Dr. Naranjan S. Dhalla
– Experimental Cardiology

Dr. Naranjan S. Dhalla
Principal Investigator, Distinguished Professor,
Experimental Cardiology
Institute of Cardiovascular Sciences

Research Focus

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 540 full length papers in refereed journals and 145 papers in books and monographs. His research work has been cited more than 9,200 times and he edited 40 books on various aspects of the cardiovascular system. He has been an invited speaker at more than 235 national and international conferences and 190 institutions. Dr. Dhalla has trained more than 145 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 25 years. He has been Editor-in-Chief of a major international journal “Molecular and Cellular Biochemistry” for the past 20 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 General Hospital Research Centre
351 Tache Avenue
Winnipeg, MB R2H 2A6 Canada

Tel. 204.235.3417
Fax. 204.233.6723
E-mail. nsdhalla@sbrc.ca

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In Detail

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.

Top

Saini HK, Shao Q, Musat S, Takeda N, Tappia PS and Dhalla NS. Imidapril treatment improves the attenuated inotropic and intracellular calcium responses to ATP in heart failure due to myocardial infarction. Br J Pharmacol 144:202-211, 2005

Shao Q, Ren B, Saini HK, Netticadan T, Takeda N and Dhalla NS. Sarcoplasmic reticulum Ca2+-transport and gene expression in congestive heart failure are modified by imidapril treatment. Am J Physiol Heart Circ Physiol 288:H1674-H1682, 2005

Saini HK and Dhalla NS. Defective calcium handling in cardiomyocytes isolated from hearts subjected to ischemia-reperfusion. Am J Physiol Heart Circ Physiol 288: H2260-H2270, 2005

Shao Q, Ren B, Elimban V, Tappia PS, Takeda N and Dhalla NS. Modification of sarcolemmal Na+-K+-ATPase and Na+/Ca2+ exchanger expression in heart failure by blockade of renin-angiotensin system. Am J Physiol Heart Circ Physiol 288:H2637-H2646, 2005

Chohan PK, Singh RB, Dhalla NS and Netticadan T. L-arginine administration recovers sarcoplasmic reticulum function in ischemic/reperfused hearts by preventing caplain activation. Cardiovasc Res 69:152-163, 2006

Saini HK, Tripathi ON, Zhang S, Elimban V and Dhalla NS. Involvement of Na+-Ca2+ exchanger in catecholamine-induced increase in intracellular calcium in cardiomyocytes. Am J Physiol Heart Circ Physiol 290: H373-H380, 2006

Xu Y-J, Saini HK, Zhang M, Elimban V and Dhalla NS. MAPK activation and apoptotic alterations in hearts subjected to calcium paradox are attenuated by taurine. Cardiovasc Res 72: 163-174, 2006

Saini HK and Dhalla NS. Modification of intracellular calcium concentration in cardiomyoctyes by inhibition of sarcolemmal Na+-H+ exchanger. Am J Physiol Heart Circ Physiol 291: H2790-H2800, 2006

Makazan Z, Saini HK and Dhalla NS. Role of oxidative stress in alterations of mitochondrial function in the ischemic reperfused hearts. Am J Physiol Heart Circ Physiol 292: H1986-H1994, 2007

Saini HK and Dhalla NS. Sarcolemmal cation channels and exchangers modify the increase in intracellular calcium in cardiomyocytes upon inhibiting Na+-K+ ATPase. Am J Physiol Heart Circ Physiol 293: H-169-H181, 2007

Dr. Naranjan S. Dhalla has received more than 125 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 has also recently been featured in “Greatest Manitobans”, a book published by the Winnipeg Free Press.

For more information on the book, click here.

Canadian Institutes of Health Research – $125,804 per year
“Subcellular remodeling in cardiac hypertrophy and heart failure”

Canadian Institutes of Health Research – $139,226 per year
“Pathophysiology of cardiac defects in ischemic heart disease “

Heart and Stroke Foundation of Manitoba – $42,000 per year
“Studies on the biochemical basis of heart function: Adrenergic mechanisms in failing hearts”

There are no opportunities available at this time.

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