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At least 19 records

Activity of the right cardiac ventricle and metabolism in healthy persons during an orthostatic test after short term immobilization

A 15 minute orthostatic test was performed on healthy male volunteers under conditions of catheterization of the right ventricle of the heart and the radial (or brachial) artery before and after 5 day bedrest in an antiorthostatic position of the body (with the foot of the bed raised 4.5 degrees). The change to a vertical position after immobilization was attended by a more marked increase in the rate of cardiac contractions, an increase of max dp/dt pressure in the right ventricle, and a decrease of cardiac and stroke indices. The decrease of the cardiac index was compensated for, to a certain measure, by a further increase in the extraction and utilization of O2 by the tissues. The arterial blood pH did not change essentially, while the decrease in pCO2 and content of standard bicarbonate was more marked.

Chestukhin, V. V.↗

Advanced Methodology and Preliminary Measurements of Molecular and Mechanical Properties of Heart Valves under Dynamic Strain

Mammalian heart valves are soft tissue assemblies with multi-scale material properties. This is because they are constructs comprising both muscle and non-contractile extracellular matrix proteins (such as collagens and proteoglycans) and transition regions where one form of tissue structure becomes another, significantly different form. The leaflets of the mitral and tricuspid valves are connected to chordae tendinae which, in turn, bind through papillary muscles to the cardiac wall of the ventricle. The transition regions between these tissue subsets are complex and diffuse. Their material composition and mechanical properties have not been previously described with both micro and nanoscopic data recorded simultaneously, as reported here. Annotating the mechanical characteristics of these tissue transitions will be of great value in developing novel implants, improving the state of the surgical simulators and advancing robot-assisted surgery. We present here developments in multi-scale methodology that produce data that can relate mechanical properties to molecular structure using scanning X-ray diffraction. We correlate these data to corresponding tissue level (macro and microscopic) stress and strain, with particular emphasis on the transition regions and present analyses to indicate points of possible failure in these tissues.

valve failure↗

Modeling of Cardiovascular Response to Weightlessness

It was the hypothesis of this Project that the Simple lack of hydrostatic pressure in microgravity generates several purely physical reactions that underlie and may explain, in part, the cardiovascular response to weightlessness. For instance, hydrostatic pressure within the ventricles of the heart may improve cardiac performance by promoting expansion of ventricular volume during diastole. The lack of hydrostatic pressure in microgravity might, therefore, reduce diastolic filling and cardiac performance. The change in transmural pressure is possible due to the difference in hydrostatic pressure gradients between the blood inside the ventricle and the lung tissue surrounding the ventricle due to their different densities. On the other hand, hydrostatic pressure within the vasculature may reduce cardiac inlet pressures because of the typical location of the heart above the hydrostatic indifference level (the level at which pressure remains constant throughout changes in gravity). Additional physical responses of the body to changing gravitational conditions may influence cardiovascular performance. For instance, fluid shifts from the lower body to the thorax in microgravity may serve to increase central venous pressure (CVP) and boost cardiac output (CO). The concurrent release of gravitational force on the rib cage may tend to increase chest girth and decrease pedcardial pressure, augmenting ventricular filling. The lack of gravity on pulmonary tissue may allow an upward shifting of lung mass, causing a further decrease in pericardial pressure and increased CO. Additional effects include diuresis early in the flight, interstitial fluid shifts, gradual spinal extension and movement of abdominal mass, and redistribution of circulatory impedance because of venous distention in the upper body and the collapse of veins in the lower body. In this project, the cardiovascular responses to changes in intraventricular hydrostatic pressure, in intravascular hydrostatic pressure and, to a limited extent, in extravascular and pedcardial hydrostatic pressure were investigated. A complete hydraulic model of the cardiovascular system was built and flown aboard the NASA KC-135 and a computer model was developed and tested in simulated microgravity. Results obtained with these models have confirmed that a simple lack of hydrostatic pressure within an artificial ventricle causes a decrease in stroke volume. When combined with the acute increase in ventricular pressure associated with the elimination of hydrostatic pressure within the vasculature and the resultant cephalad fluid shift with the models in the upright position, however, stroke volume increased in the models. Imposition of a decreased pedcardial pressure in the computer model and in a simplified hydraulic model increased stroke volume. Physiologic regional fluid shifting was also demonstrated by the models. The unifying parameter characterizing of cardiac response was diastolic ventricular transmural pressure (DVDELTAP) The elimination of intraventricular hydrostatic pressure in O-G decreased DVDELTAP stroke volume, while the elimination of intravascular hydrostatic pressure increased DVDELTAP and stroke volume in the upright posture, but reduced DVDELTAP and stroke volume in the launch posture. The release of gravity on the chest wall and its associated influence on intrathoracic pressure, simulated by a drop in extraventricular pressure4, increased DVDELTAP ans stroke volume.

