Professor Wolfram Doehner, M.D., Ph.D.

Research Group Döhner

Professor Wolfram Doehner, M.D., Ph.D.
Charité, Center for Stroke Research Berlin
Interdiscplinary stroke research
wolfram.doehner(at)charite.de

Profile

Dr. Doehner is professor for interdisciplinary stroke research at the CSB. He is also a cardiologist, specialist for internal medicine and for nutritional medicine, and is associated scientist with the Department of Cardiology at the Charité (Campus Virchow). In his clinical work, cardiovascular knowledge is linked with stroke acute therapy and rehabilitation. His research is focused on metabolic pathophysiology in chronic disease contributing to peripheral tissue wasting, muscle loss, sarcopenia and cachexia.

Wolfram Döhner coordinates the Study Group on Heart and Brain Interaction in Patients with Heart Failure of the European Association of Heart Failure (HFA). He is Vice Chair (2016-2018) or Chair (2018-2020) of the European Society of Cardiology's Council on Stroke Board.

List of Publications / Charité Research Data Base

Selected Publications

Joint statement of the European Association for the Study of Obesity and the European Society of Hypertension: obesity and heart failure.
Jordan J, Toplak H, Grassi G, Yumuk V, Kotsis V, Engeli S, Cuspidi C, Nilsson PM, Finer N, Doehner W.
J Hypertens. 2016 Sep;34(9):1678-88. doi: 10.1097/HJH.0000000000001013.
PMID:27488547

Evaluation of C-terminal Agrin Fragment as a marker of muscle wasting in patients after acute stroke during early rehabilitation.
Scherbakov N, Knops M, Ebner N, Valentova M, Sandek A, Grittner U, Dahinden P, Hettwer S, Schefold JC, von Haehling S, Anker SD, Joebges M, Doehner W.
J Cachexia Sarcopenia Muscle. 2016 Mar;7(1):60-7. doi: 10.1002/jcsm.12068.
PMID:27066319

Influence of essential amino acids on muscle mass and muscle strength in patients with cerebral stroke during early rehabilitation: protocol and rationale of a randomized clinical trial (AMINO-Stroke Study).
Scherbakov N, Ebner N, Sandek A, Meisel A, Haeusler KG, von Haehling S, Anker SD, Dirnagl U, Joebges M, Doehner W.
BMC Neurol. 2016 Jan 22;16:10. doi: 10.1186/s12883-016-0531-5.
PMID:26793971

Protective overweight in cardiovascular disease: moving from 'paradox' to 'paradigm'.
Doehner W, von Haehling S, Anker SD.
Eur Heart J. 2015 Oct 21;36(40):2729-32. doi: 10.1093/eurheartj/ehv414. No abstract available.
PMID:26341892

Stroke-related sarcopenia: specific characteristics.
Scherbakov N, Sandek A, Doehner W.
J Am Med Dir Assoc. 2015 Apr;16(4):272-6. doi: 10.1016/j.jamda.2014.12.007. Review.
PMID:25676847

Catabolic signaling and muscle wasting after acute ischemic stroke in mice: indication for a stroke-specific sarcopenia.
Springer J, Schust S, Peske K, Tschirner A, Rex A, Engel O, Scherbakov N, Meisel A, von Haehling S, Boschmann M, Anker SD, Dirnagl U, Doehner W.
Stroke. 2014 Dec;45(12):3675-83. doi: 10.1161/STROKEAHA.114.006258.
PMID:25352483

Stroke induced Sarcopenia: muscle wasting and disability after stroke.
Scherbakov N, von Haehling S, Anker SD, Dirnagl U, Doehner W.
Int J Cardiol. 2013 Dec 10;170(2):89-94. doi: 10.1016/j.ijcard.2013.10.031. Review.
PMID:24231058

Impetus

Loss of skeletal muscle, sarcopenia, is a major yet understudied complication after stroke. The skeletal muscle is the main effector organ accountable for disability in stroke (60% of patients remain with some physical disablement). However, a surprising paucity of data exists for structural, metabolic or functional changes in muscle tissue after stroke, as disability is traditionally attributed to the brain injury itself. Changes in muscle tissue start as early as 4 hours after cerebral infarction, and a complex interaction between denervation, disuse, inflammation, remodeling and spasticity accounts for a phenotypical pattern that we have addressed as stroke-specific sarcopenia.

