Introduction
Materials and methods
Anesthesia and surgical preparation
Measurements and calculations
Experimental protocols
Statistical analysis
Results
Characterization of sepsis models
Baseline | 12 hours | 18 hours | 22 hours | |
---|---|---|---|---|
Mean arterial pressure (mm Hg)
| ||||
Control | 95 [87-109] | 86.5 [83-94] | 80 [73-90] | 84 [68-87] |
Infusion | 112 [103-122] | 88 [79-100]a | 82 [77-90]a | 79 [74-88]a |
Peritonitis | 97 [92-104] | 89 [73-99] | 81 [69-97]a | 76 [68-91]a |
Cardiac output (ml/kg)
| ||||
Control | 98 (90-105) | 97 (85-100) | 80 (76-87) | 85 (77-98) |
Infusion | 90 (80-101) | 98 (80-128) | 98 (81-130) | 106 (83-145) |
Peritonitis | 81 (67-97) | 118 (97-148)a | 129 (110-157)ab | 152 (101-181)ab |
Systemic vascular resistance (dyne.s.cm
-5
)
| ||||
Control | 2,453 (1,838-2,700) | 2,075 (1,935-2,299) | 1,961 (1,872-2,169) | 1,912 (1,648-2,262) |
Infusion | 2,457 (1,956-2,643) | 1,562 (1,384-1,788)a | 1,382 (1,116-1,698)ab | 1,179 (873-1,692)a |
Peritonitis | 2,737 (2,003-2,858) | 1,635 (1,102-1,978)b | 1,165 (849-1,595)ab | 853 (651-1,393)ab |
ITBVI (ml/kg)
| ||||
Control | 31 (28-33) | 24 (21-34) | 23 (21-30) | 26 (23-28) |
Infusion | 27 (22-29) | 25 (22-27) | 24 (20-28) | 23 (21-24) |
Peritonitis | 23 (22-26) | 26 (22-31) | 27 (23-29) | 23 (19-34) |
DO
2
systemic (ml/min/kg)
| ||||
Control | 11.9 (9.9-12.2) | 11.1 (9.3-12.1) | 9.2 (8.7-10.7) | 9.6 (8.8-10.3) |
Infusion | 11.5 (9.6-12.5) | 12 (9.2-15.5)c | 12.2 (10.1-15) | 11.9 (9.6-16.1)c |
Peritonitis | 11.4 (9-13.6) | 16 (14.5-23.2)b | 16.4 (15-21.9)ab | 22.1 (13.4-24.5)ab |
VO
2
systemic (ml/min/kg)
| ||||
Control | 5.6 (4.6-5.9) | 5.5 (5.2-5.7) | 4.8 (4.7-5.8) | 3.3 (2.7-4.3)a |
Infusion | 4.5 (4.2-5.0) | 5.2 (5-7.4)a | 5.1 (4.7-6.9) | 4.6 (3.5-6.2) |
Peritonitis | 4.8 (4.3-5.6) | 5.9 (5.2-6.8) | 5.6 (4.8-6.3) | 7.2 (4.2-9.5) |
PaO
2
/FiO
2
(mm Hg)
| ||||
Control | 489 (445-514) | 399 (374-456) | 412 (320-434) | 432 (272-449) |
Infusion | 463 (348-502) | 251 (164-352)ab | 292 (191-350) | 135 (66-205)ab |
Peritonitis | 456 (336-497) | 340 (309-381) | 173 (115-305)b | 137 (80-286)a |
TNF-α (pg/g of protein)
| ||||
Control | 1 (1-5) | 3 (1-5) | 2 (1-6) | 2 (1-5) |
Infusion | 2 (2-3) | 5 (4-7)a | 16 (10-23)ab | 13 (7-25)ab |
Peritonitis | 1 (1-2) | 7 (5-10)ab | 13 (5-24)ab | 18 (5-33)ab |
