Regional lung derecruitment and inflammation during 16 hours of mechanical ventilation in supine healthy sheep

Abstract

Background: Lung derecruitment is common during general anesthesia. Mechanical ventilation with physiological tidal volumes could magnify derecruitment, and produce lung dysfunction and inflammation. The authors used positron emission tomography to study the process of derecruitment in normal lungs ventilated for 16 h and the corresponding changes in regional lung perfusion and inflammation.

Methods: Six anesthetized supine sheep were ventilated with VT=8 ml/kg and positive end-expiratory pressure=0. Transmission scans were performed at 2-h intervals to assess regional aeration. Emission scans were acquired at baseline and after 16 h for the following tracers: (1) F-fluorodeoxyglucose to evaluate lung inflammation and (2) NN to calculate regional perfusion and shunt fraction.

Results: Gas fraction decreased from baseline to 16 h in dorsal (0.31±0.13 to 0.14±0.12, P<0.01), but not in ventral regions (0.61±0.03 to 0.63±0.07, P=nonsignificant), with time constants of 1.5-44.6 h. Although the vertical distribution of relative perfusion did not change from baseline to 16 h, shunt increased in dorsal regions (0.34±0.23 to 0.63±0.35, P<0.01). The average pulmonary net F-fluorodeoxyglucose uptake rate in six regions of interest along the ventral-dorsal direction increased from 3.4±1.4 at baseline to 4.1±1.5 10(-3)/min after 16 h (P<0.01), and the corresponding average regions of interest F-fluorodeoxyglucose phosphorylation rate increased from 2.0±0.2 to 2.5±0.2 10(-2)/min (P<0.01).

Conclusions: When normal lungs are mechanically ventilated without positive end-expiratory pressure, loss of aeration occurs continuously for several hours and is preferentially localized to dorsal regions. Progressive lung derecruitment was associated with increased regional shunt, implying an insufficient hypoxic pulmonary vasoconstriction. The increased pulmonary net uptake and phosphorylation rates of F-fluorodeoxyglucose suggest an incipient inflammation in these initially normal lungs.

Fig. 1

Mean regional gas fraction (F_gas) for all animals (n = 6) at baseline and after 16 h of mechanical ventilation in six coronal regions of interest (ROIs) of equal height along the ventral-dorsal axis (ROI 1 is the most ventral, and ROI 6, the most dorsal). Note that a significant decrease in gas fraction occurred only in dorsal regions (ROIs 5-6). * P < 0.05 (baseline vs. 16 h); # P < 0.01 (vs. previous ROI at baseline); ‡ P < 0.05 (vs. previous ROI at 16 h).

Fig. 2

Images of (A) lung aeration, (B) perfusion, (C) density normalized perfusion, and (D) ¹⁸F-FDG net uptake rate at the beginning (baseline) and end of the study (16 h) for a typical case. In this example, there is a decrease in gas fraction in dorsal regions from baseline to 16 h (A), associated with an increase in perfusion in the same regions (B). After normalization by density (lung tissue) (C), such increase in perfusion in dorsal regions was no longer visualized. ¹⁸F-FDG uptake (D) increased from baseline to 16 h.

Fig. 3

Time course of gas fraction (F_gas) in six coronal regions of interest (ROIs) of equal height along the ventral-dorsal axis (ROI 1 is the most ventral, and ROI 6, the most dorsal) during 16 h of mechanical ventilation for two animals with different time constants of dorsal lung derecruitment. Temporal changes in Fgas were not significant in nondependent regions. In contrast, dorsal regions (ROIs 5 and 6) showed systematic loss of aeration, with variability in time constants (τ): (A) Case of equal and long time constants in ROI 5 and 6. (B) Case with different and shorter time constants for the same ROIs. The dotted lines indicate the exponential fitting.

Fig. 4

Amount of nonaerated lung (gas fraction less than 0.1) for all animals (n = 6) at baseline and at 16 h shown as percentage of lung volume (A) and percentage of lung tissue mass (B). Median (solid line) and interquartile range (gray box) are represented.

Fig. 5

Regional relative perfusion versus six coronal regions of interest (ROIs) of equal heights along the ventral-dorsal axis (ROI 1 is the most ventral and ROI 6 the most dorsal) at baseline and after 16 h of mechanical ventilation presented for all animals (n = 6) # P < 0.01 (vs. previous ROI at baseline); ‡ P < 0.05 (vs. previous ROI at 16 h).

Fig. 6

Regional shunt fraction at baseline and after 16 h for the six coronal regions of interest (ROIs) along the ventral-dorsal axis measured in all animals (n = 6) (ROI 1 is the most ventral, and ROI 6, the most dorsal). * p < 0.05 (baseline vs. 16 h); # P < 0.01 (vs. previous ROI at baseline); ‡ P < 0.05 (vs. previous ROI at 16 h).

Fig. 7

Regional net ¹⁸F-fluorodeoxyglucose uptake rate (K_i) (A), rate of ¹⁸F-FDG trapping, proportional to hexokinase activity (k₃) (B), and fraction of lung volume occupied by the extravascular substrate compartment (Fe) (C) at baseline and after 16 h for all animals (n = 6) in six coronal regions of interest (ROIs) of equal height along the ventral-dorsal axis (ROI 1 is the most ventral, and ROI 6, the most dorsal). # P < 0.01 (vs. previous ROI at baseline); ‡ P < 0.05 (vs. previous ROI at 16 h).