The right ventricle (RV) of the heart is clearly an extremely important component of cardiovascular function and physiology. The RV is affected in many cardiovascular disease processes, including pulmonary arterial hypertension (PAH), congenital heart disease, and left ventricular failure. In PAH, the performance of the RV is the strongest predictor of morbidity and mortality. Several advances in PAH therapies have occurred over the past decade, including the use of phosphodiesterase-5 (PDE5) inhibitors, endothelin receptor antagonists (ETRAs), and experimental metabolic modulators (Dichloroacetate-DCA). Most therapies for PAH are focused on decreasing RV afterload by vasodilation of the pulmonary vasculature, though there is a surprising lack of focus on direct effects of therapies on the RV. In PAH, the RV compensates to the increase in afterload by hypertrophy, this hypertrophic defense mechanism eventual falls short and the RV progresses to failure and patient death. The specific aims of our investigations are to assess the effects of PAH therapies on RV in normal and hypertrophied states, as seen in PAH. We utilize human RV samples attained from cardiac surgical procedures to perform in-vitro analysis of protein and mRNA expression of the targets of PAH therapies. We also use a rat model of PAH and subsequent RV hypertrophy to verify human data and to also perform applied physiology experiments to isolate ex-vivo effects of PAH therapies on the RV. The experiments and data gathered in this thesis represent the insight into the importance of the RV in PAH therapies and how these therapies directly mediate the state of inotropy of the RV. A conclusion of greater importance is the better understanding of RV-specific changes in gene expression when the RV undergoes hypertrophy. By demonstrating the up-regulation of protein expression in RVH we are able to potentially tailor therapies to only improve performance of the diseased RV, while sparing the LV if it is otherwise normal. This is a true shift in paradigm as all current cardiac therapeutics effect both right and left ventricle. / Experimental Medicine

No description available.

Thesis (M.S.)--University of Missouri-Columbia, 2005. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "May 2005" Includes bibliographical references.

A predominantly right ventricular variant of isolated noncompaction cardiomyopathy is a potentially lethal disease entity, which only recently has become recognized in the clinical and cardiac imaging literature. There are currently few established morphologic criteria for the diagnosis other than right ventricular dilation and presence of excessive regional trabeculation. To date, there have been no autopsy reports of cases following either clinical diagnosis or sudden death. We report 2 adult cases of sudden unexpected death in which unexplained right ventricular dilation and prominent apical hypertrabeculation were the principal findings. The gross and microscopic results suggest pathological similarities between, or coexistence of, right ventricular noncompaction and arrhythmogenic right ventricular cardiomyopathies.

A predominantly right ventricular variant of isolated noncompaction cardiomyopathy is a potentially lethal disease entity, which only recently has become recognized in the clinical and cardiac imaging literature. There are currently few established morphologic criteria for the diagnosis other than right ventricular dilation and presence of excessive regional trabeculation. To date, there have been no autopsy reports of cases following either clinical diagnosis or sudden death. We report 2 adult cases of sudden unexpected death in which unexplained right ventricular dilation and prominent apical hypertrabeculation were the principal findings. The gross and microscopic results suggest pathological similarities between, or coexistence of, right ventricular noncompaction and arrhythmogenic right ventricular cardiomyopathies.

Pacemaker-lead-associated right ventricular perforation is a life-threatening complication. Acute perforation usually presents within 24 hours. Patients with lead perforation are often asymptomatic but fatal complications like hemopericardium, leading to cardiac tamponade and death, are reported. Diagnosis is based on chest x-ray, computed tomography (CT) scan, and echocardiography. The management of the lead perforation is based on clinical presentation. Extraction is avoided in cases of chronic asymptomatic lead perforations because of the associated complications. Urgent intervention is needed in hemodynamically unstable patients with pericardial effusion or cardiac tamponade physiology.

No description available.

Pulmonary arterial hypertension (PAH) is a lethal disease, characterized by functional or structural abnormalities involving distal pulmonary arterioles that result in increased pulmonary vascular resistance (PVR) and ultimately right heart failure. Our objective is to establish a conditional transgenic system in mice, to test the hypothesis that lung EC apoptosis at the level of distal pulmonary arterioles is necessary and sufficient to cause a PAH phenotype. In a pilot study, the Fas-Induced Apoptosis (FIA) construct was expressed under the control of endothelial-specific Tie2 promoter in transgenic mice (i.e. EFIA mice). Administration of a small molecule dimerizing agent, AP20187, resulted in lung modest dose-dependent PAH, which was associated with proliferative vascular lesions localized to distal lung arterioles in a small proportion of mice. Due to the low level of transgene expression in preliminary EFIA lines, we re-designed the transgenic vector by incorporating a more robust endothelial promoter (superTie2). The new construct was transfected into HUVEC and BAEC and analyzed by monitoring immunofluorescence (DsRed). Data from the EFIA model suggests that EC apoptosis may be sufficient to induce a PAH phenotype with the characteristic lung vascular lesions. The EFIA model will allow us to better explore the mechanism that links distal lung EC apoptosis with reactive vascular cell proliferation in the pathogenesis of this devastating disease.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2008. / Title from PDF title page (viewed on July 16, 2010). Includes bibliographical references.

Pulmonary arterial hypertension (PAH) is a lethal disease, characterized by functional or structural abnormalities involving distal pulmonary arterioles that result in increased pulmonary vascular resistance (PVR) and ultimately right heart failure. Our objective is to establish a conditional transgenic system in mice, to test the hypothesis that lung EC apoptosis at the level of distal pulmonary arterioles is necessary and sufficient to cause a PAH phenotype. In a pilot study, the Fas-Induced Apoptosis (FIA) construct was expressed under the control of endothelial-specific Tie2 promoter in transgenic mice (i.e. EFIA mice). Administration of a small molecule dimerizing agent, AP20187, resulted in lung modest dose-dependent PAH, which was associated with proliferative vascular lesions localized to distal lung arterioles in a small proportion of mice. Due to the low level of transgene expression in preliminary EFIA lines, we re-designed the transgenic vector by incorporating a more robust endothelial promoter (superTie2). The new construct was transfected into HUVEC and BAEC and analyzed by monitoring immunofluorescence (DsRed). Data from the EFIA model suggests that EC apoptosis may be sufficient to induce a PAH phenotype with the characteristic lung vascular lesions. The EFIA model will allow us to better explore the mechanism that links distal lung EC apoptosis with reactive vascular cell proliferation in the pathogenesis of this devastating disease.