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Interleukin-1 (IL-1) regulates intestinal glutamine metabolism in vivo
11. Interieukin-1(IL.-l) Regulates Intestinal Glutamine Metabolism ia viva T. Austgen, MD, M. Chen, MD, P. Dudrick, E. Copeland, MD, W. Souba, MD, Dept. of Surgery, University of Florida, Gainesville, FL
MD,
S. D. Fitzgerald, C. H. Andrus,
Glutamine (GLN) is the major energy substrate for the gut mucosa. During severe infection and endotoxemia, the ability of the gut to utilize (GLN) is impaired. This may contribute to the breakdown in gut barrier function observed in critical illness. This study examined the role of the cytokines interleukin-1 (IL-l) and tumor necrosis factor (TNF) in uiuo as potential mediators of these alterations. Rats (250 g) received endotoxin (ENDO, 7.5 mg/kg intraperitoneally, n = 18), IL-l (50 pg/kg intraperitoneally, n = 16), TNF (50 rg/kg intraperitoneally, n = 16), or saline (CONT, n = 12). Rats were studied post-absorption at various timepoints (4 hours, 12 hours) after intraperitoneal injection. Blood samples were obtained from the carotid (A) and portal veins (PV) for determination of GLN levels (PM). Blood cultures were taken from a tail vein. C-14 PAH was used to determine PV blood flow (mL/minute/lOO g body weight). Gut flux (nmol/lOO g body weight/minute) was calculated by: [(A-PV) X PV flow]. Mucosal glutaminase activity (GLNase, rmol/hour/mg protein) was determined. A portion of the 4-hour (IL-l, TNF) and 12hour data (CONT, ENDO) is shown in the Table.
CONT ENDC IL- 1 TNF l
Art GLN
Qut Flow
A-PV
Gut Flux
715f21 69li32 596fl4” 567 f 12”
3.5 f 0.1 3.0 l 0.3 3.3hO.2 3.5 i 0.2
139 f 9 106 * 13’ 76i9’ 126 f 7
477 f 26 336 i 46’ 253f31’ 443 f 26
p < 0.05,
L. J. Baudendistel, T. E. Dahms, D. L. Kaminski, Depts. of Surgery and Anesthesiology, St. Louis University Hospital, St. Louis, MO Patients with cardiopulmonary insufficiency undergoing laparoscopic surgery with CO2 pneumoperitoneum may retain CO*, resulting in clinically significant respiiatory acidosis. A canine model of pulmonary emphysema induced by papain inhalation was utilized to evaluate the respiratory effects of both CO2 and helium pneumoperitoneum. Prior to papain inhalation and 5 and 8 weeks after treatment, ventilation was adjusted to maintain ET CO1 = 40 mm Hg during baseline and pneumoperitoneum periods. Hemodynamic and arterial blood gas parameters were compared using paired r-test analysis. Average baseline respiratory parameters before papain treatment without pneumoperitoneum were: PaC02 = 43.0 f 1.5 mm Hg, Min Vol/kg = 224.1 f 65.1, PaCOz-ET CO2 = 2.7 f 1.3 mm Hg, and pH = 7.39 f 0.03. Respiratory parameters 8 weeks after papain inhalation (with ventilation adjusted for ET CO2 = 40 mm Hg) are shown in the Table. None
CO2
P Value
Hellum
P Value
49 h 3.6 191.0 f 57.0 10.9 f 4.6
53.1 & 4.1 210.0 f 39.2 11.6 i 3.7
0.004 0.0001 0.001
44.9 f 3.0 172.1 f 21.6 6.5 f 2.3
NS NS NS
7.33 h .04
NS
GLNaSe 8.7 f 0.6 6.2 f 0.2” 6.lzkO.3” 6.6 zlz 0.6
** p < 0.01 vs. CONT (by ANOVA).
Treatment with both END0 and IL-1 resulted in a significant decrease in gut GLN uptake and in GLNase activity. In Il-l-treated rats, these alterations were still present 12 hours after injection. TNF had no such effects at either 4 or 12 hours or at larger doses. Furthermore, in 4/16 IL-1 rats and 4/18 END0 rats, blood cultures demonstrated gram-negative bacteremia. All blood cultures were negative in the TNF and CONT rats. The derangements in gut GLN metabolism occurred earlier in the IL- 1 rats compared with the END0 rats, consistent with endotoxin-initiated de twvoIL-1 synthesis. IL-1 appears to be an important mediator of the altered gut GLN metabolism observed during severe infection.
708
12. Hypewarbia During Carbon Dioxide (CO2) Pneumoperitoneumin a Canine Modei of Chronic ObstructivePulmonary Disease (COPD)
THE AMERICAN JOURNAL OF SURGERY
PaC02 Mln W/kg PaCO2 ET CO2 PH
7.32
f
.02
7.31 l .02
0.03
In this model, emphysematous dogs had consistent hypercarbia during CO2 pneumoperitoneum. The occurrence of hypercarbia during CO2 pneumoperitoneum may be underestimated by ET CO2 monitoring as was noted by an increased PaCOz-ET CO2 gradient. The absence of hypercarbia and acidosis in this emphysema model during helium pneumoperitoneum suggests that helium may be a reasonable alternative in patients at risk for CO2 retention.
