{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T01:33:49Z","timestamp":1775093629579,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Resuscitec GmbH, Freiburg, Germany"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: Based on extracorporeal circulation, targeted reperfusion strategies have been developed to improve survival and neurologic recovery in refractory cardiac arrest: Controlled Automated Reperfusion of the whoLe Body (CARL). Furthermore, animal and human cadaver studies have shown beneficial effects on cerebral pressure due to head elevation during conventional cardiopulmonary resuscitation. Our aim was to evaluate the impact of head elevation on survival, neurologic recovery and histopathologic outcome in addition to CARL in an animal model. Methods: After 20 min of ventricular fibrillation, 46 domestic pigs underwent CARL, including high, pulsatile extracorporeal blood flow, pH\u2013stat acid\u2013base management, priming with a colloid, mannitol and citrate, targeted oxygen, carbon dioxide and blood pressure management, rapid cooling and slow rewarming. N = 25 were head-up (HUP) during CARL, and N = 21 were supine (SUP). After weaning from ECC, the pigs were extubated and followed up in the animal care facility for up to seven days. Neuronal density was evaluated in neurohistopathology. Results: More animals in the HUP group survived and achieved a favorable neurological recovery, 21\/25 (84%) versus 6\/21 (29%) in the SUP group. Head positioning was an independent factor in neurologically favorable survival (p &lt; 0.00012). Neurohistopathology showed no significant structural differences between HUP and SUP. Distinct, partly transient clinical neurologic deficits were blindness and ataxia. Conclusions: Head elevation during CARL after 20 min of cardiac arrest independently improved survival and neurologic outcome in pigs. Clinical follow-up revealed transient neurologic deficits potentially attributable to functions localized in the posterior perfusion area, whereas histopathologic findings did not show corresponding differences between the groups. A possible explanation of our findings may be venous congestion and edema as modifiable contributing factors of neurologic injury following prolonged cardiac arrest.<\/jats:p>","DOI":"10.3390\/jcm12227054","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T02:46:47Z","timestamp":1699843607000},"page":"7054","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Impact of Head Position on Neurological and Histopathological Outcome Following Controlled Automated Reperfusion of the Whole Body (CARL) in a Pig Model"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5945-198X","authenticated-orcid":false,"given":"Domagoj","family":"Damjanovic","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6882-2009","authenticated-orcid":false,"given":"Jan-Steffen","family":"Pooth","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yechi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabienne","family":"Frensch","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Wolkewitz","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Statistics, Division Methods in Clinical Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, D-79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joerg","family":"Haberstroh","sequence":"additional","affiliation":[{"name":"Experimental Surgery, Center for Experimental Models and Transgenic Service, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 66, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soroush","family":"Doostkam","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Breisacherstr. 64, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi Ramona","family":"Cristina Schmitz","sequence":"additional","affiliation":[{"name":"Experimental Surgery, Center for Experimental Models and Transgenic Service, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 66, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Foerster","sequence":"additional","affiliation":[{"name":"Center for Experimental Models and Transgenic Service, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Stefan-Meier-Str. 17, D-79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9904-9757","authenticated-orcid":false,"given":"Itumeleng","family":"Taunyane","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tabea","family":"Neubert","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Scherer","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patric","family":"Diel","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Benk","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2975-2751","authenticated-orcid":false,"given":"Friedhelm","family":"Beyersdorf","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5664-8971","authenticated-orcid":false,"given":"Georg","family":"Trummer","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, D-79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.resuscitation.2017.05.024","article-title":"Prevalence, natural history, and time-dependent outcomes of a multi-center North American cohort of out-of-hospital cardiac arrest extracorporeal CPR candidates","volume":"117","author":"Reynolds","year":"2017","journal-title":"Resuscitation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13049-017-0440-7","article-title":"Neurological outcomes and duration from cardiac arrest to the initiation of extracorporeal membrane oxygenation in patients with out-of-hospital cardiac arrest: A retrospective study","volume":"25","author":"Yukawa","year":"2017","journal-title":"Scand. J. Trauma Resusc. Emerg. