Oxidative Stress as A Mechanism for Functional Alterations in Cardiac Hypertrophy and Heart Failure

Although heart failure due to a wide variety of pathological stimuli including myocardial infarction, pressure overload and volume overload is associated with cardiac hypertrophy, the exact reasons for the transition of cardiac hypertrophy to heart failure are not well defined. Since circulating levels of several vasoactive hormones including catecholamines, angiotensin II, and endothelins are elevated under pathological conditions, it has been suggested that these vasoactive hormones may be involved in the development of both cardiac hypertrophy and heart failure. At initial stages of pathological stimuli, these hormones induce an increase in ventricular wall tension by acting through their respective receptor-mediated signal transduction systems and result in the development of cardiac hypertrophy. Some oxyradicals formed at initial stages are also involved in the redox-dependent activation of the hypertrophic process but these are rapidly removed by increased content of antioxidants in hypertrophied heart. In fact, cardiac hypertrophy is considered to be an adaptive process as it exhibits either normal or augmented cardiac function for maintaining cardiovascular homeostasis. However, exposure of a hypertrophied heart to elevated levels of circulating hormones due to pathological stimuli over a prolonged period results in cardiac dysfunction and development of heart failure involving a complex set of mechanisms. It has been demonstrated that different cardiovascular abnormalities such as functional hypoxia, metabolic derangements, uncoupling of mitochondrial electron transport, and inflammation produce oxidative stress in the hypertrophied failing hearts. In addition, oxidation of catecholamines by monoamine oxidase as well as NADPH oxidase activation by angiotensin II and endothelin promote the generation of oxidative stress during the prolonged period by these pathological stimuli. It is noteworthy that oxidative stress is known to activate metallomatrix proteases and degrade the extracellular matrix proteins for the induction of cardiac remodeling and heart dysfunction. Furthermore, oxidative stress has been shown to induce subcellular remodeling and Ca2+-handling abnormalities as well as loss of cardiomyocytes due to the development of apoptosis, necrosis, and fibrosis. These observations support the view that a low amount of oxyradical formation for a brief period may activate redox-sensitive mechanisms, which are associated with the development of cardiac hypertrophy. On the other hand, high levels of oxyradicals over a prolonged period may induce oxidative stress and cause Ca2+-handling defects as well as protease activation and thus play a critical role in the development of adverse cardiac remodeling and cardiac dysfunction as well as progression of heart failure.

Right and Left-sided Valve Disease: A Case of Subclinical Intrapulmonary Shunt in an Adult with Malignant Carcinoid

Carcinoid tumors are highly differentiated neuroendocrine tumors (NET) that most commonly originate from the gastrointestinal tract. Liver metastases bypass first-pass metabolism and liberate vasoactive hormones into systemic circulation, causing flushing and diarrhea. Prolonged levels of circulating serotonin may adversely affect the heart by creating fibrotic endocardial deposits on native valves. The remaining serotonin is metabolized in the pulmonary circuit that leads to pathognomonic valvular disease isolated to the right side of the heart. We present a case of an adult male with known carcinoid syndrome who presented with involvement of right, as well as left-sided valves. He was found to have an intrapulmonary shunt on transesophageal echocardiogram (TEE) with bubble study. Intrapulmonary shunt should be considered, in conjunction with right-to-left shunt, lung involvement, and high levels of serotonin, for carcinoid patients with right and left-sided valve disease.

Mechanisms of Cardiac Dysfunction in Heart Failure due to Myocardial Infarction

Acute myocardial infarction (MI) is associated with marked elevation of plasma vasoactive hormones, ventricular arrhythmias, scar formation in the ischemic portion of left ventricle (LV) and hypertrophy of the viable LV as well as the right ventricle (RV). Particularly, elevated levels of plasma catecholamines and angiotensin II activate their membrane receptors and stimulate different signal transduction systems for producing cardiac hypertrophy, augmenting the activities of subcellular organelles and increasing cardiac function. While marked arrhythmias due to acute MI produce 30 to 40% mortality, hypertrophic alterations in the viable LV as well as RV are compensatory for maintaining hemodynamic homeostasis due to loss of cardiomyocytes. On the other hand, prolonged elevation of plasma vasoactive hormones in chronic MI produce deleterious effects on the hypertrophied heart by promoting the formation of oxyradicals, inducing Ca2+ - handling abnormalities in subcellular organelles, depressing cardiac gene expression, activating different proteases and resulting in the development of cardiac dysfunction. Thus, in view of the complexities of mechanisms for both acute and chronic effects of MI, there is a real challenge of developing new interventions for preventing the transition of cardiac hypertrophy to heart failure as well as progression of the MI-induced cardiovascular abnormalities.

Nocturnal Blood Pressure Decrease in Hypertensive Patients and Normotensives- Association with Obstructive Sleep Apnoea and Renal Function

Background:Blunted nocturnal Blood Pressure (BP) decrease is seen in patients with hypertension and obstructive sleep apnoea (OSA). The influence of OSA and renal function on nocturnal BP decrease is not fully clarified.Objective:In this case control study of hypertensive patients and healthy controls, we aimed to analyse the relationship between nocturnal BP decrease on one hand and presence of OSA, renal function, plasma levels of syndecan and vasoactive hormones, and urinary sodium excretion on the other.Methods:In 75 hypertensive patients and 56 controls, we performed brachial and central 24h ambulatory BP measurement and cardio respiratory monitoring. We measured syndecan, renin, angiotensinII, aldosterone, vasopressin, and brain natriuretic peptide in plasma and 24h urinary excretion of sodium, aquaporin2, and a component of the epithelial sodium channel (u-ENaCγ).Results:Nocturnal BP decrease was lower in patients than controls, brachial (13% versus 17%,p=0.001) and central (8% versus 10%,p=0.019). Moderate-to-severe OSA was present in 13% of patients, 2% of controls (p<0.005). Neither brachial nor central nocturnal BP decrease was associated with OSA, renal function, plasma levels of vasoactive hormones, syndecan-1, or urinary sodium excretion. P-syndecan and u-ENaCɣ were higher in patients than controls.Conclusion:Both brachial and central nocturnal BP decrease was lower in patients than in controls. Neither brachial nor central nocturnal BP decrease was associated with the presence of OSA, renal function, or plasma levels of vasoactive hormones. Increased syndecan in plasma in hypertensive patients suggested damage to the endothelial glycocalyx.