Indu Poornima

Direct Effects of Glucagon-Like Peptide-1 on Myocardial Contractility and Glucose Uptake in Normal and Postischemic Isolated Rat Hearts

Recent evidence suggests that glucagon-like peptide-1 (GLP-1) enhances recovery of left ventricular (LV) function after transient coronary artery occlusion. However, it is uncertain whether GLP-1 has direct effects on normal or ischemic myocardium and whether the mechanism involves increased myocardial glucose uptake. LV function and myocardial glucose uptake and lactate production were measured under basal conditions and after 30 min of low-flow ischemia and 30 min of reperfusion in the presence and absence of GLP-1-(7–36) amide. The response was compared with standard buffer alone or buffer containing insulin (100 μU/ml). GLP-1 decreased the left ventricular developed pressure (baseline: 100 ± 2 mm Hg; GLP-1: 75 ± 3 mm Hg, p < 0.05) and LV dP/dt (baseline: 4876 ± 65 mm Hg/s; GLP-1: 4353 ± 76 mm Hg/s, p < 0.05) in normal hearts. GLP-1 increased myocardial glucose uptake (baseline: 33 ± 3 μmol/min/g; GLP-1: 81 ± 7 μmol/min/g, p < 0.05) by increasing nitric oxide production and glucose transporter (GLUT)-1 translocation. GLP-1 enhanced recovery after 30 min of low-flow ischemia with significant improvements in LV end-diastolic pressure (control: 13 ± 4 mm Hg; GLP-1: 3 ± 2 mm Hg, p < 0.05) and LV developed pressure (control: 66 ± 6 mm Hg; GLP-1: 98 ± 5 mm Hg, p < 0.05). GLP-1 increased LV function, myocardial glucose uptake, and GLUT-1 and GLUT-4 translocation during reperfusion to an extent similar to that with insulin. GLP-1 has direct effects on the normal heart, reducing contractility, but increasing myocardial glucose uptake through a non-Akt-1-dependent mechanism, distinct from the actions of insulin. However, GLP-1 increased myocardial glucose uptake and enhanced recovery of cardiac function after low-flow ischemia in a fashion similar to that of insulin.

Chronic Glucagon-Like Peptide-1 Infusion Sustains Left Ventricular Systolic Function and Prolongs Survival in the Spontaneously Hypertensive, Heart Failure–Prone Rat

Background—Glucagon-like peptide-1 (GLP-1) treatment leads to short-term improvements in myocardial function in ischemic and nonischemic cardiomyopathy. It is unknown whether GLP-1 improves survival when administered over a longer time period. Spontaneously hypertensive, heart failure–prone (SHHF) rats progress to advanced heart failure and death over a 15-month period. The authors sought to determine whether a continuous infusion of GLP-1 would reduce mortality in this model. Methods and Results—At 9 months of age, 50 SHHF rats were randomized to receive a 3-month, continuous infusion of either GLP-1 or saline. Metabolic parameters were measured and cardiac ultrasounds performed at study initiation and completion of treatment. Surviving rats were euthanized at 12 months. Hearts were perfused in an isolated, isovolumic heart preparation, and Tunel staining of myocardial samples was performed. Baseline metabolic and cardiac functional parameters were comparable. GLP-1–treated SHHF rats had greater survival (72% versus 44%, P=0.008) at 12 months of age. In addition, GLP-1 treatment led to higher plasma insulin, lower plasma triglycerides, and preserved left ventricular (LV) function. GLP-1–treated rats demonstrated decreased myocyte apoptosis by Tunel staining as well as reduced caspase-3 activation. No increase in p-BAD expression was seen. In isolated hearts, the LV systolic pressure and LV-developed pressure were greater in the GLP-1 group. Myocardial glucose uptake was also increased in GLP-1–treated SHHF rats. Conclusions—Chronic GLP-1 treatment prolongs survival in obese SHHF rats. This is associated with preserved LV function and LV mass index, increased myocardial glucose uptake, and reduced myocyte apoptosis.

