Background Right ventricular (RV) diastolic function has been associated with outcomes for patients with pulmonary hypertension; however, the relationship between biomechanics and hemodynamics in the right ventricle has not been studied. Methods and Results Rat models of RV pressure overload were obtained via pulmonary artery banding (PAB; control, n=7; PAB, n=5). At 3 weeks after banding, RV hemodynamics were measured using a conductance catheter. Biaxial mechanical properties of the RV free wall myocardium were obtained to extrapolate longitudinal and circumferential elastic modulus in low and high strain regions (E-1 and E-2, respectively). Hemodynamic analysis revealed significantly increased end-diastolic elastance (E-ed) in PAB (control: 55.1 mm Hg/mL [interquartile range: 44.785.4 mm Hg/mL]; PAB: 146.6 mm Hg/mL [interquartile range: 105.8155.0 mm Hg/mL]; P=0.010). Longitudinal E1 was increased in PAB (control: 7.2 kPa [interquartile range: 6.718.1 kPa]; PAB: 34.2 kPa [interquartile range: 18.144.6 kPa]; P=0.018), whereas there were no significant changes in longitudinal E-2 or circumferential E-1 and E-2. Last, wall stress was calculated from hemodynamic data by modeling the right ventricle as a sphere: (stress = Pressure x radius/2 x thickness Conclusions RV pressure overload in PAB rats resulted in an increase in diastolic myocardial stiffness reflected both hemodynamically, by an increase in E-ed, and biomechanically, by an increase in longitudinal E-1. Modest increases in tissue biomechanical stiffness are associated with large increases in E-ed. Hemodynamic measurements of RV diastolic function can be used to predict biomechanical changes in the myocardium.

This study examines the α-adrenergic constrictor tone varies with intensity of exercise, the effects of coronary α1-adrenergic blockade on left ventricular contractile function and regional myocardial perfusion, and compares the effects of increasing coronary blood flow by removing α1-constrictor tone.

Examples of asymmetric organs are found throughout the animal kingdom. Whether it is superficial like the fiddler crab’s claw or within an organism like our visceral organs, asymmetries have repeatedly evolved in nature. However, the genetic and developmental origins for asymmetric organ development remain unclear, especially for superficially paired structures. Within zebrafish, a striking example of asymmetry occurs within the ace/fgf8 mutant. The pharyngeal cartilages of these mutants develop asymmetrically 35% of the time, with more cartilages developing on the left or right side of the head, but the origins of this asymmetry are unknown. A significant proportion of mutants also exhibit situs inversus, whereby the visceral organs develop on the opposite side of the body. Here we seek to understand the temporal window most sensitive to giving rise to this asymmetry, and to understand if there is a correlation between the developing heart field and pharyngeal cartilage with respect to the direction of the asymmetry. Wild type (WT) zebrafish were exposed to SU5402 during different periods of development, and heart position as well as cartilage development was observed within the developing larvae. The direction of asymmetry (i.e., left or right biased) was also recorded in ace/fgf8 mutant heart position and cartilage number to observe if there was a correlation between the two developing fields. SU5402 experiments revealed that the time window most sensitive to the development of cartilage asymmetries was during heart looping and pharyngeal arch segmentation. Furthermore, ace/fgf8 mutants exhibited a robust correlation between ventricle position and the side of cartilage asymmetry, with more cartilages forming on the side where the ventricle is located. Given the close proximity of the heart and pharyngeal cartilage fields we suggest that the heart field is influencing the developing cartilage, with signaling permeating from the developing heart to the pharyngeal mesoderm to provide a buffer on the side of the developing ventricle.

