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Updated: Aug 27, 2026
Characterization of the Isolated, Ventilated, and Instrumented Mouse Lung Perfused with Pulsatile Flow
Published on: April 29, 2011
Physiologic responses to small emboli and hemodynamic effects of changes in deformability of polymorphonuclear
Hiroshi Tanaka1, Masato Nishino, Thomas E Dahms
1Department of Acute Critical Medicine, Osaka University Medical School, Osaka 565-0871, Japan.
Abstract:
We hypothesized that polymorphonuclear leukocytes (PMNs) exposed to lipopolysaccharide (LPS) or chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) would alter the pulmonary hemodynamics of buffer-perfused rabbit lung. Pulmonary arterial pressure (Ppa) was measured at baseline, at peak response, and at 30 min after PMN infusion in the perfusate (Ppa x time, PT product). Infusion of peritoneal-harvested PMNs resulted in a transient increase in both pulmonary vascular resistance (PVR) and lung weight. PVR also increased when glutaraldehyde-treated rabbit PMNs (GPMNs) or beads were infused. Upstream PVR (Pao-Pdo) remained high with the infusion of GPMNs and beads and returned to baseline only when PMNs were infused 30 min thereafter. FMLP-exposed PMNs increased the peak Ppa and PT product. Pretreatment with 3-isobutyl-1-methylxanthine (IBMX) blocked this increase in pressure, suggesting the release of vasoconstrictor(s) or a direct effect of FMLP. PMNs exposed to LPS increased peak Ppa and PT product with and without the addition of IBMX. Cytochalasin D treatment of PMNs prevented the increase in PT product, suggesting that actin polymerization of PMNs is involved. The effects of these agents on PMN rigidity were verified by means of 6.5-microm polycarbonate filters. PMN suspension treated with FMLP or LPS increased filter perfusion pressure and PT product. Cytochalasin D prevented these increases. These results suggest that, initially after injection, PMNs behave like small beads embolizing primarily the small arteries in the lung and that they then move distally through the vasculature. Exposure to FMLP or LPS alters PMN deformability and the ability of PMNs to pass through the pulmonary vasculature, resulting in increased pulmonary vascular resistance.
Insights
Polymorphonuclear leukocytes (PMNs) exposed to LPS or FMLP alter lung hemodynamics. PMN deformability changes affect pulmonary vascular resistance, impacting lung function.
Area of Science:
- Pulmonary Medicine
- Immunology
- Physiology
Background:
- Polymorphonuclear leukocytes (PMNs) play a role in inflammatory responses.
- Pulmonary hemodynamics can be affected by circulating cells and inflammatory mediators.
Purpose of the Study:
- To investigate how lipopolysaccharide (LPS) or N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) exposure affects PMN function and pulmonary hemodynamics.
- To determine the role of PMN deformability in pulmonary vascular resistance.
Main Methods:
- Buffer-perfused rabbit lung model.
- Measurement of pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (PVR).
- Infusion of PMNs, glutaraldehyde-treated PMNs (GPMNs), beads, and PMNs treated with LPS, FMLP, or Cytochalasin D.
Main Results:
- PMN infusion caused transient increases in PVR and lung weight.
- GPMNs and beads increased upstream PVR, while PMNs normalized it.
- FMLP- and LPS-exposed PMNs increased Ppa and the Ppa x time (PT) product.
- Cytochalasin D prevented PT product increases, indicating actin polymerization involvement.
Conclusions:
- PMNs can embolize small pulmonary arteries, affecting hemodynamics.
- LPS and FMLP alter PMN deformability, increasing pulmonary vascular resistance.
- PMN actin polymerization is crucial for their response in the pulmonary vasculature.