Chronic Glucagon-Like Peptide-1 Infusion Sustains Left Ventricular Systolic Function and Prolongs Survival in the Spontaneously Hypertensive, Heart Failure–Prone RatCLINICAL PERSPECTIVE

Background—Glucagon-like peptide-1 (GLP-1) treatment leads to short-term improvements in myocardial function in ischemic and nonischemic cardiomyopathy. It is unknown whether GLP-1 improves survival when administered over a longer time period. Spontaneously hypertensive, heart failure–prone (SHHF) rats progress to advanced heart failure and death over a 15-month period. The authors sought to determine whether a continuous infusion of GLP-1 would reduce mortality in this model. Methods and Results—At 9 months of age, 50 SHHF rats were randomized to receive a 3-month, continuous infusion of either GLP-1 or saline. Metabolic parameters were measured and cardiac ultrasounds performed at study initiation and completion of treatment. Surviving rats were euthanized at 12 months. Hearts were perfused in an isolated, isovolumic heart preparation, and Tunel staining of myocardial samples was performed. Baseline metabolic and cardiac functional parameters were comparable. GLP-1–treated SHHF rats had greater survival (72% versus 44%, P=0.008) at 12 months of age. In addition, GLP-1 treatment led to higher plasma insulin, lower plasma triglycerides, and preserved left ventricular (LV) function. GLP-1–treated rats demonstrated decreased myocyte apoptosis by Tunel staining as well as reduced caspase-3 activation. No increase in p-BAD expression was seen. In isolated hearts, the LV systolic pressure and LV-developed pressure were greater in the GLP-1 group. Myocardial glucose uptake was also increased in GLP-1–treated SHHF rats. Conclusions—Chronic GLP-1 treatment prolongs survival in obese SHHF rats. This is associated with preserved LV function and LV mass index, increased myocardial glucose uptake, and reduced myocyte apoptosis.

Anatomical Factors Triggering Platypnea‐Orthodeoxia in Adults

Right to left shunting through a patent foramen ovale (PFO) or atrial septal defect (ASD) can cause platypnea‐orthodeoxia even in a setting of normal pulmonary artery pressures. However, the late onset of symptoms despite the congenital origin of the anatomical defects is not well understood. We report a case series of patients presenting with dyspnea and orthodeoxia who developed right to left shunting as a result of associated anatomical changes that occur with aging such as tortuosity and elongation of the aorta. We propose that these acquired anatomical changes can favor right to left shunting in the setting of congenital abnormalities, therefore explaining the late onset of symptoms. Copyright

Acute Myocardial Infarction Associated with Dietary Supplements Containing 1,3-Dimethylamylamine and Citrus aurantium

We describe the case of a previously healthy 22-year-old man who presented with anginal chest pain and was diagnosed with a non-ST-elevation myocardial infarction. For 3 weeks, he had been ingesting the dietary supplements Jack3d® (principal ingredient, 1,3-dimethylamylamine) and Phenorex™ (principal ingredient, Citrus aurantium) daily, before undertaking physical activity. Coronary angiograms revealed a proximal left anterior descending coronary artery thrombus with distal embolization. A combined medical regimen led to resolution of the thrombus. Three months later, the patient was asymptomatic with no evidence of ischemia. The primary ingredients in the sympathomimetic supplements taken by our patient are controversial in the medical community and have been individually associated with adverse cardiac events. There are no safety data on their simultaneous use. We discuss other reports of adverse effects associated with these supplements and recommend that the relevant safety guidelines be revised.

Relationship between circulating serum osteoprotegerin and total receptor activator of nuclear κ-B ligand levels, triglycerides, and coronary calcification in postmenopausal women.

ObjectiveThis study evaluates the relationship of blood osteoprotegerin (OPG) and receptor activator of nuclear &kgr;-B ligand (RANKL) levels with coronary artery calcium (CAC) and cardiovascular risk factors in two studies of postmenopausal women. OPG, a marker of bone turnover, and its ligand, RANKL, may contribute to cardiovascular disease risk. MethodsWe tested the hypothesis that serum OPG and RANKL levels were associated with CAC and cardiovascular disease risk factors among postmenopausal women in the Women On the Move through Activity and Nutrition Study (WOMAN Study; n = 86; mean [SD], age 58 [2.9] y) and replicated our findings in the Healthy Women Study (HWS; n = 205; mean [SD] age, 61 [2.3] y). Serum OPG, total RANKL, and CAC were measured at baseline and 48 months in the WOMAN Study and on the eighth postmenopausal visit in the HWS. ResultsIn the WOMAN Study, higher OPG was associated with higher CAC, and higher total RANKL was associated with lower CAC and triglycerides. In the HWS, higher total RANKL was also associated with lower CAC and triglycerides. In logistic regression models adjusted for body mass index and triglycerides, the odds ratios (95% CIs) for CAC per unit increase in OPG were 1.78 (1.17-2.73) for the WOMAN Study and 1.02 (0.84-1.24) for the HWS, and the odds ratios (95% CIs) for CAC per unit increase in log total RANKL were 0.86 (0.64-1.17) for the WOMAN Study and 0.83 (0.72-0.96) for the HWS. ConclusionsThe inverse association of total RANKL with CAC and triglycerides is a new finding and may have important implications given the increasing use of drugs that modify total RANKL and its receptor, receptor activator of nuclear &kgr;-B.

