title: Adaptation of external counterpulsation based on individual shear rate therapy improves endothelial function and claudication distance in peripheral artery disease.
abstract: BACKGROUND
  External counterpulsation therapy enhances blood flow and was shown to improve endothelial function and quality of life in coronary artery disease patients. However, high pressures of up to 300 mmHg may lead to malperfusion of the ischaemic limb. To improve the clinical outcome of patients with peripheral artery disease (PAD), we adjusted external counterpulsation and developed a novel non-invasive approach termed individual shear rate therapy (ISRT).
  
  
  METHODS
  In the present study, 14 patients with a Fontaine stage IIb and femoral-popliteal PAD underwent 30 hours of ISRT over 5 weeks. For ISRT, individual treatment pressures that do not exceed 160 mmHg were assessed by Doppler flow parameters during counterpulsation (individual shear rate diagnosis) in order to enhance and maximise peripheral perfusion. The study aimed to enhance peripheral perfusion and evaluate the primary clinical endpoint endothelial function, as well as to perform preliminary analysis of the ankle brachial index (ABI) and walking distance.
  
  
  RESULTS
  Doppler flow measurements in the lower limb (ankle) validated that maximum blood flow velocity during systole and acceleration doubled during ISRT. Study results demonstrated that long-term ISRT significantly increased flow-mediated dilation (FMD) in the brachial artery (0.13+/- 0.09 mm to 0.38+/- 0.05 mm; p < 0.05), while nitromediated dilation (0.36+/- 0.10 mm to 0.45+/- 0.08 mm) remained and common femoral artery FMD did not reach statistical significance (0.38+/- 0.08 mm to 0.67+/- 0.19 mm; p<0.05). Initial claudication distance considerably improved for all patients after 30 hours of ISRT (92.6 +/- 8.2 metres to 280+/- 101.3 metres, p<0.05), just like the absolute claudication distance, which showed a more than 2.5-fold increase (167.8+/- 18.1 metres to 446.7+/- 133.3 metres; p<0.05). The ABI did not improve (0.58+/- 0.03 to 0.65+/- 0.04).
  
  
  CONCLUSIONS
  Our data demonstrate that long-term ISRT is a potential novel non-invasive treatment to improve endothelial function and absolute pain-free walking distance for PAD patients.
authors.affiliation: 1 , Department for Angiology, Brandenburg/ Havel, Germany.|3 Department of Physiology, Charité Benjamin Franklin Berlin, Germany.
authors.forename: Eva-Elina
authors.initials: EE
authors.lastname: Buschmann
authors.affiliation: 2 Richard-Thoma Laboratories for Arteriogenesis, Experimental and Clinical Research Center (ECRC), Center for Cardiovascular Research (CCR), Charité Universitaetsmedizin Berlin, Germany.
authors.forename: Michele
authors.initials: M
authors.lastname: Brix
authors.affiliation: 1 , Department for Angiology, Brandenburg/ Havel, Germany.|2 Richard-Thoma Laboratories for Arteriogenesis, Experimental and Clinical Research Center (ECRC), Center for Cardiovascular Research (CCR), Charité Universitaetsmedizin Berlin, Germany.
authors.forename: Lulu
authors.initials: L
authors.lastname: Li
authors.affiliation: 2 Richard-Thoma Laboratories for Arteriogenesis, Experimental and Clinical Research Center (ECRC), Center for Cardiovascular Research (CCR), Charité Universitaetsmedizin Berlin, Germany.|4 Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité Universitaetsmedizin Berlin, Germany and Institute of Chemistry and Biochemistry, FU Berlin, Germany.
authors.forename: Janke
authors.initials: J
authors.lastname: Doreen
authors.affiliation: 2 Richard-Thoma Laboratories for Arteriogenesis, Experimental and Clinical Research Center (ECRC), Center for Cardiovascular Research (CCR), Charité Universitaetsmedizin Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zietzer
authors.affiliation: 2 Richard-Thoma Laboratories for Arteriogenesis, Experimental and Clinical Research Center (ECRC), Center for Cardiovascular Research (CCR), Charité Universitaetsmedizin Berlin, Germany.
authors.forename: Meijing
authors.initials: M
authors.lastname: Li
authors.affiliation: 1 , Department for Angiology, Brandenburg/ Havel, Germany.|2 Richard-Thoma Laboratories for Arteriogenesis, Experimental and Clinical Research Center (ECRC), Center for Cardiovascular Research (CCR), Charité Universitaetsmedizin Berlin, Germany.
authors.forename: Ivo
authors.initials: I
authors.lastname: Buschmann
authors.affiliation: 1 , Department for Angiology, Brandenburg/ Havel, Germany.|2 Richard-Thoma Laboratories for Arteriogenesis, Experimental and Clinical Research Center (ECRC), Center for Cardiovascular Research (CCR), Charité Universitaetsmedizin Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Hillmeister
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001783:Blood Flow Velocity / Q000502:physiology*; D001916:Brachial Artery / Q000000981:diagnostic imaging; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D048228:Intermittent Pneumatic Compression Devices; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000503:physiopathology / Q000628:therapy*; D018608:Ultrasonography, Doppler
keywords: Peripheral artery disease; ankle brachial index; arteriogenesis; counterpulsation; endothelium; exercise; fluid shear stress; individual shear rate therapy; intermittent pneumatic compression devices