Assessment of vascular permeability in an ovine model of acute lung injury and pneumonia-induced Pseudomonas aeruginosa sepsis

Matthias Lange, Atsumori Hamahata, Perenlei Enkhbaatar, Aimalohi Esechie, Rhykka Connelly, Yoshimitsu Nakano, Collette Jonkam, Robert A. Cox, Lillian D. Traber, David Herndon, Daniel L. Traber

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

OBJECTIVE: To assess the time changes and mechanism of pulmonary and peripheral vascular permeability in sheep with acute lung injury and sepsis. DESIGN: Prospective, controlled, randomized trial. SETTING: University research laboratory. SUBJECTS: A total of 21 chronically instrumented, adult female sheep. INTERVENTIONS: Sheep were instrumented with lung and prefemoral lymph fistulas and allocated to either an uninjured control group (n = 5) or sepsis group (n = 5). The sheep in the sepsis group received cotton smoke inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. All sheep were mechanically ventilated and fluid resuscitated for the entire duration of the 24-hr experiment. Additional sheep (n = 11) received injury and were killed at different time points for the measurement of vascular endothelial growth factor in lung tissue. MEASUREMENTS AND MAIN RESULTS: The injury induced a hypotensive-hyperdynamic circulation; increases in pulmonary capillary pressure, net fluid balance, lung and prefemoral lymph flow and protein content, lung water content, abdominal and thoracic fluid and protein content, neutrophil accumulation in the lung, and vascular endothelial growth factor expression in lung tissue; and decreases in Pao2/Fio2 ratio, plasma protein concentration, plasma oncotic pressure, and myocardial contractility. CONCLUSIONS: Lung edema formation in this model was the result of marked increases in both pulmonary microvascular permeability and pressure. Pulmonary vascular hyperpermeability peaked 12 hrs postinjury and was related to vascular endothelial growth factor overexpression. Early myocardial failure was a potential contributor to the constant increase in pulmonary capillary pressure. The sepsis-induced increase in peripheral microvascular permeability was associated with significant accumulation of fluid and protein in the third space.

Original languageEnglish (US)
Pages (from-to)1284-1289
Number of pages6
JournalCritical Care Medicine
Volume36
Issue number4
DOIs
StatePublished - Apr 2008

Fingerprint

Acute Lung Injury
Capillary Permeability
Pseudomonas aeruginosa
Sheep
Sepsis
Pneumonia
Lung
Vascular Endothelial Growth Factor A
Pressure
Lymph
Smoke Inhalation Injury
Proteins
Water-Electrolyte Balance
Wounds and Injuries
Fistula
Blood Vessels
Blood Proteins
Edema
Neutrophils
Thorax

Keywords

  • Microvascular hyperpermeability
  • Myocardial failure
  • Pulmonary edema
  • Sepsis
  • Transvascular fluid flux
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Assessment of vascular permeability in an ovine model of acute lung injury and pneumonia-induced Pseudomonas aeruginosa sepsis. / Lange, Matthias; Hamahata, Atsumori; Enkhbaatar, Perenlei; Esechie, Aimalohi; Connelly, Rhykka; Nakano, Yoshimitsu; Jonkam, Collette; Cox, Robert A.; Traber, Lillian D.; Herndon, David; Traber, Daniel L.

In: Critical Care Medicine, Vol. 36, No. 4, 04.2008, p. 1284-1289.

Research output: Contribution to journalArticle

Lange, M, Hamahata, A, Enkhbaatar, P, Esechie, A, Connelly, R, Nakano, Y, Jonkam, C, Cox, RA, Traber, LD, Herndon, D & Traber, DL 2008, 'Assessment of vascular permeability in an ovine model of acute lung injury and pneumonia-induced Pseudomonas aeruginosa sepsis', Critical Care Medicine, vol. 36, no. 4, pp. 1284-1289. https://doi.org/10.1097/CCM.0b013e318169ef74
Lange, Matthias ; Hamahata, Atsumori ; Enkhbaatar, Perenlei ; Esechie, Aimalohi ; Connelly, Rhykka ; Nakano, Yoshimitsu ; Jonkam, Collette ; Cox, Robert A. ; Traber, Lillian D. ; Herndon, David ; Traber, Daniel L. / Assessment of vascular permeability in an ovine model of acute lung injury and pneumonia-induced Pseudomonas aeruginosa sepsis. In: Critical Care Medicine. 2008 ; Vol. 36, No. 4. pp. 1284-1289.
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AU - Lange, Matthias

AU - Hamahata, Atsumori

AU - Enkhbaatar, Perenlei

AU - Esechie, Aimalohi

AU - Connelly, Rhykka

AU - Nakano, Yoshimitsu

AU - Jonkam, Collette

AU - Cox, Robert A.

