Veena Raizada

Intracardiac and Intrarenal Renin-Angiotensin Systems : Mechanisms of Cardiovascular and Renal Effects

The renin-angiotensin system (RAS) is a hormonal system that controls body fluid volume, blood pressure, and cardiovascular function in both health and disease. Various tissues, including the heart and kidneys, possess individual locally regulated RASs. In each RAS, the substrate protein angiotensinogen is cleaved by the peptidases renin and angiotensin-converting enzyme to form the biologically active product angiotensin II, which acts as an intracrine cardiac and renal hormone. The components of each RAS, including aldosterone (ALDO), may be produced locally and/or may be delivered by or sequestered from the circulation. Overactivity of the cardiac RAS has been associated with cardiac diseases, including cardiac hypertrophy due to volume and/or pressure overload, heart failure, coronary artery disease with myocardial infarction, and hypertension. Overactivity of the renal RAS has been associated with various kidney diseases, including nephropathies and renal artery stenosis. The principal effects of an overactive RAS include the generation of reactive oxygen species, which leads to “oxidative stress,” activation of the nuclear transcription factor κB, and stimulation of pathways and genes that promote vasoconstriction, endothelial dysfunction, cell hypertrophy, fibroblast proliferation, inflammation, excess extracellular matrix deposition, atherosclerosis, and thrombosis. It has been suggested that oxidative stress is the central mechanism underlying the pathogenesis of RAS-related and ALDO-related chronic cardiovascular and renal tissue injury and of cardiac arrhythmias and conduction disturbances.

Cardiac chamber-specific alterations of ANP and BNP expression with advancing age and with systemic hypertension.

The present study determined cardiac chamber-specific alterations of the expression of the atrial and brain natriuretic peptide (ANP and BNP) genes with a small increase in age beyond adulthood and with systemic hypertension of intermediate duration. The expression distributions of these genes was determined using in situ hybridization in the right and left atria (RA and LA), and the right and left ventricles (RV and LV) in Wistar Kyoto rats (WKY) and age-matched Spontaneously Hypertensive rats (SHR) at ages 6 months (adult) and 8 months (advanced-age beyond adulthood).In all rat groups, both genes were expressed (ANP > BNP) in the LA and LV, and were not expressed in the RA and RV. The genes were expressed in the LA in all rat groups; the ANP, but not the BNP, expression increased with advancing age and with superimposed hypertension. They were expressed in the LV of the advanced-age WKY, adult and advanced-age SHR, but not in the adult WKY. The ANP mRNA labeling in the LA was diffuse and interspersed with dense accumulations, whereas BNP labeling was diffuse. The labeling of both genes in the form of sparse clusters was seen in the LV of the advanced-age SHR. Our study showed that ANP and BNP expression in left heart chambers increased with a small increase in age, with hypertension of intermediate duration, and with modest left ventricular hypertrophy. The chamber-specific expression distribution could be due to special groups of cardiac cells, or to local chamber-specific factors.

Auscultation of the Normally Functioning Prosthetic Valve

Before prosthetic function can be adequately assessed, physicians must be acquainted with the normal acoustic events associated with these devices. The auscultatory findings of the most commonly used devices--ball, disk, porcine, and bileaflet valves--are reviewed. The mechanisms of sound production and their timing are discussed.

