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Biomedical subjects

S Sideman

Publications and source records attributed to S Sideman.

At least 37 records · Page 2Linked to original sources

Modulation of the arterial coronary blood flow by asynchronous activation with ventricular pacing.

UNLABELLED: This study aims to test the assumptions that: (1) coronary arterial flow is attenuated in an early activated region by ventricular pacing; (2) asynchronous mechanical activation caused by ventricular pacing under controlled perfusion pressure and intact coronary tone is associated with reduced coronary flow compared to atrial pacing; and (3) abolishment of vascular tone under controlled perfusion pressure diminishes the expected difference in blood flow between atrial and ventricular pacing. Blood flow velocity (BFV) in the left anterior descending (LAD) and the left circumflex arteries (CFX) and a wall thickening index were measured in 14 open-chest dogs under normal conditions, and constant perfusion pressure. Four pacing sites were used: right atrium (RAp), mid-right ventricle (RVp), mid-left ventricle (LVp), and left ventricular apex (Apexp). Pacing modes were either sequential ventriculoatrial (VA) (protocol A, n = 7), or sequential atrioventricular (AV) (protocol B, n = 7), with a shorter AV difference (30 msec) than normal. RESULTS: BFV was decreased in the LAD during RVp and Apexp pacing by 9.7%-12.9% versus RAp and by 11.6%-14.6% versus LVp (P < 0.05). No BFV variations were observed in the CFX. Flow velocity conductance (FVC = mean blood flow velocity divided by the mean aortic pressure) was higher by 16%-28% in the CFX for the three ventricular pacing sites versus the atrial pacing, and higher by 14.1% +/- 6.1% only in LVp versus RAp pacing in the LAD (P < 0.05). Wall thickening index reduced during ventricular pacing in all three ventricular sites by 50%-64% (P < 0.05) compared to atrial pacing. Under constant perfusion pressure, LAD blood flow decreased with ventricular pacing as compared to right atrial pacing; this was particularly pronounced during the diastolic phase (16.6%-45.5%, P < 0.02). Normalized oscillatory flow amplitude (OFAn) was reduced in RVp pacing compared to RAp and LVp pacing (16.2 +/- 3.5 and 21.7% +/- 4.1%, respectively, P < 0.03). The variations in blood flow and OFAn disappeared with adenosine-mediated maximum vasodilatation. SUMMARY: (1) Mean and phasic flows are reduced in the early activated LAD region by ventricular pacing (RVp, Apexp). (2) Under controlled perfusion pressure and intact vascular tone, ventricular pacing compromises blood flow compared with atrial pacing. (3) This effect disappears when vascular tone is eliminated by intracoronary injection of adenosine, suggesting that the coronary autoregulation is responsible for some of the effects.

Animals↗

An integrated model of LV muscle mechanics, coronary flow, and fluid and mass transport.

An integrated left ventricular (LV) model that accounts for the three-phase (fiber-blood-interstitium) myocardial structure and composition is used to study the interactions among myocardial mechanics, coronary flow, and fluid and mass transport. Effects of ventricular load, coronary perfusion pressure, and fluid and mass transport on ventricular performance and coronary dynamics are studied here. In agreement with experimental observations, the analysis shows that 1) coronary flow impediment is not significantly affected by changes in the afterload and preload at constant coronary perfusion pressures, 2) an increase in coronary perfusion pressure increases the intramyocardial pressure (IMP) as well as the mean flow and oscillatory flow amplitude, 3) contractility has a direct effect on IMP and coronary flow impediment, and 4) changes in blood osmolarity and lymphatic outflow, which may cause myocardial edema, affect both ventricular mechanics and coronary flow. Clearly, accounting for fluid and mass transport allows to study the interactions among coronary flow, ventricular and myocardial mechanics, and intramyocardial fluid shifts.

Animals↗

Analysis of coronary circulation under ischaemic conditions.

