Fibrin adhesives have been advocated as a protective seal in colonic anastomosis to prevent leakage. In order to assess the effect of fibrin glue sealing we compared the healing of sutured colonic anastomosis in the rat (group 1) with the addition of human-derived fibrin sealant (group 2). As a control for a possible reaction to foreign protein, in group 3 the sutured anastomosis was sealed with specially prepared rat fibrin adhesive. On days 2, 4 and 7, ten animals in each group were killed. Adhesion formation was scored and the in situ bursting pressure was measured. The collagen concentration and degradation were estimated by measuring hydroxyproline. Adhesion formation was significantly increased in groups 2 and 3 compared with the control group. On days 2 and 7 the bursting pressure was not different between the groups. On day 4 the bursting pressure in groups 2 and 3 was significantly lower than in group 1 (P less than 0.001). These findings correspond with the results of collagen measurements. On day 4 the concentration of hydroxyproline was significantly reduced in groups 2 and 3. Histological examination showed infiltration of neutrophilic granulocytes into the sealant on days 2 and 4; on day 7 the sealant had vanished. From these results it is concluded that fibrin sealing of the colonic anastomosis in the rat does not improve healing, as demonstrated by bursting pressure and hydroxyproline concentration. On the contrary, it seems to have a negative influence.

No abstract

In 90 rats a colonic anastornosis was constructed with I2 interruptedLeakage from colonic and rectal anastomoses has a reported incidence of up to 50 per cent' and is associated with significantly increased mortality and morbidity rates'. Fibrin sealant is a multicomponent biological adhesive made from concentrated human fibrinogen which can be used to establish haemostasis or as an adhesive in wound repair. Additional sealing with fibrin sealant has been advocated in normal and high-risk colonic anastomosis to prevent anastomotic leakage3-7. Experimental studies provide conflicting results and prospective, randomized clinical studies are l a~k i n g~*~. A negative influence of additional fibrin sealant on the healing colonic anastomosis has recently been demonstrated in the rat". This negative effect might be caused by an increased inflammatory reaction near the anastomosis9~' ' .The quantity and quality of collagen in the submucosal layer of the intestinal wall determines the strength of the healing intestine' '. After colonic anastomosis there is first a period of breakdown of collagen, followed by ~y n t h e s i s '~-'~. Collagen is highly resistant to proteolytic agents but is readily degraded by collagenase. Factors directly influencing the activity of collagenase are infection and inflammation around infected anastomoses15.'6. Bacteria and inflammatory cells are known to produce ~o l l a g e n a s e '~~'~. As every colonic anastomosis must be considered to be contaminated by intestinal bacteria, the fibrin clot will be infected too. It is possible to mix antibiotics with fibrin glue without impairment of its adhesive and clotting properties. High local antibiotic concentrations are then slowly released from the fibrin clot".This study was designed to determine whether the addition of antibiotics abolishes the negative effect of fibrin sealing on the strength and collagen metabolism of healing colonic anastomoses in the rat. Materials and methodsNinety male Wag/Rij rats, weighing 180-230 g, were randomly allocated to three treatment groups and were allowed water (acidified, pH 3.0) and food (AM 11; Hope Farms, Woerden, The Netherlands) ad libitum before and after operation. Using ether anaesthesia and through a midline incision, 1 cm of the left colon, 3 cm proximal to the peritoneal reflection, was resected. A single-layer end-to-end anastomosis was performed with 12 interrupted, inverting 7/0 polypropylene (Prolene; Ethicon, Norderstedt, Germany) stitches in a standard fashion. The resected segment of colon was frozen and kept at -80°C until analysis, to serve as an individual control. The experimental groups were: group 1, control sutured anastomosis; group 2, sutured anastomosis plus human fibrin sealant; group 3, sutured anastomosis plus fibrin-antibiotic complex. The human fibrin sealant (Tissucol; Immuno AG, Vienna, Austria) was prepared according to the manufacturer's instructions. The sealant consists of a freeze-dried protein concentration of human fibrinogen ( 120 mg/ml) which is reconstituted i...

