transfused dogs than in those with spleens intact. During shock dP/dt DP20 was more depressed in the splenectomized and splenectomized transfused dogs than in those with spleens intact. In addition, an increase in left ventricular end-diastolic volume was accompanied by an increase in left ventricular stroke work in dogs with spleens intact. In contrast, stroke work remained depressed in both splenectomized groups despite increased left ventricular volume. Progressive acidosis and decreased left ventricular blood flow were similar in all dogs during haemorrhage. The greater reduction in left ventricular performance during haemorrhagic shock in the splenectomized and splenectomized transfused dogs was not related to excess lactate, changes in plasma volume, or red blood cell mass. Decreased left ventricular performance, despite improved ventricular filling, indicates greater cardiac dysfunction during haemorrhagic shock. This study suggests that, in dogs, the spleen maintains left ventricular performance during haemorrhage by mechanisms other than autotransfusion.     

Early morphological alterations of pressure-overloaded cat right ventricular myocardium

Pressure overload of the right ventricle results in an increase in ventricular mass. It also results in abnormal in vitro contractile function in advance of the onset of congestive heart failure as determined in papillary muscles removed from these ventricles. To correlate these functional abnormalities with any early underlying morphological changes, a band was placed around the proximal pulmonary artery of cats. This band restricted the lumen to 20% of normal and was left in place for 2 weeks. At that time, hemodynamic variables were measured to insure that right ventricular pressure overload had been produced. The hearts were then perfusion fixed, and papillary muscles from the right ventricle were prepared for light and transmission electron microscopy. Quantitative morphological data were obtained for the volume density both of several tissue components and of several organelles. It was found that there are significant increases in myocyte cross-sectional area and diameter in hypertrophied tissue with a concurrent increase in the volume density of interstitial tissue. There are no alterations in the volume density of organelles in the hypertrophied myocytes. We suggest that the substantial increase in the proportion of connective tissue and the decrease in the surface area to volume ratio that accompany pressure overload cardiac hypertrophy may be early underlying structural changes that relate directly to the abnormal contractile function found in this type of hypertrophy.     

Dynamics of the interventricular septum and free ventricular walls during selective left ventricular volume loading in dogs

A previous study suggested that a change in the position of the interventricular septum played an important role in regulating cardiac performance during selective right ventricular volume loading. In the present study the cardiac response to selective left ventricular volume loading induced by a shunt between the subclavian artery and the left atrium was examined in anesthetized open-chest dogs. Opening the shunt increased left and reduced right ventricular stroke volume, particularly after blood volume expansion. The end-diastolic transseptal pressure difference increased. Myocardial segment length in the septum and free walls of both ventricles and the distances between the septum and the free walls were measured by an ultrasonic technique. Comparisons at similar left ventricular stroke volume with the shunt open and closed showed that the Frank-Starling mechanisms of the free wall of the left ventricle and the septum were stimulated less with the shunt open. At similar right ventricular stroke volume the end-diastolic dimension of the right ventricular free wall was larger with the shunt open. The distance decreased across the right ventricle and increased across the left ventricle when the shunt was open. We conclude that a change in the position of the septum improves left and reduces right ventricular performance during selective left ventricular volume loading.     

Cardiac function and morphology with aging in the spontaneously hypertensive rat.

To determine the effects of a chronic pressure load on cardiac function and morphology, spontaneously hypertensive rats (SHR) and two normotensive strains of Wistar rats (WKY and NWR) were studied under ether anesthesia at 13, 25, 52, and 90 wk of age. Although resting cardiac index of the SHR was comparable to that of WKY and NWR at all ages, the peak cardiac output and peak stroke volume per gram of left ventricle determined during a rapid intravenous infusion of Tyrode solution was markedly reduced in the SHR only at 90 wk of age. Autonomic inhibition did not alter the peak stroke volume attained, but reduced peak cardiac output at all ages in each of the strains. Absolute left ventricular dimensions in the SHR increased out of proportion to body growth, consistent with concentric hypertrophy. As peak pumping ability markedly declined from 52 to 90 wk of age in the SHR, the free wall of the left ventricle greatly thickened whereas the septum remained unchanged. At this time the right ventricle also hypertrophied. This disproportionate thickening of the walls of the left ventricle and the hypertrophy of the right ventricle were reflected in measurements of their fiber diameters. These alterations in ventricular architecture may contribute to the decrease in pumping ability observed in long-standing hypertension.     

Non-blood contacting electro-hydraulic artificial myocardium (EHAM) improves the myocardial tissue perfusion.

