Acute effects of intracranial hypertension and ARDS on pulmonary and neuronal damage: a randomized experimental study in pigs

Abstract

Purpose: To determine reciprocal and synergistic effects of acute intracranial hypertension and ARDS on neuronal and pulmonary damage and to define possible mechanisms.

Methods: Twenty-eight mechanically ventilated pigs were randomized to four groups of seven each: control; acute intracranial hypertension (AICH); acute respiratory distress syndrome (ARDS); acute respiratory distress syndrome in combination with acute intracranial hypertension (ARDS + AICH). AICH was induced with an intracranial balloon catheter and the inflation volume was adjusted to keep intracranial pressure (ICP) at 30-40 cmH2O. ARDS was induced by oleic acid infusion. Respiratory function, hemodynamics, extravascular lung water index (ELWI), lung and brain computed tomography (CT) scans, as well as inflammatory mediators, S100B, and neuronal serum enolase (NSE) were measured over a 4-h period. Lung and brain tissue were collected and examined at the end of the experiment.

Results: In both healthy and injured lungs, AICH caused increases in NSE and TNF-alpha plasma concentrations, extravascular lung water, and lung density in CT, the extent of poorly aerated (dystelectatic) and atelectatic lung regions, and an increase in the brain tissue water content. ARDS and AICH in combination induced damage in the hippocampus and decreased density in brain CT.

Conclusions: AICH induces lung injury and also exacerbates pre-existing damage. Increased extravascular lung water is an early marker. ARDS has a detrimental effect on the brain and acts synergistically with intracranial hypertension to cause histological hippocampal damage.

Fig. 1

CT scans of representative animals from each group taken at end-expiration at 240 min. Control control; AICH acute intracranial hypertension; ARDS acute respiratory distress syndrome; ARDS + AICH acute respiratory distress syndrome and acute intracranial hypertension

Fig. 2

Mean changes in lung density [delta Hounsfield units from T ₂₄₀ to T ₀ (mean + SE)] in control and AICH (upper panel) and in ARDS and ARDS + AICH (lower panel) from segment 1 (non-dependent) to segment 10 (dependent). Control control; AICH acute intracranial hypertension; ARDS acute respiratory distress syndrome; ARDS + AICH acute respiratory distress syndrome and acute intracranial hypertension. Significant (p < 0.05) difference between control and AICH in segments 1–8 and 10; significant (p < 0.05) difference between ARDS and ARDS + AICH in segments 9 and 10

Fig. 3

Extravascular lung water index (ELWI) (mean + SE). Control control; AICH acute intracranial hypertension; ARDS acute respiratory distress syndrome; ARDS + AICH acute respiratory distress syndrome and acute intracranial hypertension. ^#Significant (p < 0.05) effect of time in AICH, ARDS, and ARDS + AICH; *significant difference between control versus AICH after 240 min (p < 0.05). *Significant difference between ARDS versus ARDS + AICH at T ₁₂₀ (p < 0.05)

Fig. 4

Plasma concentration of neuron-specific enolase (NSE) and S100B (mean + SE) in control, AICH, ARDS, ARDS + AICH from T ₀ to T ₂₄₀. Control control; AICH acute intracranial hypertension; ARDS acute respiratory distress syndrome; ARDS + AICH acute respiratory distress syndrome and acute intracranial hypertension. NSE: ^#significant (p < 0.05) effect of time in AICH, ARDS and ARDS + AICH; *significant (p < 0.05) difference between control and AICH at T ₀ and T ₂₄₀. Significant (p < 0.05) difference between control, AICH and ARDS, ARDS + AICH at T₆₀, T₁₂₀, and T₂₄₀. S100B: ^#significant (p < 0.05) effect of time in all groups; significant (p < 0.05) difference between control and AICH at T ₂₄₀. Significant difference between control, AICH and ARDS, ARDS + AICH at T ₆₀, T ₁₂₀, and T ₂₄₀