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Effects of Two‐Hit Lipopolysaccharide (LPS) Administration on Anoxic Gasping in Spontaneously Breathing Adult Male C57BL/6 Mice
Author(s) -
Ahmad Mohammed S,
Wadolowski Robert M,
Wadolowski Steven B,
Solomon Irene C
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1053.2
Subject(s) - medicine , lipopolysaccharide , anesthesia , saline , pharmacology , airway , lung , sepsis , immunology
Ongoing studies designed to induce peripheral inflammation, and its accompanying neuroinflammation, have begun to examine various aspects of neural control of breathing. These studies typically administer the bacterial endotoxin lipopolysaccharide (LPS) systemically or in an airway/lung targeted manner in order to produce models of sepsis and acute lung injury (ALI). Recently, a ‘two‐hit’ LPS administration protocol in which systemic LPS (ip, 3 mg/kg) is administered ~24 hr prior to an airway/lung targeted (intratracheal (IT); 0.5 mg/kg) LPS injection has been used to better reflect chronic (lung/airway) disease states. Here we evaluate and characterize the impact of this two‐hit (ip‐IT) administration approach on the anoxic gasping response (recorded as EMG activities from diaphragm (EMG Dia ) and genioglossus (EMG GG ) muscles) in urethane‐anesthetized spontaneously breathing adult male C57BL/6 mice at 3–6 hr post LPS administration. A two‐hit protocol using ip‐IT saline injections served as a control. We found that following two‐hit LPS administration, the temporal characteristics of the gasping response were modified in LPS‐treated mice (compared to saline‐treated control mice), such that (1) the apneic pause that precedes the onset of gasping was eliminated, (2) the onset latency to gasping occurred earlier (expressed relative to anoxic duration; 39.2±2.8% vs 59.4±3.3%; P<0.001), (3) the duration of gasping was longer (109±8 s vs 51±7 s; P<0.001), (4) the total number of primary gasps was greater (23±2 vs 12±1; P<0.001), and (5) the number of terminal gasps increased (5.7±0.2 vs 4.8±0.3; P=0.021). In addition, changes in gasp pattern and duration were observed in LPS‐treated mice (compared to saline‐treated control mice), with the peak amplitude shifting to a slightly earlier time point in the inspiratory burst (P<0.001) albeit the decrease in gasp burst duration was attenuated (~10% vs ~40% decrease; P=0.029) and more highly variable. While our prior work found that ‘two‐hit’ LPS administration markedly alters basal ventilatory behaviors, the current work extends these observations to indicate that central neural mechanisms controlling gasping activities are also modified. Moreover, our data support using a ‘two‐hit’ administration approach as viable option for investigating the impact of LPS‐induced on ventilatory control.