Small wonder that the AH Couch Trust chose to award Otago Medical School student Kyra
Sinclair a 2022 scholarship in support of her PhD study of possible links between epicardial
adipose tissue (EAT) and atrial fibrillation (AF).
For one thing AF is the most common abnormal heart rhythm, a huge problem in ageing
populations world-wide. A better understanding of its causes is likely to improve the
medical response from its prevailing invasive defibrillation techniques, or catheter ablations
that cauterise parts of the heart. Even the standard drug regime for AF, beta blockers,
typically brings in its train a pronounced fatigue.
But secondly, in 2019, researchers from Otago University’s School of Biomedical Sciences
and the Dunedin School of Medicine showed that human EAT – more simply known as
heart fat – could, under chemical stimulus, cause spontaneous contractions in human heart
muscle. That proof of direct connection between human EAT and AF was a world first, and
Kyra Sinclair’s PhD was designed to expand on that breakthrough work.
Heart fat is good to have – it sits hand-in-glove beside the heart muscle, and shares the
same blood supply. Its dissolved fats are the heart’s local energy source and it also keeps
the heart warm but the question now was, can good heart fat go bad?
Kyra Sinclair graduated with a Biomedical Science degree in 2018, before the Otago
researchers published their research findings, but her interest in hearts had been sparked by
BBiomedSc lecturers and even after being accepted into Otago Medical School’s five-year
degree course in 2019 that specialist interest remained. She says, simply – ‘I love hearts’ –
and took advantage of the two gap years between year three and year four of the medical
degree, to pursue her interest at a PhD research level. The so-called ‘metabolic diseases’
obesity and diabetes typically have more heart fat and much higher rates of AF than the
population at large, and by examining that pronounced correlation, her PhD would try to
isolate a cause.
During open-heart surgery, slivers of heart muscle are routinely discarded, and Kyra gained
42 consents from obese and non-obese heart patients awaiting open-heart surgery at
Dunedin Hospital to take those slivers for research. Many of those patients also accepted an
invitation to donate a small sample of heart fat.
In lab experiments, Kyra exposed heart fat samples for 24 hours to a fluid superfused with
dissolved sugars, fats, and insulin, mimicking the typical metabolic stressors circulating in
the blood of the obese, also diabetics.
“Most people know that fat helps keep us warm,” says Kyra, “but fat is also a really active
organ and secretes lots of hormones and chemical messengers, so over that 24-hour period
the heart fat samples should have been secreting their chemical messengers into the fluid
that’s surrounding it.”
Heart tissue samples were then stretched onto force transducers to record any spontaneous
contractions, and placed downstream of the circulating fluid, for an hour. The answer to
one of the questions posed by her PhD then hung in the balance. Would the heart fat from
obese patients cause abnormal heart beats in the heart tissue?
“Surprisingly, it didn’t,” says Kyra. “What I think is going on is that I’m testing a really acute
mechanism. I’m testing if the heart fat messengers are causing abnormal heart rhythms
within a very short time frame, but obesity is a chronic condition people have developed
over many years so I think the mechanism behind it is probably a chronic pathway as well.”
“So I haven’t got any positive findings of like – ‘It’s definitely this pathway’ – but my work, I
think, has quite thoroughly ruled that out. Has shown it’s not this pathway, if that makes
sense.”
Science is science – truthful as to its results even if they don’t fit the original hypothesis, and
though a negative result doesn’t make newspaper headlines it’s part of an incremental
research process towards isolating causes and suggesting new approaches.
Kyra’s research now moves on to analyzing the ‘messenger soup’ of the cultured heart fat
saved within the superfused fluids. Heart fat is good until it turns bad. Too much of it can
produce pro-inflammatory cytokines – in particular Activin A, a chemical messenger within
heart fat which animal studies have shown can scar the heart.
“We all need a fat layer around the heart, but if you have too much of it then the profile of
those chemical messengers that it sends can turn from being beneficial to your heart to
being quite negative,” says Kyra. “I’m going to look at what they are, and see if the
metabolic stress increased the amount of those messengers that can promote scarring of
the heart. Because that would then lean towards that as being a chronic pathway.”
The A H Couch scholarship supported Kyra Sinclair at $22,500 a year as she pursued her
heart research part-time over the past two years, while still managing the last two full-time
years of her medical degree.
“The support was awesome,’ says Kyra, “and what I think is really important also about the
scholarships that AH Couch has given to me and the other three Otago medical students
that also have the scholarships is that it’s priming those of us that aren’t doctors yet, but are
going to become medical doctors to continue an interest in research and particularly heart
research. I have the view that it’s like an investment – that AH Couch has invested in me to
learn how to do research now, then also to do more research later once I have the
experience and the qualifications.“
She’s as yet unsure what specialist route she’ll take after her pending basic cardiology
training, but as regards the three main streams of that discipline, intervention, imaging, and
electrophysiology, says she’d lean towards intervention for its wide range of satisfying
procedures. Her parents were veterinarians who ran a small farm north of Paraparaumu
and she still has vivid childhood memories of the farm shed, her parents performing a c-
section on a sheep, and the miraculous presentation of live lambs.
Meantime if all goes well, her Doctorate and her MB ChB will both be done and dusted by
the end of 2025 – “I’ll go from no doctor to doctor squared I guess.”
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