Effects of hemodynamic alterations on wall motion in the canine right ventricle.

Regional right ventricular (RV) wall motion was analyzed in six closed-chest, anesthetized, paced dogs by measuring distances between chronically implanted radiopaque markers on RV free wall and septum. Normally, contraction started in the sinus region 25 ms before conus region. Highest velocities of shortening occurred in the conus region (2.42 +/- 0.33 lengths/s) and in septum-to-free-wall direction (2.56 +/- 0.40 l/s). Percent shortening for all regions was between 12% and 17%. The data indicate that the RV ejects blood by a uniform reduction in its free wall surface area and septal-to-free-wall distance. Reduced venous return decreased end-diastolic length, percent shortening, maximum velocity of shortening, and time to end-systolic length. RV pressure overload increased end-diastolic length and decreased percent shortening and maximum velocity of shortening. LV pressure overload led to a nonhomogeneous contraction pattern. Percent shortening and maximum velocity of shortening increased in sinal and conal transverse directions and decreased in sinal and conal longitudinal directions; these changes indicate a mechanical interaction between RV and LV.     

An energetically coherent lumped parameter model of the left ventricle specially developed for educational purposes

We present a Bond Graph model and simulation of the cardiac dynamics of the left ventricle (LV). It models all the levels from the mechanisms of contraction up to the hemodynamics of the LV. We validate our model by presenting several case studies. The goal is to build a model with a strong physiological basis that may be understood in physical terms but, in contrast with other existing models, may be simulated sufficiently fast to use it as a teaching tool in cardiovascular physiology and allow its integration as a boundary condition in more sophisticated 3D finite-element models.     

Effects of myocardial contraction on coronary blood flow: An integrated model

The effects of myocardial contraction on the coronary flow are studied by means of an integrated structural model of left ventricular (LV) mechanics, coronary flow, and fluid and mass transport. This model relates global LV performance, and in particular coronary flow dynamics, to myocardial composition and structure and contractile sarcomere activity. Extravascular pressure is identified with hydrostatic tissue pressure,i. e., intramyocardial pressure (IMP), and is determined by the dynamics of myocardial contraction and fluid transport. Consistent with available experimental data, changes in myocardial function and contractile state are simulated by changing the sarcomere contractile properties or changing the LV loading conditions. The model's predictions are successfully compared with a wide range of experimental studies; all but one were performed at a constant coronary perfusion pressure and maximal vasodilation. The results indicate a domiant effect of the myocardial contractile state on coronary flow and a dissocation between coronary compression and LV cavity pressure (LVP) when the pressure is controlled by load changes. However, when active sarcomere contraction is regionally impaired by lidocaine, LVP plays an important role in the coronary flow characteristics. The model adequately predicts observations on the effect of cardiac contraction on systolic and diastolic coronary flows, as well as the role of LVP at different loading and contractile conditions. The analysis supports the hypothesis that coronary compression, as mediated through IMP, is independent of LV loading conditions and depends on myocardial contractility and coronary perfusion pressure.     

CardioClasp: a new passive device to reshape cardiac enlargement

In dilated heart failure, geometric distortions place an extra load on the myocardial cells. If this extra burden can be eliminated, the myocardial wall stress would decrease leading to improved systolic ventricular performance. In a dilated heart failure model, we wanted to see whether the CardioClasp (which uses two indenting bars to reshape the left ventricle [LV] as two widely communicating "lobes" of reduced radius) could improve systolic performance by passively reshaping the LV and reducing the wall stress. In mongrel dogs (n = 7; 25-27 kg), rapid ventricular pacing (210 ppm 1st week to 240 ppm 4th week) induced dilated heart failure. After 4 weeks, LV performance was evaluated at baseline and with the CardioClasp by measuring LV end-diastolic and peak LV systolic pressure, LV +dP/dt, LV -dP/ dt, and cardiac output. With the Clasp on, LV wall stress was reduced to 58.6+/-3.5 from 108.3+/-8.2 g/cm2. The fractional area of contraction (FAC) with the Clasp on (28.4+/-4.4) was significantly increased (p < 0.05) from baseline (20.8+/-4.6) and consistent with improved systolic performance. Cardiac output, LV peak systolic and end-diastolic pressures, and regional myocardial blood flow were unaltered. The Clasp was able to acutely reshape the left ventricle, while preserving the contractile mass, and reduced the tension on the myocardial cells and increased the fractional area of contraction without decreasing the systolic blood pressure.     

