scholarly journals Attenuated sarcomere lengthening of the aged murine left ventricle observed using two-photon fluorescence microscopy

2015 ◽  
Vol 309 (5) ◽  
pp. H918-H925 ◽  
Author(s):  
Michael E. Nance ◽  
Justin T. Whitfield ◽  
Yi Zhu ◽  
Anne K. Gibson ◽  
Laurin M. Hanft ◽  
...  

The Frank-Starling mechanism, whereby increased diastolic filling leads to increased cardiac output, depends on increasing the sarcomere length ( Ls) of cardiomyocytes. Ventricular stiffness increases with advancing age, yet it remains unclear how such changes in compliance impact sarcomere dynamics in the intact heart. We developed an isolated murine heart preparation to monitor Ls as a function of left ventricular pressure and tested the hypothesis that sarcomere lengthening in response to ventricular filling is impaired with advanced age. Mouse hearts isolated from young (3–6 mo) and aged (24–28 mo) C57BL/6 mice were perfused via the aorta under Ca2+-free conditions with the left ventricle cannulated to control filling pressure. Two-photon imaging of 4-{2-[6-(dioctylamino)-2-naphthalenyl]ethenyl}1-(3-sulfopropyl)-pyridinium fluorescence was used to monitor t-tubule striations and obtain passive Ls between pressures of 0 and 40 mmHg. Ls values (in μm, aged vs. young, respectively) were 2.02 ± 0.04 versus 2.01 ± 0.02 at 0 mmHg, 2.13 ± 0.04 versus 2.23 ± 0.02 at 5 mmHg, 2.21 ± 0.03 versus 2.27 ± 0.03 at 10 mmHg, and 2.28 ± 0.02 versus 2.36 ± 0.01 at 40 mmHg, indicative of impaired sarcomere lengthening in aged hearts. Atomic force microscopy nanoindentation revealed that intact cardiomyocytes enzymatically isolated from aged hearts had increased stiffness compared with those of young hearts (elastic modulus: aged, 41.9 ± 5.8 kPa vs. young, 18.6 ± 3.3 kPa; P = 0.006). Impaired sarcomere lengthening during left ventricular filling may contribute to cardiac dysfunction with advancing age by attenuating the Frank-Starling mechanism and reducing stroke volume.

1982 ◽  
Vol 52 (2) ◽  
pp. 333-339 ◽  
Author(s):  
T. C. Lloyd

We studied cardiopulmonary interdependence in ten pentobarbital sodium-anesthetized dogs by 1) measuring the increase of left atrial pressure (Pla) required to hold cardiac output (Q) constant on application of a positive end-expiratory pressure (PEEP), 2) determining the reduction of Pla required to mimic the Q fall observed when PEEP was applied while Pla was held constant, and 3) comparing left ventricular pressure-volume curves measured in freshly dead dogs during ventilation with and without PEEP. The atrial pressure changes can be divided into terms for pleural pressure change, lung deformation, and an undefined residual component and can be used to obtain a compliance opposing ventricular filling. Another compliance was derived from the pressure-volume curves. The latter compliance (6.8 ml/cm H2O) significantly exceeded the former (3.9 ml/cm H2O). The difference may have been caused by ventricular interdependence. The respiratory system compliance opposing ventricular filling was approximately one-twentieth of that predicted from lung and chest wall compliances. Deformation of lungs and chest wall appears to be a significant component of the elastic load imposed on ventricular diastolic filling.


1983 ◽  
Vol 245 (5) ◽  
pp. H741-H748 ◽  
Author(s):  
W. Y. Lew ◽  
M. M. LeWinter

We employed sonomicrometers in open-chest dogs to study lengthening of short segments of circumferentially oriented myocardium located at the base, midportion, and apex of the anterior left ventricular free wall. Left ventricular pressure was varied by inferior vena caval occlusion and volume expansion. Diastole was divided into rapid and slow lengthening phases. Rapid lengthening was completed first at the basal site at each of three successive levels of left ventricular diastolic pressure (LVDP). At the base, significant further lengthening occurred during the slow lengthening phase while at the apex virtually all lengthening was completed during the rapid phase. At low LVDPs, peak lengthening rates (dl/dt) were greatest at the apex. As LVDP was increased, regional differences in dl/dt diminished. These results indicate that there is regional variation in the timing of the phases of diastole and in lengthening patterns of the left ventricle. The volume-dependent variation in lengthening rates that we observed is consistent with the concept of regional differences in elastic recoil, which may contribute to active ventricular filling.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Katsuomi Iwakura ◽  
Hiroshi Ito ◽  
Atsunori Okamura ◽  
Yasushi Koyama ◽  
Motoo Date ◽  
...  

