Glucagon immunoneutralization in diabetic rats normalizes urea synthesis and decreases nitrogen wasting.

To study the effect of glucagon neutralization on urea synthesis in diabetic rats, animals with newly induced (75 mg/kg streptozocin) experimental diabetes mellitus were divided into two groups. One group was given one weekly injection of nonimmune rabbit serum (n = 6), and the other group was given one weekly injection of a specific high-titer antibody against pancreatic glucagon (n = 6). Four weeks later, serum-treated diabetic rats had fasting glucagon concentrations 2-3 times higher than nondiabetic controls given one weekly injection of saline (control). Plasma glucagon binding capacity of diabetic rats given glucagon antibodies was 10-15 times higher than the glucagon concentration. A second group of nondiabetic controls were given nonimmune serum. Blood glucose concentration and urinary glucose output were identical in both groups of diabetic animals. Food intake doubled in both groups of diabetic rats. In control rats, the accumulated nitrogen balance, determined weekly for 4 wk, was positive at 81 +/- 3.1 mmol/96 h; in serum-treated diabetic rats, the accumulated nitrogen balance was negative, -8.3 +/- 2.4 mmol/96 h throughout the 4 wk, whereas it was higher at 4.7 +/- 2.3 mmol/96 h in the glucagon antibody-treated diabetic rats (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal and neural blockade prevents the postoperative increase in amino acid clearance and urea synthesis.

The combined effect of continuous blockade of glucagon and cortisol by somatostatin and etomidate and thoracic epidural analgesia on hepatic conversion of amino nitrogen was studied in eight patients who underwent elective cholecystectomy on day 1 after operation and was compared with 16 patients who underwent operation without blockade. Surgery increased the plasma clearance of total alpha-amino nitrogen from 5.2 +/- 0.3 to 6.6 +/- 0.3 ml/sec (mean +/- sem; p less than 0.05). This increase was due to increased elimination by the liver, because the hepatic effectiveness for amino nitrogen conversion measured by the functional hepatic nitrogen clearance increased from 9 +/- 2 to 16 +/- 4 ml/sec (p less than 0.05). In contrast, during the combined neural and hormonal blockade, surgery decreased the plasma clearance of amino nitrogen from 5.3 +/- 0.3 to 3.9 +/- 0.3 ml/sec (p less than 0.05), and the blockade prevented the postoperative increase in functional hepatic nitrogen clearance. The results suggest that glucagon, cortisol, and afferent neural reflexes are mediators of the hepatic contribution to catabolism after operation.

Indomethacin prevents the increase in urea synthesis capacity and the weight loss after hysterectomy in rats.

Prostaglandins have been suggested to be mediators of post-operative catabolism. Previous studies have shown that stimulation of urea synthesis contributes to post-operative nitrogen loss. The effect of prostaglandins on this hepatic function was assessed in hysterectomized rats on the first post-operative day by measurements of the Capacity of Urea-N Synthesis (CUNS) with and without indomethacin treatment. Hysterectomy increased CUNS by 1 3 and led to a weight loss of 10 g in one day. Indomethacin prevented the increase in CUNS and the post-operative weight loss in operated animals; it also decreased CUNS by 1 3 in control rats. Blood amino-nitrogen concentration of indomethacin treated hysterectomized rats was 1 3 lower than in untreated animals, indicating an even more marked effect of indomethacin on post-operative tissue amino-acid release than on CUNS. Indomethacin exerts a nitrogen sparing effect, possibly depending on normalization of both post-operative hepatic amino-nitrogen conversion and tissue proteolysis. This may be of clinical importance in controlling post-operative catabolism.

Effects of hysterectomy and semi-starvation on amino-acid gradients across liver, muscle and gut in rats.