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1161\/CIRCULATIONAHA.113.002408","article-title":"Duration of resuscitation efforts and functional outcome after out-of-hospital cardiac arrest: When should we change to novel therapies?","volume":"128","author":"Reynolds","year":"2013","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1017\/cem.2016.8","article-title":"Potential Candidates for a Structured Canadian ECPR Program for Out-of-Hospital Cardiac Arrest","volume":"18","author":"Grunau","year":"2016","journal-title":"CJEM"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e003732","DOI":"10.1161\/JAHA.116.003732","article-title":"Minnesota Resuscitation Consortium\u2019s Advanced Perfusion and Reperfusion Cardiac Life Support Strategy for Out-of-Hospital Refractory Ventricular Fibrillation","volume":"5","author":"Yannopoulos","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.resuscitation.2016.10.029","article-title":"Outcomes of sudden cardiac arrest in a state-wide integrated resuscitation program: Results from the Minnesota Resuscitation Consortium","volume":"110","author":"Adabag","year":"2017","journal-title":"Resuscitation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.resuscitation.2017.08.014","article-title":"Improving trend in ventricular fibrillation\/pulseless ventricular tachycardia out-of-hospital cardiac arrest in Rochester, Minnesota: A 26-year observational study from 1991 to 2016","volume":"120","author":"Okubo","year":"2017","journal-title":"Resuscitation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.resuscitation.2014.09.010","article-title":"Refractory cardiac arrest treated with mechanical CPR, hypothermia, ECMO and early reperfusion (the CHEER trial)","volume":"86","author":"Stub","year":"2015","journal-title":"Resuscitation"},{"key":"ref_9","first-page":"163","article-title":"Hyperinvasive approach to out-of hospital cardiac arrest using mechanical chest compression device, prehospital intraarrest cooling, extracorporeal life support and early invasive assessment compared to standard of care. A randomized parallel groups comparative study proposal","volume":"10","author":"Belohlavek","year":"2012","journal-title":"Prague OHCA Study J. Transl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1001\/jama.2022.1025","article-title":"Effect of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment on Functional Neurologic Outcome in Refractory Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial","volume":"327","author":"Belohlavek","year":"2022","journal-title":"JAMA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1093\/ejcts\/ezw186","article-title":"Preserved brain morphology after controlled automated reperfusion of the whole body following normothermic circulatory arrest time of up to 20 minutes","volume":"50","author":"Taunyane","year":"2016","journal-title":"Eur. J. Cardio-Thorac. Surg. Off. J. Eur. Assoc. Cardio-Thorac. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1177\/0267659117742478","article-title":"Twenty minutes of normothermic cardiac arrest in a pig model: The role of short-term hypothermia for neurological outcome","volume":"33","author":"Foerster","year":"2018","journal-title":"Perfusion"},{"key":"ref_13","first-page":"1299","article-title":"Management of Intracranial Pressure","volume":"21","author":"Freeman","year":"2015","journal-title":"Contin. Minneap. Minn."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.resuscitation.2016.01.033","article-title":"The Effect of Head Up Cardiopulmonary Resuscitation on Cerebral and Systemic Hemodynamics","volume":"102","author":"Ryu","year":"2016","journal-title":"Resuscitation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.resuscitation.2018.04.009","article-title":"Consistent head up cardiopulmonary resuscitation haemodynamics are observed across porcine and human cadaver translational models","volume":"132","author":"Moore","year":"2018","journal-title":"Resuscitation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.resuscitation.2020.09.030","article-title":"Controlled sequential elevation of the head and thorax combined with active compression decompression cardiopulmonary resuscitation and an impedance threshold device improves neurological survival in a porcine model of cardiac arrest","volume":"158","author":"Moore","year":"2021","journal-title":"Resuscitation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1177\/02676591211073779","article-title":"Limiting calcium overload after cardiac arrest: The role of human albumin in controlled automated reperfusion of the whole body","volume":"38","author":"Pooth","year":"2023","journal-title":"Perfusion"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Brixius, S.J., Pooth, J.