The optimal timing of valve replacement surgery in chronic severe aortic regurgitation (AR) has remained a major clinical problem in the management of these patients. Although the onset of symptoms is the generally accepted indication for aortic valve replacement (AVR), the unpredictable development of pre-symptomatic left ventricular (LV) dysfunction as a result of prolonged volume overload has resulted in numerous reports attempting to formulate a risk profile for these patients. Although aortic root and LV cineangiography have been the "gold standard" for defining the severity of AR and its effect on LV performance, serial follow-up by these means is impractical. More recently numerous non-invasive measures of LV size (echocardiogram) and function both at rest and on exercise (echocardiogram and equilibrium radionuclide angiocardiography., ERNA) have been serially utilised~ In these endeavours, the thinking has been clouded by a tendency to equate these two measures and failing to appreciate that apparent preoperative LV dysfunction (particularly on exercise) may be rapidly reversible by AVR and the consequent changes in LV loading conditions. This study was a prospective, sequential evaluation of left ventricular function using both non-invasive and invasive techniques in symptomatic and asymptomatic patients with isolated chronic, severe (4+) AR at cardiac catheterisation. The aims of the study were to (I) Identify differences in the clinical, echocardiographic, resting and exercise haemodynamic and I radionuclide measures of left ventricular function in symptomatic and asymptomatic patients with chronic severe A.R. with particular reference to the incidence of presymptomatic development of left ventricular dysfunction. (II) Critically evaluate the role of exercise stress (both isotonic and isometric) in the assessment of patients with chronic severe A.R. (III) Evaluate the influence of time (sequential studies) on the haemodynamic burden in asymptomatic patients. (IV) Study the impact of successful aortic valve replacement on the reversibility of abnormal pre-operative LV function in an attempt to predict which patients would benefit from this therapeutic intervention and whether operation for symptoms alone is the correct clinical practice.

Understanding the mechanisms governing left ventricular function and dysfunction is critical to analyze cardiovascular disorders and gaining insights into possible therapies. Left ventricular function can be evaluated using Magnetic Resonance Imaging (MRI). Cardiac displacements and corresponding strains are then computed from the imaging data. In measuring and assessing the left ventricle’s motion, images are taken either in the short axis (top-down) or long axis (side) views. In this project, we will use DENSE MRI data, which measures the displacements of individual tissue voxels during the cardiac cycle. After extracting the myocardial tissue by segmenting the MR images, strains are computed by differentiating the displacement field in the radial direction (across the thickness of the heart wall), longitudinal direction (along the left ventricle long axis), and in the circumferential direction. Current approaches focus mainly on evaluating cardiac motion and strains during ventricular systole, when the ventricles contract and blood is pumped out of the heart ~\cite{srichai2009cardiovascular}. Our aim is to characterize strains during atrial systole, which corresponds to the late filling of the ventricles before the next contraction occurs. Understanding the deformation of the left ventricle during late filling is particularly important to evaluate the passive response of the myocardium, which is related to several cardiac diseases, such as heart failure with preserved ejection fraction and diabetic cardiomyopathy. During this study we will use preclinical data already acquired in healthy swine subjects. Our goal is to evaluate inter subject variability at peak atrial systole and how different segmentations (intra and inter observer variability) affect the computed strains.

Congenital heart disease (CHD) is the most common congenital anomaly, with single ventricle (SV) defects accounting for nearly 10% of all CHD. SV defects tend to be the most severe forms of CHD: all patients born with SV require multiple open heart surgeries, often beginning in the neonatal period, ultimately leading to the Fontan procedure. Due to improvements in surgical procedures and medical care, more patients are surviving into adolescence and adulthood. Brain imaging and pathology studies have shown that patients with SV have differences in brain structure and metabolism even before the first surgery, and as early as in utero. Furthermore, a significant number of patients have new or more severe lesions after the initial surgery, and many still have brain abnormalities into early childhood. However, there are no detailed brain structural data of SV patients in adolescence. Our group recruited a large cohort of post-Fontan SV patients aged 10-19 years. Separate analyses of neuropsychological and behavioral outcomes in these patients show deficits in multiple areas of cognition, increased rates of attention deficit-hyperactivity disorder (ADHD), and increased use of remedial and/or special education services compared to a control group. Post-Fontan adolescents have more gross brain abnormalities, including evidence of chronic ischemic stroke. Furthermore, there are widespread reductions in cortical and subcortical gray matter volume and cortical thickness, some of which are associated with medical and surgical variables. Diffusion tensor imaging (DTI) analyses show widespread areas of altered white matter microstructure in deep subcortical and cerebellar white matter. In this dissertation, I use graph theory methods to characterize structural connectivity based on gray matter (cortical thickness covariance) and white matter (DTI tractography), and examine associations between brain structure and neurodevelopment. I found that brain network connectivity differs in post-Fontan patients compared with controls, both at the global and regional level. Additionally, deficits in overall network structure were associated with impaired neurodevelopment in several domains, including general intelligence, executive function, and visuospatial skills. These data suggest that early neuroprotection should be a major focus in the care of SV patients, with the goal of improving long-term neurodevelopmental outcomes.

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