Mitral annulus after mitral repair: geometry and dynamics

The study of systolic changes in both the inflow and outflow of the left ventricle after mitral repair elucidates the geometric characteristics after surgery. The study included eight normal subjects and six patients after mitral repair without a prosthesis. The left ventricular (LV) base, consisting of both mitral valve annulus (MVA) and left ventricular outflow tract (LVOT) orifice, was reconstructed from magnetic resonance images. The angle between the planes of the MVA and LV base (MB angle), and the proportionate share of the LVOT at the LV base were calculated. After mitral repair, both the MVA and LV base became almost normal in size, showing flexible change (i.e., contraction and dorsiflexion) in the MVA and contraction of the LV base in systole. Compared with the normal heart at 100 ms delay from the electrocardiogram R wave, the hearts of the patients at the same phase had a mean 1.05 cm2 larger LVOT orifice, resulting in a mean 8.0 degree larger MB angle. Furthermore, the LVOT orifice occupied a mean of 49.5% of the LV base (41.9% in normal subjects). We hypothesize that the higher MB angle at early systole may weaken the tension of the chordae of the anterior mitral leaflet.     

左心室辅助装置控制模式影响双心室搏动同步性的数值研究

右心室(RV)衰竭已成为左心室辅助装置(LVAD)治疗的一种致命并发症。由LVAD引起的双心室搏动的不同步是引发RV功能障碍的重要因素。本文采用数值方法研究LVAD的控制模式对左、右心室搏动同步性的影响。数值结果表明:左心室(LV)与RV的收缩持续时间在无泵模式下没有显著差异(分别为48.52%和51.77%)。连续模式下,LV收缩期明显短于RV收缩期(LV vs.RV:24.38%vs.49.16%)和无泵模式的LV收缩期。搏动模式下,LV收缩期明显短于RV收缩期(LV vs.RV:28.38%vs.50.41%)但长于连续模式的LV收缩期。反搏动模式中的LV、RV收缩期差异较小(LV vs.RV:43.13%vs.49.23%),而LV收缩期短于无泵模式,并且长于连续模式。与连续和搏动模式相比,由反搏动模式提供的收缩期转速(RS)降低显著地校正了LV收缩持续时间,连续模式下缩短的收缩持续时间在反搏动模式下被校正为LV和RV之间的重新同步。因此,本文认为LV和RV收缩的再同步有助于预防RV功能障碍。总之,使用在收缩期间降低RS的反搏动模式有望用于由LVAD引起的双心室搏动不同步的临床校正。     

Predictability of O2 consumption from contractility and mechanical energy of absolute arrhythmic beats in canine heart

Left ventricular (LV) O2 consumption (V(O2)) per minute is measurable for both regular and arrhythmic beats. LV V(O2) per beat can then be obtained as V(O2) per minute minute divided by heart rate per minute minute for regular beats, but not for arrhythmic beats. We have established that V(O2) of a regular stable beat is predictable by V(O2) = a PVA + b E(max) + c, where PVA is the systolic pressure-volume area as a measure of the total mechanical energy of an individual contraction and E(max) is the end-systolic maximum elastance as an index of ventricular contractility of the contraction. Furthermore, a is the O2 cost of PVA, b is the O2 cost of E(max), and c is the basal metabolic V(O2) per beat. We considered it theoretically reasonable to expect that the same formula could also predict LV V(O2) of individual arrhythmic beats from their respective PVA and E(max) with the same a, b, and c. We therefore applied this formula to the PVA - Emax data of individual arrhythmic beats under electrically induced atrial fibrillation (AF) in six canine in situ hearts. We found that the predicted V(O2) of individual arrhythmic beats highly correlated linearly with either their V(O2) (r = 0.96 +/- 0.01) or E(max) (0.97 +/- 0.03) while both also highly correlated linearly with each other (0.88 +/- 0.04). This suggests that the above formula may be used to predict LV Vo2 of absolute arrhythmic beats from their Emax and PVA under AF.     

