Heart energetics research gains funding

Heart energetics research gains funding

Media Release - University of Auckland - 23 May 2016

The response of heart muscle in heart failure will come under closer scrutiny with the award of an emerging researcher grant by the Health Research Council.

The Emerging Researcher grant of $111,000 over three years was made to Dr June-Chiew (JC) Han, from the University of Auckland, for a project investigating the disturbed energetics in heart failure.

“This project will prompt a paradigm shift in our perception of the energetics disturbances and tranverse-tubule (t-tubule) disruption in heart failure,” says Dr Han. “The aim is to improve health outcomes for heart failure patients in New Zealand.”

The research will investigate both diabetic and hypertensive right-ventricular failure (related to rheumatic heart disease) to determine if there is any underlying basis for the higher prevalence of heart failure in Māori.

Dr Han is a postdoctoral research fellow at the University’s Auckland Bioengineering Institute (ABI). He gained a Bachelor of Engineering and a doctorate in Bioengineering at the University.

This is a crossdisciplinary project with associate investigators, Associate Professor Andrew Taberner, Associate Professor Denis Loiselle, Dr MarieLouise Ward and Dr David Crossman from ABI and the University’s Department of Physiology.

Research evidence shows that a change in the organisation (remodelling) of the transverse tubule (t-tubule) is directly linked to ionic abnormality and mechanical dysfunction in human and animal models of heart failure, he says.

A recent study further shows that t-tubule remodelling is an early pathological event occurring even before heart failure.

“T-tubules are not just simple invaginations of cell membrane, they are one of the key components in modulating cardiac function,” says Dr Han.

The ‘osmotic shock’ technique involves using a pharmacological agent to acutely disrupt the t-tubules. This mimics ionic and mechanical changes commonly found in heart failure.

“The effect of t-tubule remodelling on heart energetics (in particular, heat production and energy efficiency) remains unknown,” he says. “A comprehensive understanding of this association is crucial to deciphering energetic disturbances in heart failure, potentially benefiting earlier diagnosis and targeted treatment.”

His research will investigate the association of t-tubular organisation with energetics in cardiac muscle, in both non-diseased and diseased states.

This will be achieved by acutely disrupting the t-tubular network (‘detubulation’) and systematically assessing its putative effect on myocardial work output (and crossbridge dynamic stiffness), heat output and hence mechanical efficiency.

To do this work, Dr Han will use the world’s only flow-through calorimeter for measuring simultaneously the mechanical (force, length) and energetic (heat production) properties of realistically-contracting individual heart muscles.

The calorimeter was developed at the ABI’s Bioinstrumentation Laboratory and enables researchers to vary the amount of work done by a living heart muscle while measuring its energy consumption.

This unique device combines sensitive temperature sensors with a sophisticated laser-interferometer -based force-length control system.

“We electrically stimulate the muscle, causing it to contract, and describe a force-length 'work-loop' modelled on the pressure-volume behaviour of the whole heart,” says Dr Han.

“We measure the rate at which heat is produced by the muscle to 100nW resolution while controlling muscle length to 2nm resolution and force to 1N resolution.”

ENDS

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