Frasch, Martin G

Giussani, Dino A

EClinicalMedicine

English

PubMed

Apollo (Cambridge)

EClinicalMedicine 37 (2021) 100994Contents lists available at ScienceDirectEClinicalMedicinejournal homepage: https://www.journals.elsevier.com/eclinicalmedicineCommentaryHeart during acidosis: Etiology and early detection of cardiac dysfunctionMartin G. Frascha,*, Dino A. GiussanibaDepartment of Obstetrics and Gynecology and Center on Human Development and Disability (CHDD), University of Washigton School of Medicine,Seattle, WA, USAb Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, UKA R T I C L E I N F OArticle History:Received 1 June 2021Revised 2 June 2021Accepted 7 June 2021Commentary on “Systemic Acidemia Impairs Cardiac Function inCritically Ill Patients" by Rodrigez-Villar et al. (EClinical Medicine,2021)Physiology can inform and help transform clinical practice. Inturn, clinical practice demands physiological mechanisms to deter-mine intervention and treatment. And so the spiral of fresh scientificdiscovery and its clinical application goes on.Lactic acidosis is a common adverse finding in the critically illpatient. Physiological studies in preclinical animal models have longestablished that systemic acidemia can impair cardiovascular func-tion, weakening cardiac contractility and reducing peripheral vascu-lar reactivity to constrictor agonists [1]. However, underlyingmechanisms have not been delineated, particularly in humans. Ofgreater importance, no human clinical trial until the work by Rodri-gez-Villar et al. published in this issue of EClinicalMedicine [2] hadestablished a threshold arterial pH, below which cardiac functionbecomes compromised. This commendable and difficult-to-executestudy not only confirms a negative relationship between arterial pHand cardiac dysfunction in humans, but it demands questions withpotential answers that have the power to transform the clinical man-agement of patients with severe acidemia, such as those sufferingfrom septic shock or cardiac arrest. What is so critical about a thresh-old arterial pH of 7.28 below which cardiac function deteriorates?What is the underlying physiological mechanism linking acidemiaand cardiac dysfunction in humans? Is acidemia a cause or effect ofcardiac dysfunction in critically ill men and women? Can respiratoryversus metabolic acidosis differentially affect cardiac function? Whatis the best therapy for normalising pH and is there a statistical rela-tionship between buffering pH and improved cardiac function in theICU patient?DOI of original article: http://dx.doi.org/10.1016/j.eclinm.2021.100956.* Corresponding author.E-mail address:mfrasch@uw.edu (M.G. Frasch).https://doi.org/10.1016/j.eclinm.2021.1009942589-5370/© 2021 Published by Elsevier Ltd. This is an open access article under the CC BY-NHow acidemia affects cardiovascular function during fetal life beforebirth has also been an area of intense scientific interest for many years,largely because it is a common outcome of labour and delivery [3]. Dur-ing labour, compression of the umbilical cord can lead to fetal hypoxiaand trigger a carotid chemoreflex that reduces heart rate and redistrib-utes cardiac output away from peripheral circulations towards the fetalbrain, the so-called fetal brain sparing response [4,5]. Lactic acidemia inthe fetus results from the anaerobic metabolism of glucose in tissues,particularly in those undergoing peripheral vasoconstriction as a resultof the fetal brain-sparing reflex [6]. A study in late gestation, mature,fetal sheep showed that acidemia enhanced the magnitude of the fetalcardiovascular and endocrine defences to acute stress, but it reversedthe increase in umbilical vascular conductance to vasoconstriction, dur-ing an episode of acute hypoxia. Therefore, it is clear that acidemia infetal as well as adult life can significantly impact cardiovascular func-tion, however underlying mechanisms remain to be fully explored. It isalso clear that, whether in fetal or adult life, acidemia rarely occurs inisolation, often being accompanied by altered arterial blood gas statusand increased levels of stress hormones in the circulation. If this is thecase, then how can the clinician detect incipient cardiac decompensa-tion either during complicated labour in the fetus or in the ICU settingin the critically ill to offer life-saving interventions such as ECMO [7]?This challenge has been tackled recently in preclinical studies where amachine learning algorithm leveraging continuous heart rate data hasenabled more precise, individualized medicine with real-time predic-tion of cardiovascular decompensation [8].Interestingly, the study of Rodrigez-Villar et al. does not present real-time cardiovascular data in the patients, such as the electrocardiogram(ECG) and arterial blood pressure (ABP), because these cardiovascularoutcomes were not accessible to the researchers. This can no longer bethe status quo in 21st century medicine. Hospitals spend considerableresources to be able to afford real-time monitoring of such indispens-able physiological data in the ICU setting. Patients enrolled in the studyhave the right to these data, yet clinicians are often unable to access theraw data to conduct the critical clinical analysis. In light of the growingmass of evidence that unequivocally supports that access to such datacan transform clinical care, this situation needs to change. Access to ECGand ABP in-depth data analysis would enable the development of real-time prediction of cardiovascular decompensation. In turn, this wouldlead to earlier interventions, reducing morbidity and mortality. There-fore, we call upon themanufacturers of the clinical ICUmonitoring devi-ces to remove their silos around accessing cardiovascular raw data.Doing so would boost badly needed clinical research and algorithmC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)2 M.G. Frasch and D.A. Giussani / EClinicalMedicine 37 (2021) 100994development, both of which have the potential to help save thousandsof lives.Declaration of Competing InterestM. G. Frasch has patents on aECG (WO2018160890) and EEG tech-nologies for fetal monitoring (US9215999). The authors declare thatthe research was conducted in the absence of any other commercialor financial relationships that could be construed as a potential con-flict of interest.References[1] Levy B, Collin S, Sennoun N, et al. Vascular hyporesponsiveness to vasopressors inseptic shock: from bench to bedside. Intensive Care Med 2010;36:2019–29.[2] Rodríguez-Villar S, Kraut JA, Arevalo-Serrano J, et al. Systemic acidemia impairscardiac function in critically Ill patients. EClin Med 2021. doi: 10.1016/j.eclinm.2021.100956.[3] Li X, Xu Y, Herry C, et al. Sampling frequency of fetal heart rate impacts the abilityto predict pH and BE at birth: a retrospective multi-cohort study. Physiol Meas2015;36:L1–12.[4] Giussani DA, Spencer JA, Moore PJ, Bennet L, Hanson MA. Afferent and efferentcomponents of the cardiovascular reflex responses to acute hypoxia in term fetalsheep. J Physiol 1993;461:431–49.[5] Lear CA, Wassink G, Westgate JA, et al. The peripheral chemoreflex: indefatigableguardian of fetal physiological adaptation to labour. J Physiol 2018;596:5611–23.[6] Giussani DA. The fetal brain sparing response to hypoxia: physiological mecha-nisms. J Physiol 2016;594:1215–30.[7] Brechot N, Hajage D, Kimmoun A, et al. Venoarterial extracorporeal membraneoxygenation to rescue sepsis-induced cardiogenic shock: a retrospective, multi-centre, international cohort study. Lancet 2020;396:545–52.[8] Gold N, Herry C, Wang X, Frasch M. Fetal cardiovascular decompensation duringlabor predicted from the individual heart rate tracing: a machine learningapproach in a near-term fetal sheep model. Front Pediatr 2021;9:355.

Heart during acidosis: Etiology and early detection of cardiac dysfunction.

Martin G. Frasch

Dino A. Giussani

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Heart during acidosis: Etiology and early detection of cardiac dysfunction

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Heart during acidosis: Etiology and early detection of cardiac dysfunction.

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