Sharp, M. Keith↗

Right Ventricular Tissue Doppler Assessment in Space During Circulating Volume Modification using the Braslet-M Device

This joint U.S. - Russian work aims to establish a methodology for assessing cardiac function in microgravity in association with manipulation of central circulating volume. Russian Braslet-M occlusion cuffs were used to temporarily increase the volume of blood in the lower extremities, which effectively reduces the volume returning to the heart in the central circulation. A novel methodology was tested on the International Space Station (ISS) to assess the volume status of crewmembers by evaluating the responses to application and release of the Braslet-on-occlusion cuffs, as well as to modified Valsalva and Mueller maneuvers. Baseline echocardiographic tissue Doppler imaging (TDI) of the right ventricular free wall with no Braslet applied shows early diastolic E' (16 cm/sec), late diastolic A' (14 cm/sec), and systolic (12 cm/sec) velocities compatible with normal subjects on Earth. TDI of the RV free wall with Braslet applied shows that early diastolic E' decreased by 50% (8 cm/sec), late diastolic A' increased by 45%, and systolic S' remains unchanged. TDI of the RV free wall approximately 8 beats after the Braslet was released shows early diastolic E' (8 cm/sec), late diastolic A' (12 cm/sec), and systolic S' (13 cm/sec) velocities. During this portion of the release, early diastolic E' did not recover to baseline values but late diastolic A' and systolic S' recovered to pre-Braslet values. The pre-systolic cross-sectional area of the internal jugular vein with Braslet off was 1.07 cm(sup 2) and 1.13 cm(sup 2) 10 min after the Braslet was applied. The presystolic cross-sectional area of the common femoral vein with Braslet off was 0.50 cm(sup 2), and was 0.54 cm(sup 2) 10 min after the Braslet was applied. The right ventricular myocardial performance Tei index also was calculated for comparison with typical values found in healthy subjects on Earth. Baseline and Braslet-on values for Tei index were 0.25 and 0.22 respectively. Braslet Tei indices are within normal ranges found in healthy subjects and temporarily become greater than 0.4 during the dynamic Braslet release portion of this study. Tissue Doppler imaging of the right ventricle revealed that the Braslet influenced cardiac preload and that fluid was sequestered in the lower-extremity interstitial and vascular space after only 10 minutes of application. This report demonstrates that Braslet application affects right ventricular physiology in long-duration space flight based on TDI and that this effect is in part due to venous hemodynamics.

Hamilton, D. R.↗

Design and execution of a verification, validation, and uncertainty quantification plan for a numerical model of left ventricular flow after LVAD implantation

