Complement-mediated Hemodynamic Depression in the Early Postburn Period

Schirmer, William J.; Schirmer, James M.; Naff, George B.; Fry, Donald E.

doi:10.1097/00005373-198907000-00005

Cited by 10 publications

(4 citation statements)

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“…Our laboratory recently showed in a rat model of hemorrhagic shock producing a degree of hypotension and acidosis comparable to that in the present studies that CH 50 was reduced by 35% (25). Reductions of CH 50 by roughly one-third have also been seen in models of mesenteric ischemia (12) and in human acute respiratory distress syndrome (14) and burn patients (19). Although the degree of complement activation is severe, the present experiments indicate that complement activation, independent of other insults, is sufficient to cause profound alterations in systemic perfusion, acid-base status, and vascular integrity.…”

Section: Discussionsupporting

confidence: 87%

Systemic and lung physiological changes in rats after intravascular activation of complement

Younger¹,

Sasaki

Delgado³

et al. 2001

Journal of Applied Physiology

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Systemic complement activation has been noted in a variety of shock states, and there is growing evidence that, in addition to being proinflammatory effectors, products of complement activation contribute directly to generalized manifestations of shock, such as hypotension and acidosis. To study the effects of complement activation, we examined responses in rats to systemic activation of complement with cobra venom factor (CVF), including blood pressure, metabolic acidosis, changes in vascular permeability, and lung function. High doses of CVF produced circulatory collapse (mean arterial pressure = 110 +/- 16 and 35 +/- 9 mmHg in control and with CVF, respectively, P < 0.05), metabolic acidosis (HCO concentration = 27.8 +/- 1.7 and 9.6 +/- 3.4 meq/l in control and with CVF, respectively, P < 0.05), extravasation of albumin into the lung and gut, and modest arterial hypoxemia (PO2 = 486 +/- 51 and 201 +/- 36 Torr in control and during 100% O2 breathing, respectively, P < 0.05). Prior depletion of complement protected against these abnormalities. Other interventions, including neutrophil depletion and cyclooxygenase inhibition, prevented lung injury but had much less effect on systemic hemodynamics or gut permeability, suggesting that complement activation products induce injury by neutrophil- and cyclooxygenase-dependent pathways in the lung but not in the gut. These studies underscore the significant systemic abnormalities developing after systemic activation of complement.

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Section: Discussionsupporting

confidence: 87%

Systemic and lung physiological changes in rats after intravascular activation of complement

Younger¹,

Sasaki

Delgado³

et al. 2001

Journal of Applied Physiology

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show abstract

“…In this context, Schirmer et al (20) have reported that animals with an intact complement system exhibit cardiac output depression and deterioration of hemodynamic parameters such as mean arterial pressure and systemic vascular resistance as early as 15 min after burn injury, whereas the hemodynamics of complement depleted animals are unaffected by burn injury. Acute thermal injury to the skin has been proven to initiate local complement activation, and the progressive increase in vascular permeability is linked to complement activation and histamine release (21).…”

Section: Discussionmentioning

confidence: 99%

Cardiomyocyte Function After Burn Injury and Lipopolysaccharide Exposure: Single-Cell Contraction Analysis and Cytokine Secretion Profile

Niederbichler¹,

Westfall²,

et al. 2006

Shock

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A component of multiorgan dysfunction in burned patients is heart failure. Burn trauma induces cytokine synthesis of interleukin (IL) 1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) which can negatively impact cardiac function. Infectious complications are common following severe burn injury. We hypothesized that burn injury and lipopolysaccharide (LPS) exposure independently influence peak cardiomyocyte contraction and cytokine secretion. Rats underwent a full-thickness 30% total body surface area scald or sham burn. At 1, 6, 12, and 24 h after burn, cardiomyocytes were isolated and incubated with increasing LPS doses. Peak sarcomere shortening and contractile velocity parameters were recorded using a variable-rate video camera with sarcomere length detection software. Supernatants were assayed for IL-1beta, IL-6, and TNF-alpha by ELISA. Peak sarcomere shortening was decreased in the burn group at 1, 6, 12, and 24 h after burn. IL-1beta, IL-6, and TNF-alpha levels were increased in cardiomyocytes isolated 1 h after burn compared with sham controls, but returned to sham levels at 6, 12, and 24 h after burn. LPS exposure caused dose-dependent decreases in sarcomere shortening in sham and burn animals. LPS exposure did not produce increased cardiomyocyte cytokine expression. Burn injury diminished peak sarcomere shortening. Whereas exposure to LPS did not have an effect on cardiomyocyte cytokine expression, LPS significantly inhibited sarcomere shortening in a dose-dependent fashion. Combined burn and LPS exposure inhibited sarcomere shortening more than each alone. These results demonstrate that LPS exposure and burn injury independently decrease peak cardiac shortening. These decreases did not directly correlate with the levels of cytokines released in response to each stressor.

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“…Various myocardial depressant factors that collectively trigger cardiac contractility deficits in systemic inflammation have been described, but no single agent responsible for myocardial dysfunction could be identified [81–87]. In previous reports, complement activation has been linked to hemodynamic depression, but the mechanisms by which complement activation products might cause dysfunction of cardiomyocytes remain to be defined in detail [81, 88, 89]. In experimental studies, C5a has been demonstrated to induce cardiac dysfunction with impaired cardiomyocyte contractility, which could be restored by blockade of C5a [90, 91].…”

Section: Cardiac Dysfunctionmentioning

confidence: 99%

Role of Complement in Multiorgan Failure

Rittirsch

Redl

Huber‐Lang

2012

Clinical and Developmental Immunology

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Multiorgan failure (MOF) represents the leading cause of death in patients with sepsis and systemic inflammatory response syndrome (SIRS) following severe trauma. The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation products contributes to an ensuing dysfunction of various organ systems. In the present review, mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement system are discussed.

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Complement-mediated Hemodynamic Depression in the Early Postburn Period

Cited by 10 publications

References 0 publications

Systemic and lung physiological changes in rats after intravascular activation of complement

Systemic and lung physiological changes in rats after intravascular activation of complement

Cardiomyocyte Function After Burn Injury and Lipopolysaccharide Exposure: Single-Cell Contraction Analysis and Cytokine Secretion Profile

Role of Complement in Multiorgan Failure

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