Summary – day 2 of the seminar

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Erich Gnaiger visiting the mitochondrial lab

Thursday evening involved a refreshing expedition in extreme weather followed by a delicious dinner in traditional surroundings. Luckily, everybody survived the storm and were ready for a new day full of scientific input. Day 2 started with a session focusing on mitochondrial function. First speaker was professor Erich Gnaiger from Medical University of Innsbruck, Austria – with the most suitable tie of the day:) His scientific contribution to the field of mitochondrial physiology and pathology is quite impressive, including significant contribution to more than 200 publications. Gnaiger is also the initiator and chairman of the International Mitochondrial Physiology Society. His lesson gave insight into mitochondrial respiratory control and early defects of oxidative phosphorylation in hearts affected by heart failure. Several studies have also shown the negative effects of an inactive lifestyle on the mitochondrial function in the heart. We even learned that human beings have very much in common with pigs – although there are some differences.

Dr. Boyett and CERG's Morten A. Høydal

Dr. Boyett and CERG’s Morten A. Høydal

The next session addressed basic mechanisms of cardiac function. Professor of Cardiac Electrophysiology Mark Boyett from the University of Manchester has been investigating the “ion channels” of the heart for several years, and held the presentation “Exercise training reduces the resting heart rate via downregulation of the funny channel, HCN4, and the funny current, If”. Further, Dr. Daniele Catalucci from Humanitas Clinical and Research Center and National Research Counsil (CNR) in Italy presented “Novel insights and new corrective strategies for the recovery of cardiac perfomance”.The calcium handling in the myocytes represents a very central part of the research activity in CERG, for instance as shown in this blog post. Several of our researchers therefore listened extra carefully when dr. Luigi Venetucci from the University of Manchester spoke about inherited calcium channelopathies in the pathophysiology of arrhytmias. This research plays an important role in the development of new drugs. However, as shown in our group, exercise training also affects the calcium handling in the myocytes, for instance with reduced phosphorylation of cytosolic CaMKII, which again is associated with improved contractile function.

IMGP4791Almost 40 % of heart failure patients have atrial fibrillation. Dr. Anthony J. Workman, University of Glasgow, gave us a very useful introduction to basic mechanisms of this disease, with insights from human atrial cells and cells from rabbits with heart failure. Workman and his colleagues have demonstrated that electric currents and voltage signals generated by single heart cells obtained from patients with AF are disturbed in a way that may exacerbate the disease, by so-called “electrical remodelling”. For example, the atrial cell’s refractory period is reduced, which may promote a rapid and chaotic rhythm. He also investigates the effects of beta-blockers, as well as the effect of heart failure, on electric currents, calcium movements and the proteins which regulate these, in human atrial cells and tissues.

IMGP4796Is cardiopulmonary exercise testing (CPET) more than VO2max? Definitely yes, according to dr. Sandy Jack, from the University of Southampton. She is a routined teacher of several CPET courses, with many of the CERG researchers as satisfied students. Her lesson highlighted the use of exercise testing in preoperative assessment and perioperative management, including prehabilitation in cancer patients undergoing major surgery. Further, research suggests that exercise enhances the effect of chemotherapy in cancer patients.

The scientific program was followed by the arrangement “Man in Extreme Environments” at Samfundet. More about that in the next blog post!

Maria Henningsen, CERG

Revealing the heart’s innermost secrets – through the microscope

Cardiac health can be studied from several perspectives – from the clinical patient trial to the tiny protons inside the cells. Here in CERG we include the whole spectre to better understand the heart and its physiology, and the group members come from many different branches of the science tree. Our newest employees are post docs. Allen Kelly and Nathan Scrimgeour, both electrophysiologists from the University of Glasgow and the University of Adelaide, respectively. I have challenged them to describe their research fields, that might be a little bit complicated for us mere mortals to comprehend. However, basic research represents one of the cornerstones in CERG’s research and provides important knowledge on how the heart works and how exercise affects heart function.

IMG_5715One common way of explaining the cardiovascular system is to compare it to a plumbing system in a house, where water pumped to all the rooms is like blood being pumped to all of the organs. In this analogy, pipes represent blood vessels as the paths through which the fluid circulates, and a pump represents the heart, providing the force that drives the fluid through those paths. However, just as a house also requires an electrical system for everything, including the pump, to work, our bodies need an electrical system for everything, including the heart, to work.

The tightly orchestrated movement of ions (electrically charged atoms) in and out of cardiac (heart) muscle cells is what effectively flips the “on” switch, transmitting this signal and triggering a wave of contraction through the heart, and consequently pumping blood around the body. There are specialised molecules that allow ions in, others that allow ions out, and some that work to return everything back to the way it started to flip the switch back to “off”, ready for the next heartbeat. But what happens if one or more parts of this ionic movement “orchestra” are out of time or out of tune with the rest?

Our research background involves the study of different kinds of heart failure. A major cause of heart failure is myocardial infarction, or heart attack; blockage of a blood vessel in the heart leading to damage of the heart muscle and the formation of scar tissue.  One of the most important areas of research in heart disease focuses on understanding the processes occurring inside the heart muscle that cause this damage, so that we might find ways to minimize it. Just 10 years ago, being able to visualise these processes as they happen immediately after a heart attack would have been the stuff of dreams. However, in December last year, Li and colleagues (2012), using a special type of imaging technique known as two-photon microscopy, were able to see the immune system response to a myocardial infarction in a beating heart, tracking the movement of immune cells that are just two hundredths of a mm across (about 10 times smaller than the width of a human hair).  It is advances such as this which drive the rapid pace of heart research today.

IMG_5711Here at CERG, a similar newly-installed two-photon imaging system is helping researchers understand and enhance the benefits of exercise as a treatment strategy in heart disease.  Using this technology, we will be studying how heart disease alters the electrical activity of the heart and normal control of the heartbeat. In heart disease, changes within the heart muscle may disrupt the normal heart beat, leading to uncoordinated beats, or arrhythmias. Arrhythmias are becoming increasingly common and are associated with conditions such as heart disease or high blood pressure. The uncoordinated heart contractions of an arrhythmia mean that blood is inefficiently pumped, leading  to anything from dizziness, uncomfortable palpitations, increased risk of stroke, or sudden cardiac death – one of the most common causes of death in western societies. By visualising changes in the heart muscle that cause these arrhythmias, and how these changes are affected by exercise, we can develop new and improved therapies to prevent these potentially fatal arrhythmias from occurring.

One of the problems with trying to understand specifically why arrhythmias occur and what can be done to prevent or treat them, is understanding which part of the “orchestra” isn’t working properly to start with. As electrophysiologists, we are able to record the electrical activity of cardiac muscle cells, and attempt to understand how each part of this “orchestra” responds to different conditions – for example following heart failure, after an exercise programme, or in response to therapeutic drugs – to lead to better outcomes for patients.

Having just arrived at NTNU, we are joining a team of research scientists who continually contribute to the accelerated pace of current research with many publications on the benefits of exercise to society not just as a lifestyle enhancement, but as an effective treatment for heart disease. Yes, the pace of research may seem overwhelming at first, but it is an exciting time to be a cardiac physiologist.

Allen Kelly and Nathan Scrimgeour, post docs at CERG.