Left ventricular assist devices (LVADs) are implantable pumps that act as a life support therapy for patients with severe heart failure. Despite improving the survival rate, LVAD therapy can carry major complications. Particularly, the flow distortion introduced by the LVAD in the left ventricle (LV) may induce thrombus formation. While previous works have used numerical models to study the impact of multiple variables in the intra-LV stagnation regions, a comprehensive validation analysis has never been executed. The main goal of this work is to present a model of the LV-LVAD system and to design and follow a verification, validation and uncertainty quantification (VVUQ) plan based on the ASME V&V40 and V&V20 standards to ensure credible predictions. The experiment used to validate the simulation is the SDSU cardiac simulator, a bench mock-up of the cardiovascular system that allows mimicking multiple operation conditions for the heart-LVAD system. The numerical model is based on Alya, the BSC’s in-house platform for numerical modelling. Alya solves the Navier-Stokes equation with an Arbitrary Lagrangian-Eulerian (ALE) formulation in a deformable ventricle and includes pressure-driven valves, a 0D Windkessel model for the arterial output and a LVAD boundary condition modeled through a dynamic pressure-flow performance curve. The designed VVUQ plan involves: (a) a risk analysis and the associated credibility goals; (b) a verification stage to ensure correctness in the numerical solution procedure; (c) a sensitivity analysis to quantify the impact of the inputs on the four quantities of interest (QoIs) (average aortic root flow $Q^{avg}_{Ao}$, maximum aortic root flow $Q^{max}_{Ao}$, average LVAD flow $Q^{avg}_{VAD}$, and maximum LVAD flow $Q^{max}_{VAD}$; (d) an uncertainty quantification using six validation experiments that include extreme operating conditions. Numerical code verification tests ensured correctness of the solution procedure and numerical calculation verification showed a grid convergence index (GCI)95% <3.3%. The total Sobol indices obtained during the sensitivity analysis demonstrated that the ejection fraction, the heart rate, and the pump performance curve coefficients are the most impactful inputs for the analysed QoIs. The Minkowski norm is used as validation metric for the uncertainty quantification. It shows that the midpoint cases have more accurate results when compared to the extreme cases. The total computational cost of the simulations was above 100 [core-years] executed in around three weeks time span in Marenostrum IV supercomputer. This work details a novel numerical model for the LV-LVAD system, that is supported by the design and execution of a VVUQ plan created following recognised international standards. We present a methodology demonstrating that stringent VVUQ according to ASME standards is feasible but computationally expensive.

59 BASIC BIOLOGICAL SCIENCES↗

Right Ventricular Tissue Doppler in Space Flight

Tissue Doppler (TD) registers movement of a given sample of cardiac tissue throughout the cardiac cycle. TD spectra of the right ventricle (RV) were obtained from a long-duration ISS crewmember as a portion of an ongoing experiment ("Braslet" test objective). To our knowledge, this is the first report of RV TD conducted in space flight, and the data represent reproducibility and fidelity of this application in space and serve as the first "space normal" data set. Methods RV TD was performed by astronaut scientists remotely guided by an ultrasound expert from Mission Control Center, Houston, TX. In four of the subjects, RV TD was acquired from the free wall near the tricuspid annulus in two separate sessions 4 to 7 days apart. A fifth subject had only one session. All digital DICOM frames were exported for off-line analysis. Systolic (S ), early diastolic (E ) and late diastolic (A ) velocities were measured. RV Tei-index was calculated using diastolic and systolic time intervals as a combined measure of myocardial performance. Results and Discussion The mean values from the first 4 subjects (8 sessions) were used as the on-orbit reference data, and subject 5 was considered as a hypothetical patient for comparison (see Table). The greatest difference was in the early diastolic A (31 %) yet the standard deviation (a) for A amongst the reference subjects was 2.25 (mean = 16.02). Of interest is the Tei index, a simple and feasible indicator of overall ventricular function; it was similar amongst all the subjects. The late diastolic A seems to compensate for the variance in E . Normal Tei index for the RV is < 0.3, yet our data show all but one subject consistently above this level, notwithstanding their nominal responses to daily exercise in microgravity. These data remind us that the physiology of RV preload in altered gravity environments is still not completely understood.