Artificial heart (AH) and ventricular assist devices (VAD) are widely used in the clinical setting to assist severe heart failure patients. The concept of direct cardiac compression (DCC) has been in use for several decades and has advantages over intravascular VAD. The process involves compressing the dysfunctional heart from its epicardial surface to avoid the thromboembolic events and decrease the complications and mortality. An Electro-hydraulic Artificial Myocardium (EHAM) system was designed and fabricated by Tohoku University. This system may assist cardiac contraction and create pulsatile blood flow. The aim of this study was to clearly define the hemodynamic efficiency of the EHAM system in myocardial tissue perfusion during its application in acute animal experiment. Eight healthy adult goats were used; left lateral thoracotomy was performed and the chest was opened by the resection of the 4th and 5th ribs. Hemodynamic parameters including ECG, blood pressure and cardiac output were continuously monitored. Myocardial tissue perfusion was measured by using Omega flow laser fiber attached to the surface of the heart. During the EHAM compression, and increase in blood pressure and myocardial tissue perfusion was observed in all animals when compared with pre-assisted mode. To conclude, EHAM effectively improves myocardial tissue perfusion and increases the pressure on the initiation of direct cardiac compression immediately. Thus it can be a potentially valuable adjunct in the management of severe heart failure.     

短链酰基辅酶A脱氢酶在大鼠生理性和病理性心肌肥大中的作用

 目的：研究短链酰基辅酶A脱氢酶(short-chain acyl-CoA dehydrogenase, SCAD)在大鼠生理性和病理性心肌肥大中的变化,探讨其与心肌肥大之间的关系。方法：以自发性高血压大鼠作为病理性心肌肥大模型,游泳运动训练性大鼠作为生理性心肌肥大模型。检测大鼠的血压、左室重量指数、血清和心肌游离脂肪酸含量、SCAD mRNA、蛋白表达及其酶活性的变化,采用超声心动图观察心脏的结构及功能。结果：与对照组比较,运动组大鼠出现了明显的离心性肥大,心肌收缩功能增强;而高血压组大鼠呈现出明显的向心性肥大,心肌收缩功能减退。与对照组比较,运动组和高血压组大鼠的左室重量指数均明显增高,但两组间比较无显著差异,二者发生了相同程度的心肌肥大。与对照组比较,运动组大鼠左心室SCAD mRNA和蛋白表达均明显上调,酶活性增高,血清和心肌游离脂肪酸含量明显减少;而自发性高血压大鼠左心室SCAD mRNA和蛋白表达均明显下调,酶活性下降,血清和心肌游离脂肪酸含量明显增多。结论：SCAD在生理性和病理性心肌肥大中呈现出不一致的变化趋势,可能作为区别2种不同心肌肥大的分子标志物以及病理性心肌肥大的潜在治疗靶点。     

Simulation of cardiovascular physiology: the diastolic function(s) of the heart

The cardiovascular system was simulated by using an equivalent electronic circuit. Four sets of simulations were performed. The basic variables investigated were cardiac output and stroke volume. They were studied as functions (i) of right ventricular capacitance and negative intrathoracic pressure; (ii) of left ventricular relaxation and of heart rate; and (iii) of left ventricle failure. It seems that a satisfactory simulation of systolic and diastolic functions of the heart is possible. Presented simulations improve our understanding of the role of the capacitance of both ventricles and of the diastolic relaxation in cardiovascular physiology.     

A new approach towards volumetric assessment of left ventricular function with MSCT

Cardiovascular CT is considered the diagnostic standard for establishing the presence of a functional and dynamic imaging system. It is difficult, however, to estimate the ventricular motion and volumes that are processed using hundreds and thousands of CT images, in a few moments.The main concept and design of our work are two fold - the development of effective semi-automatic tools for measuring the sequential left ventricular volumes from the hundreds or thousands of cardiac trans-axial images, and providing a simple interface with an interactive diagnostic tool for the volumetry of left ventricle and valuable cardiac 4D visualisation.We converted ten and more sequential volume data sets of the heart acquired from retrospective ECG-gating helical scan into 3D images by volume rendering. These sequential 3D images could be displayed as a movie (4D cardiac image) file. Furthermore, we developed a method for semi-automatic calculation of ejection fraction (EF) and cardiac cycle (%)-volume (ml) curve for estimation of the motion and the volume of the left ventricle. This method involved the use an interactive selection tool in the region of interest (ROI). All 3D processing methods, such as, cutting objects, segmentation, and image fusion were based on mask processing data. We now describe the software developed for cardiac 4D imaging and the estimation of ventricular volume.