Coronary flow patterns and pressure/flow relationships in coronary vessels with arterial stenoses are examined by using a model that combines the flow in the epicardial arterial tree with the intramyocardial perfusion. By using appropriate resistive elements, the model allows for the autoregulation of the vascular bed and for the development of coronary collaterals. Arterial flow predictions are compared to canine data. Coronary stenosis is simulated by a local pressure drop caused by a combination of viscous and inertial forces; stenosis with a constant cross-sectional area is compared to a dynamic stenosis in which the cross-sectional area is a function of the instantaneous transmural pressure. Simulation results predict that the normal phasic flow patterns in the epicardial arteries are unaffected up to 73% reduction in cross-sectional area, while the average flow remains unchanged up to 90% area reduction. At the critical level of 90% rigid stenosis, the autoregulation is saturated and the phasic nature of the arterial flow is severely damped. Dynamic stenoses demonstrate hysteresis loops of the instantaneous pressure/flow relationship. Theoretical predictions of local and global values are in excellent agreement with experimental measurements, indicating that the proposed approach can be used to realistically describe the coronary flow in the ischemic heart.

Animals↗

Analysis of flow in coronary epicardial arterial tree and intramyocardial circulation.

A mathematical model combining the coronary flow in the epicardial arterial tree and the intramyocardial circulation is presented. The epicardial arterial tree is represented by a resistive capacitive network based on its realistic anatomy. The intramyocardial flow is affected by the pump action of the contracting myocardium through the extravascular compressive pressure (ECP), which, in turn, affects the dynamic resistance and compliance changes based on the relationship between the transmural pressure and the cross-sectional area of a vessel. The model accounts for the autoregulatory mechanism of the intramyocardial compartments (arteriolar, microvascular and venular) and is structured according to the epicardial coronary anatomy. Realistic coronary epicardial arterial flow patterns are obtained, which compare well to experimentally measured data in six dogs under basal conditions and during reactive hyperemic response. Simulations of the average transmural flow in the three intramyocardial vascular compartments show that the flow in the arterial side is predominantly diastolic, with a systolic retrograde component, and is dominantly systolic antegrade flow in the venular side, consistent with experimental data. Interestingly, the transmurally average microcirculatory flow is continuous, with very small change throughout the cardiac cycle, and is practically insensitive to changes in the model parameters. The model presents a quantitative tool that describes the dynamic patterns of coronary flow in relationship to muscular and extravascular parameters.

Animals↗

Quantitative sorting of normal and abnormal coronary flow wave form shapes.

The normal phasic flow wave form in an epicardial coronary artery has a distinct characteristic shape, which reflects the interaction between the coronary tree, myocardial function and hemodynamic conditions. Since clinical measurements of phasic coronary wave forms are becoming available, determination of abnormal coronary flow wave forms is important. We suggest here an objective and automatic method to discriminate between normal and abnormal flow wave forms based on the Karhunen-Loève Transform (KLT), and experimentally tested it. The normal flow domain was represented by the resting flow waves measured in the left anterior descending arteries in 31 anesthetized dogs. The abnormal flow conditions, imposed and tested experimentally, were varying stenosis severity and severely reduced left ventricular pressure. In addition, the effects of reactive hyperemia on the shape of the flow were examined. The sorting index was based on the mean-square error (MSE) calculated for each flow signal based on a truncated KLT expansion. The results show excellent discrimination between the normal and the abnormal groups. During reactive hyperemia, however, MSE did not change significantly. These results indicate that the shape of abnormal coronary flow wave forms can be identified and discriminated from normal wave forms.

Animals↗

In-vivo study of the mechanical properties of epicardial coronary arteries.

This study proposes a method to examine the in-vivo pressure-volume (P-V) relationship of an epicardial coronary artery. With the proximal left anterior descending (LAD) artery in a dog occluded, the distal LAD flow oscillates around zero. Integration of the flow with respect to time yields the intraluminal arterial segment volume changes in the region between the site of occlusion and the flow probe. The distal LAD pressure is measured via a diagonal branch. The segmental P-V relationship exhibits a hysteresis loop. The area bound by the hysteresis loop corresponds to the energy loss on the arterial wall during one cycle (12.63 +/- 8.25 [erg.cm-1], n = 7), while the dynamic arterial compliance is calculated based on the ratio of the volume to pressure excursions (1.13 +/- 0.73 [ml.mmHg-1.cm-1.10(-4)]). These results represent first estimates of the in-vivo mechanical properties of the coronary arterial wall based on P-V measurements.