Chronic Glucagon-like Peptide-1 (GLP-1) Infusion Sustains LV Systolic Function and Prolongs Survival in the Spontaneously Hypertensive-Heart Failure Prone Rat

Background—Glucagon-like peptide-1 (GLP-1) treatment leads to short-term improvements in myocardial function in ischemic and nonischemic cardiomyopathy. It is unknown whether GLP-1 improves survival when administered over a longer time period. Spontaneously hypertensive, heart failure–prone (SHHF) rats progress to advanced heart failure and death over a 15-month period. The authors sought to determine whether a continuous infusion of GLP-1 would reduce mortality in this model. Methods and Results—At 9 months of age, 50 SHHF rats were randomized to receive a 3-month, continuous infusion of either GLP-1 or saline. Metabolic parameters were measured and cardiac ultrasounds performed at study initiation and completion of treatment. Surviving rats were euthanized at 12 months. Hearts were perfused in an isolated, isovolumic heart preparation, and Tunel staining of myocardial samples was performed. Baseline metabolic and cardiac functional parameters were comparable. GLP-1–treated SHHF rats had greater survival (72% versus 44%, P=0.008) at 12 months of age. In addition, GLP-1 treatment led to higher plasma insulin, lower plasma triglycerides, and preserved left ventricular (LV) function. GLP-1–treated rats demonstrated decreased myocyte apoptosis by Tunel staining as well as reduced caspase-3 activation. No increase in p-BAD expression was seen. In isolated hearts, the LV systolic pressure and LV-developed pressure were greater in the GLP-1 group. Myocardial glucose uptake was also increased in GLP-1–treated SHHF rats. Conclusions—Chronic GLP-1 treatment prolongs survival in obese SHHF rats. This is associated with preserved LV function and LV mass index, increased myocardial glucose uptake, and reduced myocyte apoptosis.

CAN THE FUNCTIONAL CAPACITY MEASURED BY DUKE ACTIVITY STATUS INDEX INCREASE THE VALUE OF IMAGING DURING STRESS TESTING

Determination of pretest probability of coronary artery disease (CAD) is recommended prior to noninvasive stress testing. The incidence of abnormal myocardial perfusion imaging (MPI) is reportedly very low in patients exercising >10 METs without ST depression. We sought to determine if prospectively

An unprecedented case report of primary cardiac lymphoma exclusive to left ventricle: a diagnostic and therapeutic challenge

Abstract Introduction Primary cardiac lymphoma accounts for <2% of all primary cardiac tumours. It is uncommon in immunocompetent patients, often fatal and diagnosed at autopsy. Tumour usually involves the right heart chambers and pericardium. With advances in imaging, early diagnosis is possible and treatment including chemotherapy and surgery affords good prognosis. Case presentation We present a 50-year-old woman with abdominal pain and fevers for 5 days. Computed tomography of the abdomen showed splenic and renal infarcts but no mass or vegetation was noted on echocardiography. Thoracic computed tomography divulged a large left ventricular filling defect. Cardiac magnetic resonance imaging delineated a 3.5 × 4.5 cm anterobasal mass with frond-like projections and endocardial invasion without extracardiac involvement suggestive of a low-vascularity tumour. Echo-guided endomyocardial biopsy and minithoracotomy with needle biopsy were inconclusive. A sarcoid-protocol cardiac positron emission tomography-fluorodeoxyglucose scan showed focally elevated uptake in the basal anteroseptum without extracardiac uptake, supporting a malignant entity. This prompted open heart mass resection. Pathology revealed diffuse large B-cell lymphoma. Discussion Our case is a unique report of cardiac lymphoma isolated to the left ventricle. Location of the tumour and lack of specific imaging characteristics made it a diagnostic challenge. It underscores the importance of including lymphoma in the differential for intracardiac masses as it is responsive to chemotherapy. Additionally, it emphasizes the complementary role of imaging modalities and multidisciplinary team approach in diagnosis. Early diagnosis and therapy is the key to establishing successful outcomes.

Rapidly progressive cardiac sarcoidosis: Initial presentation with sinus node dysfunction and right bundle branch block ☆

Introduction Complete heart block is the most common electrocardiogram (ECG) finding in patients with cardiac sarcoidosis because of the predilection of granulomatous infiltration of the basal septum or involvement of the atrioventricular nodal artery. We report a cardiac sarcoid case presenting with sinus node dysfunction and describe the utility of fluorine-18fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT) scans in making the initial diagnosis.