title: Increased cyclic guanosine monophosphate levels and continuous-flow left-ventricular assist devices: Implications for gastrointestinal bleeding.
abstract: OBJECTIVE
  We examine the hypothesis that cyclic guanosine monophosphate (cGMP) levels are elevated in recipients of continuous-flow left ventricular assist devices (CF-LVADs) and that elevated cGMP levels are associated with a risk of gastrointestinal (GI) bleeding events.
  
  
  METHODS
  The levels of cGMP, nitric oxide, platelet activation markers, platelet-derived growth factors (PDGF) AB/BB and AA, and the inflammatory mediator C-reactive protein (CRP) were examined in 19 CF-LVAD recipients, 21 patients who had heart failure, and 19 healthy control-group participants.
  
  
  RESULTS
  The median level of cGMP was significantly higher in CF-LVAD recipients, compared with healthy participants (6.6 vs 2.1 pmol/mL, u = 62.5; P = .001; r = -0.55). Median cGMP levels in the heart failure group (12.5 pmol/L) were higher, compared with both CF-LVAD recipients (u = 75.0; P = .001; r = -0.53) and healthy participants (u = 4.0; P < .001; r = -0.83). Compared with the healthy group, median CRP levels were significantly higher in CF-LVAD recipients (2.9 vs 8.0 mg/L; u = 58.0; P < .001; r = -0.63) and heart failure patients (2.9 vs 7.0 mg/L; u = 59.0; P < .001; r = -0.65). In the subgroup of patients supported with the HeartMate II (Thoratec Corporation, Pleasanton, Calif), pulsatility index was significantly negatively correlated with cGMP levels (r = -0.73; P < .05), indicating that low pulsatility index is associated with higher cGMP levels. High cGMP levels were significantly associated with GI bleeding events, but not with bleeding events in general.
  
  
  CONCLUSIONS
  The primary finding of this study is that GI bleeding in CF-LVAD recipients is associated with significantly elevated cGMP levels, despite high levels of CRP, which interfere with cGMP production. Further studies are required to determine whether elevated cGMP levels can be used as a clinical marker for increased risk of GI bleeding in CF-LVAD recipients.
authors.affiliation: Division of Cardiovascular Surgery, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada; Department of Exercise Sciences, Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Liza
authors.initials: L
authors.lastname: Grosman-Rimon
authors.affiliation: Division of Cardiovascular Surgery, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Tumiati
authors.affiliation: Division of Cardiovascular Surgery, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Avi
authors.initials: A
authors.lastname: Fuks
authors.affiliation: Department of Exercise Sciences, Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ira
authors.initials: I
authors.lastname: Jacobs
authors.affiliation: Division of Cardiovascular Surgery, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Spencer D
authors.initials: SD
authors.lastname: Lalonde
authors.affiliation: Division of Nephrology, University Health Network, Toronto, Ontario, Canada.
authors.forename: David Z I
authors.initials: DZ
authors.lastname: Cherney
authors.affiliation: Division of Cardiovascular Surgery, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada. Electronic address: Vivek.Rao@uhn.ca.
authors.forename: Vivek
authors.initials: V
authors.lastname: Rao
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D006152:Cyclic GMP / Q000097:blood*; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D011474:Prosthesis Design; D011673:Pulsatile Flow; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D002097:C-Reactive Protein; D006152:Cyclic GMP
keywords: continuous-flow left ventricular assist device; cyclic guanosine monophosphate; gastrointestinal bleeding