The recently discovered atrial natriuretic peptide (ANP) has potent diuretic, natriuretic and hypotensive effects, and is believed to be involved in the maintenance of sodium homeostasis in both normal and pathological conditions. The mammalian aging process is associated with a host of abnormalities that include, among others, a compromised ability to regulate sodium homeostasis. There are reports that demonstrate a positive correlation between plasma ANP levels and age in man; accordingly, the aim of this study was to examine whether age-related sodium imbalance is associated with disturbances in the homeostasis of ANP. Specifically, the intracellular storage, processing and secretion of ANP from the atrium was studied and associated with circulating ANP concentrations and ANP receptor binding kinetics. Studies were conducted with four groups of male Wistar rats designated as 1-, 3-, 10-, and 20-month-old. 24-hour renal clearances were conducted to assess age-related changes in renal functions. GFR and UNaV increased steadily from 1 to 10 months of age and decreased in the 20-month-old, while fractional excretion of water (FEH₂O) and sodium (FENa) declined initially (from 1 to 10 months) and then rose in the 20-month-old group. Circulating ANP levels in the rats was significantly correlated with the increase in age (N = 147, r = 0.59, p < 0.0005). Atria of the animals were isolated and superfused with a modified Langendorff apparatus. The spontaneous release of ANP increased from 1 to 3 months, and steadily decreased after 3 months. The results indicate that ANP secretion increases with maturation and thereafter declines with advancing age. ANP concentrations in the right and left atria were also quantified. The results revealed that atrial ANP content increased from 1 to 3 months and decreased progressively with age. There was a positive correlation between the rate of ANP release and atrial ANP content (N= 42, r=0.50, p<0.01), suggesting that the release of ANP from the right atrium was associated with the atrial content. The concurrence of a reduction in ANP secretion but with elevation in plasma ANP concentration in the aged (20-month-old) rats, suggests that there may be an impairment in renal clearance of ANP. It was established that the main molecular species present in the atrium was γ-ANP and that this was unaffected by age as assessed by reverse-phase high performance liquid chromatography (RP-HPLC) coupled with radioimmunoassay. The molecular forms of ANP secreted by the atrium consisted of predominantly α-ANP, with a smaller amounts of γ-ANP. γ-ANP constituted only 1% of the total secreted ANP in the 1-, 3-, or 10-month-old rats, but up to 8% was detected in 20-month-old rats. Although both α-ANP and γ-ANP were present in the circulation, the ratio of γ-ANP/α-ANP increased significantly with age. The concentration of γ-ANP in the plasma of the 20-month-old rats was two- to three-fold higher than in the two younger groups (1- and 3-month-old). These data imply that the post-transcriptional processing of prohormone γ-ANP to active α-ANP is altered with age. Radio-ligand binding experiments were carried out using glomerular ANP receptors to determine whether the age-related alterations in plasma ANP levels has an effect on the binding of ANP to its target tissues. Both the receptor density (Bmax) and the equilibrium dissociation constant (kd increased from 1 to 3 months but decreased from 3 to 20 months. Collectively, these results suggest that: 1) Aging affects atrial ANP content and consequently influences the release of ANP from the isolated atria. 2) The processing of prohormone γ-ANP to active α-ANP is modified with age. 3) Plasma levels of ANP increase with age, which may result in down-regulation of ANP receptor density and increased efficacy in receptor binding affinity. These may represent the compensatory responses. / Medicine, Faculty of / Medicine, Department of / Experimental Medicine, Division of / Graduate

No description available.

Thesis (M. Res. (Med.))--University of Hong Kong, 2006.

La Fibrilación Auricular constituye la arritmia más frecuente vista en los servicios de emergencia. La amiodarona constituye una estrategia de tratamiento eficaz como cardiovertor químico en la fibrilación auricular, siendo su uso cada vez mayor por sus excelentes cualidades. El propósito del presente trabajo fue evaluar la eficacia de la amiodarona en la cardioversión de arritmias auriculares a ritmo sinusal de reciente inicio. Se estudiaron 40 pacientes ingresados al Servicio de Emergencia del Hospital Militar Central, con diagnóstico de fibrilación auricular de reciente inicio, usando la amiodarona por vía endovenosa, observando una cardioversión química exitosa en el 87.5% de los pacientes, siendo el medicamento bién tolerado, no hallándose efectos adversos o de importancia. Por lo tanto la amiodarona endovenosa constituye un eficaz cardiovertor químico de la fibrilación auricular de reciente inicio respaldado con diversos estudios. Es una droga bien tolerada. / Atrial Fibrilation is a frequent arrhytmia. A therapeutic option for this pathology is quimic cardioversion. The objective of this study was to investigate the efficacy of intravenous amiodarona in recent onset atrial fibrilation. We studied 40 patients who where admitted to the emergency department with diagnostic of recent onset atrial fibrillation who recibed intravenous amiodarone. Quimic cardioversion was achieved in 87.5% of them, with good tolerance and side effects presenting in 10 % of the patients. Conclusion: the precocious therapy with intravenous amiodarona as a quimic cardiovertor is effective and well tolerated. Amiodarone is well tolerated as a precocious treatment for quimic cardioversion in patients with atrial fibrillation.

published_or_final_version / Medicine / Master / Doctor of Medicine

published_or_final_version / Medicine / Master / Master of Philosophy

Hydroxymethylgluteryl-CoA reductase inhibitors (statins) are commonly used in the treatment of cardiovascular diseases. These drugs have been shown to induce cell death in various cell types. It is unclear if this is a class effect or a phenomenon specific to certain compounds. We hypothesize that lipophilic statins induce cell death in primary human atrial myofibroblasts (hATMF) whereas hydrophilic statins do not. hATMF were treated with atorvastatin, simvastatin (lipophilic statins) or pravastatin (hydrophilic statin). Cell viability was assessed using MTT assay. Induction of apoptosis and autophagy were estimated with western blot analysis. We found that lipophilic statin treatment of hATMF reduced cell viability in a time and dose-dependent manner and increased expression of apoptotic markers. These effects were not observed with the hydrophilic statin. In conclusion, there are substantial differences between various compounds in the statin family. These differences should be considered when selecting a drug for a particular patient.

No description available.

Hydroxymethylgluteryl-CoA reductase inhibitors (statins) are commonly used in the treatment of cardiovascular diseases. These drugs have been shown to induce cell death in various cell types. It is unclear if this is a class effect or a phenomenon specific to certain compounds. We hypothesize that lipophilic statins induce cell death in primary human atrial myofibroblasts (hATMF) whereas hydrophilic statins do not. hATMF were treated with atorvastatin, simvastatin (lipophilic statins) or pravastatin (hydrophilic statin). Cell viability was assessed using MTT assay. Induction of apoptosis and autophagy were estimated with western blot analysis. We found that lipophilic statin treatment of hATMF reduced cell viability in a time and dose-dependent manner and increased expression of apoptotic markers. These effects were not observed with the hydrophilic statin. In conclusion, there are substantial differences between various compounds in the statin family. These differences should be considered when selecting a drug for a particular patient.

Thesis (M. Res.(Med.))--University of Hong Kong, 2007.