IL-6 (pg/g of protein)
| ||||
Control | 2 (1-2) | 1 (1-1)a | 1 (0-1)a | 1 (1-2) |
Infusion | 2 (1-5) | 7 (5-18)b | 34 (27-101)ab | 72 (23-175)ab |
Peritonitis | 3 (1-5) | 29 (11-193)ab | 126 (16-484)ab | 203 (20-1,296)ab |
TBARS (nmol/g of protein)
| ||||
Control | 16 (14-18) | 19 (16-28)a | 24 (18-34)a | 23 (16-26)a |
Infusion | 14 (13-15)c | 22 (19-27)c | 32 (23-39)ac | 30 (27-46)ac |
Peritonitis | 18 (17-24) | 52 (37-76)ab | 84 (51-114)ab | 70 (46-107)ab |
Characteristics of animals with and without S-AKI
Baseline | 12 hours | 18 hours | 22 hours | |
---|---|---|---|---|
Mean arterial pressure (mm Hg)
| ||||
AKI | 106 (97-115) | 82 (72-99)a | 82 (70-96)a | 76 (62-88)a |
Non-AKI | 104 (90-114) | 92 (80-100) | 82 (76-91)a | 78 (73-87)a |
Control | 95 (87-109) | 87 (83-94) | 80 (73-90) | 84 (68-87) |
Cardiac output (ml/kg)
| ||||
AKI | 93 (68-103) | 103 (94-139) | 125 (97-157)b | 107 (93-153) |
Non-AKI | 85 (79-97) | 106 (76-137) | 109 (82-129)a | 145 (98-168)ab |
Control | 98 (90-105) | 97 (85-100) | 80 (76-87) | 85 (77-98) |
Systemic vascular resistance (dyne.s.cm
-5
)
| ||||
AKI | 2,693 (1,912-2,826) | 1,437 (846-1,840)ab | 1,097 (722-1,333)ab | 1,121 (809-1,663)ab |
Non-AKI | 2,477 (2,355-2,712) | 1,676 (1,539-1,973)a | 1,489 (1,282-1,699)ab | 1,113 (819-1,668)ab |
Control | 2,453 (1,838-2,700) | 2,075 (1,935-2,299) | 1,961 (1,872-2,169) | 1,912 (1,648-2,262) |
ITBVI (ml/kg)
| ||||
AKI | 23 (21-29) | 25 (19-30) | 27 (22-31) | 21 (18-24) |
Non-AKI | 26 (23-29) | 26 (23-30) | 24 (21-26) | 24 (22-29) |
Control | 31 (28-33) | 24 (21-34) | 23 (21-30) | 26 (23-28) |
Fluid intake (ml/kg/h)
| ||||
AKI | 12 (9-14) | 16 (15-17)a | 18 (14-18)a | 13 (9-16) |
Non-AKI | 13 (12-15) | 18 (17-22)a | 18 (17-22) | 17 (13-22) |
Control | 13 (11-17) | 16 (13-21) | 13 (13-18) | 13 (10-15) |
VO
2
systemic (ml/min/kg)
| ||||
AKI | 4.8 (4.6-5.2) | 6.0 (5.0-7.4) | 5.6 (4.8-7.0) | 5.8 (4.2-8.6) |
Non-AKI | 4.4 (4.1-5.1) | 5.4 (4.9-6.2) | 5.3 (4.6-6.1) | 4.2 (3.5-7.3) |
Control | 5.6 (4.6-5.9) | 5.5 (5.2-5.7) | 4.8 (4.7-5.8) | 3.3 (2.7-4.3)a |
Arterial base excess (mmol/L)
| ||||
AKI | 6 (5-8.5) | 4 (-0.6-7.5) | 2.7 (-8.6-6.5) | 1.4 (-8.7-3.8)ab |
Non-AKI | 6.6 (4.7-11.8) | 5.6 (4.7-8.5) | 4.1 (2.7-6.7) | 2.2 (1.1-7.7)a |
