MedicalResearch.com Interview with:
Prof David Montaigne MD
Faculté de Médecine de Lille H Warembourg
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: It is well known for many decades that cardiovascular diseases exhibit a diurnal variation with for instance higher incidence of myocardial infarction in the early morning as opposed to the evening. Although studies on circadian gene knock-out and mutant mice argue for a biorhythm in myocardial ischemia-reperfusion tolerance, whether a biorhythm in the myocardial tolerance to ischemia, exists in humans was unclear because of conflicting reports in the context of myocardial infarction.
We demonstrated for the first time in humans that the myocardial tolerance to ischemia-reperfusion is different along the day, in line with rodent experiments performed in the early 2010s.
We demonstrated that this biorhythm is clinically meaningful and that it can be targeted as a cardioprotective strategy.
In this topic, Rever-alpha is of specific interest. It belongs at the same time to circadian genes and nuclear receptor families: being a nuclear receptor, it is a feasible pharmacological target, conversely to other circadian genes.
MedicalResearch.com: What should clinicians and patients take away from your report?
Response: Cardiac surgery, and aortic valve replacement specifically, are very safe nowadays as well shown in our study.
Circadian rhythm impacted not only cardiovascular physiology but also pathophysiology and will for sure be a drug target in few years allowing to induce an organ jet-lag … with a view to increase a therapeutic effect or avoid side-effects.
Importantly, regarding cardiac surgery, the point is not to alter the scheduling of surgery for all patients:
Changing the time of surgery for low risk patients (the most numerous) makes no sense: they do not develop complications. However, this should be considered in high-risk patients. We are working on refining who are the high-risk patients and what would be the best time for each sub-group of “high risk patient”.
Finally, our observation has to be confirmed in other centers using similar approaches to deal with the numerous confounding factors related to patients, surgeons and peri-operative care.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Future research in the topic of ischemia-reperfusion and cardioprotection should take into consideration the major impact of time-of-day on myocardial injury, i.e. time-of-day must be part of the design and interpretation of both bench-side and clinical study regarding IR.
Moreover, our proof-of-concept study in cardiac surgery should stimulate research in the field of myocardial infarction and organ transplantation, conditions with major cardiac injury (conversely to cardiac surgery) and no effective cardioprotective strategy to date.
MedicalResearch.com: Is there anything else you would like to add?
Response: Just would like to thank the support from our fundings Fondation de France, Fédération Française de Cardiologie, EU-FP7-Eurhythdia, Agence Nationale pour la
Recherche ANR-10-LABX-46, and CPER-Centre Transdisciplinaire de Recherche sur la Longévité.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Montaigne D, Marechal X, Modine T, 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. The Lancet. Published online October 26 2017
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