Introduction
Materials and methods
Animals and protocols
Intravital microscopy
Platelet preparation
Analysis of leukocyte-endothelial and platelet-endothelial interactions
Analysis of blood flow in liver sinusoids and postsinusoidal venules
Statistical analysis
Results
Macrohemodynamic parameters and laboratory values
Time after cecal ligation and puncture | ||||||
---|---|---|---|---|---|---|
0 h | 1 h | 3 h | 5 h | 10 h | 20 h | |
HR (beats/min) | 358 (12) | 365 (14) | 369 (14) | 340 (19) | 331 (11) | 339 (15) |
MAP (mm Hg) | 100 (6) | 100 (5) | 86 (4) | 92 (4) | 82 (2)a | 81 (1)a |
PBF (ml/minute) | 17 (6) | 9 (1)a | 10 (1)a | 9 (1)a | 7 (1)a | 6 (1)a |
Time after cecal ligation and puncture | ||||||
---|---|---|---|---|---|---|
0 h | 1 h | 3 h | 5 h | 10 h | 20 h | |
Weight (g) | 247 (5) | 231 (9) | 233 (9) | 249 (7) | 220 (7) | 219 (7) |
WBC (× 103/μl) | 3.8 (0.3) | 3.6 (0.2) | 2.5 (0.2)a | 2.4 (0.2)a | 1.8 (0.2)a | 2.0 (0.3)a |
Plt (× 103/μl) | 843 (39) | 900 (29) | 750 (25)a | 829 (26) | 669 (25)a | 488 (44)a |
Hkt (%) | 51 (1) | 51 (1) | 46 (2) | 48 (2) | 48 (2) | 47 (4) |
AST (U/l) | 61 (9) | 65 (4) | 65 (4) | 72 (9) | 145 (26)a | 234 (33)a |
ALT (U/l) | 30 (3) | 27 (1) | 24 (1) | 29 (1) | 61 (6)a | 115 (11)a |
Albumin (g/l) | 12 (0.4) | 12 (0.4) | 11 (0.2)a | 12 (0.3) | 11 (0.2)a | 10 (0.3)a |
Bili (mg/dl) | 0.32 (0.03) | 0.26 (0.02) | 0.29 (0.02) | 0.23 (0.02) | 0.26 (0.03) | 0.48 (0.08)a |
Intravital microscopy
Measurement | Time point during intravital microscopy | |||||
---|---|---|---|---|---|---|
0 h | 1 h | 3 h | 5 h | 10 h | 20 h | |
MEV (mm/s) | ||||||
Venules | 0.81 (0.03) | 0.75 (0.03) | 0.75 (0.04) | 0.83 (0.03) | 0.49 (0.02)a | 0.40 (0.02)a |
Sinusoids | 0.39 (0.02) | 0.38 (0.03) | 0.29 (0.01)a | 0.28 (0.02)a | 0.25 (0.02)a | 0.25 (0.02)a |
Roller (mm2 ES) | ||||||
Leukocytes | 48 (16) | 150 (36) | 221 (49)a | 111 (21) | 222 (54)a | 269 (69)a |
Platelets | 6 (4) | 36 (7)a | 37 (9)a | 47 (11)a | 38 (6)a | 43 (9)a |
Sinusoid diameter (μm) | 8.00 (0.40) | 7.90 (0.30) | 7.20 (0.30) | 7.30 (0.50) | 7.00 (0.30)a | 6.50 (0.30)a |
Thrombotic sinusoids (%) | 0 (0) | 0 (1) | 1 (1) | 5 (1)a | 8 (1)a | 11 (2)a |
Discussion
Animal model
Liver perfusion
Leukocyte-endothelial and platelet-endothelial interactions
Conclusion
Key messages
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The hepatic microperfusion damage during endotoxemia follows a time course of ongoing processes.
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Platelet-endothelial adherence during endotoxemia in the liver is an early event.
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Leukocyte-endothelial adherence occurs after the onset of platelet-endothelial adherence.
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Decrease of liver perfusion is the consequence of inflammatory platelet and leukocyte adhesion.
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Hepatocellular damage is a combination of early toxic and late microperfusion related hepatocyte injury.