Disease Area Outcomes research, Public health, Cardiovascular

A Stitch in Time

Circadian rhythm – and its importance to human health – has received a lot of press lately. Not least because of last month’s announcement that the 108th Nobel Prize in physiology or medicine has been awarded to a trio of scientists who discovered the molecular mechanisms controlling it (1). Although it is becoming increasingly clear that we should pay more attention to our biological clocks, the ways in which they influence human health remain somewhat mysterious. Now, researchers at the University of Lille, France, have found that heart surgery performed in the afternoon appears to result in better outcomes than surgery performed in the morning. Notably, the team discounted procedures between 12 and 6am in an attempt to exclude the potential effects of tired staff with reduced efficiency. Previous research has found that the risk of heart attack is higher in the morning, with the heart working better in the afternoon (reviewed in (2)).

The researchers looked at patients who underwent scheduled aortic valve replacement between 2009 and 2015. Of the 298 patients operated on in the morning, 54 had a major adverse cardiac event, compared with 28 of the 298 patients operated on in the afternoon – one less major adverse event for every 11 patients (3).

But why? Transcriptomic analyses of heart muscle biopsies from both the morning and afternoon patients showed that the expression of some 287 genes differed depending on the time of day, which appears to be linked to the heart tissue’s tolerance for hypoxia–reoxygenation events. One gene that showed great variation depending on the time of day (with the highest levels in the morning) was Rev-Erbα. To investigate further, the team looked at the effect of Rev-Erbα knockout and inhibition in mouse hearts; myocardial hypoxia–reoxygenation tolerance was improved in both cases.

The team notes the need for further validation, but suggests several potential avenues to improve patient outcomes. Time of surgery could be considered – although this could prove impractical in some settings (for example, when organ donors are involved). Another option could be to develop novel compounds to effectively and safely inhibit Rev-Erbα to “hack” the biological clock.

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  1. Nobelprize.org, “The Nobel Prize in Physiology or Medicine 2017”, (2017). Available at: bit.ly/2hFP1yo. Accessed October 30, 2017.
  2. CJ Morris et al., “The impact of the circadian timing system on cardiovascular and metabolic function”, Prog Brain Res, 199, 337–358 (2012). PMID: 22877674.
  3. D Montaigne et al., “Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbα antagonism: a single-centre propensity-matched cohort study and a randomised study”, Lancet, [ePub ahead of print] (2017).
About the Author
Roisin McGuigan

I have an extensive academic background in the life sciences, having studied forensic biology and human medical genetics in my time at Strathclyde and Glasgow Universities. My research, data presentation and bioinformatics skills plus my ‘wet lab’ experience have been a superb grounding for my role as a deputy editor at Texere Publishing. The job allows me to utilize my hard-learned academic skills and experience in my current position within an exciting and contemporary publishing company.

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