Mechanoenergetics characterizing oxygen wasting effect of caffeine in canine left ventricle

Caffeine causes a considerable O(2) waste for positive inotropism in myocardium by complex pharmacological mechanisms. However, no quantitative study has yet characterized the mechanoenergetics of caffeine, particularly its O(2) cost of contractility in the E(max)-PVA-VO(2) framework. Here, E(max) is an index of ventricular contractility, PVA is a measure of total mechanical energy generated by ventricular contraction, and VO(2) is O(2) consumption of ventricular contraction. The E(max)-PVA-VO(2) framework proved to be powerful in cardiac mechanoenergetics. We therefore studied the effects of intracoronary caffeine at concentrations lower than 1 mmol/l on left ventricular (LV) E(max) and VO(2) for excitation-contraction (E-C) coupling in the excised cross-circulated canine heart. We enhanced LV E(max) by intracoronary infusion of caffeine after beta-blockade with propranolol and compared this effect with that of calcium. We obtained the relation between LV VO(2) and PVA with E(max) as a parameter. We then calculated the VO(2) for the E-C coupling by subtracting VO(2) under KCl arrest from the PVA-independent (or zero-PVA) VO(2) and the O(2) cost of E(max) as the slope of the E-C coupling VO(2)-E(max) relation. We found that this cost was 40% greater on average for caffeine than for calcium. This result, for the first time, characterized integratively cardiac mechanoenergetics of the O(2) wasting effect of the complex inotropic mechanisms of intracoronary caffeine at concentrations lower than 1 mmol/l in a beating whole heart.     

Myocardial relaxation. VI. Effects of beta-adrenergic tone and asynchrony on LV relaxation rate

We studied the effect of left ventricular (LV) asynchrony and alterations in beta-adrenergic tone on the systolic load (pressure) dependency of LV isovolumic relaxation rate in anesthetized dogs. The time constant (T) of isovolumic exponential pressure decline was used as an index of relaxation rate. Variably afterloaded LV contractions resulted in a progressive increase in LV end-systolic pressure from 124 +/- 6 in the control beat to 176 +/- 11 mmHg in the third beat and a progressive lengthening of T from 19 +/- 2 to 30 +/- 4 ms. The direct relation between LV end-systolic pressure and T was nearly linear (r = 0.98), and the slope (k) of this relation was taken to reflect the systolic load dependency of T. Administration of isoproterenol (n = 6) produced a decrease in k from 0.11 +/- 0.02 to 0.08 +/- 0.02 (P less than 0.05); with propranolol (n = 6), k increased from 0.08 +/- 0.02 to 0.27 +/- 0.04 (P less than 0.01). Right ventricular epicardial pacing (n = 6) produced an asynchronous LV contraction and an increase in k from 0.09 +/- 0.02 (atrial pacing) to 0.25 +/- 0.04 (P less than 0.01). These studies confirm the dependency of LV relaxation rate on systolic loads and indicate that this form of load-dependent relaxation can be modified by alterations in beta-adrenergic tone and LV asynchrony. The observed alterations suggest the importance of temporal dispersion of the contraction-relaxation sequence as a mechanism responsible for disturbed relaxation.     

Homogeneity of Cardiac Contraction Despite Physiological Asynchrony of Depolarization: A Model Study

The use of mathematical models combining wave propagation and wall mechanics may provide new insights in the interpretation of cardiac deformation toward various forms of cardiac pathology. In the present study we investigated whether combining accepted mechanisms on propagation of the depolarization wave, time variant mechanical properties of cardiac tissue after depolarization, and hemodynamic load of the left ventricle (LV) by the aortic impedance in a three-dimensional finite element model results in a physiological pattern of cardiac contraction. We assumed that the delay between depolarization for all myocytes and the onset of crossbridge formation was constant. Two simulations were performed, one in which contraction was initiated according to the regular depolarization pattern (NORM simulation), and another in which contraction was initiated after synchronous depolarization (SYNC simulation). In the NORM simulation propagation of depolarization was physiological, but wall strain was unphysiologically inhomogeneous. When simulating LV mechanics with unphysiological synchronous depolarization (SYNC) myofiber strain was more homogeneous and more physiologic. Apparently, the assumption of a constant delay between depolarization and onset of crossbridge formation results in an unrealistic contraction pattern. The present finding may indicate that electromechanical delay times are heterogeneously distributed, such that a contraction in a normal heart is more synchronous than depolarization. © 2003 Biomedical Engineering Society. PAC2003: 8719Hh, 8719Nn, 8718Bb, 8710+e, 8719Xx     

Does the progression of myocardial fibrosis lead to atrial fibrillation in patients with hypertrophic cardiomyopathy?

