Dr. Naranjan S. Dhalla
Experimental Cardiology, Institute of Cardiovascular Sciences
Distinguished Professor, Faculty of Medicine
Professor of Physiology, University of Manitoba
Senior Fellow, Centre for the Advancement of Medicine
The Experimental Cardiology Laboratory is engaged in studying the pathophysiology and pharmacotherapy of congestive heart failure, ischemia-reperfusion injury and diabetes induced cardiomyopathy. Our objective is to understand the molecular and subcellular basis of cardiac dysfunction in experimental animals with or without various drug treatments. Furthermore, we wish to identify new targets for discovering improved therapies for treatment of heart disease. In particular, we are focussed to examine renin-angiotensin system, sympathetic nervous system, oxidative stress, intracellular Ca2+-overload and subcellular remodeling for the transition of cardiac adaptation (hypertrophy and dilation) to maladepletion (cardiac dysfunction and heart failure).
Why is this work important?
In view of the fact that heart disease is the major killer and the currently available medications are not satisfactory, our research is of critical importance for defining the exact molecular defects in cardiac dysfunction and improving drug therapy.
What techniques and equipment are used in this laboratory?
Our laboratory uses experimental models of heart failure due to myocardial infarction and volume load, isolated hearts preparations for ischemia-reperfusion injury, and rat cardiomyopathy for type I and type II diabetes. Cardiomyocytes preparations are used for studying intracellular Ca2+-handling as well as protein and gene expression in addition to β-adrenoceptor mediated signal transduction mechanisms. Different subcellular organelles such as sarcolemma, sarcoplasmic reticulum, myofibrils and mitochondria are used for studying subcellular remodeling and molecular abnormalities in heart disease.
About Dr. Naranjan S. Dhalla
Dr. Naranjan S. Dhalla has published more than 607 full length papers in refereed journals and 161 papers in books and monographs. His research work has been cited more than 14,000 times and he edited 45 books on various aspects of the cardiovascular system. He has been an invited speaker at more than 297 national and international conferences and 206 institutions. Dr. Dhalla has trained more than 161 graduate students, postdoctoral fellows and visiting scientists. In his capacity as Secretary General and President of the International Society for Heart Research, he was engaged in promoting the scientific basis of cardiovascular medicine for 30 years. He has been Editor-in-Chief of a major international journal “Molecular and Cellular Biochemistry” for the past 26 years and is also serving as Executive Director of the International Academy of Cardiovascular Sciences since 1996.
For more information, contact:
Naranjan S. Dhalla, MD (Hon), DSc (Hon), FRSC
Distinguished Professor and Director of Cardiovascular Developments
Institute of Cardiovascular Sciences
St. Boniface Hospital Research
351 Tache Avenue
Winnipeg, MB R2H 2A6 Canada
Tel. (204) 235-3417
Fax. (204) 233-0347
Cardiac Hypertrophy and Congestive Heart Failure
Any time the heart is presented with an extraordinary load, it responds by becoming bigger or hypertrophic. Up to a point this is a healthy process, but beyond that point it becomes pathological, leading to congestive heart failure. Dr. Dhalla believes that a remodeling of subcellular organelles begins at the time of hypertrophy and it is this restructuring that interferes with calcium handling and eventually leads to heart failure. He further hypothesizes that interventions that improve heart function do so by affecting gene expression in such a way that this remodeling is prevented. Currently, the mechanisms by which drugs improve heart function are not understood. If these secrets can be uncovered, more precisely targeted therapies can be developed.
Understanding Ischemia-Reperfusion Injury
In ischemic heart disease, an obstruction in arterial blood supply reduces the levels of oxygen available to the tissue. Restoring the flow, or reperfusing, can be accomplished in a variety of ways – balloon angioplasty, clot dissolving drugs or bypass surgery. If reperfusion occurs within a certain time frame, it is usually successful. However, if that time frame is passed, reperfusion can have a negative effect known as “stunning” of the myocardium. When this occurs, recovery can be slow or tenuous. Dr. Dhalla’s laboratory is trying to determine whether oxygen free radicals formed during the reperfusion are responsible and whether cardio-protective drugs can solve the problem.
Heart Dysfunction in Diabetes
Dr. Dhalla’s laboratory has demonstrated that heart dysfunction in chronic diabetics is linked to oxidative stress. In oxidative stress, a number of mechanisms which regulate calcium become unbalanced. Calcium regulation is vital to the proper contraction and relaxation of the heart’s muscle cells and thus, abnormalities in calcium handling are intimately associated with heart dysfunction. Accordingly, drugs are being developed with calcium regulatory targets in mind for the treatment of diabetes induced heart disease. Recently, Dr. Dhalla has identified a new mechanism for the entry of calcium into the cardiac cell. This target has helped him to discover two novel interventions for reducing arrhythmias, infarct size and mortality due to heart attacks which are associated with chronic diabetes.
1. Dent MR, Tappia PS and Dhalla NS. Gender differences in β-adrenoceptor system in cardiac hypertrophy due to arteriovenous fistula. J Cell Physiol 226:181-186, 2011
2. Machackova J, Sanganalmath SK, Elimban V and Dhalla NS. β-adrenergic blockade attenuates cardiac dysfunction and myofibrillar remodeling in congestive heart failure. J Cell Mol Med 15:545-554, 2011
3. Xu YJ, Zhang M, Ji L, Elimban V, Chen L and Dhalla NS. Suppression of high lipid diet induced atherosclerosis by sarpogrelate. J Cell Mol Med 16:2394-2400, 2012
4. Babick A, Chapman D, Zieroth S, Elimban V and Dhalla NS. Reversal of subcellular remodelling by losartan in heart failure due to myocardial infarction. J Cell Mol Med 16: 2958-2967, 2012
5. Müller AL, Hryshko LV and Dhalla NS. Extracellular and intracellular proteases in cardiac dysfunction due to ischemia-reperfusion injury. Int J Cardiol 164:39-47, 2013
Dr. Naranjan S. Dhalla has received more than 170 honours and awards from all over the world. These include the Order of Canada, Order of Manitoba, Order of the Buffalo Hunt from the Province of Manitoba, Fellowship in the Royal Society of Canada, Medal of Honour of the Canadian Medical Association, Research Achievement Award of the Canadian Cardiovascular Society, Chair in Cardiovascular Research and Honorary Professorship at different Universities.
Dr. Dhalla was elected 2nd Greatest Manitoban of All Time and was featured in “Greatest Manitobans”, a book published by the Winnipeg Free Press.
For more information on the book, click here.