To study the effects of surgical stress and insufficient food intake on amino-acid exchange of liver, gut, and muscle, blood was sampled in random sequence from the aorta, the inferior caval vein, the portal vein, and the hepatic veins in 3 groups of 20 rats each. Control rats were fed ad libitum, hysterectomised rats were studied on the first and third post-operative day, and semi-starved rats were pair-fed to hysterectomised rats to an intake of 13% of control on the first day. Both groups lost 5-8% of body weight. Surgery increased the concentration gradient (release) of urea across liver by 60%, the glucose gradient (release) by 35%, and doubled the concentration gradients (uptake) across liver of alanine, arginine, glycine, lysine, proline, serine, and threonine, and decreased their plasma concentrations. There was no major change in hepatic amino-acid gradients in semi-starved animals, and there was no appreciable change in gradients of single amino-acids across gut or muscle in animals subjected to surgery or semi-starvation. Post-surgical increases in urea synthesis and hepatic uptake of uragenic and gluconeogenic amino-acids are due to the surgical stress and not to the post-operative semi-starvation.

Elective cholecystectomy increases plasma amino-acid clearance and hepatic capacity for urea synthesis for one week.

The importance of the liver in post-operative catabolism was studied in 6 cholecystectomy patients given a mixture of amino-acids as prime-continuous infusions pre-operatively and on the 1st, 3rd, 6th and 12th post-operative day. The plasma clearance of total alpha-amino-nitrogen and of single amino-acids, the urea-nitrogen synthesis rate, and the functional hepatic nitrogen clearance were calculated. Surgery decreased fasting blood amino-nitrogen concentration by 15% (p < 0.01), and increased the plasma clearance of amino-nitrogen by 30% (P < 0.05) on the 1st, 3rd and 6th post-operative day. Surgery doubled the functional hepatic nitrogen clearance (p < 0.01) on the 1st, 3rd and 6th post-operative day. This indicates that post-operative stress catabolism is partly due to a hepatic condition by which the liver eliminates more amino-nitrogen despite lower amino-acid concentration in the blood, for one week post-operatively.

Xylitol normalizes the accelerated hepatic capacity for conversion of amino nitrogen to urea nitrogen in diabetic rats.

In diabetes, the capacity of urea nitrogen synthesis, ie, a substrate-independent measure of the hepatic conversion of amino nitrogen to urea nitrogen, is increased. Xylitol decreases urea synthesis in normal rats. Capacity of urea nitrogen synthesis and nitrogen balance were measured during intravenous alanine loading in control rats, rats with experimental diabetes (streptozocin 75 mg/kg), and rats with experimental diabetes infused with xylitol to 1 mmol/L. In control rats, capacity of urea nitrogen synthesis was 9.4 +/- 1.1 mumol/min per 100 g of body weight, and nitrogen balance -2.7 +/- 1.2 mumol/min per 100 g of body weight. In the diabetics, these values were markedly increased to 26.6 +/- 1.9 and -16.3 +/- 2.1 mumol/min per 100 g of body weight, respectively (p < 0.01). The infusion of xylitol normalized these values to 11.2 +/- 1.0 and -3.6 +/- 2.1 mumol/min per 100 g of body weight for capacity of urea nitrogen synthesis and nitrogen balance, respectively. Xylitol did not change glucagon or insulin. Xylitol improved the nitrogen economy of uncontrolled diabetic rats by decreasing urea synthesis. The mechanism is not settled, but it does not involve insulin or glucagon.

Double-stapled esophagogastric anastomosis for resection of esophagogastric or cardia cancer: new application for an old technique.

In colorectal surgery, the double-stapled technique is used extensively, because it is a fairly safe and simple procedure and is useful in relatively inaccessible areas. For these reasons, we adapted the procedure to the upper gastrointestinal tract. The present study reports our first experiences of the surgical efficacy using an esophagogastric double-stapled end-to-end anastomosis for subtotal esophagectomy and cardia resection. We retrospectively studied 31 patients treated between January 1991 and January 1997 with respect to hospital mortality, anastomotic leakage, cancer recurrence, and benign stricture rate. No hospital mortality was seen. One nonfatal anastomotic leak occurred (3%). In three patients, esophageal resection was not radical (10%). Of the remaining 28 patients, one had an anastomotic cancer recurrence (4%). Eleven of the remaining 27 patients (41%) developed a benign anastomotic stricture. All achieved normal swallowing after a median of two endoscopic dilatation procedures using TTS balloons. In conclusion, the double-stapled end-to-end anastomosis technique after resection for esophagogastric or cardia cancer is a simple and expeditious procedure, carrying an acceptable perioperative morbidity and cancer recurrence rate. Larger staplers are recommended to lower the high stricture rate observed after the usage of a 21-mm stapler in this study.