Control | 8.5 (6.9-12.6) | 7.7 (6.7-8.3) | 7.6 (5.1-11.2) | 6.1 (5.1-7.3) |
Arterial lactate-to-pyruvate ratio
| ||||
AKI | 10 (5-18) | 15 (10-23) | 36 (19-72)a | 38 (21-60)a |
Non-AKI | 10 (8-22) | 12 (10-15) | 22 (10-39) | 20 (10-85) |
Control | 9 (8-26) | 17 (12-29) | 17 (11-75) | 15 (10-37) |
NOx (μmol/g of protein)
| ||||
AKI | 0.8 (0.6-1) | 1 (0.7-1.7) | 1.4 (1-2) | 1.3 (1-1.7)a |
Non-AKI | 0.8 (0.7-1) | 0.8 (0.5-1.2) | 0.9 (0.7-1.3) | 1 (0.8-1.7)a |
Control | 1.1 (0.8-1.4) | 0.6 (0.5-0.7)a | 0.7 (0.6-0.9) | 0.8 (0.6-1) |
Renal effects of sepsis in pigs with and without AKI
Baseline | 12 hours | 18 hours | 22 hours | |
---|---|---|---|---|
Creatinine (μmol/L)
| ||||
AKI | 98 (88-105) | 105 (91-134) | 124 (89-164) | 137 (130-176)abc |
Non-AKI | 94 (90-109) | 96 (81-102) | 95 (87-106) | 101 (89-111) |
Control | 83 (75-96) | 82 (72-100) | 90 (76-101) | 88 (77-99) |
Diuresis (ml/kg/h)
| ||||
AKI | 1.5 (1.3-2) | 2.0 (1.6-2.8) | 2.1 (0.9-4.7) | 0.7 (0.1-1.2)bc |
Non-AKI | 1.9 (1.4-2.4) | 4.2 (2.7-4.9)a | 4.2 (2.2-6.4)a | 1.5 (1.2-3.2) |
Control | 2.4 (1.8-3.2) | 3.9 (2.3-6.6) | 3.3 (2.5-5.7) | 2.2 (1.8-3.2) |
Renal perfusion pressure (mm Hg)
| ||||
AKI | 91 (85-101) | 70 (58-83) | 64 (55-78)a | 60 (53-73)a |
Non-AKI | 91 (76-97) | 76 (64-83) | 65 (57-71)a | 59 (52-69)a |
Control | 86 (78-91) | 70 (68-82) | 67 (59-77)a | 71 (51-77)a |
Renal venous pressure (mm Hg)
| ||||
AKI | 14 (12-15) | 17 (15-19) | 18 (18-19)ab | 19 (18-21)a |
Non-AKI | 14 (11-15) | 16 (15-17) | 18 (15-20)a | 20 (18-22)a |
Control | 11 (9-16) | 14 (13-16) | 14 (12-16) | 17 (13-18) |
Change of renal vascular resistance from baseline (%)
| ||||
AKI | 100 (100-100) | 114 (78-145) | 111 (95-183) | 242 (121-9,430)abc |
Non-AKI | 100 (100-100) | 94 (75-110) | 82 (58-113) | 92 (69-112) |
Control | 100 (100-100) | 112 (89-118) | 101 (63-125) | 81 (59-118) |
Renal VO
2
(ml/min/kg)
| ||||
AKI | 0.2 (0.2-0.3) | 0.2 (0.1-0.3) | 0.2 (0.1-0.2) | 0.1 (0-0.2)a |
Non-AKI | 0.2 (0.1-0.2) | 0.2 (0.2-0.2) | 0.2 (0.2-0.2) | 0.2 (0.2-0.2) |
Control | 0.1 (0.1-0.2) | 0.1 (0.1-0.2) | 0.1 (0.1-0.2) | 0.2 (0.1-0.2) |
Renal cortical microcirculation (laser Doppler flowmetry) (% of baseline value)
| ||||
AKI | 100 (100-100) | 61 (43-80)ab | 62 (45-97)a | 48 (27-67)a |
Non-AKI | 100 (100-100) | 70 (57-108) | 70 (60-100) | 61 (49-86)a |
