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HeartOtago’s work to fix broken hearts

Your heart is an organ like no other – an indefatigable ball of muscle that provides your beat of life. Unfortunately, unlike other structures in your body, its dynamic activity and specific tissue properties mean your heart is not very good at fixing itself. Problems with the heart or blood flow to the heart, can lead to heart damage, which itself can lead to scarring and further damage. The implications of this chain reaction are well known – heart failure remains a major cause of death and disability in New Zealand and worldwide. Every third time your heart beats, one broken heart stops.

It is not easy to fix broken hearts, and even with the advances of modern medicine, few options are available. A combination of drug therapies and surgical interventions attempt to fix or alleviate the underlying conditions. For some of these conditions, such as high blood pressure or blocked heart arteries, the treatments are very successful, but other conditions, such as heart stiffening due to diabetes, have no effective treatments. One real challenge remains attempting to boost the heart’s own ability to repair damage.

 

Unique Collaboration

HeartOtago is a large collaboration combining efforts of cardiovascular researchers and clinicians located at the University of Otago and the Dunedin Public Hospital. The broad scope of their research includes studying heart function and failure, and investigating diseases of heart muscle – cardiomyopathies. Researchers combine patients’ symptoms with clinical observations and basic science measurements to identify new treatment targets, and then test how useful these findings are in people.

Bench to bedside

The close physical proximity of laboratory research facilities to the Dunedin Hospital means that samples from surgery can be tested very quickly after they are obtained. This allows highly specialised testing such as measuring the strength of individual heart muscle contractions (read more here), which can only be done within the first two hours while the cardiac muscle fibers are still functional outside the body. This bench to bedside approach effectively combines clinical and basic science sectors to maximize the amount of clinical findings directly relevant for patients.

 

Unlocking the repairing capacity of the heart

One example of the HeartOtago approach can be seen in addressing ways of encouraging the hearts’ natural healing processes by stimulating the function of resident cardiac stem cells.

Image: Cardiac progenitor cells, cultured for 10 days in cardiomyocyte differentiation medium (stained for myosin heavy chain)

Stem cells are a unique type of cells that have the capacity to multiply and turn into various specialized types of cells. This has an essential role in regeneration and repair of all tissues around your body. Some tissues have very active stem cells, such as your skin or the gut, while others have a poor capacity to do so, including heart tissue.

Stem cells that reside in the heart are believed to help repair injured tissue after heart damage. Research groups around the world have studied diverse ways of improving this capability, for example by supplying damaged hearts with stems cells from elsewhere in the patient’s bodies, or by attempting to activate the existing cardiac stem cells.

 

Vitamin B1 might be the solution

Associate Professor Rajesh Katare, one of the researchers in the HeartOtago collaboration, discovered that the function of the resident cardiac stem cells depends on a number of chemical pathways involving vitamin B1 (thiamine). He also found that using drugs similar to thiamine in laboratory settings improved their ability to regenerate. It had earlier been shown that patients undergoing cardiac surgery often have thiamine deficiency, which might lead to lower activity of the stem cells, and cardiac surgery itself lowers thiamine levels further.

 

HeartOtago thiamine study

Clinical researchers Dr Sean Coffey and Professor Michael Williams, working with Associate Professor Katare, then combined the findings above to test if high dose thiamine supplements might awaken resident stem cells. Patients who had been admitted to hospital as an emergency with coronary artery problems (such as heart attacks), and who were scheduled to have heart surgery, were invited to take part to help test if this strategy would work in real life patients. By isolating cells from patients’ hearts, the researchers can determine the effect of thiamine supplementation on the number and function of the resident stem cells. If the study findings are positive, this could potentially be a simple, cheap, and safe method to improve patients’ quality of life.

 

Study with us

The field of cardiovascular medicine is broad and highly interdisciplinary, and the HeartOtago collaboration has a number of projects looking at various aspects of the cardiovascular system in health and disease. HeartOtago and the Department of Medicine have opportunities for postgraduate and undergraduate students of all backgrounds (medical and non-medical). Read more about opportunities here.

 

Follow for updates: Dr Sean Coffey @DrSeanCoffey, HeartOtago @HeartOtago, the Department of Medicine @OtagoMedDept for updates on the HeartOtago research and findings.

 

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