The majority of left ventricular (LV) inflow volumes in hypertrophic cardiomyopathy (HCM) depend on atrial contraction because of impaired LV relaxation. If HCM is complicated by atrial fibrillation (AF), heart failure can develop because of the loss of atrial contraction. The purpose of this study was to determine the relationship between the development of AF and myocardial fibrosis or intramyocardial small artery (IMSA) stenosis in autopsied hearts with HCM. Studies were performed in five HCM hearts with AF (AF group) and five HCM hearts without AF (non-AF group). LV specimens were divided into the inner (IT), middle (MT), and outer (OT) thirds. We selected at random 120 fields and 20 IMSAs from each layer and assessed them quantitatively using an image analyzer. We determined the extent of fibrosis (%F) and the degree of stenosis of each IMSA (%L). The %F in the AF group was greater than in the non-AF group (P<.01). In the AF group, the %F of the IT was greater than in the MT and the OT (P<.01). In the non-AF group, the %F of the IT was greater than in the MT (P<.05), and the %F of the MT was greater than in the OT (P<.01). The %L was similar in the AF and non-AF groups. In both groups, the %L of the IT was lower than in the MT (P<.01), which was lower than that of the OT (P<.05). LV fibrosis is more severe in patients with HCM and AF than in those without AF. Therefore, myocardial fibrosis might impair LV relaxation, resulting in hemodynamic intolerance to AF.     

A curvature-based approach for left ventricular shape analysis from cardiac magnetic resonance imaging

It is believed that left ventricular (LV) regional shape is indicative of LV regional function, and cardiac pathologies are often associated with regional alterations in ventricular shape. In this article, we present a set of procedures for evaluating regional LV surface shape from anatomically accurate models reconstructed from cardiac magnetic resonance (MR) images. LV surface curvatures are computed using local surface fitting method, which enables us to assess regional LV shape and its variation. Comparisons are made between normal and diseased hearts. It is illustrated that LV surface curvatures at different regions of the normal heart are higher than those of the diseased heart. Also, the normal heart experiences a larger change in regional curvedness during contraction than the diseased heart. It is believed that with a wide range of dataset being evaluated, this approach will provide a new and efficient way of quantifying LV regional function.     

Mapping the sequence of contraction of the canine left ventricle

A method has been developed to map the sequence of contraction as measured at the epicardial surface of the anterior free wall of the canine left ventricle during sinus rhythm and electrical stimulation of the ventricle. In an area of 35×45 mm, 40–60 white markers were attached to the epicardial surface. The motion of the markers was recorded on video and analysed off-line by computer. In an array of 35 regions, regional surface deformation and epicardial fibre strain were calculated from the motion of the markers. Between all adjacent regions, the differences in timing of contraction were determined by cross-correlation of the related fibre strain signals. A map of the time sequence of contraction has been calculated so that the sum of the squares of the deviations between time intervals of the map and the measurements was minimised. If individual correlation coefficients were found to be less than 0.85, the related time difference was discarded from the analysis. If more than 25% of the time differences were discarded because of this reason, the whole map was obtained by determining time of the negative peak of the second time derivative in the early phase of contraction. The accuracy in time marking was sufficient (±7 ms), as compared to the time differences over the epicardial surface, which were found to be on the average between 10 and 80 ms in case of sinus rhythm and electrical stimulation of the right ventricular outflow tract, respectively.     