Acute Aortic Regurgitation

Aortic regurgitation (AR) is characterized by regurgitation of blood from the aorta to the left ventricle (LV) during diastole and is attributable to diverse congenital and acquired abnormalities of the aortic valve or the wall of the aortic root. AR can be either chronic or acute. The classic features of chronic AR have been known to clinicians for nearly 2 centuries. Corrigan described chronic AR in 1832 in his text “On Permanent Patency of the Mouth of the Aorta, or Inadequacy of the Aortic Valves.”1 Patients with chronic AR remain asymptomatic for many years as the LV becomes gradually enlarged; cardiac symptoms and clinical congestive heart failure then develop. On the other hand, acute severe AR, if untreated, leads to advanced heart failure and early death. Acute severe AR may be difficult to recognize clinically and is often erroneously diagnosed as another acute condition such as sepsis, pneumonia, or nonvalvular heart disease. Acute or subacute infective endocarditis, aortic dissection, and aortic valve damage caused by trauma are known causes of acute AR. We present 2 cases of acute AR (case 1, infective endocarditis; case 2, Stanford type A aortic dissection), and we propose management plans for each case (Figure 1A and 1B). Figure 1. Proposed management plan for acute aortic regurgitation (AR) due to infective endocarditis ( A ) and aortic dissection ( B ). CHF indicates congestive heart failure; TTE, transthoracic echocardiogram; TEE, transesophageal echocardiogram; IE, infective endocarditis; AR, aortic regurgitation; PMVC, premature mitral valve closure; DMR, diastolic mitral regurgitation; ESMR, early systolic mitral regurgitation; ICU, intensive care unit; EKG, electrocardiogram; LVOT, left ventricular outflow tract; and AV, aortic valve. A 23-year-old man admitted to an intensive care unit with Staphylococcus bacteremia presented with soft heart sounds and a to-and-fro murmur, which progressed to a silent precordium within 24 hours. Bedside transthoracic …

Angiotensin II–Mediated Left Ventricular Abnormalities in Chronic Kidney Disease

Angiotensin II (ATII), the biologically active product of the renin-angiotensin system (RAS), is involved in modulation of left ventricular (LV) structure and function in chronic kidney disease (CKD). Because the RAS system is overactive in CKD, excess ATII accumulates in the heart, thereby promoting myocyte hypertrophy, fibroblast proliferation, interstitial accumulation of collagen, and microvessel disease. These cardiac abnormalities are further enhanced by a possible interaction between enhanced RAS activity and hypercalcemia, hyperphosphatemia and secondary hyperparathyroidism, and vitamin D deficiency. The ATII-associated stimulation of aldosterone production from the adrenal gland and the increase in activity of the sympathetic system in CKD, further contribute to LV abnormalities. Myocardial structural changes are major determinants of an increase in myocardial stiffness, leading to LV diastolic and systolic function impairment, and clinical congestive heart failure. Other complications include cardiac conduction disturbances, QT prolongation, and arrhythmias, which all contribute to elevated cardiovascular mortality in patients with CKD.

Aortic Intramural Hematoma and Its Complications

> It has long been an axiom of mine that the little things are infinitely the most important.1 > > Sherlock Holmes to Dr Watson > > —Arthur Conan Doyle, > > The Adventures of Sherlock Holmes: A Case of Identity. Case Presentation: A 70-year-old woman with hypertension presents for evaluation of a single episode of nonexertional chest pain of moderate intensity, atypical for myocardial infarction. Clinical signs of acute aortic dissection and cardiac tamponade are absent. A 12-lead ECG and blood test for troponin are negative for acute myocardial infarction. M-mode transthoracic echocardiogram of the aortic root shows dense echoes anteriorly and posteriorly at the level of the aortic valve and a large pericardial effusion (Figure 1A). After discussing a diagnosis of acute aortic syndrome, she asks, “What other tests will I need to confirm the diagnosis? Will I undergo surgery?” Figure 1. A and B , M-mode echocardiogram at the level of the aortic valve. Dense echoes along right and noncoronary sinuses caused by periaortic hematoma from a perforated aortic ulcer (white arrows, A ) compared with a normal echo ( B ). C , Cardiac computed tomography angiography orthogonal view equivalent to transthoracic echocardiographic parasternal long-axis view. This view is optimized to visualize (white arrow) perforated ulcer in the ascending aorta, hemorrhagic pericardial effusion with blood collection along right and noncoronary aortic sinuses correlating with M mode echo at the level of the aortic valve. AV indicates aortic valve; LA, left atrium; LV, left ventricle; PA, pulmonary artery; and RV, right ventricle. Intramural hematoma (IMH) is a life-threatening aortic disease included within acute aortic syndrome, together with aortic dissection and penetrating aortic ulcer (PAU).2,3 IMH is a contained aortic wall hematoma with bleeding within the media but without initial intimal flap formation (Figure 2).3 Its natural history is variable; it may be reabsorbed …

Myocardial atrophy in acquired immunodeficiency syndrome—associated wasting

This study evaluated the effects of acquired immunodeficiency syndrome wasting syndrome (AWS) on the heart in a population free of overt opportunistic infection or clinical evidence of cardiac disease. Data from 53 patients with AWS and 16 healthy age-matched controls were studied. By echocardiography, a significant reduction in left ventricular mass was found in patients with AWS that remained significantly reduced when corrected for body surface area. Mean ejection fraction was within the normal range in patients with AWS but was significantly less than in controls. End-systolic volume index was slightly elevated in patients with AWS. Although no difference in end-systolic wall stress was seen, the end-systolic wall stress-shortening relation differed significantly. These findings are consistent with myocardial atrophy and subtle left ventricular dysfunction in patients with AWS.