Control | 100 (100-100) | 97 (73-125) | 70 (63-109) | 73 (58-118) |
Base excess renal vein (mmol/L)
| ||||
AKI | 7.3 (6.1-8.5) | 3.3 (0.1-6.7)b | 2.9 (-5.6-6.7) | -1.9 (-11.8-3.3)ab |
Non-AKI | 8.9 (6.7-11) | 6.2 (5.4-9.1) | 4.9 (3.9-9.1) | 4.1 (1.6-10.2) |
Control | 8.7 (7-13.7) | 7.8 (6.9-9.7) | 7.8 (5.3-9.6) | 6.7 (4.8-7.4) |
Lactate/pyruvate ratio: renal vein
| ||||
AKI | 11 (7-17) | 15 (12-21) | 20 (9-43) | 28 (18-43) |
Non-AKI | 10 (7-20) | 7 (5-18) | 13 (5-27) | 10 (7-19) |
Control | 16 (9-21) | 7 (6-20) | 16 (7-32) | 8 (6-17) |
Renal effects of sepsis in pigs with AKI: comparison of sepsis models
Baseline | 12 hours | 18 hours | 22 hours | |
---|---|---|---|---|
Creatinine (μmol/L)
| ||||
AKI-INF | 95 (84-114) | 92 (88-148) | 105 (85-168) | 150 (134-180)ab |
AKI-PERIT | 98 (93-105) | 107 (97-128) | 129 (112-158)c | 131 (129-166)ac |
NONAKI-INF | 106 (97-120) | 100 (95-107) | 102 (95-110) | 109 (95-117) |
NONAKI-PERIT | 91 (84-91) | 81 (78-96) | 81 (77-91) | 89 (84-94) |
Renal vascular resistance (mm Hg/L/min)
| ||||
AKI-INF | 359 (235-635) | 373 (288-700) | 576 (273-1,161) | 2,433 (1061-2,727)a |
AKI-PERIT | 376 (302-459) | 448 (280-637) | 516 (236-821) | 464 (404-1,425) |
NONAKI-INF | 471 (352-539) | 388 (341-503) | 415 (315-556) | 355 (325-779) |
NONAKI-PERIT | 500 (431-541) | 386 (320-407) | 302 (273-340)a | 383 (339-438) |
Renal-to-systemic vascular resistance ratio
| ||||
AKI-INF | 14 (11-17) | 21 (13-32) | 28 (17-58) | 94 (49-170)a |
AKI-PERIT | 12 (10-14) | 25 (14-59) | 39 (20-59)a | 38 (20-143)a |
NONAKI-INF | 15 (14-19) | 18 (16-35) | 23 (16-40) | 30 (19-63)a |
NONAKI-PERIT | 16 (14-16) | 18 (13-21) | 16 (15-17) | 24 (18-48) |
Renal flow (ml/min/kg)
| ||||
AKI-INF | 6 (6-11) | 6 (3-8) | 4 (2-7) | 1 (1-2)a |
AKI-PERIT | 7 (5-8) | 4 (3-5) | 4 (2-6) | 3 (1-4)a |
NONAKI-INF | 5 (4-7) | 4 (3-5) | 5 (3-5) | 4 (2-5) |
NONAKI-PERIT | 6 (5-6) | 7 (6-8) | 7 (7-9)a | 6 (4-6) |
Renal cortical microcirculation (laser Doppler flowmetry) (% of baseline value)
| ||||
AKI-INF | 100 (100-100) | 70 (57-105) | 67 (55-97) | 35 (25-51)a |
AKI-PERIT | 100 (100-100) | 59 (36-72)a | 61 (41-85) | 57 (32-75)a |
NONAKI-INF | 100 (100-100) | 63 (53-111) | 64 (52-101) | 65 (47-92) |
NONAKI-PERIT | 100 (100-100) | 88 (70-99) | 75 (62-111) | 59 (49-85)a |
