Broken heart syndrome arms against epinephrine high

By Piriya Mahendra

Takotsubo cardiomyopathy, or "broken heart syndrome," may actually protect the heart from very high levels of epinephrine (adrenaline), suggest results from an animal study.

The study simulated the condition by exposing anesthetized rats to high levels of intravenous epinephrine and showed that they were protected from a potentially fatal overstimulation of the heart by the activation of the beta 2-adrenergic receptor-inhibitory G protein (β2-AR-Gi) signaling.

At high concentrations of epinephrine, β2-AR couples to the Gi protein and mediates cardiodepression.

The findings indicate that this specific epinephrine signaling process may have evolved as a cardioprotective strategy to limit myocardial toxicity during acute stress, report Alexander Lyon (National Heart and Lung Institute, London, UK) and team in Circulation.

They found that preventing the activation of this pathway in response to high epinephrine levels increased mortality, from approximately 50% to 100%.

Takotsubo cardiomyopathy is most commonly seen in older women who experience severe emotional stress after bereavement. Patients usually demonstrate symptoms that resemble those of a heart attack, but most fully recover after a short period of time.

The researchers found that beta blockers exacerbated the epinephrine signaling pathway in Takotsubo cardiomyopathy. Indeed, propranolol significantly enhanced and prolonged the negative effects of epinephrine at apex and base, but did not increase mortality.

By contrast, levosimendan, a heart failure drug that does not act on epinephrine receptors, had a beneficial effect. It prevented further decline in cardiac function and reduced mortality.

"Adrenaline's stimulatory effect on the heart is important for helping us get more oxygen around the body in stressful situations, but it can be damaging if it goes on for too long," said co-author Sian Harding, also from the National Heart and Lung Institute, in a press statement.

"In patients with Takotsubo cardiomyopathy, adrenaline works in a different way and shuts down the heart instead. This seems to protect the heart from being overstimulated."

Lyon stressed that it is not currently known how to treat Takotsubo cardiomyopathy, but that the findings from the study show that the condition may protect patients from harm.

"We've identified a drug treatment that might be helpful, but the most important thing is to recognise the condition, and not to make it worse by giving patients with Takotsubo cardiomyopathy more adrenaline or adrenaline-like medications," he warned.

Shannon Amoils, a research advisor at the British Heart Foundation, which funded the study, called the study "fascinating" but cautioned: "We must remember though that this is a study in rats, and the findings need to be confirmed in people before we can be sure of their relevance to patients."

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