Search

Utilizing a 24 hour fasting rabbit (N = 30), we measured free amino acids in the femoral artery and vein and the quadriceps femoris muscle. The endotoxin E. coli 026, 3.0mg/kg (LD100) was injected and free amino acid plasma levels were monitored for 6 hours. Changes in free amino acid plasma levels were variable and marked after endotoxin injection. By 360 min. after endotoxin injection: (a) the rate of increase in free amino acid levels in the femoral artery was 366 mumole/l of alanine, 162 mumole/l of glycine and 85 mumole/l of proline; (b) the rate of increase in free amino acid of the quadriceps femoris muscle was 1376 nmole/g of alanine, 156 nmole/g of glycine and 109 nmole/g of serine; and (c) the femoral arteriovenous difference was -225 nmole/l of alanine, -118 nmole/l of glycine and -77nmole/l of proline. Within 10 min. after endotoxin injection, alanine concentration was higher in the femoral vein. This change in concentration became significant by 60 min. The results show the following: Skeletal muscle appears to be an important source of amino acids for amino acid metabolism during endotoxemia, especially plasma alanine which is closely connected with alanine levels in skeletal muscle.

Tissue circulation of the adrenal gland which is known as antishock organ was investigated by the hydrogen clearance method in hemorrhagic and endotoxin shock using rabbits. Mean blood pressure was maintained at 35 mmHg for two hours in the hemorrhagic group, while 2mg/kg of endotoxin was injected intravenously in the endotoxin group. The data obtained were as follows: Adrenal tissue circulation and renal circulation were reduced to 40% and 14.9%, respectively in the hemorrhagic group and reduced to 69% and 48%, respectively in the endotoxin group. Plasma corticosterone concentration was significantly elevated in both groups. Plasma beta-glucuronidase was significantly elevated in both groups and most animals died within 72 hours. From these data we concluded that adrenal circulation was distributed preferentially at the sacrifice of renal circulation in the shocked state.

Anastomotic leakage and fistula of alimentary tract are accompanied by peritonitis because of exudation of contents in the digestive canal. In order to inquire about metabolism of protein and amino acids in surgical infection, this study was performed by the method of a time related cross-over trial, comparing high branched chain amino acids (BCAA) solution with low BCAA solution. The following results were obtained. When metabolism is physiologically compensated in infection, it was suggested that there appeared to be gluconeogenesis, ureagenesis and a liver disturbance accompanied in the early phase of sepsis. Administration of BCAA leads to an inhibition of muscle protein break down and a promotion of visceral protein synthesis in the case of severe infection. Administration of BCAA enriched amino acids solution have an important therapeutic measure under severe stressed condition and a significant role in medicine.

It is known that intrinsic endotoxemia is caused by two main mechanisms, reticuloendothelial system dysfunction and intestinal circulatory failure. We investigated the escape of endotoxin from the intestine under occlusion of the superior mesenteric artery 3 days after 70% liver resection in rabbits. Twelve rabbits were given intra-intestinal antibiotics (Antibiotics group) and other twelve rabbits were given saline only (Control group). The results were as follows. Indocyanine green clearance and lipid clearance were deteriorated in both groups after hepatectomy but the antibiotics group showed a better clearance rate than the control group. Serum endotoxin level was elevated slightly after hepatectomy and then grossly elevated after superior mesenteric artery occlusion, but the antibiotics group showed a lower endotoxin level than that of the control group. Seventy-two hours survival rate was apparently better in the antibiotics group. From those data we conclude that the administration of intraintestinal antibiotics contributed to the maintenance of reticuloendothelial function of remnant hepatic lobe and suppressed the serum endotoxin level after superior mesenteric artery occlusion.

We postulate that high plasma concentrations of gastrointestinal-derived glucagon may be used to identify severe sepsis and correlate with the effect of therapy. Eighteen adult dogs were separated into three groups: Group I-LD100 E. coli alone, group II-LD100 E. coli + tobramycin (TOB) and group III-LD100 E. coli + TOB + methylprednisolone sodium succinate (MPSS). E. coli was infused intravenously for one hour. Each animal was monitored for six hours and observed for a 7-day recovery period. Percent survival (greater than 7 days): I = 0%, II = 17% and III = 83%. Concentrations of gastrointestinal glucagon were 3417 pg/ml in group I, 5167 pg/ml in group II and 1081 pg/ml in group III at six hours after E. coli infusion. In group III these concentration returned to control values by 7 days after E. coli infusion. Increases in gastrointestinal glucagon were more readily induced by E. coli infusion than those of pancreatic glucagon. Gastrointestinal glucagon concentrations were related to the severity of E. coli induced shock and the beneficial effects of MPSS/TOB therapy. Therefore, plasma gastrointestinal glucagon concentrations may be useful in recognizing the presence of severe sepsis and directly related to the beneficial effects of therapy.

Sixty three percent of 60 cases of clinically diagnosed Disseminated Intravascular Coagulation (DIC) developed to Multiple Organ Failure (MOF) and the mortality was high in the group which showed organ failure before the manifestation of DIC. The mortality of MOF cases was 91.6% and the presence of organ failure before or after DIC manifestation did not affect the mortality. Among 41 autopsy cases, microscopic examination showed pathohistological DIC in 19 cases even in basic lesion bearing cases without any clinical DIC signs (31.3%). Clinically and experimentally it was suggested that intrinsic and extrinsic endotoxin, namely, hepatic failure, infection etc. may play an important role in manifestation of DIC and development of MOF. Once DIC appears, hypercoagulability and hyperfibrinolysis will develop, then microthrombus in organs will appear in quite early phase of clinical course. Organ specificity and intraorganic specificity might be explained by anatomical factor and local fibrinolysis, etc.. In conclusion, the early detection of DIC and employment of protective treatment for organ failure are though necessary to improve prognosis.