Animals↗

Pressure-flow characteristics of the coronary collaterals: a model study.

The pressure-flow relationship of the coronary collaterals is investigated by using an electrical analog model that combines the coronary epicardial arteries with the nonlinear characteristics of the intramyocardial circulation. The study aims to examine some controversial issues concerning the collateral circulation, including the transmural distribution of the collaterals, the distensibility of the collateral vessels (whether rigid or complaint), the effects of microcirculatory embolization, the collateral zero-flow pressure, and the nonlinearity of the collateral pressure-flow relationship. The study is carried out by simulating and comparing two basic experimental set-ups in which a coronary artery is ligated and the retrograde flow serves as an index of collateral flow. In the first "free-flow" setup, flow is allowed to bleed retrogradely against atmospheric pressure while perfusion pressure to the rest of the coronary arteries is varied over a wide range. In the second "back-pressure" setup, the coronary perfusion pressure is maintained at the control levels while the back pressure to the retrograde flow in the excised artery is varied. According to the analysis, the nonlinear pressure-flow relationships depend heavily on the experimental setup and are a function of the distensibility of the collaterals, which are distributed mainly on the epicardial surface, and the nonlinear contraction characteristics of the myocardium. The measured retrograde flow tends to underestimate the total collateral flow for the back-pressure setup because of antegrade flow escape.

Animals↗

Coupling calcium binding to troponin C and cross-bridge cycling in skinned cardiac cells.

This study examines the coupling of calcium binding to troponin with the force developed by the cross bridges in the skinned cardiac muscle. It emphasizes the key role of the troponin complex in regulating cross-bridge cycling and defines four distinct states of the troponin complex in the single-overlap region. These include a "loose-coupling" state, wherein cross bridges can exist in the strong conformation without having calcium bound to the neighbor troponin C. Published simultaneous measurements of the force and the bound calcium are used to calculate the apparent calcium binding coefficients. The force-length relationships at different free calcium concentrations are used to evaluate the cooperative mechanism. The dependence of the affinity of troponin for calcium on the number of force-generating cross bridges is the dominant cooperative mechanism. The proposed loose-coupling model, with a positive feedback of force on calcium binding, describes the role of calcium in force regulation and the force-length relationship in skinned cardiac muscle. The ability to simulate the rate of force development is demonstrated.

Animals↗

Mechanical regulation of cardiac muscle by coupling calcium kinetics with cross-bridge cycling: a dynamic model.

This study describes the regulation of mechanical activity in the intact cardiac muscle, the effects of the free calcium transients and the mechanical constraints, and emphasizes the central role of the troponin complex in regulating muscle activity. A "loose coupling" between calcium binding to troponin and cross-bridge cycling is stipulated, allowing the existence of cross bridges in the strong conformation without having bound calcium on the neighboring troponin. The model includes two feedback mechanisms: 1) a positive feedback, or cooperativity, in which the cycling cross bridges affect the affinity of troponin for calcium, and 2) a negative mechanical feedback, where the filament-sliding velocity affects cross-bridge cycling. The model simulates the reported experimental force-length and force-velocity relationships at different levels of activation. The dependence of the shortening velocity on calcium concentration, sarcomere length, internal load, and rate of cross-bridge cycling is described analytically in agreement with reported data. Furthermore, the model provides an analytic solution for Hill's equation of the force-velocity relationship and for the phenomena of unloaded shortening velocity and force deficit. The model-calculated changes in free calcium in various mechanical conditions are in good agreement with the available experimental results.

Animals↗

Myocardial mechanics and coronary flow dynamics.

