title: Platelet mitochondrial dysfunction in critically ill patients: comparison between sepsis and cardiogenic shock.
abstract: BACKGROUND
  Platelet mitochondrial respiratory chain enzymes (that produce energy) are variably inhibited during human sepsis. Whether these changes occur even during other acute critical illness or are associated with impaired platelet aggregation and secretion (that consume energy) is not known. The aims of this study were firstly to compare platelet mitochondrial respiratory chain enzymes activity between patients with sepsis and those with cardiogenic shock, and secondly to study the relationship between platelet mitochondrial respiratory chain enzymes activity and platelet responsiveness to (exogenous) agonists in patients with sepsis.
  
  
  METHODS
  This was a prospective, observational, case-control study. Platelets were isolated from venous blood of 16 patients with severe sepsis or septic shock (free from antiplatelet drugs) and 16 others with cardiogenic shock, within 48 hours from admission to Intensive Care. Platelet mitochondrial respiratory chain enzymes activity was measured with spectrophotometry and expressed relative to citrate synthase activity, a marker of mitochondrial density. Platelet aggregation and secretion in response to adenosine di-phosphate (ADP), collagen, U46619 and thrombin receptor activating peptide were measured with lumiaggregometry only in patients with sepsis. In total, 16 healthy volunteers acted as controls for both spectrophotometry and lumiaggregometry.
  
  
  RESULTS
  Platelets of patients with sepsis or cardiogenic shock similarly had lower mitochondrial nicotinamide adenine dinucleotide dehydrogenase (NADH) (P < 0.001), complex I (P = 0.006), complex I and III (P < 0.001) and complex IV (P < 0.001) activity than those of controls. Platelets of patients with sepsis were generally hypo-responsive to exogenous agonists, both in terms of maximal aggregation (P < 0.001) and secretion (P < 0.05). Lower mitochondrial NADH (R (2) 0.36; P < 0.001), complex I (R (2) 0.38; P < 0.001), complex I and III (R (2) 0.27; P = 0.002) and complex IV (R (2) 0.43; P < 0.001) activity was associated with lower first wave of aggregation with ADP.
  
  
  CONCLUSIONS
  Several platelet mitochondrial respiratory chain enzymes are similarly inhibited during human sepsis and cardiogenic shock. In patients with sepsis, mitochondrial dysfunction is associated with general platelet hypo-responsiveness to exogenous agonists.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00541827 . Registered 8 October 2007.
authors.affiliation: U.O. Terapia Intensiva 'Emma Vecla', Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, via F.sco Sforza 35, 20100, Milan, Italy. alessandro.protti@policlinico.mi.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Protti
authors.affiliation: U.O. Neurologia - Centro Dino Ferrari, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, via F.sco Sforza 35, 20100, Milan, Italy. francesco.fortunato@unimi.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Fortunato
authors.affiliation: Centro Emofilia e Trombosi Angelo Bianchi Bonomi, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, via F.sco Sforza 35, 20100, Milan, Italy. andrea.artoni@policlinico.mi.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Artoni
authors.affiliation: Centro Emofilia e Trombosi Angelo Bianchi Bonomi, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, via F.sco Sforza 35, 20100, Milan, Italy. anna.lecchi@policlinico.mi.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Lecchi
authors.affiliation: Centro Emofilia e Trombosi Angelo Bianchi Bonomi, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, via F.sco Sforza 35, 20100, Milan, Italy. giovanna.motta@policlinico.mi.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Motta
authors.affiliation: U.O. Anestesia e Rianimazione, A.O. San Paolo, Università degli Studi di Milano, via A. Di Rudinì 8, 20100, Milan, Italy. giovanni.mistraletti@unimi.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mistraletti
authors.affiliation: Laboratorio Centrale di Analisi Chimico Cliniche e Microbiologia, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, via F.sco Sforza 35, 20100, Milan, Italy. cristina.novembrino@policlinico.mi.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Novembrino
authors.affiliation: U.O. Neurologia - Centro Dino Ferrari, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, via F.sco Sforza 35, 20100, Milan, Italy. giacomo.comi@unimi.it.
authors.forename: Giacomo Pietro
authors.initials: GP
authors.lastname: Comi
authors.affiliation: U.O. Terapia Intensiva 'Emma Vecla', Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, via F.sco Sforza 35, 20100, Milan, Italy. gattinon@policlinico.mi.it.
authors.forename: Luciano
authors.initials: L
authors.lastname: Gattinoni
mesh_terms: D001792:Blood Platelets / Q000166:cytology / Q000201:enzymology*; D016638:Critical Illness; D004579:Electron Transport / Q000502:physiology; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D010974:Platelet Aggregation / Q000502:physiology*; D011446:Prospective Studies; D018805:Sepsis / Q000378:metabolism*; D012770:Shock, Cardiogenic / Q000378:metabolism*
chemical_list: D045222:Electron Transport Chain Complex Proteins