VOLUME 161 JUNE 1991
MD,
S. D. Fitzgerald, C. H. Andrus,
Glutamine (GLN) is the major energy substrate for the gut mucosa. During severe infection and endotoxemia, the ability of the gut to utilize (GLN) is impaired. This may contribute to the breakdown in gut barrier function observed in critical illness. This study examined the role of the cytokines interleukin-1 (IL-l) and tumor necrosis factor (TNF) in uiuo as potential mediators of these alterations. Rats (250 g) received endotoxin (ENDO, 7.5 mg/kg intraperitoneally, n = 18), IL-l (50 pg/kg intraperitoneally, n = 16), TNF (50 rg/kg intraperitoneally, n = 16), or saline (CONT, n = 12). Rats were studied post-absorption at various timepoints (4 hours, 12 hours) after intraperitoneal injection. Blood samples were obtained from the carotid (A) and portal veins (PV) for determination of GLN levels (PM). Blood cultures were taken from a tail vein. C-14 PAH was used to determine PV blood flow (mL/minute/lOO g body weight). Gut flux (nmol/lOO g body weight/minute) was calculated by: [(A-PV) X PV flow]. Mucosal glutaminase activity (GLNase, rmol/hour/mg protein) was determined. A portion of the 4-hour (IL-l, TNF) and 12hour data (CONT, ENDO) is shown in the Table.
CONT ENDC IL- 1 TNF l
Art GLN
Qut Flow
A-PV
Gut Flux
715f21 69li32 596fl4” 567 f 12”
3.5 f 0.1 3.0 l 0.3 3.3hO.2 3.5 i 0.2
139 f 9 106 * 13’ 76i9’ 126 f 7
477 f 26 336 i 46’ 253f31’ 443 f 26
p < 0.05,
L. J. Baudendistel, T. E. Dahms, D. L. Kaminski, Depts. of Surgery and Anesthesiology, St. Louis University Hospital, St. Louis, MO Patients with cardiopulmonary insufficiency undergoing laparoscopic surgery with CO2 pneumoperitoneum may retain CO*, resulting in clinically significant respiiatory acidosis. A canine model of pulmonary emphysema induced by papain inhalation was utilized to evaluate the respiratory effects of both CO2 and helium pneumoperitoneum. Prior to papain inhalation and 5 and 8 weeks after treatment, ventilation was adjusted to maintain ET CO1 = 40 mm Hg during baseline and pneumoperitoneum periods. Hemodynamic and arterial blood gas parameters were compared using paired r-test analysis. Average baseline respiratory parameters before papain treatment without pneumoperitoneum were: PaC02 = 43.0 f 1.5 mm Hg, Min Vol/kg = 224.1 f 65.1, PaCOz-ET CO2 = 2.7 f 1.3 mm Hg, and pH = 7.39 f 0.03. Respiratory parameters 8 weeks after papain inhalation (with ventilation adjusted for ET CO2 = 40 mm Hg) are shown in the Table. None
CO2
P Value
Hellum
P Value
49 h 3.6 191.0 f 57.0 10.9 f 4.6
53.1 & 4.1 210.0 f 39.2 11.6 i 3.7
0.004 0.0001 0.001
44.9 f 3.0 172.1 f 21.6 6.5 f 2.3
NS NS NS
7.33 h .04
NS
GLNaSe 8.7 f 0.6 6.2 f 0.2” 6.lzkO.3” 6.6 zlz 0.6
** p < 0.01 vs. CONT (by ANOVA).
Treatment with both END0 and IL-1 resulted in a significant decrease in gut GLN uptake and in GLNase activity. In Il-l-treated rats, these alterations were still present 12 hours after injection. TNF had no such effects at either 4 or 12 hours or at larger doses. Furthermore, in 4/16 IL-1 rats and 4/18 END0 rats, blood cultures demonstrated gram-negative bacteremia. All blood cultures were negative in the TNF and CONT rats. The derangements in gut GLN metabolism occurred earlier in the IL- 1 rats compared with the END0 rats, consistent with endotoxin-initiated de twvoIL-1 synthesis. IL-1 appears to be an important mediator of the altered gut GLN metabolism observed during severe infection.
708
12. Hypewarbia During Carbon Dioxide (CO2) Pneumoperitoneumin a Canine Modei of Chronic ObstructivePulmonary Disease (COPD)
THE AMERICAN JOURNAL OF SURGERY
PaC02 Mln W/kg PaCO2 ET CO2 PH
7.32
f
.02
7.31 l .02
0.03
In this model, emphysematous dogs had consistent hypercarbia during CO2 pneumoperitoneum. The occurrence of hypercarbia during CO2 pneumoperitoneum may be underestimated by ET CO2 monitoring as was noted by an increased PaCOz-ET CO2 gradient. The absence of hypercarbia and acidosis in this emphysema model during helium pneumoperitoneum suggests that helium may be a reasonable alternative in patients at risk for CO2 retention.
VOLUME 161 JUNE 1991