The interaction between cardiac mechanics and coronary flow is highlighted here. Left ventricular (LV) structure and geometry are related to coronary flow dynamics and used in the analysis of experimental coronary flow data. The important role of the collagen mesh in the generation of the intramyocardial pressure (IMP), the pressure in the interstitial fluid, at a wide range of loading conditions is emphasized. The calculated IMP, based on a structural model of the LV myocardium, can explain most of the observed coronary compression characteristics under a variety of loading and contractility conditions. A more general compression function, the extravascular compressive pressure (ECP), is suggested to define coronary compression and is presented here based on the dynamics of the coronary inflow under constant perfusion conditions. Coronary compression is shown to be affected by fluid transport and the bi-directional coupling of coronary hemodynamics and IMP dynamics.

Animals↗

Intramyocardial fluid transport effects on coronary flow and left ventricular mechanics.

An integrated left ventricular (LV) model is used to solve, simultaneously and interactively, the LV mechanics, the coronary blood flow and capillary and interstitial fluid and mass transport, and to analyze the LV behavior under normal as well as pathological conditions. Accounting for the interstitial fluid mass balance in a LV flow-mechanical model allows to determine the LV wall volume in terms of the prevailing mechanical and flow conditions; it allows to uniquely define the flow-mechanical relationship and study pathologies, such as myocardial edema, which are directly related to changes in the myocardial fluid transport and content.

Biological Transport↗

Calcium kinetic and mechanical regulation of the cardiac muscle.

A comprehensive dynamic model of the excitation contraction coupling, developed for a single cardiac muscle, is extended to a multi-cell system (duplex). The model defines the mechanical activation level based on calcium kinetics and crossbridge cycling and emphasizes the central role of the troponin regulatory proteins in regulating muscle activity. The intracellular control mechanism includes two feedback loops that affect the affinity of troponin for calcium and the crossbridge cycling. The model is used to simulate the basic mechanical characteristics of the cardiac muscle, i. e. the force-length and the force-velocity relationships, and describes their dependence on the mechanical activation level. The two-cell duplex unit is used to study the influence of inter-cellular interactions and the effect of inhomogeneity on muscle performance, due to non-uniformity in the electrical stimulation or inhomogeneity in calcium kinetics. Better understanding of the performance of the inhomogeneous muscle is obtained due to our ability to describe the control of the activation level in each cell.

Biomechanical Phenomena↗

Effect of interconnecting collagen fibres on left ventricular function and intramyocardial compression.

OBJECTIVE: The aim was to study the effects of the collagen mesh that interconnects the myocardial fibres on left ventricular mechanics and intramyocardial pressure. METHODS: An earlier model which integrates a symmetrical left ventricular geometry and transmural muscle fibre structure with muscle fibre mechanics was expanded to include radial stiffness generated by dynamically stretched radial collagen fibres. The calculated end systolic pressure-volume relationship (ESPVR) was compared to left ventricular pressure and volume data from six open chest dogs, obtained over a wide load range. Midwall intramyocardial pressure measurements by flat intramyocardial transducer in six different dogs were also used. RESULTS: Consistent with the experiments, inclusion of radial stiffness yielded an ESPVR that was more curvilinear than the collagen-free model, and modified global left ventricular function in that the end systolic volume increased. A diastolic suction effect, manifested by a negative pressure with a steep diastolic pressure-volume relationship at low end systolic volumes, was predicted. The intramyocardial pressure was higher than the left ventricular pressure at the end of isovolumetric relaxation, when radial stretch is maximal and fibre stresses are relaxed. This is attributed to the radial fibre stress component. Intramyocardial pressure was only weakly dependent on left ventricular cavity pressure under wide load manipulations at constant contractility. The experiments also confirmed model predictions that (1) peak intramyocardial pressure is insensitive to load, (2) intramyocardial pressure is markedly higher than left ventricular pressure at the end of isovolumetric relaxation, and (3) intramyocardial pressure continues to rise during ejection towards a maximum value near end ejection. CONCLUSIONS: The transverse radial stiffness due to radial collagen interconnections between myocardial fibrils affects the global systolic left ventricular function, the diastolic suction effect, and the mechanism of systolic coronary compression.

Animals↗

Geodesics as a mechanically optimal fiber geometry for the left ventricle.

