Apoptosis and necrosis in the development of acute lung injury after hemorrhagic shock

T. Wright Jernigan, Martin Croce, Timothy C. Fabian

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Acute lung injury can be a complication of hemorrhagic shock. Mechanisms of injury include neutrophil-derived inflammatory products that induce necrosis within the lung. Recent data has shown apoptosis, in addition to necrosis, as a pathway leading toward acute lung injury in shock models. This study quantitates apoptotic and necrotic cells in the lung after hemorrhagic shock. Mongrel pigs (20-30 kg) under general anesthesia (with pancuronium and pentobarbital) underwent instrumentation with placement of carotid and external jugular catheters. The animals were randomized to sham hemorrhage (n = 6) and to hemorrhagic shock (n = 7). The hemorrhagic shock group then underwent hemorrhage (40-45% blood volume) to a systolic blood pressure of 40-50 mm Hg for 1 hour. The animals were then resuscitated with shed blood plus crystalloid to normalization of heart rate and blood pressure. The animals were observed under general anesthesia for 6 hours after resuscitation, then sacrificed, and lungs were harvested. Lung injury parameters including histology (H&E stain), apoptosis [terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL)], and myeloperioxidase activity (spectrophotometric assay) were assessed. Hemorrhagic shock induced marked loss of lung architecture, neutrophil infiltration, alveolar septal thickening, hemorrhage, and edema in H&E staining. Furthermore, MPO activity, a marker for neutrophil infiltration and activation, was more than doubled as compared to controls (44.0 vs 20.0 Grisham units activity/g). Apoptosis (cell shrinkage, membrane blebbing, apoptotic bodies) and necrosis (cellular swelling, membrane lysis) in neutrophils, macrophages, as well as in alveolar cells was demonstrated and quantified by H&E staining use. Apoptosis was confirmed and further quantified by positive TUNEL signaling via digital semiquantitative analysis, which revealed a significant increase in apoptotic cells (16.0 vs 2.5 cells/hpf, shock vs control, respectively) and necrotic cells (16.0 vs 2.0 cells/hpf, shock vs control, respectively). Acute lung injury is a complex pathophysiologic process. Apoptosis in cells (neutrophils, macrophages, alveolar cells) is induced within the lung after hemorrhagic shock. The role of apoptosis in pulmonary dysfunction after hemorrhagic shock has yet to be determined.

Original languageEnglish (US)
Pages (from-to)1094-1098
Number of pages5
JournalAmerican Surgeon
Volume70
Issue number12
StatePublished - Dec 1 2004

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Hemorrhagic Shock
Acute Lung Injury
Necrosis
Apoptosis
Lung
Alveolar Epithelial Cells
Shock
Neutrophils
Neutrophil Infiltration
Hemorrhage
Biotin
Blood Pressure
General Anesthesia
Macrophages
Staining and Labeling
Pancuronium
Neutrophil Activation
DNA Nucleotidylexotransferase
Lung Injury
Pentobarbital

All Science Journal Classification (ASJC) codes

  • Surgery
  • Medicine(all)

Cite this

Apoptosis and necrosis in the development of acute lung injury after hemorrhagic shock. / Jernigan, T. Wright; Croce, Martin; Fabian, Timothy C.

In: American Surgeon, Vol. 70, No. 12, 01.12.2004, p. 1094-1098.

Research output: Contribution to journalArticle

Jernigan, T. Wright ; Croce, Martin ; Fabian, Timothy C. / Apoptosis and necrosis in the development of acute lung injury after hemorrhagic shock. In: American Surgeon. 2004 ; Vol. 70, No. 12. pp. 1094-1098.
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