Importantly, studies from our group and from others show that the wasting of muscle tissue is not limited to the affected paralytic limb. Indeed, a global effect of catabolic over-activation and anabolic blunting affects all skeletal muscles and even the myocardium. As a result, the functional impairment of patients after stroke is not only driven by the paralytic motoric disablement but is further aggravated by the global decrease of muscle tissue. Any effort to prevent and/or reverse such muscle wasting may improve functional capacity and will help to regain physical independence.

Currently, stroke-related muscle wasting (sarcopenia) is not recognized in the guide-lines for stroke therapy and rehabilitation. The lack of sufficient evidence on post-stroke muscle pathology, tissue degradation and metabolic and functional impairment needs to be addressed in an interdisciplinary integrated approach. Innovative interventional approaches to prevent or attenuate muscle atrophy and sarcopenia will support patient rehabilitation and improve long-term outcome.  

Most Important Project

Prevent complications

AMINO-Stroke - Effect of Essential Amino Acids on Muscle Size and Strength in Patients with Acute Ischemic Stroke during Rehabilitation

This study assess the effect of essential amino acid supplementation on muscle wasting, muscle strength, mobility, and self-dependence in patients during rehabilitation after acute stroke.
More information/project description

Further Projects

Muscle Functional and Metabolic Changes in Patients during Rehabilitation
Rehabilitation efforts after stroke aim to restore functional capacity and independence in everyday life. We investigate muscle structural, metabolic and functional changes in stroke patients during hospitalized rehabilitation periods.

Local Activation of Skeletal Muscle Apoptosis after Stroke in a Stroke Model
Direct signaling and specific stroke-induced muscle changes are investigated in a mouse model of stroke (MCAO). Early results indicate direct time-dependent signals towards increased protein degradation and apoptotic activity in relation to cerebral infarction size and degree of denervation. Pathways of proteolytic signaling and apoptosis and specific treatments to inhibit these effects are being tested.

WAKOS
Patients with Persistent Vegetative State are studied in longitudinal observational studies (WAKOS) to investigate the change in metabolic balance and to monitor the body composition relating to the course of the disease, and complications such as infections.

SECURE
Professor Doehner is the national PI of the SECURE project, an EU-funded (HORIZON 2020) multinational controlled interventional trial to study the efficacy of a polypill over current standards of care in patients with advanced cardiovascular disease after myocardial infarction.

METRIS HF
Clinical randomized controlled trial (IIT) to investigate the metabolic effect of metformin in patients with heart failure and insulin resistance (non-diabetes mellitus) on performance, myocardial function and metabolism. The study is funded by the German Centre for Cardiovascular Research (DZHK) as part of the study program for early clinical trials.

Team

Melanie Heigl (project manager)
Anja Kresse (study nurse)
Dr. Antje Meyer (clinical scientist and project coordinator)
Nancy Neumann (technician and master student)
Dr. Dr. med. Nadja Scherbakov (clinical scientist)
Azadeh Shafieesabet (clinical research fellow)  
Kathleen Weigt (project coordinator)

Higher degree students
Several MD Students, Master Students, DAAD Students  

Research Fields

  • Interdisciplinary complications in stroke
  • Metabolic regulation in acute and chronic disease and during rehabilitation
  • Muscle metabolism and function in stroke and post stroke rehabilitation
  • Cachexia, sarcopenia and frailty in disease, in rehabilitation and in in the elderly
  • insulin resistance, energy metabolism, xanthine oxidase metabolism in cardiovascular disease
  • peripheral vascular (endothelium) function
  • clinical proof-of concept trials on metabolic interventions in patients with cardiovascular disease   

Methods

Clinical and experimental studies are performed with a wide range of pathophysiologic and functional tests and methods. 
Observational (cross sectional and longitudinal) as well as interventional studies are included to test novel therapeutic concepts in proof-of-concept trials (AMINOS, IRIS-HF, UDCA-HF, Allopurinol in HF, Leucopene in HF). Metabolic, hormonal and immunological characterization will be performed on a whole body and systemic level, as well as on tissue interstitial and on intra cellular levels. Functional assessment of vascular reactivity (endothelium function), muscle function (strength, fatigability) and metabolism (energy expenditure, skeletal muscle insulin sensitivity), cardiovascular stress response, and respiratory and exercise capacity are established methods with a long-standing experience. 

