Platelet mitochondrial dysfunction in critically ill patients: comparison between sepsis and cardiogenic shock

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• 作者：Alessandro Protti (1)
  Francesco Fortunato (2)
  Andrea Artoni (3)
  Anna Lecchi (3)
  Giovanna Motta (3)
  Giovanni Mistraletti (4)
  Cristina Novembrino (5)
  Giacomo Pietro Comi (2)
  Luciano Gattinoni (1)
  
  1. U.O. Terapia Intensiva 鈥楨mma Vecla鈥? Fondazione IRCCS Ca鈥?Granda 鈥?Ospedale Maggiore Policlinico ; Universit脿 degli Studi di Milano ; via F.sco Sforza 35 ; 20100 ; Milan ; Italy
  2. U.O. Neurologia 鈥?Centro Dino Ferrari ; Fondazione IRCCS Ca鈥?Granda 鈥?Ospedale Maggiore Policlinico ; Universit脿 degli Studi di Milano ; via F.sco Sforza 35 ; 20100 ; Milan ; Italy
  3. Centro Emofilia e Trombosi Angelo Bianchi Bonomi ; Fondazione IRCCS Ca鈥?Granda 鈥?Ospedale Maggiore Policlinico ; Universit脿 degli Studi di Milano ; via F.sco Sforza 35 ; 20100 ; Milan ; Italy
  4. U.O. Anestesia e Rianimazione ; A.O. San Paolo ; Universit脿 degli Studi di Milano ; via A. Di Rudin矛 8 ; 20100 ; Milan ; Italy
  5. Laboratorio Centrale di Analisi Chimico Cliniche e Microbiologia ; Fondazione IRCCS Ca鈥?Granda 鈥?Ospedale Maggiore Policlinico ; Universit脿 degli Studi di Milano ; via F.sco Sforza 35 ; 20100 ; Milan ; Italy
  
• 刊名：Critical Care
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：19
• 期：1
• 全文大小：470 KB
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• 刊物主题：Intensive / Critical Care Medicine; Emergency Medicine;
• 出版者：BioMed Central
• ISSN：1364-8535

文摘

Introduction 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鈥揷ontrol 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聽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鈥?鈥?.001), complex I (P鈥?鈥?.006), complex I and III (P鈥?鈥?.001) and complex IV (P鈥?鈥?.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鈥?鈥?.001) and secretion (P鈥?鈥?.05). Lower mitochondrial NADH (R 2 0.36; P鈥?鈥?.001), complex I (R 2 0.38; P鈥?鈥?.001), complex I and III (R 2 0.27; P鈥?鈥?.002) and complex IV (R 2 0.43; P鈥?鈥?.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. Trial registration ClinicalTrials.gov NCT00541827. Registered 8 October 2007.