AU - Traber, Lillian D.

AU - Herndon, David

AU - Traber, Daniel L.

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N2 - OBJECTIVE: To assess the time changes and mechanism of pulmonary and peripheral vascular permeability in sheep with acute lung injury and sepsis. DESIGN: Prospective, controlled, randomized trial. SETTING: University research laboratory. SUBJECTS: A total of 21 chronically instrumented, adult female sheep. INTERVENTIONS: Sheep were instrumented with lung and prefemoral lymph fistulas and allocated to either an uninjured control group (n = 5) or sepsis group (n = 5). The sheep in the sepsis group received cotton smoke inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. All sheep were mechanically ventilated and fluid resuscitated for the entire duration of the 24-hr experiment. Additional sheep (n = 11) received injury and were killed at different time points for the measurement of vascular endothelial growth factor in lung tissue. MEASUREMENTS AND MAIN RESULTS: The injury induced a hypotensive-hyperdynamic circulation; increases in pulmonary capillary pressure, net fluid balance, lung and prefemoral lymph flow and protein content, lung water content, abdominal and thoracic fluid and protein content, neutrophil accumulation in the lung, and vascular endothelial growth factor expression in lung tissue; and decreases in Pao2/Fio2 ratio, plasma protein concentration, plasma oncotic pressure, and myocardial contractility. CONCLUSIONS: Lung edema formation in this model was the result of marked increases in both pulmonary microvascular permeability and pressure. Pulmonary vascular hyperpermeability peaked 12 hrs postinjury and was related to vascular endothelial growth factor overexpression. Early myocardial failure was a potential contributor to the constant increase in pulmonary capillary pressure. The sepsis-induced increase in peripheral microvascular permeability was associated with significant accumulation of fluid and protein in the third space.

AB - OBJECTIVE: To assess the time changes and mechanism of pulmonary and peripheral vascular permeability in sheep with acute lung injury and sepsis. DESIGN: Prospective, controlled, randomized trial. SETTING: University research laboratory. SUBJECTS: A total of 21 chronically instrumented, adult female sheep. INTERVENTIONS: Sheep were instrumented with lung and prefemoral lymph fistulas and allocated to either an uninjured control group (n = 5) or sepsis group (n = 5). The sheep in the sepsis group received cotton smoke inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. All sheep were mechanically ventilated and fluid resuscitated for the entire duration of the 24-hr experiment. Additional sheep (n = 11) received injury and were killed at different time points for the measurement of vascular endothelial growth factor in lung tissue. MEASUREMENTS AND MAIN RESULTS: The injury induced a hypotensive-hyperdynamic circulation; increases in pulmonary capillary pressure, net fluid balance, lung and prefemoral lymph flow and protein content, lung water content, abdominal and thoracic fluid and protein content, neutrophil accumulation in the lung, and vascular endothelial growth factor expression in lung tissue; and decreases in Pao2/Fio2 ratio, plasma protein concentration, plasma oncotic pressure, and myocardial contractility. CONCLUSIONS: Lung edema formation in this model was the result of marked increases in both pulmonary microvascular permeability and pressure. Pulmonary vascular hyperpermeability peaked 12 hrs postinjury and was related to vascular endothelial growth factor overexpression. Early myocardial failure was a potential contributor to the constant increase in pulmonary capillary pressure. The sepsis-induced increase in peripheral microvascular permeability was associated with significant accumulation of fluid and protein in the third space.

KW - Microvascular hyperpermeability

KW - Myocardial failure

KW - Pulmonary edema

KW - Sepsis

KW - Transvascular fluid flux

KW - Vascular endothelial growth factor

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