Use of negative intrathoracic pressure to obtain end-systolic pressure volume relations in dogs

Left ventricular contractility can be assessed from the end-systolic pressure-volume relationship (ESPVR). In this study we test the hypothesis that the same ESPVR can be obtained by varying LV loading with different levels of negative intrathoracic pressure as by varying LV filling. In six dogs mean aortic transmural pressure was used to approximate LV end-systolic pressure and LV volume was determined from data gathered from biplane cineradiograms of multiple markers placed in the LV midwall. In each preparation right heart bypass allowed control of cardiac output while the thoracic pressure was varied with a box surrounding a midsternal thoracotomy. Reflex effects were minimized by ganglionic blockade and bilateral vagotomy. ESPVRs were obtained by varying the cardiac output at constant thoracic pressure or by changing intrathoracic pressure at constant cardiac output. The slopes of the ESPVRs were not significantly different. This result implies that LV loading by negative intrathoracic pressure, in this highly controlled preparation, can be used to generate a systolic LV elastance similar to that obtained by varying LV filling.     

Volume overload left ventricular hypertrophy: effects on coronary microvascular reactivity in rabbits

The mechanisms controlling the coronary vascular responses of vessels perfusing the left ventricular (LV) myocardium that is hypertrophied from chronic volume overload are unclear. We hypothesised that endothelial function is compromised, and receptor-mediated contraction is exacerbated, in coronary resistance vessels from rabbits with LV hypertrophy compared to controls. The mitral valve of 10 rabbits was damaged surgically to cause mitral regurgitation and chronic volume overload, resulting in LV hypertrophy (LV hypertrophy rabbits). Echocardiographic assessment at 12 weeks verified that mitral regurgitation was present in LV hypertrophy but not sham-operated, weight- and age-matched animals (control rabbits; n = 17). Percentage increases from weeks 0 to 12 in LV cross-sectional area (47 +/- 7 % vs. 2 +/- 8 %), LV volume (47 +/- 14 % vs. 7 +/- 10 %) and LV mass (27 +/- 4 % vs. 3 +/- 6 %), were greater (all P < 0.05) in LV hypertrophy vs. control rabbits, respectively. At 12 weeks, coronary resistance vessel (approximately 130 microm, internal diameter) reactivity was evaluated using wire myography. Endothelium-dependent (i.e. acetylcholine, 10(-8)-10(-5) M) and -independent (i.e. sodium nitroprusside, 10(-9)-10(-4) M) relaxation, and receptor-mediated vasocontraction (i.e. endothelin-1, 10(-11)-10(-7) M) were similar between groups. However, tension development in response to nitric oxide synthase inhibition (10(-6) M N (G)-monomethyl-L-arginine) was greater (P < 0.05) in LV hypertrophy compared to control rabbits. These results indicate that while coronary resistance vessel function is similar between groups, our estimate of basal nitric oxide production is greater in vessels from LV hypertrophy than control rabbits.     

动物实验模型中多极导管心室除颤系统电除颤对心脏功能的影响

评价新型的双极和三极导管自动心室除颤系统电除颤对左心室收缩和舒张功能的影响。动物麻醉后,在X光机指导下,分别在10只犬心脏内装置双极导管自动除颤系统（组Ⅰ）;在10只猪心脏内装置三极导管自动除颤系统（组Ⅱ）;并行电除颤试验。使用食管超声心动图在电除颤前后记录二维、M型和多谱勒超声图像。组I动物接受4次电除颤,电量为64J;组Ⅱ接受平均8次电除颤,电量为210J。结果显示：左室收缩面积分数、左室等容舒张时间和二尖瓣血流E波与A波速度比值以及时间-流速积分比值等反映左室舒缩功能的指标在两组动物除颤后均无显著改变。研究表明：两种经静脉导管自动心室除颤系统中反复低能量心内膜电除颤对左室舒缩功能无明显损伤作用;研究结果为经静脉多极导管自动心室除颤系统在临床的应用和电生理研究提供了可靠的实验数据。     