Clinical methods

Body compositionDual Energy X-ray Absorptiometry (DEXA Scan) and Bio impedance to assess total and regional tissue distribution of fat and lean tissue.
Peripheral blood flowocclusion plethysmography
Endothelium functionreactive hyperaemia assessment (EndoPAT)
Muscle strengthHandgrip, finger press, knee extension tests, cycling (MOTOMED), treadmill, maximum isometric quadriceps muscle strength, fatigability protocol
Physical functionShort physical performance battery test, 6 min walking test
Whole body insulin sensitivityby intravenous glucose tolerance testing and minimal modelling, short insulin sensitivity test, HOMA
Interstitial tissue metabolitesmicrodialysis in muscle and fat tissue
Energy expenditureindirect calorimetry
Tissue analysesThrokar biopsy methods for muscle and fat tissue.
Clinical cardiovascular testsEchocardiography, 24h ECG recording, Spiroergometric exercise testing, non-invasive cardiac output


Experimental studies
include a number of animal models  (MCAO Reperfusion, Hepatoma tumour model, Heart failure model). Pathophysiologic tests in animal models include body composition (NMR spectroscopy) indirect calorimetric testing, 24 h activity monitoring, Echocardiography. These studies are performed in cooperation with the Dept. of Experimental neurology and the Center of Cardiovascular Research (CCR).    

Collaborations and partners

Colaborations within the Charite

  • Functional / metabolic profile in CFS patients and  effect of immune modulation therapy. Cooperation with the Department of medical immunology (Prof. C Scheibenbogen)  
  • Metabolic studies investigating comorbidities in heart Failure (SICA-HF FP7 Project, agreement No 241558)
  • Collaboration with the Department of Cardiology, Virchow Hospital  
  • Studies on micronutrients in patients with cardiovascular hospitalization Collaboration with the Department of experimental endocrinology (Prof. Schomburg). 

International collaborating partners include

  • University Wroclaw, Poland (Prof. P. Ponikowski, Prof. E Jankowska) University Hull (Prof. Cleland)
  • IRCCS San Raffaele Pisana, Rome, Italy (Prof. G Rosano)
  • University Golnik, Slovenia  (Prof. M Lainscak)
  • University of Warwick, UK (Prof. A Coats)
  • University of Moscow, Russia (Prof. V Tkachuk)
  • University St.-Petersburg, Russia (Prof. Shlyakhto, Prof. A. Zaritskey ) University Madrid, Spain (Prof.  J Castellano, Prof. V Fuster)
  • University Umea, Sweden (Prof. M Henein)

Contributions to various clincal projects within the CSB

  • COSBID
  • DISCHARGE
  • INSPIRE
  • Stroke Unit Plus
  • HEBRAS

 

 

Education and Teaching

  • Master Studiengang Cerebrovasculäre Medizin
  • Bachelor Studiengang der Universität Potsdam (DIfE)  für Ernährungswissenschaften
  • Online education program der European Heart Failure Association
  • Betreuung von Promotionsstudenten in verschiedenen Studiengängen (Dr med, Dr med vet. und Masterstudenten für Ernährungswissenschaften
  • Regelmäßige Einladungen zu Weiterbildungsvorträgen in zahlreichen Kliniken (z.B. Universität Rostock, Medizinische Hochschule Hannover, Universität Münster, Universität Dresden, Kliniken Esslingen, Halle, Heidelberg)
  • Co-Autorenschaft bei mehreren Lehrbüchern

Funding

  • EU (SICA-HF, FP7)
  • Bundesministerium für Bildung und Forschung
  • Deutsches Zentrum für Herz Kreislaufforschung
  • Deutscher Akademischer Austauschdienst
  • Hannelore Kohl Stiftung
  • Brandenburgklinik Bernau
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