ArticleIntensive care medicine2010
Impaired microvascular perfusion in sepsis requires activated coagulation and P-selectin-mediated platelet adhesion in capillaries.
Article in Intensive care medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01897792 (Effect of Antioxidant Vitamins on Coagulopathy and Nosocomial Pneumonia After Severe Trauma), which is not on this map. Cited by 44 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of Antioxidant Vitamins on Coagulopathy and Nosocomial Pneumonia After Severe Trauma
Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Protective effect of exercise on animals with sepsis: a systematic review of the existing literature.BMC infectious diseases · 2025Pooled it
- Effect of high-dose intravenous ascorbic acid on microcirculation and endothelial glycocalyx during sepsis and septic shock: a double-blind, randomized, placebo-controlled study.BMC anesthesiology · 2023Trial
- Lung-Cardiovascular Interactions and Derangements in ARDS.Comprehensive physiology · 2026Review
- Dialyzer characteristics are associated with differential effects on intradialytic microvascular tissue perfusion.Annals of medicine and surgery (2012) · 2026Article
- Minimally-Invasive Imaging of Sublingual Vessels-A New Method to Study Microvascular Changes in Mice.Life (Basel, Switzerland) · 2025Article
- Non-invasive point-of-care optical technique for continuous in vivo assessment of microcirculatory function: Application to a preclinical model of early sepsis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Unwinding the potentials of vitamin C in COVID-19 and other diseases: An updated review.Nutrition and health · 2023Review
- High-Dose Vitamin C Alleviates Pancreatic Necrosis by Inhibiting Platelet Activation Through the CXCL12/CXCR4 Pathway in Severe Acute Pancreatitis.Journal of inflammation research · 2023Article
- α1-Adrenergic Stimulation Increases Platelet Adhesion to Endothelial Cells Mediated by TRPC6.Advances in experimental medicine and biology · 2023Article
- Association between Vitamin C Deficiency and Mortality in Patients with Septic Shock.Biomedicines · 2022Article
- Spectroscopy detects skeletal muscle microvascular dysfunction during onset of sepsis in a rat fecal peritonitis model.Scientific reports · 2022Article
- Intravital microscopic observation of the microvasculature during hemodialysis in healthy rats.Scientific reports · 2022Article
- Endothelial Activation and Microcirculatory Disorders in Sepsis.Frontiers in medicine · 2022Review
- Targeting Oxidative Stress in Septic Acute Kidney Injury: From Theory to Practice.Journal of clinical medicine · 2021Review
- The effectiveness of vitamin C for patients with severe viral pneumonia in respiratory failure.Journal of thoracic disease · 2021Article
- The role of platelets in sepsis.Research and practice in thrombosis and haemostasis · 2021Article
- Reactive Oxygen Species in Venous Thrombosis.International journal of molecular sciences · 2020Review
- Vitamin C alone does not improve treatment outcomes in mechanically ventilated patients with severe sepsis or septic shock: a retrospective cohort study.Journal of thoracic disease · 2019Article
- Modelling physical resilience in ageing mice.Mechanisms of ageing and development · 2019Review
- The isothiocyanate sulforaphane modulates platelet function and protects against cerebral thrombotic dysfunction.British journal of pharmacology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeImpaired microvascular perfusion in sepsis is not treated effectively because its mechanism is unknown. Since inflammatory and coagulation pathways cross-activate, we tested if stoppage of blood flow in septic capillaries is due to oxidant-dependent adhesion of platelets in these microvessels.
methodsSepsis was induced in wild type, eNOS(-/-), iNOS(-/-), and gp91phox(-/-) mice (n = 14-199) by injection of feces into the peritoneum. Platelet adhesion, fibrin deposition, and blood flow stoppage in capillaries of hindlimb skeletal muscle were assessed by intravital microscopy. Prophylactic treatments at the onset of sepsis were intravenous injection of platelet-depleting antibody, P-selectin blocking antibody, ascorbate, or antithrombin. Therapeutic treatments (delayed until 6 h) were injection of ascorbate or the glycoprotein IIb/IIIa inhibitor eptifibatide, or local superfusion of the muscle with NOS cofactor tetrahydrobiopterin or NO donor S-nitroso-N-acetylpenicillamine (SNAP).
resultsSepsis at 6-7 h markedly increased the number of stopped-flow capillaries and the occurrence of platelet adhesion and fibrin deposition in these capillaries. Platelet depletion, iNOS and gp91phox deficiencies, P-selectin blockade, antithrombin, or prophylactic ascorbate prevented, whereas delayed ascorbate, eptifibatide, tetrahydrobiopterin, or SNAP reversed, septic platelet adhesion and/or flow stoppage. The reversals by ascorbate and tetrahydrobiopterin were absent in eNOS(-/-) mice. Platelet adhesion predicted 90% of capillary flow stoppage.
conclusionImpaired perfusion and/or platelet adhesion in septic capillaries requires NADPH oxidase, iNOS, P-selectin, and activated coagulation, and is inhibited by intravenous administration of ascorbate and by local superfusion of tetrahydrobiopterin and NO. Reversal of flow stoppage by ascorbate and tetrahydrobiopterin may depend on local eNOS-derived NO which dislodges platelets from the capillary wall.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.