Harry uman Va Medical Center

Columbia, MI, United States

Harry uman Va Medical Center

Columbia, MI, United States
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Young C.N.,Medical Pharmacology and Physiology | Deo S.H.,Medical Pharmacology and Physiology | Chaudhary K.,Harry uman Va Medical Center | Thyfault J.P.,Nutrition and Exercise Physiology | And 3 more authors.
Journal of Physiology | Year: 2010

Recent animal studies indicate that insulin increases arterial baroreflex control of lumbar sympathetic nerve activity; however, the extent to which these findings can be extrapolated to humans is unknown. To begin to address this, muscle sympathetic nerve activity (MSNA) and arterial blood pressure were measured in 19 healthy subjects (27 ± 1 years) before, and for 120 min following, two common methodologies used to evoke sustained increases in plasma insulin: a mixed meal and a hyperinsulinaemic euglycaemic clamp. Weighted linear regression analysis between MSNA and diastolic blood pressure was used to determine the gain (i.e. sensitivity) of arterial baroreflex control of MSNA. Plasma insulin was significantly elevated within 30 min following meal intake (Δ34 ± 6 uIU ml-1; P < 0.05) and remained above baseline for up to 120 min. Similarly, after meal intake, arterial baroreflex-MSNA gain for burst incidence and total MSNA was increased and remained elevated for the duration of the protocol (e.g. burst incidence gain: -3.29 ± 0.54 baseline vs.-5.64 ± 0.67 bursts (100 heart beats)-1 mmHg-1 at 120 min; P < 0.05). During the hyperinsulinaemic euglycaemic clamp, in which insulin was elevated to postprandial concentrations (Δ42 ± 6 μIU ml-1; P < 0.05), while glucose was maintained constant, arterial baroreflex-MSNA gain was similarly enhanced (e.g. burst incidence gain: -2.44 ± 0.29 baseline vs.-4.74 ± 0.71 bursts (100 heart beats)-1 mmHg-1 at 120 min; P < 0.05). Importantly, during time control experiments, with sustained fasting insulin concentrations, the arterial baroreflex-MSNA gain remained unchanged. These findings demonstrate, for the first time in healthy humans, that increases in plasma insulin enhance the gain of arterial baroreflex control of MSNA. © 2010 The Authors. Journal compilation © 2010 The Physiological Society.


Lishmanov A.,University of Missouri | Senthilkumar A.,Harry uman Va Medical Center | Chockalingam A.,Harry uman Va Medical Center
Congestive Heart Failure | Year: 2010

Tachycardia-induced cardiomyopathy is caused by sustained rapid ventricular rates and is one of the well-known forms of reversible myocardial dysfunction. The diagnosis is usually made retrospectively after marked improvement in systolic function is noted following control of the heart rate. Physicians should be aware that patients with seemingly idiopathic systolic dysfunction may have tachycardia-induced cardiomyopathy and that controlling the heart rate may result in improvement or even complete restoration of systolic function. © 2010 Wiley Periodicals, Inc.


Mittal M.K.,University of Missouri | Chockalingam A.,University of Missouri | Chockalingam A.,Harry uman Va Medical Center
American Journal of Therapeutics | Year: 2011

Heart failure (HF) is a leading cause of morbidity and mortality. Appropriate medical therapy using angiotensin converting enzyme inhibitors and beta-blockers improves outcomes in HF, whereas the role of digoxin is still not clearly defined. Digoxin is currently recommended for patients with HF who are symptomatic despite standard therapy and for controlling the ventricular rate in atrial fibrillation. Digoxin is a time-tested drug that accounts for 20 million drug prescriptions annually in the United States. It has favorable hemodynamic effects for patients with HF and atrial tachyarrhythmias. We conducted a systematic literature search for the current indications for digoxin. Despite extensive research and safety data, the literature suggests that digoxin is underused in clinical settings. Citing the literature where available, our review highlights the various clinical settings where digoxin is indicated. Despite difficulties with designing prospective studies in acute HF settings and lack of outcomes data, we believe that digoxin will continue to serve an important role in optimizing care in certain acute and chronic cardiac conditions. © 2011 Lippincott Williams & Wilkins.


Sowers J.R.,Diabetes and Metabolism | Sowers J.R.,University of Missouri | Sowers J.R.,Diabetes and Cardiovascular Center | Sowers J.R.,Harry uman Va Medical Center | And 4 more authors.
CardioRenal Medicine | Year: 2011

The presence of a group of interactive maladaptive factors including hypertension, insulin resistance, metabolic dyslipidemia, obesity, microalbuminuria, and/or reduced renal function constitute the cardiorenal metabolic syndrome (CRS). Overweight, obesity, and chronic kidney disease (CKD) have grown to pandemic proportions in industrialized countries during the past decade. The fact that these interactive factors promote heart and renal disease has been documented in large population-based studies. Obesity seems to be the driving force behind the development of heart disease and CKD and therefore the CRS. The relationship between overweight/obesity and kidney disease begins in early childhood and appears to be related to overconsumption of high-fructose corn syrup and insufficient physical activity. Today, 13 million children are obese, and over 70% of these children are likely to become obese adults. Indeed, approximately 30% of male and 34% of female adults in the United States are obese. This lifestyle-related epidemic will be a major societal medical and economic problem that will accentuate the current epidemic of CKD in the United States and other industrialized and emerging industrialized countries. In this article, we will review the potential mechanisms by which obesity and other metabolic abnormalities interact to promote heart and progressive kidney disease. Copyright © 2011 S. Karger AG, Basel.