Patients with atrial fibrillation (AF) are frequently associated with reduced left ventricular (LV) diastolic dysfunction. It is still unclear whether reduced diastolic function is associated with the risk of left atrial (LA) thrombus in AF. The ratio of transmitral E velocity to mitral annular velocity (e′) is an echocardiographic estimate of diastolic LV filling pressure even under AF rhythm. We investigated whether reduced LV diastolic function is associated with the risk of LA thrombus in AF patients, using E/e′ ratio as an index. We enrolled consecutive 405 patients with non-valvular, paroxysmal or chronic AF, who underwent both transthoracic- (TTE) and transesophagial echocardiography (TEE) examination within a month. We measured LA and LV dimensions, LV ejection fraction (%EF), wall thickness, E and e′ velocities on TTE, and determined E/e′ ratio. LA appendage thrombus was found in 33 patients (8.1%). Patients with LA thrombus showed lower e′ velocity (5.3±1.8 vs. 7.0±2.2 cm/s, p<.0001) and higher E/e′ ratio (17.2±9.2 vs. 11.5±5.9, p<.0001) than those without it. Using 12.4 as an optimal cutoff point, E/e′ predicted LA thrombus with 70% sensitivity and 70% specificity (AUC=0.72). Odds ratio for LA thrombus in patients in the highest quartile of E/e′ was 6.38 (3.06–13.9). Multivariate logistic regression analysis indicated that the highest quartiles of E/e′ ratio was an independent predictor of LA thrombus among echocardiographic parameters, along with LA dimension and %EF, whereas e′ was not. LA appendage flow velocity was significantly correlated with E/e′ ratio (p<.0001), implying that increased diastolic filling pressure could be associated with impaired blood flow within LA. Increased LV filling pressure increased the risk of LA thrombus in patients with AF, partially through impaired LA hemodynamics. E/e′ ratio on TTE could be useful for detecting high-risk patients for LA thrombus.


1957 ◽  
Vol 192 (1) ◽  
pp. 157-163 ◽  
Author(s):  
E. Braunwald ◽  
S. J. Sarnoff ◽  
R. B. Case ◽  
W. N. Stainsby ◽  
G. H. Welch

Although the general dependence of coronary flow on myocardial qo2 was confirmed in an in situ heart preparation, changes in aortic pressure and cardiac output were observed to be capable of influencing this relationship. Neither myocardial qo2 nor coronary flow were found to be dependent on left ventricular filling pressure.


1979 ◽  
Vol 236 (2) ◽  
pp. H323-H330 ◽  
Author(s):  
D. Ling ◽  
J. S. Rankin ◽  
C. H. Edwards ◽  
P. A. McHale ◽  
R. W. Anderson

In eight chronically instrumented conscious dogs, apical and middle left ventricular transverse diameters were measured with pulse-transit ultrasonic dimension transducers. Intracavitary apical and midventricular pressures and intrapleural pressure were measured with micromanometers. Both diameters were normalized as a percent extension from the dimension at zero transmural pressure, determined during a transient vena caval occlusion. During the rapid phase of diastolic filling, there was a 2--5 mmHg pressure gradient from the midventricle to the apex. During late rapid filling, the apical transmural pressure and diameter increased more rapidly and reached diastasis 17 +/- 4 ms earlier than the corresponding midventricular measurements (P less than 0.01). The static diastolic pressure-dimension characteristics at the apical and midventricular levels were not significantly different (P greater than 0.30). The dynamic diastolic pressure-dimension relationship was also similar at the two levels and could be represented by a model incorporating parallel viscous properties. Because of regional differences in pressures and dimensions, however, the dynamic relationship could not be modeled when pressure was compared to the dimension at a different level. Thus, diastolic pressures should be measured at the same level as dimensions when assessing left ventricular diastolic mechanics.


