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आयतन 3, मुद्दा 4 (2015)

शोध आलेख

Intracellular Renin Protects Cardiomyocytes from Ischemic Injury in Diabetic Heart

Daishi Nonaka, Hideki Katoh, Azumi Kumazawa, Terumori Satoh, Masao Saotome, Tsuyoshi Urushida, Hiroshi Satoh and Hideharu Hayashi

Background: Local Renin-Angiotensin-Aldosterone system (RAS) is important in cardiac pathophysiology. We investigated the expression and distribution of intracellular renin after ischemia, and the effects of renin on mitochondrial function in diabetic heart.

Methods: In Goto-Kakizaki (DM) and Wistar (non-DM) rats, Langendorff-perfused hearts were subjected to ischemia by coronary artery ligation for 90 min. Infarct Size (IS) and expression of RAS components were examined. Mitochondrial membrane potential (ΔΨm), uncoupling protein-2 (UCP2), NAD/NADH ratio, and ATP were measured in renin-treated myocytes or isolated mitochondria.

Results: After ischemia, LV function (LVDP; 76 ± 4 vs. 52 ± 4 mmHg, LVEDP; 18 ± 2 vs. 29 ± 4 mmHg, p<0.05, DM; n=9, non-DM; n=9, respectively) was prevented and IS (44.2 ± 2.1 vs. 53.7 ± 2.9 %, p<0.05) was significantly small in DM hearts. These cardioprotective effects were abolished when DM hearts were treated with direct renin inhibitor (LVDP; 77 ± 3 vs. 55 ± 4 mmHg, LVEDP; 16 ± 1 vs. 27 ± 3 mmHg, IS; 40.8 ± 2.9 vs. 52.1 ± 3.4 %, p<0.05, DM; n=5, DM plus DRI; n=5, respectively). Renin expression in the ischemic area was increased in DM hearts. Electron microscopy showed predominant renin localization within mitochondria. In permeabilized myocytes or isolated mitochondria, renin hyperpolarized ΔΨm, increased NAD/NADH ratio and preserved ATP content. Ischemiainduced UCP2 expression was reduced in DM.

Conclusions: Intracellular renin, which mainly localizes within mitochondria, increased during ischemia and protected cardiomyocytes in diabetic hearts. This protective effect of renin is at least partially because of the reduction of UCP2 and the acceleration of electron transport chain, which resulted in the prevention of mitochondrial depolarization and ATP production.

मामला का बिबरानी

Tombstone ST Segment Elevation in Double Vessel Coronary Artery Disease; Who is the Culprit?

Yutthapong Temtanakitpaisan, Renee Dallasen and Craig S. Smith

We describe a 66 year-old male who presented with chest pain and ST segment elevation in the anterior leads. The typical culprit lesion is in the left anterior descending artery (LAD). However, concomitant lesions in the other coronary arteries may make an accurate diagnosis of the actual “culprit lesion” more challenging. Understanding the electrical basis of electrocardiograms can provide important clues in identifying and treating the true lesion.

शोध आलेख

Wavelet Analysis of Doppler Flow Velocity Waveforms from the Ocular Circulation Detects Abnormalities in Micro-vascular Function in Heart Failure

Kristopher S Lyons, Aaron McCann, Auleen Millar, Vivienne McClenaghan, Caroline Bleakley, Gary E McVeigh and Mark T Harbinson

Aims: Many pathological processes may result in Heart Failure (HF), however, the final clinical phenotype appears to be common to all aetiologies. Microvascular abnormalities in HF have been demonstrated in a variety of vascular beds however the effect of HF on the retrobulbar circulation is not known. We employed a novel method of analysing blood flow velocity waveforms in order to quantify changes in the Doppler signal obtained from the retrobulbar arteries between HF patients and controls. FMD was also assessed.

Methods and Results: 32 patients with systolic HF on maximal medical therapy and 10 age and sex-matched controls were studied. Doppler waveforms were obtained from the ophthalmic, central retinal and brachial artery in all subjects. Waveforms were analysed using a wavelet technique which expressed each waveform in constituent frequency bands, allowing direct comparisons to be made. Significant differences were found in ophthalmic and central retinal waveforms but not brachial waveforms between patients and controls. Flow mediated dilatation was also found to be abnormal in patients.

Conclusion: This study suggests that abnormalities in microvascular function in the retrobulbar circulation are present in HF and that these changes can be detected by a novel wavelet analysis technique.

मामला का बिबरानी

Multiple Inflammatory Aortic Pseudoaneurysms

Meena P Rao, Lauren Cooper, G. Chad Hughes, Lynne M. Hurwitz and Thomas M. Bashore

Multiple mycotic pseudoaneurysms of the aorta are rarely seen. This case summarizes a patient who survived primary rupture of his proximal ascending aortic pseudoaneurysm but was an unacceptable candidate for surgical therapy. He survived for approximately four months prior to death from massive hemoptysis. The case presents a rare look at an unusual condition and the difficulties in the management of these patients.