Some Aspects of the Renin-Angiotensin-System in Hemodialysis Patients.

Understanding of the renin-angiotensin system (RAS) has changed remarkably over the past decade. Renin, angiotensin converting enzyme (ACE), angiotensin II (Ang II), and Ang II receptors are the main components of the RAS. Recent studies identified the ACE2/Ang 1-7/Mas receptor axis, which counter-regulates the classical RAS. Many studies have examined the effects of the RAS on the progression of cardiovascular disease and chronic kidney disease (CKD). In addition, many studies have documented increased levels of ACE in hemodialysis (HD) patients, raising concerns about the negative effects of RAS activation on the progression of renal disease. Elevated ACE increases the level of Ang II, leading to vasoconstriction and cell proliferation. Ang II stimulation of the sympathetic system leads to renal and cardiovascular complications that are secondary to uncontrolled hypertension. This review provides an overview of the RAS, evaluates new research on the role of ACE2 in dialysis, and reviews the evidence for potentially better treatments for patients undergoing HD. Further understanding of the role of ACE and ACE2 in HD patients may aid the development of targeted therapies that slow the progression of CKD and cardiovascular disease.

Accelerated glycolysis in early hypertensive left ventricular hypertrophy.

Changes in energy metabolism have been demonstrated in established left ventricular hypertrophy (LVH). It is not known if cardiac energy metabolism is shifted toward anaerobic pathways during the early stage of hypertensive LVH. Accordingly, glycogen, pyruvate, and lactate levels from left ventricular homogenate were measured in 8-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Systolic arterial pressure and left ventricular weight were determined to establish hypertensive state and LVH, respectively. The glycogen and pyruvate levels in SHR versus WKY were lower by 19 (p < 0.05) and 12% (NS), respectively. The lactate level in the SHR was 14% higher (p < 0.05) than in WKY. The lactate/pyruvate ratio in the SHR was higher than in the WKY, but did not reach statistical significance. These data suggest that the anaerobic metabolism is induced early in the development of hypertension, before the development of substantial LVH.

Antihypertensive and Metabolic Effects of Concomitant Administration of Terazosin and Methyclothiazide for the Treatment of Essential Hypertension

The efficacy and safety of once‐daily 2.5‐ or 5.0‐mg methyclothiazide (MCTZ) added to once‐daily 5.0‐mg terazosin (TRZ) versus 5.0‐mg TRZ alone was evaluated in this double‐blind, multicenter study. All patients received TRZ during a 6‐week titration period. Hypertensive patients (222) (mean blood pressure of 159/104 mm Hg) were randomized to one of three treatment groups: TRZ alone (N = 76); TRZ + MCTZ‐2.5 mg (N = 74); and TRZ + MCTZ‐5.0 mg (N = 72) for the 8‐week double‐blind period. Changes in the supine and standing SBP/DBP from preTRZ period were: TRZ alone (−4.8/−8.1 and −2.0/−6.1 mm Hg); TRZ + MCTZ‐2.5 mg (−17.3/−12.4 and −16.0/−11.2 mm Hg); and TRZ + MCTZ‐5.0 mg (−20.6/−14.4 and −23.3/−14.6 mm Hg). Blood pressure changes in the combination groups were significantly greater than those in the TRZ alone group. However, there were no statistically significant differences between the TRZ + MCTZ‐2.5‐mg and TRZ + MCTZ‐5.0‐mg groups. The combination of TRZ and MCTZ tends to mitigate the adverse effects on serum glucose, uric, potassium and lipids usually associated with thiazide diuretics. Thus, combination treatment that begins with TRZ and adds MCTZ is effective in lowering blood pressure without any significant adverse metabolic effects.