Author(s):  
Ahmad Moghaddaszade-Kermani ◽  
Peter Oshkai ◽  
Afzal Suleman

Mitral-Septal contact has been proven to be the cause of obstruction in the left ventricle with hypertrophic cardiomyopathy (HC). This paper presents a study on the fluid mechanics of obstruction using two-way loosely coupled fluid-structure interaction (FSI) methodology. A parametric model for the geometry of the diseased left ventricular cavity, myocardium and mitral valve has been developed, using the dimensions extracted from magnetic resonance images. The three-element Windkessel model [1] was modified for HC and solved to introduce pressure boundary condition to the aortic aperture in the systolic phase. The FSI algorithm starts at the beginning of systolic phase by applying the left ventricular pressure to the internal surface of the myocardium to contract the muscle. The displacements of the myocardium and mitral leaflets were calculated using the nonlinear finite element hyperelastic model [2] and subsequently transferred to the fluid domain. The fluid mesh was moved accordingly and the Navier-Stokes equations were solved in the laminar regime with the new mesh using the finite volume method. In the next time step, the left ventricular pressure was increased to contract the muscle further and the same procedure was repeated for the fluid solution. The results show that blood flow jet applies a drag force to the mitral leaflets which in turn causes the leaflet to deform toward the septum thus creating a narrow passage and possible obstruction.


Author(s):  
Kelley C. Stewart ◽  
John J. Charonko ◽  
Takahiro Ohara ◽  
William C. Little ◽  
Pavlos P. Vlachos

Diastolic dysfunction is the impairment of the filling in the left ventricle. Patients with left ventricular diastolic dysfunction (LVDD) lose the ability to adjust left ventricular filling properties without increasing left atrial pressure [1]. Although LVDD is very prevalent, it currently remains difficult to diagnose due to inherent atrioventricular compensatory mechanisms including increased heart rate, increased left ventricular (LV) contractility, and increased left atrial (LA) pressure. Although variations within the early diastolic filling velocity have been previously observed [2], the physical mechanism for the deceleration of the early filling wave is not understood.


2020 ◽  
Vol 20 (07) ◽  
pp. 2050043
Author(s):  
A. BENFOULA ◽  
L. HAMZA CHERIF ◽  
K. N. HAKKOUM

The main objective of this work is to study the effect of blood pressure and viscosity on flow in a pathological and healthy anatomy. The method chosen for this project is the numerical simulation of fluid dynamics. First, a radiological database from Tlemcen hospital was studied in order to select a patient whose aortic anatomy is representative of the pathology studied in this research project. The left ventricle was segmented using SolidWork software. The exported data made it possible to model this geometry on Comsol software. The geometry has been idealized to make it comparable to a given healthy left ventricle geometry and present the main parameters which influence the ventricular hemodynamics. A first series of numerical simulations made it possible to highlight the hemodynamic disturbances associated with the pathology of interest and described extensively in the literature. A second series of numerical simulations made it possible to model the effect of blood viscosity on flow. All the results obtained, the modeling of the left ventricle, must be valid experimentally. This study therefore does not completely justify the treatment of ventricular dilation with a flow modulator but constitutes an important first step towards a proof of concept.


1978 ◽  
Vol 234 (5) ◽  
pp. H567-H572 ◽  
Author(s):  
R. P. Cole ◽  
B. A. Wittenberg ◽  
P. R. Caldwell

An isolated dog heart preparation perfused with hemoglobin-free fluorocarbon suspension has been developed to study the role of myoglobin in myocardial function. The coronary vasculature was perfused at constant flow, with oxygen consumption determined from arteriovenous PO2 differences. Muscle function was assessed by measurement of pressures generated in a latex balloon placed in the left ventricle. The perfusate consisted of 20% perfluorotributylamine and 80% Ringer's lactate with 16 mM glucose. Steady-state oxygen consumption decreased from 0.30 to 0.11 ml/min per gram dry weight left ventricle, as perfusate PO2 decreased from 690 to 150 mmHg. Left ventricular pressure generation and oxygen consumption were determined before and after addition of 8 mM sodium nitrite, which changed functional ferrous myoglobin to high-spin ferric myoglobin. Over the range of perfusate PO2 studied, nitrite addition did not alter mechanical performance or myocardial oxygen consumption. These data suggest that those conditions necessary for substantial myoglobin-facilitated diffusion of oxygen in the myocardium are not present in the isolated fluorocarbon-perfused dog heart.


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