Hamilton, Douglas R.↗

Cardiac mechanics: Physiological, clinical, and mathematical considerations

Recent studies concerning the basic physiological and biochemical principles underlying cardiac muscle contraction, methods for the assessment of cardiac function in the clinical situation, and mathematical approaches to cardiac mechanics are presented. Some of the topics covered include: cardiac ultrastructure and function in the normal and failing heart, myocardial energetics, clinical applications of angiocardiography, use of echocardiography for evaluating cardiac performance, systolic time intervals in the noninvasive assessment of left ventricular performance in man, evaluation of passive elastic stiffness for the left ventricle and isolated heart muscle, a conceptual model of myocardial infarction and cardiogenic shock, application of Huxley's sliding-filament theory to the mechanics of normal and hypertrophied cardiac muscle, and a rheological modeling of the intact left ventricle. Individual items are announced in this issue.

Mirsky, I.↗

Mechanisms of a novel regulatory light chain–dependent cardiac myosin inhibitor

Hypertrophic cardiomyopathy (HCM) is a genetic disease of the heart characterized by thickening of the left ventricle (LV), hypercontractility, and impaired relaxation. HCM is caused primarily by heritable mutations in sarcomeric proteins, such as β myosin heavy chain. Until recently, medications in clinical use for HCM did not directly target the underlying contractile changes in the sarcomere. Here, we investigate a novel small molecule, RLC-1, identified in a bovine cardiac myofibril high-throughput screen. RLC-1 is highly dependent on the presence of a regulatory light chain to bind to cardiac myosin and modulate its ATPase activity. In demembranated rat LV trabeculae, RLC-1 decreased maximal Ca2+-activated force and Ca2+ sensitivity of force, while it increased the submaximal rate constant for tension redevelopment. In myofibrils isolated from rat LV, both maximal and submaximal Ca2+-activated force are reduced by nearly 50%. Additionally, the fast and slow phases of relaxation were approximately twice as fast as DMSO controls, and the duration of the slow phase was shorter. Structurally, x-ray diffraction studies showed that RLC-1 moved myosin heads away from the thick filament backbone and decreased the order of myosin heads, which is different from other myosin inhibitors. In intact trabeculae and isolated cardiomyocytes, RLC-1 treatment resulted in decreased peak twitch magnitude and faster activation and relaxation kinetics. In conclusion, RLC-1 accelerated kinetics and decreased force production in the demembranated tissue, intact tissue, and intact whole cells, resulting in a smaller cardiac twitch, which could improve the underlying contractile changes associated with HCM.

Physiology↗

Influence of gravity on cardiac performance

Results obtained by the investigators in ground-based experiments and in two parabolic flight series of tests aboard the NASA KC-135 aircraft with a hydraulic simulator of the human systemic circulation have confirmed that a simple lack of hydrostatic pressure within an artificial ventricle causes a decrease in stroke volume of 20%-50%. A corresponding drop in stroke volume (SV) and cardiac output (CO) was observed over a range of atrial pressures (AP), representing a rightward shift of the classic CO versus AP cardiac function curve. These results are in agreement with echocardiographic experiments performed on space shuttle flights, where an average decrease in SV of 15% was measured following a three-day period of adaptation to weightlessness. The similarity of behavior of the hydraulic model to the human system suggests that the simple physical effects of the lack of hydrostatic pressure may be an important mechanism for the observed changes in cardiac performance in astronauts during the weightlessness of space flight.

NASA Discipline Cardiopulmonary↗

Noncontacting electrokinetography system

Noncontact acoustic technique utilizing air-coupled ultrasonic transducers for measuring motion of chest wall during cardiac cycle gives information on changes in size and compliance of heart ventricles. Information is digitized and fed to microprocessor for rapid storage and analysis for aid in diagnosis of heart condition.

Davis, J. G.↗

A biplane roentgen videometry system for dynamic /60 per second/ studies of the shape and size of circulatory structures, particularly the left ventricle.

A roentgen-television digital-computer technique and a display system developed for dynamic circulatory structure studies are described. Details are given for a videoroentgenographic setup which is used for obtaining biplane roentgen silhouettes of a left ventricle. A 60 per sec measurement of the shape and volume of angiographically outlined cardiac chambers can be made by this technique along with simultaneous ECG, pressure, and flow measurements accessible for real-time digital computer processing and analysis.