Development of "plug and play" TransApical to aorta VAD

Our TransApical to Aorta pump, a simple and minimally invasive left ventricular (LV) assist device, has a flexible, thin-wall conduit connected by six struts to a motor with ball bearings and a turbine extending into the blood path. Pulsatile flow is inherent in the design as the native heart contraction preloads the turbine. In six healthy sheep, the LV apex was exposed by a fifth intercostal left thoracotomy. The pump was inserted from the cardiac apex through the LV cavity into the ascending aorta. Aortic and LV pressure waveforms, pump flow, motor current, and pressure were directly measured. All six cannula pumps were smoothly advanced on the first attempt. Pump implantation was <15 minutes (13.6 +/- 1.8 minutes). Blood flow was 2.8 l/min to 4.4 l/min against 86 +/- 8.9 mm Hg mean arterial blood pressure at maximum flow. LV systemic pressure decreased significantly from 102.5 +/- 5.55 mm Hg to 58.8 +/- 15.5 mm Hg at the fourth hour of pumping (p = 0.042), and diastolic LV pressure decreased from 8.4 +/- 3.7 to 6.1 +/- 2.3 mm Hg (p > 0.05). The pump operated with a current of 0.4 to 0.7 amps and rotation speed of 28,000 to 33,000 rpm. Plasma free hemoglobin was 4 +/- 1.41 mg/dl (range, 2 to 5 mg/dl) at termination. No thrombosis was observed at necropsy.A left ventricular assist device using the transapical to aorta approach is quick, reliable, minimally invasive, and achieves significant LV unloading with minimal blood trauma.     

A conical model to describe the nonuniformity of the left ventricular twisting motion

The systolic contraction and fiber shortening in the left ventricle (LV) produces torsional moments in the myocardium, resulting in a gradient of angular displacements about the long axis. This is manifested as a counterclockwise rotation of the apex relative to the base, when viewed from the apex. Recent studies with magnetic resonance imaging (MRI), using noninvasive magnetic tags, have revealed three important properties of the LV twist: (a) The angle of twist (i.e., the angular rotation of a slice relative to the basal slice) is consistently higher at the endocardium as compared to the epicardium; (b) The twist increases towards the apex; and (c) Straight MRI-tagged radial lines at end-diastole (ED) are slightly curved at end-systole (ES), implying a nonlinear transmural variation of the twist. The present study suggests that the geometry of the LV at ES can be represented by a thick-walled hollow cone, and that the transmural twist patterns from ED to ES can be described using the continuum mechanics approach and a small strain analysis of an isotropic cone subjected to external torque. The predicted results are compared with the noninvasive MRI measurements of transmural twist in eight human volunteers. Given the epicardial angles of twist of each slice, the predicted endocardial angles of twist are in good correlation with the experimental findings (r=0.86, slope=1.09, SEE=4.1°). In addition, the model reliably describes the changes in the twist magnitude from apex to base (no significant difference from experimental values,P=0.2), and predicts the curvilinear pattern at ES of the originally straight ED radial lines. Thus, the conical model with uniform properties of the LV, reliably predicts the nonuniformity of the twist patterns, implying that the LV twist is strongly affected by LV geometry.     

Continuous mechanical contraction modulates expression of alveolar epithelial cell phenotype

We have previously reported that mechanical distention of alveolar epithelial type II cells in culture favored the expression of the type I cell phenotype and inhibited the expression of the type II cell phenotype. The objective of the present study was to investigate the effects of continuous mechanical contraction on the expression of specific markers for the type I and type II cell phenotypes in cultured alveolar type II cells. Type II cells were mechanically contracted in culture at varying amplitudes and times. Cells were analyzed for mRNA and protein content of markers of the type I (RTI40) and type II (surfactant proteins [SPs] A, B, and C) phenotypes. Continuous contraction of culture membrane surface area by 25% for a duration of 4 h resulted in an 83% increase in SP-A, a 42% increase in SP-B, and a 230% increase in SP-C, in comparison with controls. After 12 h of contraction, RTI40 mRNA content decreased to 59% of control levels. A minimal contraction of 20% of culture membrane surface area was required to modulate expression of the type II cell markers. In summary, mechanical contraction favors expression of the type II cell phenotype and inhibits expression of the type I cell phenotype in a time- and amplitude-dependent manner.     

Analysis of effect of two concurrent ischaemic zones on left ventricular function

Left ventricular (LV) function due to two concurrent ischaemic zones (IZs) is investigated using a cardiovascular system model. The model comprises a three-compartment LV, the venous return and the arterial system. Haemodynamic responses of the LV to changes in the IZ size and myocardial contraction timings are explored. Results show that the greater the degree of asynschonisation is between the normal zone and the IZ, and the larger the ischaemic size, the more severe the LV dysfunction. Pre-load augmentation improves LV function. Model-predicted features are consistent with reported observations associated with myocardial ischaemia. The extent of the usefulness and limitations of this model is also discussed.