01.08.2010 | Research | Ausgabe 4/2010 Open Access

Simvastatin attenuates ventilator-induced lung injury in mice
- Zeitschrift:
- Critical Care > Ausgabe 4/2010
Electronic supplementary material
Competing interests
Authors' contributions
Introduction
Materials and methods
Mice
Mechanical ventilation
Simvastatin treatment
Blood gas analyses
Lung permeability
Electron microscopy
Differential cell count lung
Differential cell count blood
Quantification of cytokines
Measurement of Alanine transaminase levels
Statistic analyses
Results
Simvastatin prevented oxygenation failure in VILI
Simvastatin reduced VILI-associated pulmonary vascular leakage
Simvastatin attenuated endothelial injury in ventilated mice
Simvastatin limited the recruitment of PMN and Gr-1high monocytes to the lung in VILI
Simvastatin treatment attenuated VILI-associated pulmonary cytokine production
Simvastatin treatment attenuated VILI-associated IL-12p40 increase in plasma
NV
|
NV + Simva
|
6 h Vent.
|
6 h Vent. + Simva
|
|||||
---|---|---|---|---|---|---|---|---|
mean (pg/μl)
|
SD
|
mean (pg/μl)
|
SD
|
mean (pg/μl)
|
SD
|
mean (pg/μl)
|
SD
|
|
IL-1β
|
445.30
|
100.70
|
505.30
|
52.19
|
763.2 ***
|
95.38
|
738.8 ###
|
100.40
|
IL-6
|
57.58
|
62.99
|
133.40
|
90.38
|
915.3 ***
|
459.00
|
993.9 ###
|
364.60
|
IL-12p40
|
462.10
|
99.32
|
593.10
|
128.60
|
2,352 ***
|
783.40
|
1,785 ###,
a
|
372.50
|
MIP-1α
|
307.20
|
149.10
|
386.50
|
78.94
|
918.6 ***
|
318.60
|
900.8 ###
|
128.20
|
MIP-2
|
15.28
|
35.02
|
10.03
|
9.42
|
95.32 **
|
49.21
|
67.25 #
|
23.73
|
MCP-1
|
99.84
|
17.33
|
153.50
|
29.41
|
758.9 *
|
404.90
|
559.70
|
133.30
|
Hemodynamics, urine output electrolytes, acid-base homeostasis and markers of hepatic and renal function
6 h Vent.
|
6 h Vent. + Simva
|
|||
---|---|---|---|---|
mean
|
SD
|
mean
|
SD
|
|
Na
+
(mmol/l)
|
159
|
5
|
159
|
4
|
K
+
(mmol/l)
|
4.7
|
0.5
|
4.7
|
0.4
|
Cl
-
(mmol/l)
|
124
|
4
|
125
|
4
|
Ca
2+
(mmol/l)
|
1.29
|
0.06
|
1.30
|
0.05
|
ph
|
7.45
|
0.08
|
7.51
|
0.08
|
p
a
CO
2
(mmHg)
|
42.2
|
4.8
|
34.5
|
10.0
|
SBE (mmol/l)
|
3.0
|
2.1
|
3.5
|
1.7
|
HCO
3
-
(mmol/l)
|
26.7
|
2.6
|
26.6
|
2.7
|
Lactate (mmol/l)
|
1.5
|
0.4
|
1.6
|
0.3
|
ALT (U/l)
|
30
|
12
|
21
|
4
|
Cystatin C (ng/ml)
|
443
|
64
|
479
|
65
|
MAP 0 h (mmHg)
|
91
|
7
|
87
|
10
|
MAP 1 h (mmHg)
|
74
|
7
|
72
|
7
|
MAP 2 h (mmHg)
|
68
|
5
|
70
|
6
|
MAP 3 h (mmHg)
|
70
|
6
|
70
|
7
|
MAP 4 h (mmHg)
|
68
|
5
|
69
|
7
|
MAP 5 h (mmHg)
|
69
|
6
|
67
|
7
|
MAP 6 h (mmHg)
|
73
|
8
|
72
|
10
|
Urine Output 6 h (μl)
|
908
|
294
|
669
|
207
|
Discussion
Conclusions
Key messages
-
Simvastatin improved microvascular leakage and improved oxygenation in VILI.
-
Simvastatin limited pulmonary hyperinflammation in VILI.
-
Simvastatin protected against VILI induced pulmonary endothelial injury.
-
Simvastatin offers a promising perspective to limit VILI in addition to lung protective ventilation.