Ritman, E. L.↗

Alterations in left ventricular volumes induced by Valsalva manoeuvre

Five patients were studied with left ventriculography during different phases of the Valsalva manoeuvre. Small doses of contrast medium allowed adequate repetitive visualization of the left ventricle for volume calculation. During strain phase, the volume of the left ventricle decreased by nearly 50 per cent in each case, and stroke volume and cardiac output also dropped strikingly. Release of straining was attended by a sharp rebound of left ventricular volume to control levels, with a transient surge of increased cardiac output 42 per cent above that of the resting state.

Brooker, J. Z.↗

Effect of Actual and Simulated Microgravity on Cardiac Mass and Function in the Rat

The purpose of this study was to test the hypothesis that exposure to actual or simulated microgravity induces cardiac atrophy in male Sprague-Dawley rats. For the microgravity study, rats were subdivided into four groups: Preflight (PF, n = 12); Flight (FL, n = 7); Flight Cage Simulation (SIM, n = 6), and Vivarium Control (VIV, n = 7). Animals in the FL group were exposed to 7 days of microgravity during the Spacelab 3 mission. Animals in the simulated microgravity study were subdivided into three groups: Control (CON, n = 20); 7 day hindlimb unloaded (7HU, n = 10); and 28 day unloaded (28HU, n = 19). In a subset of CON (n = 7) and 28HU (n = 6) rats, a catheter was advanced into the left ventricle to measure the rate of rise in ventricular pressure (+dP/dt) during standing as an estimate of cardiac contractility. After completion of their respective treatments, hearts were removed and weighed. Animals in the PF group were sacrificed 24 hr prior to launch while the FL group was sacrificed 11- 17 hr after landing. The SM and VIV groups were sacrificed 48 and 96 hr after the FL group, respectively. Heart mass was unchanged in adult animals exposed to 7 days of actual microgravity (PF 1.33 +/- .03 g; FL 1.32 +/- 0.02 g; SIM 1.28 +/- 0.04 g; VIV 1.35 +/- 0.04 g). Similarly, heart mass was unaltered with hin~limb unloading (CON 1.40 +/- 0.04 g; 7HU 1.35 +/- 0.06 g; 28HU 1.42 +/- 0.03 g). Hindlimb unloading also had no effect on myocardial contractility (CON 8055 +/- 385 mmHg/sec; 28HU 8545 +/- 755 mmHg/sec). These data suggest that cardiac atrophy does not occur following short-term exposure to microgravity, and that neither short- nor long-term simulated microgravity alter cardiac mass or function.

Ray, Chester H.↗

Distribution of plutonium and radium in the human heart

Since 1968, the United States Transuranium and Uranium Registries (USTUR) has studied the biokinetics and tissue dosimetry of uranium and transuranium elements in nuclear workers. As part of the USTUR collaboration with the Million Person Study of Low-Dose Health Effects, radiation dose to different parts of the human heart is being estimated for workers with documented intakes of 239 Pu or 226 Ra. The study may be expanded for workers with intakes of 238 U and other radionuclides. The distribution of radionuclides, expressed in terms of concentration (Bq per kg of tissue) serves as an important parameter for estimating radiation dose. Based on available organs from workers who donated their bodies or tissues for research, nine undissected hearts were selected: seven from USTUR registrants with plutonium exposure (males) and two individuals with radium intakes (female and male). For the plutonium workers, estimated 239 Pu systemic deposition ranged from <74 Bq to 1765 Bq. Estimated 226 Ra ‘initial systemic intakes’ were 10.1 MBq and 14.8 kBq for the female patient and male worker, respectively. Organ dissection was based on a heart model published by Borrego et al (2019 J. Radiol. Prot. 39 950–65). This model includes nine cardiac substructures: aorta, left main coronary artery, left atrium, left anterior descending artery, left circumflex artery, left ventricle, right atrium, right coronary artery, and right ventricle. In addition, heart valves, fat attached to epicardium, fluids, and a coronary bypass graft were collected resulting in 111 samples that are currently undergoing radiochemical analyses and mass-spectrometric measurements. The 239 Pu and 226 Ra evaluations are not completed. The results of this study are intended to support radiation worker health studies by improving associated dosimetric and epidemiological models.

