Tobias Eckle¹, Jin Ye Yeo²

¹Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, USA; ²ATM Editorial Office, AME Publishing Company

Correspondence to: Jin Ye Yeo. ATM Editorial Office, AME Publishing Company. Email: editor@atmjournal.org

Expert introduction

Prof. Tobias Eckle (Figure 1) has conducted seminal basic science and preclinical translational studies since 2000. He was the first researcher to discover the emergence of the multi-drug resistant cytomegalovirus infection in children after highly purified stem cell transplantation. He further developed novel and innovative mouse models for myocardial ischemia or acute lung injury. Prof. Eckle has conducted seminal studies on nucleotide metabolism and signalling in myocardial ischemia, acute lung injury and inflammation. He was the first to identify the link between hypoxia and circadian rhythms pathways in myocardial ischemia, and his work further discovered that intense light can be used as therapy to target circadian and hypoxia-mediated cardioprotection. Prof. Eckle has demonstrated in preclinical studies using healthy human volunteers that light therapy targeting circadian mechanisms can reduce inflammation, increase plasma levels of cardioprotective micro RNAs, prevent thrombus formation and increase the circadian amplitude.

Prof. Eckle’s work has been funded by the National Heart Lung Blood Institute, the American Heart Association, and the Foundation for Anesthesia Education and Research. Prof. Eckle has authored over 80 peer review publications (H-index 43, over 11,000 citations) in leading biomedical journals such as Journal of Clinical Investigation, Blood, Circulation, FASEB, PNAS, Nature Medicine or Cell Reports. Prof. Eckle’s current research is focused on introducing intense light therapy into the perioperative and critical care setting and funded by an NHLBI R56.

Figure 1 Prof. Tobias Eckle

Interview

ATM: What motivated you to pursue a career in anesthesiology, and subsequently dedicate your research focus to cardioprotection?

Prof. Eckle: This is a long story, but I will try to make it short. During medical school, my goal was to become a surgeon. However, I was also working on my PhD in the Institute of Virology. My thesis received a summa cum laude, and I was able to publish my work in the journal Blood. Since I was extremely successful and I really enjoyed research and bench work, I eventually decided to join a renowned immunology laboratory after medical school. Of course, everything comes differently. After my last medical exam, I was ready to start in a research laboratory and forgo any residency training. When I checked with the lab, I found out that they had not even worked on my contract yet. Disappointed, I called my friend from medical school who was doing Anesthesiology residency training. He convinced me that Anesthesiology was the best residency I could do. And that was how I started my residency training in the Department of Anesthesiology at the University Clinic of Tübingen.

During my residency training, I was still working and publishing in the field of Virology.  Eventually I ended up having 5 peer-reviewed manuscripts in prestigious journals. However, when I had a career advice session with my Anesthesia Chair, he was not really happy with the idea that I, an Anesthesiologist, was working on cytomegalovirus infections. At this point a former student of our university returned as a fully trained Anesthesiologist from Harvard Medical School. My Chair connected us, and he became my mentor. After some initial discussions, I really loved the idea of performing mouse surgery and investigating cardioprotective mechanisms. As such, I established a novel hanging weight system for in situ ischemic preconditioning of the murine heart. This was the start of a very long and successful basic science journey.

ATM: You were the first to link hypoxia and circadian rhythms in myocardial ischemia. What implication does this finding have on current or future therapies for myocardial ischemia?

Prof. Eckle: Thank you for this excellent question. First, I would like to thank all my great mentors and Chairs who made my success possible. In my opinion, the biggest implication for the hypoxia-circadian link is probably the fact that we eventually could use therapies from the circadian field to activate hypoxia pathways. Hypoxia-elicited pathways in the heart are generally protective. If we could activate those protective pathways without inducing hypoxia, and eventually use intense light – as a strong regulator of circadian rhythms - then we would be golden. Using intense light is a low risk and easy-to-adapt therapy. Currently, we are working on reducing the incidence of myocardial injury during non-cardiac surgery (MINS) using intense light therapy. We have very promising results as of now and hope that future NIH funding will allow us to proceed with a large clinical trial.

ATM: Could you share a brief overview of the current publications regarding circadian influences on myocardial ischemia-reperfusion injury and heart failure? Are there any findings that stood out to you?

Prof. Eckle: My group, together with Tami Martino from Canada, have published a very comprehensive Review article for Circulation Research in 2024 (1). Dr. Martino is currently the president of the Canadian Society of Chronobiology. We are very fortunate that she invited us to be the lead author and to incorporate all our previous studies. Hence, this manuscript really stands out in the field.

ATM: What excites you most about the potential of light therapy in clinical settings? Could you share some of the most promising results you have observed in your studies?

Prof. Eckle: We have recently exposed patients following high-risk spine surgery to intense light therapy and analyzed their plasma for our light-responsive proteins identified in our animal studies. The most promising candidate in our previous studies published in Cell Reports or Trends in Molecular Medicine was the endothelial protective factor ANGPTL4. And indeed, this endothelial factor was significantly increased in patients receiving intense light therapy after surgery. Moreover, we also observed a decline in troponin values. Troponin is the sole indicator of MINS. These data are very promising, and we believe we can use light one day to treat MINS.

ATM: In your opinion, what are some aspects of cardioprotection research that have received insufficient attention?

Prof. Eckle: The cardioprotective research is vast. I would say one field that has not received enough attention is the role of the endothelium in cardioprotection. In fact, based on our research data we could demonstrate that endothelial-specific Period 2 is responsible for intense light-elicited cardioprotection from myocardial ischemia and reperfusion injury. As such, further elucidating endothelial mechanisms during myocardial ischemia may reveal novel exciting avenues in cardioprotection. In addition, I believe that circadian rhythm-related therapies in cardioprotection are also under investigation.

ATM: You are currently leading a special series on popular topics in anesthesia and critical care medicine in ATM. Can you highlight some of the topics that you are especially excited about, and how they can impact the field?

Prof. Eckle: Thank you again, for this great opportunity! Of course, I am super excited that we were able to contribute with a review on enhancing circadian rhythms using the circadian MEGA bundle as a novel approach to treat critical illness. This is a very exciting topic, and I feel it is still highly understudied and undervalued. Another topic that I believe is one of the most relevant areas of anesthesia is residual neuromuscular blockade. As such, I am very pleased that we could get one of the top experts in the country to contribute with an article on eliminating residual neuromuscular blockade.

ATM: How has your experience been as an Editorial Board Member of ATM?

Prof. Eckle: Thank you so much for having me on the Editorial Board of ATM. I am extremely pleased and happy with my membership and I thoroughly enjoyed working on the special edition for ATM as the Guest Editor. I would like to highlight that my interactions with the journals are extremely pleasant and ATM has become one of my secret favorites in the world of publishing.

ATM: As an Editorial Board Member, what are your aspirations for the future of ATM?

Prof. Eckle: My aspiration for this journal would be to create an Anesthesia section that could perhaps allow an annual special edition that covers all kinds of different articles from the anesthesia world. In addition, I would love to create an Anesthesia section for Case Reports only. I believe that there are more excellent case reports out there than are being published. I believe this is important information that is ultimately not available to the Anesthesia community.

Reference

1. Eckle T, Bertazzo J, Khatua TN, et al. Circadian Influences on Myocardial Ischemia-Reperfusion Injury and Heart Failure. Circ Res 2024;134(6):675-694.