-S., Haberstroh, J., Damjanovic, D., Scherer, C., Greiner, P., Benk, C., Beyersdorf, F., and Trummer, G. (2022). Beneficial Effects of Adjusted Perfusion and Defibrillation Strategies on Rhythm Control within Controlled Automated Reperfusion of the Whole Body (CARL) for Refractory Out-of-Hospital Cardiac Arrest. J. Clin. Med., 11.","DOI":"10.3390\/jcm11082111"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.xjon.2021.10.006","article-title":"Application of cardiac surgery techniques to improve the results of cardiopulmonary resuscitation after cardiac arrest: Controlled automated reperfusion of the whole body","volume":"8","author":"Beyersdorf","year":"2021","journal-title":"JTCVS Open"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/j.resuscitation.2010.07.005","article-title":"Distribution of neuropathological lesions in pig brains after different durations of cardiac arrest","volume":"81","author":"Sterz","year":"2010","journal-title":"Resuscitation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.resuscitation.2014.11.019","article-title":"Tilting for perfusion: Head-up position during cardiopulmonary resuscitation improves brain flow in a porcine model of cardiac arrest","volume":"87","author":"Debaty","year":"2015","journal-title":"Resuscitation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.resuscitation.2017.02.008","article-title":"The effect of resuscitation position on cerebral and coronary perfusion pressure during mechanical cardiopulmonary resuscitation in porcine cardiac arrest model","volume":"113","author":"Kim","year":"2017","journal-title":"Resuscitation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.resuscitation.2018.04.038","article-title":"Effects of head-up vs. supine CPR on cerebral oxygenation and cerebral metabolism\u2014A prospective, randomized porcine study","volume":"128","author":"Putzer","year":"2018","journal-title":"Resuscitation"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.resuscitation.2019.12.011","article-title":"Effect of controlled sequential elevation timing of the head and thorax during cardiopulmonary resuscitation on cerebral perfusion pressures in a porcine model of cardiac arrest","volume":"149","author":"Moore","year":"2020","journal-title":"Resuscitation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1186\/s13054-021-03797-x","article-title":"The effect of the head-up position on cardiopulmonary resuscitation: A systematic review and meta-analysis","volume":"25","author":"Huang","year":"2021","journal-title":"Crit. Care"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e644","DOI":"10.1002\/hsr2.644","article-title":"Efficacy of heads-up CPR compared to supine CPR positions: Systematic review and meta-analysis","volume":"5","author":"Varney","year":"2022","journal-title":"Health Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"250","DOI":"10.15441\/ceem.18.060","article-title":"Worsened survival in the head-up tilt position cardiopulmonary resuscitation in a porcine cardiac arrest model","volume":"6","author":"Park","year":"2019","journal-title":"Clin. Exp. Emerg. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s00134-021-06368-4","article-title":"European Resuscitation Council and European Society of Intensive Care Medicine guidelines 2021: Post-resuscitation care","volume":"47","author":"Nolan","year":"2021","journal-title":"Intensive Care Med"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Haertel, F., Babst, J., Bruening, C., Bogoviku, J., Otto, S., Fritzenwanger, M., Gecks, T., Ebelt, H., Moebius-Winkler, S., and Schulze, P.C. (2023). Effect of Hemolysis Regarding the Characterization and Prognostic Relevance of Neuron Specific Enolase (NSE) after Cardiopulmonary Resuscitation with Extracorporeal Circulation (eCPR). J. Clin. Med., 12.","DOI":"10.3390\/jcm12083015"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e022679","DOI":"10.1161\/JAHA.121.022679","article-title":"Cardiac Arrest in Pigs with 48 hours of Post-Resuscitation Care Induced by 2 Methods of Myocardial Infarction: A Methodological Description","volume":"10","author":"Vammen","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109964","DOI":"10.1016\/j.resuscitation.2023.109964","article-title":"Confounders for prognostic accuracy of neuron-specific enolase after cardiac arrest: A retrospective cohort study","volume":"192","author":"Czimmeck","year":"2023","journal-title":"Resuscitation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1097\/CCM.0000000000003608","article-title":"Confirming the Clinical Safety and Feasibility of a Bundled Methodology to Improve Cardiopulmonary Resuscitation Involving a Head-Up\/Torso-Up Chest Compression Technique","volume":"47","author":"Pepe","year":"2019","journal-title":"Crit. Care Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.resuscitation.2022.07.039","article-title":"Head and thorax elevation during cardiopulmonary resuscitation using circulatory adjuncts is associated with improved survival","volume":"179","author":"Moore","year":"2022","journal-title":"Resuscitation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.resuscitation.2021.11.008","article-title":"Faster time to automated elevation of the head and thorax during cardiopulmonary resuscitation increases the probability of return of spontaneous circulation","volume":"170","author":"Moore","year":"2022","journal-title":"Resuscitation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1016\/j.resuscitation.2018.07.058","article-title":"Beneficial effects of head-elevation during Controlled Automated Reperfusion of the WhoLe Body (CARL) in the pig model","volume":"130","author":"Damjanovic","year":"2018","journal-title":"Resuscitation"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/22\/7054\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:22:02Z","timestamp":1760131322000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/22\/7054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,13]]},"references-count":35,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["jcm12227054"],"URL":"https:\/\/doi.org\/10.3390\/jcm12227054","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,13]]}}}