Ensling M.,University of Missouri | Steinmann W.,University of Missouri | Whaley-Connell A.,University of Missouri | Whaley-Connell A.,Harry uman Va Medical Center
CardioRenal Medicine | Year: 2011

Resistance to insulin metabolic signaling in adipose tissue contributes to the lipid abnormalities in obese, hyperinsulinemic, insulin-resistant patients who develop the cardiorenal syndrome. These same metabolic dyslipidemic abnormalities can be found in conditions of caloric energy restriction with decreased adiposity or normal insulin levels, such as anorexia, starvation or non-diabetic kidney disease. In this review, we assess hypoglycemia as an alternative physiological explanation for the biochemical and lipid findings in conditions of insulin resistance (IR). Therefore, PubMed databases (1961-2010) were searched for articles on the effect of hypoglycemia and starvation on non-esterified fatty acid (NEFA) elevation and abnormalities in insulin signaling in muscles as well as abnormal kidney metabolism. The search included articles on NEFA and their role in triglyceride (TG) and high-density lipoprotein (HDL) metabolism, as well as kidney and heart disease. Available studies support that hypoglycemia increases NEFA generation from adipose tissue. Elevated levels of NEFA induce increased plasma levels of TG and decreased levels of HDL cholesterol, and may cause direct kidney and myocardial damage. IR of adipose and skeletal muscle tissue, and the elevation in insulin levels in obese, insulin-resistant patients could be explained by an adaptation to their carbohydrate intake. These molecular abnormalities in insulin metabolic signaling can also be found in hypoglycemia or starvation. In conclusion, IR of adipose tissue cannot fully explain the lipid abnormalities observed in the cardiorenal syndrome. Decreased blood glucose levels (e.g. hypoglycemia) occur frequently in patients at risk for this syndrome. Hypoglycemia-induced increases in NEFA levels can promote lipid abnormalities that contribute to IR and the cardiorenal syndrome. Copyright © 2011 S. Karger AG, Basel.


Chaudhary K.,University of Missouri | Buddineni J.P.,University of Missouri | Nistala R.,University of Missouri | Whaley-Connell A.,University of Missouri | Whaley-Connell A.,Harry uman Va Medical Center
Current Diabetes Reports | Year: 2011

The metabolic syndrome is a constellation of metabolic and vascular abnormalities that include insulin resistance with compensatory hyperinsulinemia, central or visceral obesity, hypertension, dyslipidemia, microalbuminuria, and oxidative stress as well as prothrombotic and inflammatory abnormalities that contribute to a hypercoagulable state and systemic endothelial dysfunction. Visceral adipose tissue is now known to secrete into the circulation a number of protein and nonprotein factors that regulate glucose metabolism in traditional insulin-sensitive tissue as well as nontraditional insulin-sensitive tissue including cardiovascular tissue. Collectively, this constellation of factors that lead to metabolic dysregulation contributes to a substantial risk for adverse cardiovascular and renal outcomes. The development of a particularly resistant form of hypertension in these individuals can be attributed to a number of factors including vasoconstriction from increased sympathetic activation, proinflammatory cytokines, and inappropriate activation of the renin-angiotensin-aldosterone system. The management of hypertension in such patients can be challenging and generally requires nonpharmacologic as well as pharmacologic interventions. © 2010 Springer Science+Business Media, LLC (outside the USA).


Yang Y.,Yunnan Province 2nd Hospital | Yang Y.,Harry uman Va Medical Center | Hayden M.R.,University of Missouri | Sowers S.,Diabetes | And 4 more authors.
Oxidative Medicine and Cellular Longevity | Year: 2010

Diabetic retinopathy (DR) is a significant cause of global blindness; a major cause of blindness in the United States in people aged between 20-74. There is emerging evidence that retinopathy is initiated and propagated by multiple metabolic toxicities associated with excess production of reactive oxygen species (ROS). The four traditional metabolic pathways involved in the development of DR include: increased polyol pathway flux, advanced glycation end-product formation, activation of protein kinase Cisoforms and hexosamine pathway flux. These pathways individually and synergisticallycontribute to redox stress with excess ROS resulting in retinal tissue injury resulting in significant microvascular blood retinal barrier remodeling. The toxicity of hyperinsulinemia, hyperglycemia, hypertension, dyslipidemia, increased cytokines and growth factors, in conjunction with redox stress, contribute to the development and progression of DR. Redox stress contributes to the development and progression of abnormalities of endothelial cells and pericytes in DR. This review focuses on the ultrastructural observations of the blood retinal barrier including the relationship between the endothelial cell and pericyte remodeling in young nine week old Zucker obese (fa/ fa) rat model of obesity; cardiometabolic syndrome, and the 20 week old alloxan induced diabetic porcine model. Preventing or delaying the blindness associated with these intersecting abnormal metabolic pathways may be approached through strategies targeted to reduction of tissue inflammation and oxidative - redox stress. Understanding these abnormal metabolic pathways and the accompanying redox stress and remodeling mayprovide both the clinician and researcher a new concept of approaching this complicated disease process. © 2010 Landes Bioscience.


