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Muller A.L.,Institute of Cardiovascular science | Dhalla N.S.,University of Manitoba
Heart Failure Reviews

It is believed that cardiac remodeling due to geometric and structural changes is a majormechanism for the progression of heart failure in different pathologies including hypertension, hypertrophic cardiomyopathy, dilated cardiomyopathy, diabetic cardiomyopathy, and myocardial infarction. Increases in the activities of proteolytic enzymes such as matrix metalloproteinases, calpains, cathepsins, and caspases contribute to the process of cardiac remodeling. In addition to modifying the extracellular matrix, both matrix metalloproteinases and cathepsins have been shown to affect the activities of subcellular organelles in cardiomyocytes. The activation of calpains and caspases has been identified to induce subcellular remodeling in failing hearts. Proteolytic activities associated with different proteins including caspases, calpain, and the ubiquitin-proteasome systemhave been shown to be involved in cardiomyocyte apoptosis,which is an integral part of cardiac remodeling. This article discusses and compares how the activities of various proteases are involved in different cardiac abnormalitieswith respect to alterations in apoptotic pathways, cardiac remodeling, and cardiac dysfunction. An imbalance appears to occur between the activities of some proteases and their endogenous inhibitors in various types of hypertrophied and failing hearts, and this is likely to further accentuate subcellular remodeling and cardiac dysfunction.The importance of inhibiting the activities of both extracellular and intracellular proteases specific to distinct etiologies, in attenuating cardiac remodeling and apoptosis as well as biochemical changes of subcellular organelles, in heart failure has been emphasized. It is suggested that combination therapy to inhibit different proteases may prove useful for the treatment of heart failure. © 2011 Springer Science+Business Media, LLC. Source

Greensmith D.J.,Institute of Cardiovascular science
Computer Methods and Programs in Biomedicine

Here I present an Excel based program for the analysis of intracellular Ca transients recorded using fluorescent indicators. The program can perform all the necessary steps which convert recorded raw voltage changes into meaningful physiological information. The program performs two fundamental processes. (1) It can prepare the raw signal by several methods. (2) It can then be used to analyze the prepared data to provide information such as absolute intracellular Ca levels. Also, the rates of change of Ca can be measured using multiple, simultaneous regression analysis. I demonstrate that this program performs equally well as commercially available software, but has numerous advantages, namely creating a simplified, self-contained analysis workflow. © 2013 The Author. Source

Chatterjee S.S.,Institute of Cardiovascular science
Indian heart journal

To evaluate the immediate results of balloon mitral valvulplasty in mitral restenosis patients with previous surgical mitral commissurotomy. Percuteneous balloon mitral valvuloplasty (BMV) was done in 145 cases of which 70patients had the history of previous surgical commissurotomy (Group I) and 75 patients were the new cases for the BMV (Group II). In group I the age range was 35-65 years. In group I the duration of surgical commissurotomy (SC) was of 2-18 years past. In this group the result of balloon mitral valvuloplasty (BMV) was successful in 69 cases. Mitral valve area (MVA) before the procedure was 0.5-0.9 sq cm with mean 0.7 +/- 0.2 sq cm. Following procedure the MVA was 1.2-2.0 cm2 with a mean of 1.6 +/- 0.4 cm2. Mean gradient across mitral valve (MV) before the procedure was 15-25 mm of Hg with a mean 20 +/- 5 mm of Hg and after the procedure was 3-5 mm Hg with a mean of 4 +/- 1 mm Hg. In Group I, MVA > 1.8 cm2 was achieved in 25 cases & > 1.2-1.8 cm2 in 44 cases. Mitral regurgitation > or = grade 1 occurred in 8 cases (compared to previous echocardiography). In group II the age range was between 35-60 years. The result of BMV was successful in 74 cases. MVA before the procedure was 0.4-1.2 cm2 with a mean of 0.8 +/- 0.4 cm2. Following the procedure MVA was 1.3-2.1 cm2 with a mean of 1.7 +/- 0.4 cm2. Mean gradient across the mitral valve before the procedure was 15-29 mm of Hg with a mean of 22 +/- 7 mm of Hg. Mean gradient across the mitral valve after the procedure was 2-4 mm of Hg with a mean of 3 +/- 1 mm of Hg. MVA more than 1.8 cm2 was achieved in 29 cases and between 1.3-1.8 in 45 cases. BMVin patients with mitral restenosis following Surgical mitral commissurtomy can be performed with almost similar success rate like that of BMV for the first time with low risk of major cardiac complication. Source

Dent M.R.,Institute of Cardiovascular science | Tappia P.S.,University of Manitoba | Dhalla N.S.,Institute of Cardiovascular science
Journal of Cellular Physiology

This study was undertaken to determine alterations in the β-adrenoceptor (β-AR) signaling system in male and female rats at 4 weeks after the induction of arteriovenous (AV) fistula or shunt. AV shunt produced a greater degree of cardiac hypertrophy and larger increase in cardiac output in male than in female animals. Increases in plasma levels of norepinephrine and epinephrine (EPI) due to AV shunt were also higher in male than females. While no difference in the β1-AR affinity was seen in males and females, AV shunt induced increase in β1-AR density in female rats was higher than that in males. Furthermore, no changes in basal adenylyl cyclase (AC) V/VI mRNA levels were seen; however, the increase in EPI-stimulated AC activities was greater in AV shunt females than in males. AV shunt decreased myocardial β1-AR mRNA level in male rats and increased β2-AR mRNA level in female hearts; an increase in Gi-protein mRNA was detected only in male hearts. Although GRK2 gene expression was increased in both sexes, an increase in GRK3 mRNA was seen only in AV shunt female rats. β-arrestin1 mRNA was elevated in females whereas β-arrestin 2 gene expression was increased in both male and female AV shunt rats. While these data demonstrate gender associated differences in various components of the β-AR system in cardiac hypertrophy due to AV shunt, only higher levels of plasma catecholamines may account for the greater increase in cardiac output and higher degree of cardiac hypertrophy in males. © 2010 Wiley-Liss, Inc. Source

Tappia P.S.,IH Asper Clinical Research Institute | Xu Y.-J.,Institute of Cardiovascular science | Dhalla N.S.,Institute of Cardiovascular science
Clinical Lipidology

Although synthetic chemicals and pharmacological agents are being used for the treatment of cardiovascular disease in the western world, there now appears to be a cultural and philosophical shift toward Eastern Medicine and many patients are increasingly using alternative approaches for prevention and therapeutic purposes. This brief review summarizes the experimental and clinical evidence of some functional foods, herbal products and medicinal plants for improving plasma HDL cholesterol, LDL cholesterol, triglycerides and glucose levels, as well as reducing oxidative stress. In addition, the potential of acupuncture and Yogic meditation are discussed as emerging approaches for reducing cardiovascular disease risk factors. The available evidence indicates that several functional foods, herbal products and medicinal plants exert lipid-lowering and hypoglycemic actions, as well as exhibit antioxidant properties; however, a great deal of research work and extensive clinical trials are needed to establish their use in medical practice. © 2013 Future Medicine Ltd. Source

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