मामला का बिबरानी

Hypoxia and Cyanosis due to Unusual Right-to-Left Shunt in a Patient with an Atrial Septal Defect

Filipa Melao, Cristina Cruz, Rafael Noya, Joao Carlos Silva and Maria Júlia Maciel

Hypoxia due to an Atrial Septal Defect (ASD), without Eisenmenger physiology, is reported rarely and may be underestimated due to difficulty in its diagnosis. We report the case of a 67-year-old woman with chronic cyanosis and hypoxia, in whom a large ASD was diagnosed by cardiac catheterization after an extensive workup to clarify the aetiology of the hypoxia. The right-to-left shunt at the ASD occurred probably due to a well-developed Eustachian valve, partly directing the right atrial flow into the left atrium, in the absence of pulmonary arterial hypertension.

शोध आलेख

Hypertriglyceridemic-Waist Phenotype is a Useful Global Assessment Tool for Predicting Acute Myocardial Infarction

Grace M. Egeland, Jannicke Igland, Ottar Nygard, Gerhard Sulo and Grethe S. Tell

Background: There has been growing research interest in exploring the utility of the hypertriglyceridemicwaist phenotype as a predictor of cardio-metabolic risk. To date, prospective studies evaluating the phenotype as a predictor of cardiovascular disease have provided variable results. Objectives: To evaluate the usefulness of the hypertriglyceridemic-waist phenotype as an independent predictor of acute myocardial infarction beyond classical cardiovascular disease risk factors in a homogeneous Norwegian population. Methods: Norwegian health survey (Cohort Norway) participants (n=116,111), free of heart disease in 1994- 2003, were followed through 2009 by record linkages to The Cause of Death Registry and hospital discharge diagnoses through the Cardiovascular disease in Norway project. Cox proportional hazards analyses adjusted for conventional risk factors. Results: During a mean follow-up of 11.5 yrs (SD=2.8), 3,624 participants developed an acute myocardial infarction. Prevalence of an enlarged waist (>102 cm for men, and >88 cm for women) increased from the lowest to highest quartile of triglycerides for men (4.9% to 22.5%) and women (6.5% to 42.1%; P for trend < 0.01). The presence of an enlarged waist and elevated triglyceride (>1.7 mmol/L) was associated with a hazard ratio for acute myocardial infarction of 1.68 (95% CI 1.48-1.90) for men and 1.95 (95% CI 1.66-2.29) for women compared to those with normal waist and triglyceride level after adjusting for age, smoking and time since last meal. However, 75% of the excess risk was mediated by HDL and nonHDL cholesterol. Conclusions: The phenotype is a useful global assessment tool but of limited value when conventional risk factors are available. Patients presenting with the phenotype should be targeted with lifestyle interventions and referred for clinical follow-up.

समीक्षा लेख

A New Insight into Pathogenesis of Cardiovascular Diseases: Stress Induced Lipid Mediated, Vascular Diseases

Rakhshinda Zafar

Based on my clinical experience and knowledge gained through extensive research in this area, I have come up with a hypothesis which sheds more light in the pathogenesis of cardiovascular diseases. Atherosclerosis is implicated as playing the key role in the pathogenesis of cardiovascular diseases which involves large and medium sized arteries. There is now evidence that atherosclerosis is an immuno-inflammatory process. My hypothesis is that chronic psychosocial stress is the main trigger for the systemic inflammation which results by activation of Hypothalamus-Pituitary-Adrenal (HPA) axis and Sympathetic-Adrenal-Medulla (SAM) axis. This stress response sets into motion innate immune response, initiating a cascade of events which include: Release of neuro-endocrine transmitters, endothelial dysfunction, and increased permeability of micro vascular circulation and increased delivery of free fatty acids in circulation among others. Liver responds by increased Low Density Lipoproteins (LDL) production which continuously enters the arteries, excess LDL is transformed into oxidized low density lipoproteins (ox LDL). ox LDL goes through pattern recognition and is recognized as antigen. Adaptive immunity is activated. ox LDL is pro oxidant, results in inflammation, reactive oxygen species are released causing oxidative stress. This causes atherosclerosis in large and medium sized arteries and tissue damage in organs sub served by micro vasculature. Hence the process being systemic inflammation is not limited to large and medium sized arteries but is global in reach involving the entire vasculature. The pathogenesis of these disorders may be classified as “stress induced, lipid mediated vascular inflammation".