Chockalingam A.,University of Missouri | Chockalingam A.,Harry uman Va Medical Center | Mehra A.,University of Missouri | Dorairajan S.,University of Missouri | Dellsperger K.C.,University of Missouri
Chest | Year: 2010

Acute left ventricular (LV) dysfunction is common in the critical care setting and more frequently affects the elderly and patients with comorbidities. Because of increased mortality and the potential for significant improvement with early revascularization, the practitioner must first consider acute coronary syndrome. However, variants of stress (takotsubo) cardiomyopathy may be more prevalent in ICU settings than previously recognized. Early diagnosis is important to direct treatment of complications of stress cardiomyopathy, such as dynamic LV outflow tract obstruction, heart failure, and arrhythmias. Global LV dysfunction occurs in the critically ill because of the cardio-depressant effect of inflammatory mediators and endotoxins in septic shock as well as direct cate cholamine toxicity. Tachycardia, hypertension, and severe metabolic abnormalities can independently cause global LV dysfunction, which typically improves with addressing the precipitating factor. Routine troponin testing may help early detection of cardiac injury and biomarkers could have prognostic value independent of prior cardiac disease. Echocardiography is ideally suited to quantify LV dysfunction and determine its most likely cause. LV dysfunction suggests a worse prognosis, but with appropriate therapy outcomes can be optimized. © 2010 American College of Chest Physicians.


Chockalingam A.,University of Missouri | Chockalingam A.,Harry uman Va Medical Center | Dellsperger K.C.,University of Missouri
American Journal of Therapeutics | Year: 2011

Dynamic left ventricular outflow tract obstruction occurs in hypertrophic cardiomyopathy, stress cardiomyopathy, acute coronary syndromes, and with inotrope use. We describe three critical care patients who developed "isolated" left ventricular outflow tract obstruction with hypotension in the absence of these precipitants. Systolic anterior motion of anterior mitral valve leaflet with peak left ventricular outflow tract gradients of greater than 120 mmHg was noted in Cases 1 and 2. Under close supervision, intravenous (IV) β blocker was initiated with 5 mg metoprolol repeated every 5 minutes up to 15 mg and continued to maintain heart rate less than 70 beats/min. IV fluids were replaced aggressively. Bedside Doppler echocardiogram confirmed near normalization of left ventricular outflow tract gradient with improvement in systolic anterior motion and hypotension within minutes after IV β blocker confirming its specific therapeutic effect. Isolated left ventricular outflow tract obstruction can occur in the absence of recognized precipitants. Early recognition is crucial because this potentially fatal condition responds well to adequate β blocker and IV fluids with rapid relief of hypotension and symptoms. © 2011 Lippincott Williams & Wilkins.


Johnson M.S.,University of Missouri | Johnson M.S.,Harry uman Va Medical Center | Demarco V.G.,University of Missouri | Heesch C.M.,University of Missouri | And 11 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2011

The aim of this investigation was to evaluate sex differences in baroreflex and heart rate variability (HRV) dysfunction and indexes of end-organ damage in the TG(mRen2)27 (Ren2) rat, a model of renin overexpression and tissue renin-angiotensinaldosterone system overactivation. Blood pressure (via telemetric monitoring), blood pressure variability [BPV; SD of systolic blood pressure (SBP)], spontaneous baroreflex sensitivity, HRV [HRV Triangular Index (HRV-TI), standard deviation of the average NN interval (SDNN), low and high frequency power (LF and HF, respectively), and Poincaré plot analysis (SD1, SD2)], and cardiovascular function (pressure-volume loop analysis and proteinuria) were evaluated in male and female 10-wk-old Ren2 and Sprague Dawley rats. The severity of hypertension was greater in Ren2 males (R2-M) than in Ren2 females (R2-F). Increased BPV, suppression of baroreflex gain, decreased HRV, and associated end-organ damage manifested as cardiac dysfunction, myocardial remodeling, elevated proteinuria, and tissue oxidative stress were more pronounced in R2-M compared with R2-F. During the dark cycle, HRV-TI and SDNN were negatively correlated with SBP within R2-M and positively correlated within R2-F; within R2-M, these indexes were also negatively correlated with end-organ damage [left ventricular hypertrophy (LVH)]. Furthermore, within R2-M only, LVH was strongly correlated with indexes of HRV representing predominantly vagal (HF, SD1), but not sympathetic (LF, SD2), variability. These data demonstrated relative protection in females from autonomic dysfunction and end-organ damage associated with elevated blood pressure in the Ren2 model of hypertension. © 2011 the American Physiological Society.

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