Diuresis (ml/kg/h)
| ||||
AKI-INF | 1.7 (1-2.7) | 2.7 (2.2-8) | 4.8 (1.8-8.1) | 1.1 (0.1-3.8) |
AKI-PERIT | 1.5 (1.3-1.9) | 1.8 (1.5-2.3) | 1.6 (0.9-2.1) | 0.6 (0.2-0.9)ac |
NONAKI-INF | 2.2 (1.3-2.5) | 4.5 (3.8-5.5)a | 4.2 (1.7-5.4) | 1.3 (1-2.3) |
NONAKI-PERIT | 1.6 (1.3-2.4) | 2.3 (2-4.8) | 3.9 (2.9-6.5) | 1.7 (1.5-3.6) |
TNF-α (pg/g of protein)
| ||||
AKI-INF | 2 (2-3) | 8 (6-19)a | 14 (12-31)a | 25 (20-42)a |
AKI-PERIT | 1 (1-3) | 10 (5-16) | 18 (5-30)a | 18 (5-105)a |
NONAKI-INF | 2 (1-3) | 4 (4-5) | 18 (10-22)a | 7 (6-15)a |
NONAKI-PERIT | 1 (1-1) | 3 (2-7) | 9 (5-15) | 16 (6-30)a |
IL-6 (pg/g of protein)
| ||||
AKI-INF | 2 (1-5) | 62 (5-104) | 70 (33-130)a | 155 (67-383)a |
AKI-PERIT | 3 (1-8) | 118 (28-327) | 246 (70-1,161)a | 284 (68-3,981)a |
NONAKI-INF | 2 (2-5) | 6 (5-10) | 32 (27-51)a | 61 (18-84)a |
NONAKI-PERIT | 3 (1-4) | 12 (6-29) | 19 (5-221) | 33 (7-1,186)a |
NOx (μmol/g of protein)
| ||||
AKI-INF | 0.8 (0.6-1) | 0.7 (0.6-0.7) | 0.9 (0.7-1.4) | 1.3 (0.9-1.5) |
AKI-PERIT | 0.8 (0.6-1.1) | 1.6 (1.2-3)ad | 1.6 (1.3-3.5)a | 1.1 (1-2.1) |
NONAKI-INF | 0.9 (0.6-1.1) | 0.5 (0.4-0.8) | 0.7 (0.5-1) | 0.8 (0.7-1.4) |
NONAKI-PERIT | 0.8 (0.7-0.9) | 1.2 (1-1.5) | 1.3 (0.8-1.7) | 1.5 (1.3-1.7)a |
TBARS (pg/g of protein)
| ||||
AKI-INF | 14 (11-15) | 26 (14-41) | 31 (24-36)a | 36 (27-61)a |
AKI-PERIT | 21 (18-25)d | 68 (49-93)ad | 90 (58-129)ad | 75 (55-132)a |
NONAKI-INF | 14 (13-14) | 22 (19-23) | 32 (22-39)a | 30 (27-40)a |
NONAKI-PERIT | 18 (16-21) | 35 (32-48) | 77 (44-91)a | 62 (39-106)a |
Discussion
Conclusions
Key messages
-
Although sepsis appears to be a uniform clinical entity, much variation can occur in the renal hemodynamic and functional responses. This variability has to be taken into account when effects of therapeutic interventions are to be assessed.
-
Early abnormal host immune response appears to be the major pathobiologic factor predicting the development of porcine septic AKI.
-
Renal circulatory response to sepsis in animals developing AKI cannot reliably be predicted from changes in systemic hemodynamics.
-
Development of septic AKI is often accompanied by an uncoupling between systemic and renal vascular resistance, suggesting that renal circulation does not participate in sepsis-induced systemic vasodilatation.