USTUR↗

Measurements, modeling, control and simulation - as applied to the human left ventricle for purposeful physiological monitoring.

Interdisciplinary engineering research effort in studying the intact human left ventricle has been employed to physiologically monitor the heart and to obtain its 'state-of-health' characteristics. The left ventricle was selected for this purpose because it plays a key role in supplying energy to the body cells. The techniques for measurement of the left ventricular geometry are described; the geometry is effectively displayed to bring out the abnormalities in cardiac function. Methods of mathematical modeling, which make it possible to determine the performance of the intact left ventricular muscle, are also described. Finally, features of a control system for the left ventricle for predicting the effect of certain physiological stress situations on the ventricle performance are discussed.

Ghista, D. N.↗

Cardiovascular function during sustained +G/z/ stress

The development of aerospace systems capable of very high levels of positive vertical accelerators stress has created a need for a better understanding of the cardiovascular responses to acceleration. Using a canine model, the heart and cardiovascular system were instrumented to continuously measure coronary blood flow, cardiac output, left ventricular and aortic root pressure, and oxygen saturation in the aorta, coronary sinus, and right ventricle. The animals were exposed to acceleration profiles up to +6 G, 120 s at peak G; a seatback angle of 45 deg was simulated in some experiments. Radiopaque contrast medium was injected to visualize the left ventricular chamber, coronary vasculature, aorta, and branches of the aorta. The results suggest mechanisms responsible for arrhythmias which may occur, and subendocardial hemorrhage which has been reported in other animals.

Erickson, H. H.↗

Finite element stress analysis of the human left ventricle whose irregular shape is developed from single plane cineangiocardiogram

The three-dimensional left ventricular chamber geometrical model is developed from single plane cineangiocardiogram. This left ventricular model is loaded by an internal pressure monitored by cardiac catheterization. The resulting stresses in the left ventricular model chamber's wall are determined by computerized finite element procedure. For the discretization of this left ventricular model structure, a 20-node, isoparametric finite element is employed. The analysis and formulation of the computerised procedure is presented in the paper, along with the detailed algorithms and computer programs. The procedure is applied to determine the stresses in a left ventricle at an instant, during systole. Next, a portion (represented by a finite element) of this left ventricular chamber is simulated as being infarcted by making its active-state modulus value equal to its passive-state value; the neighbouring elements are shown to relieve the 'infarcted' element of stress by themselves taking on more stress.

Ghista, D. N.↗

Segmentation and tracking in echocardiographic sequences: active contours guided by optical flow estimates

This paper presents a method for segmentation and tracking of cardiac structures in ultrasound image sequences. The developed algorithm is based on the active contour framework. This approach requires initial placement of the contour close to the desired position in the image, usually an object outline. Best contour shape and position are then calculated, assuming that at this configuration a global energy function, associated with a contour, attains its minimum. Active contours can be used for tracking by selecting a solution from a previous frame as an initial position in a present frame. Such an approach, however, fails for large displacements of the object of interest. This paper presents a technique that incorporates the information on pixel velocities (optical flow) into the estimate of initial contour to enable tracking of fast-moving objects. The algorithm was tested on several ultrasound image sequences, each covering one complete cardiac cycle. The contour successfully tracked boundaries of mitral valve leaflets, aortic root and endocardial borders of the left ventricle. The algorithm-generated outlines were compared against manual tracings by expert physicians. The automated method resulted in contours that were within the boundaries of intraobserver variability.

Non-NASA Center↗