This article will review stress and pathophysiology of stress, pathophysiology of cardiovascular diseases which includes endothelial dysfunction, pathogenesis of atherosclerosis, inflammation in atherosclerosis, and current concepts of diseases comprising cardiovascular diseases, including the risk factors for CVDs. It enters the stage of hypothesis based on the knowledge gained. It discusses microcirculation, and goes over disorders involving microcirculation. Oxidative Stress is reviewed followed by a brief summary. It winds up with discussion, management and conclusion.

टिप्पणी

PARADIGM-HF Trial and its Important Clinical Meanings

Jin-lai Liu

ACEi/ARB and ß blocker and aldosterone antagonist have been a gold standard for treating chronic heart failure with reduced ejection fraction (HFrEF). The paper described simply the PARADIGM-HF study (Prospective comparison of ARNi with ACEi to Determine Impact on Global Mortality and morbidity in HF trial), and the results showed that compared to enalapril, LCZ69(ARNi) significantly reduced the primary endpoint (cardiovascular death or hospitalization for HF) [HR0.80 (95% CI 0.73-0.87)?P<0.001; NNT 21], cardiovascular death [HR0.80 (95% CI 0.71-0.89)?P<0.001; NNT 31], hospitalization for HF [HR0.79 (95% CI 0.71-0.89)?P<0.001; NNT 36], and death from any cause [HR0.84 (95% CI 0.76-0.93), P<0.001; NNT 36]. LCZ696 was well tolerated. The PARADIGM-HF study has an important clinical significance and would change the pattern of HF treatment in the future.

समीक्षा लेख

Inflammation, Metalloproteinases, Chronic Venous Disease and Sulodexide

Alberto C. Frati Munari and Luis Fernando Flota Cervera

Abstract Inflammation and extracellular Matrix Metallo Proteinases (MMPs) have been recently considered as an important step in the pathogenesis of Chronic Venous Disease (CVD). To understand how inflammation and MMP may affect venous tissue, a review on these items and on the pathogenesis of CVD was performed. Prolonged or repeated venous hypertension due to well-known predisposing factors causes abnormal shear stress leading to shredding of endothelial glycocalyx and activation of endothelial cells. The latter expose adhesion molecules and release pro-inflammatory cytokines. Diapedesis follows, leading to leukocytes infiltration of Extra Cellular Matrix (ECM) in the sub endothelial space of vein walls and valves. Activated leukocytes, mainly monocytes-macrophages, release chemotactic cytokines that amplify the inflammatory response, they also produce Nitric Oxide molecules (NO) and proteases, including MMPs. High concentration of MMPs, especially MMP-9, is found in venous wall with CVD and in venous ulcers. The role of MMP-9 in CVD is also supported by experimental data. MMP-9 can degrade components of ECM as collagen, elastin, fibronectin and laminin. MMP-9 and other proteolytic enzymes may disrupt ECM structure, damaging and debilitating venous wall that lead to varicose veins and venous ulcers. Sulodexide, a glycosaminoglycan, counteracts several of these inflammatory changes. In subjects with CVD administration of sulodexide improves venous hemodynamic changes and CVD symptoms and accelerates venous leg ulcers healing.

शोध आलेख

Development and Comparison of a Warfarin-Dosing Algorithm in Chinese Han Patients with Atrial Fibrillation

Chen Hao, Tong Jia-bin, LU You, Chong Jia, Tian Wei-meng, LI Peng, DU Xin, MA Chang-sheng and Yang Jie-fu

Abstract Objective: The objective of this study was to develop a new warfarin dosing algorithm based on polymorphisms in CYP2C9 and VKORC1 gene with other demographic variables from a retrospective study for accurate prediction of maintenance dosage in Han subjects with AF in China. Methods: A total of 131 Chinese AF patients with steady warfarin daily dosage (INR reach target range) were recruited from Beijing Hospital during January to November 2011. Blood samples were taken to detect genotype distribution and allelic frequencies of target SNPs: rs1057910 and rs9934438 by direct gene sequencing technique. Demographics variables were recorded during regular visit. All variables for multivariate regression analysis were those significant predictors derived from the univariate analysis, thereafter a stepwise multiple regression analysis was performed to deduce a new dosing algorithm. Results: Four significant predictors (CYP2C9 A1075C, VKORC1 C1173T, age and BSA) derived from univariate analysis were carried to step-wise multiple regression analysis and a new algorithm was deduced (R2=0.436). Their weights for predicting of warfarin dosage were 20.8%, 11.5%, 4.5% and 6.8%, respectively. Conclusion: For Chinese Han patients with AF who accepted oral anticoagulation drug therapy, age, BAS, CYP2C9 A1075C and VKORC1 C1173T are the predictors which highly correlated to variation of warfarin dosage. In dosing prediction system, the weight of pharmacogenetic factors is more robust than that of clinical variables. The interpretation of our algorithm could account for nearly half of heterogeneity of individualized warfarin dosage.

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