Cardiovascular Aspects of Experimental Meningococcal Sepsis in Young and Older Awake Piglets

Hazelzet, J A; Stubenitsky, René; Petrov, Andrey; Wieringen, G. W. Van; Voort, Edwin van der; Heß, Jochen; Hop, W. C. J.; Thijs, L. G.; Duncker, Dirk J.; Poolman, Jan; Verdouw, Pieter D.

doi:10.1097/00024382-199908000-00009

Cited by 10 publications

(8 citation statements)

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“…Shock is caused by capillary leakage, inappropriate vascular tone, intravascular microthrombi, and myocardial dysfunction. The central activator that elicits these derangements is meningococcal endotoxin (6,69,212), and the severity of shock correlates with the degree of endotoxinemia (54,55,57,495).…”

Section: Pathophysiology Of Fulminant Meningococcal Sepsismentioning

confidence: 99%

Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management

2000

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The only natural reservoir of Neisseria meningitidis is the human nasopharyngeal mucosa. Depending on age, climate, country, socioeconomic status, and other factors, approximately 10% of the human population harbors meningococci in the nose. However, invasive disease is relatively rare, as it occurs only when the following conditions are fulfilled: (i) contact with a virulent strain, (ii) colonization by that strain, (iii) penetration of the bacterium through the mucosa, and (iv) survival and eventually outgrowth of the meningococcus in the bloodstream. When the meningococcus has reached the bloodstream and specific antibodies are absent, as is the case for young children or after introduction of a new strain in a population, the ultimate outgrowth depends on the efficacy of the innate immune response. Massive outgrowth leads within 12 h to fulminant meningococcal sepsis (FMS), characterized by high intravascular concentrations of endotoxin that set free high concentrations of proinflammatory mediators. These mediators belonging to the complement system, the contact system, the fibrinolytic system, and the cytokine system induce shock and diffuse intravascular coagulation. FMS can be fatal within 24 h, often before signs of meningitis have developed. In spite of the increasing possibilities for treatment in intensive care units, the mortality rate of FMS is still 30%. When the outgrowth of meningococci in the bloodstream is impeded, seeding of bacteria in the subarachnoidal compartment may lead to overt meningitis within 24 to 36 h. With appropriate antibiotics and good clinical surveillance, the mortality rate of this form of invasive disease is 1 to 2%. The overall mortality rate of meningococcal disease can only be reduced when patients without meningitis, i.e., those who may develop FMS, are recognized early. This means that the fundamental nature of the disease as a meningococcus septicemia deserves more attention.

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Section: Pathophysiology Of Fulminant Meningococcal Sepsismentioning

confidence: 99%

Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management

2000

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Section: Pathophysiology Of Fulminant Meningococcal Sepsismentioning

confidence: 99%

Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management

Deuren¹,

Brandtzæg²,

Meer³

2000

Clinical Microbiology Reviews

398

236

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“…The animal should reveal the same reaction pattern when exposed to intravascular bacterial challenges as man (13). In 1999, Hazelzet et al (14) published a live porcine model and documented the potent biological effects of LPS-containing outer membrane vesicles when infused as a bolus dose. Such vesicles are shed during human meningococcemia (2).…”

Section: Introductionmentioning

confidence: 99%

A New Dynamic Porcine Model of Meningococcal Shock

Hellerud¹,

Thorgersen

Castellheim

et al. 2009

Shock

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The objective of this study was to establish a porcine analog of human meningococcal sepsis for pathophysiological investigations and possible future therapy in severe sepsis. Heat-killed Neisseria meningitidis was continuously infused in sublethal concentrations into 10 anesthetized 30-kg pigs (sepsis group). The dose was doubled every 30 min. Six pigs received saline only (control group). The changes described in the succeeding paragraphs were observed in the sepsis group but not in the control group. MAP was aimed to be kept normal by fluid infusion but declined after 3 h in parallel with a decrease in systemic vascular resistance. Pulmonary arterial pressure increased considerably after 30 to 45 min. A massive plasma extravasation was shown by increased hematocrit and a 50% reduction in plasma albumin content. Fluid accumulated in lungs, muscles, and jejunum, as shown by increased wet-dry ratios. Peak inspiratory pressures and fraction of inspired oxygen had to be increased. The cytokines TNF-alpha, IL-1beta, IL-6, IL-8, IL-10, and IL-12 increased markedly. Neutrophils fell to zero-levels, and platelets were markedly reduced. Thrombin-antithrombin complexes increased notably after 120 min. This is the first large animal model of sepsis using whole Neisseria meningitidis. The model simulates well central aspects of human meningococcal sepsis and could be used for future interventional studies.

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Cardiovascular Aspects of Experimental Meningococcal Sepsis in Young and Older Awake Piglets

Cited by 10 publications

References 0 publications

Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management

Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management

Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management

A New Dynamic Porcine Model of Meningococcal Shock

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