Anatomical findings as well as theoretical considerations indicate that the myocardial fibers lie along minimal length geodesics of the left ventricular wall. Based upon this knowledge it is shown that the energy spent by the actively contracting fibers during systole, as well as the passive fiber stresses developed through diastole, are minimal in comparison with any other possible fiber configuration. Subsequently, it is concluded that for a given succession of left ventricular states, fiber shortening course and hence the amount of mechanical work are uniquely determined. Comparison with experimental findings concerning global left ventricular systolic work indicates that a given course of afterload produces a unique course of ventricular volume and of mechanical work.

Diastole↗

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 degrees). 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.

Adult↗

Regional three-dimensional geometry and function of left ventricles with fibrous aneurysms. A cine-computed tomography study.

BACKGROUND: To assess the extent and nature of the dysfunction surrounding aneurysms of the left ventricle (LV), we examined the parameters of local and global three-dimensional shape, size, and function of LVs of eight patients with histologically confirmed anterior fibrous aneurysms. METHODS AND RESULTS: Three-dimensional reconstructions of each LV were made from 10-12 short-axis fast cine-angiographic computed tomography (cine-CT) slices encompassing the entire heart at end diastole and end systole. Regional three-dimensional wall thickness, thickening, motion, curvature, and stress index were calculated for 84 elements encompassing the entire LV. The aneurysmal border was defined by a sharp decrease in end-diastolic wall thickness and separated the LV into an aneurysmal zone and a normal zone that was further divided into adjacent normal (AN) and remote normal (RN) zones. As expected, thickening was negligible in both the aneurysmal and the border zones. Although both the AN and the RN zones had normal wall thickness (1.05 +/- 0.20 and 1.09 +/- 0.20 cm, respectively), thickening was depressed in the AN (0.22 +/- 0.08 cm) but not the RN (0.44 +/- 0.19 cm) zones. The size of the dysfunction zone (defined as less than 2 mm thickening) was found to be considerably greater than the anatomic size of the aneurysm (60.9 +/- 13.7% versus 33.6 +/- 7.6% of the left ventricular endocardial area, respectively; p less than 0.001). In addition, the AN zone had a smaller curvature and a higher stress index than the RN zone. CONCLUSIONS: LVs with fibrous aneurysms are characterized by a relatively large region of nonfunction that encompasses the thin aneurysmal area and its transitional border zone, a normally functioning remote zone, and an intermediate region of normal wall thickness but with reduced function, which may be attributed to its low curvature and high stress index.

Algorithms↗

The slope of the end-systolic pressure-volume relationship compared with the global end-systolic pressure-volume ratio in humans.

The slope of the end-systolic pressure-volume relationship (Emax), which is generated clinically by load manipulation, as well as the "absolute" peak systolic pressure end-systolic volume ratio (denoted as pressure-volume ratio), have been suggested as indices defining left ventricular function. This study represents an attempt to determine the relationship between these two indices by studying 20 patients (16 with coronary artery disease and 4 with normal coronary arteries) undergoing cardiac catheterization. Left ventriculography was performed three times in each patient: (1) in the control baseline state, (2) after rapid intravenous infusion of 250-300 cc of saline, and (3) after sublingual administration of 5 mg isosorbide dinitrate. Emax was approximated by linear regression using the peak left ventricular pressure (replacing end-systolic pressure) and the smallest left ventricular (end-systolic) volume for these three different loads. Acute ischemia with typical chest pain and ECG changes developed in 4 patients during saline loading. The pressure-volume ratio showed no change with load manipulation in patients who did not demonstrate ischemia. In the 4 patients who developed acute ischemia, the pressure-volume ratio dropped from 4.4 +/- 1.3 to 2.9 +/- 0.9 mmHg/ml (p less than 0.001). In all of the patients, the pressure-volume ratio, but not the Emax, correlated with the ejection fraction (r = 0.6; p less than 0.05). In addition, the Emax line demonstrated a markedly nonphysiological Vo. There was no correlation between Emax and pressure-volume ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