Fibrin adhesives have been advocated as a protective sealant in high-risk colonic anastomoses to prevent leakage. To assess the effect of fibrin glue sealing on the healing ischemic anastomosis, we compared the healing of sutured colonic anastomoses in the rat, with and without fibrin adhesive (Groups IA and IB), and ischemic anastomoses with and without fibrin adhesive (Groups IIA and IIB). On days two, four, and seven, 10 animals in each group were sacrificed. Adhesion formation was scored, and the in situ bursting pressure was measured. The collagen concentration and degradation were estimated by measuring hydroxyproline. Adhesion formation was more prominent in Groups IB, IIA, and IIB on day four only; abscesses were noted in the ischemic group in four rats. Anastomotic bursting pressure was significantly lower in sealed (IB) and ischemic anastomoses (IIA) than in normal anastomoses (IA) on day four. Sealing of ischemic anastomoses did not change bursting pressures on days two, four, and seven. The relative decrease of collagen in the sealed anastomoses is significantly higher on day four only. It is concluded that sealing of normal colonic anastomoses in the rat has a negative effect on wound healing. Ischemia at the anastomotic site results in weaker anastomotic strength on day four postoperatively. Also in ischemic anastomoses, fibrin sealant does not improve wound healing during the first seven days. Adhesion formation on ischemic intestinal anastomoses was not prevented by fibrin sealing.

1. In an experimental model of post-renal transplantation hypertension in rats, we studied the effect of a reduction of sodium intake on the development of this type of hypertension. 2. Systolic blood pressure, plasma- renin concentration and renal function were measured regularly in recipients of an allogeneic kidney transplant that had previously undergone active immunological enhancement. 3. Transplant recipients on a normal diet showed a rise in systolic blood pressure during the second week after transplantation. The systolic blood pressure of recipients on a low sodium diet remained normotensive throughout the 15 weeks follow-up period. 4. The plasma renin concentration was low in the hypertensive recipients on a normal diet, as compared with unilaterally nephrectomized controls. Although the plasma renin concentration of recipients on a low sodium diet fell below that of unilaterally nephrectomized controls on a low sodium diet, it was higher than that of recipients on a normal diet. 5. The renal function of transplant recipients was greatly reduced compared with that of control rats. The glomerular filtration rate was reduced to a greater extent than the effective renal plasma flow. 6. In a separate experiment it was revealed that a similar reduction in the glomerular filtration rate of kidneys permanently damaged by temporary ischaemia did not result in an increase in the systolic blood pressure. 7. Survival up to 6 weeks after transplantation was the same for both groups of recipients. Recipients on a low sodium diet, however, showed a better 15 weeks survival, probably owing to the absence of hypertension in this group. 8. The prevention of the development of hypertension by means of a reduction of sodium intake, points to an involvement of sodium retention in this post-transplantation hypertension model.

Diets high (17.7 cal%) and low (3.3 cal%) in linoleic acid were given to groups of Brown Norway female rats before and after inoculation of syngeneic tumor models with different characteristics, with regard to tumor spread, malignancy, immunogenicity, growth rate, rat strain, and histopathological features. Despite the differences in characteristics, in most tumor models, tumor growth was identical in both experimental groups. However, in 2 tumor models, an adrenal cortical carcinoma and a myeloid leukemia, differences in growth were noted. In rats given the diet low in linoleic acid, growth of the cortical carcinoma was significantly increased, whereas the opposite effect was seen in rats with myeloid leukemia.

For suppression of primary tumor growth and metastatic spread, aspirin and theophylline, either alone or combined, were given daily to inbred female BN rats after sc implantation of a syngeneic nonimmunogenic tumor. Treatment with 200 mg aspirin/kg (body wt) resulted in a statistically significant regression of tumor growth as well as of the number of metastases in the lungs. Aspirin given in a lower dose (20 mg/kg) did not show significant difference from the vehicle group. Theophylline (75 mg/kg) significantly increased primary tumor growth as well as lung metastases. Inhibition of in vitro platelet aggregation, determined in whole blood taken from non-tumor-bearing animals treated with the same therapeutic regimen, was most pronounced in those groups in which tumor growth and spread were significantly retarded. However, this positive correlation between inhibition of tumor spread and platelet aggregation was not associated with a favorable balance of prostacyclin and thromboxane A2 in these animals.

To determine the immunosuppressive effect of stress and a diet rich on linoleic acid on vascularized organ graft survival in the rat, a series of allogeneic heart and kidney grafts were carried out. Restraint stress resulted in a significant prolongation of the survival time. Although 5 days of postoperative stress gave the best results, 3 h of stress given on the first postoperative day already gave a marked prolongation of the survival time of kidney allografts. The beneficial effect of stress on heart survival was abolished when prior adrenalectomy was carried out. A diet high on polyunsaturated fatty acids gave significant prolongation of the survival times of kidney-grafted rats. A diet high on saturated fatty acids did not result in a statistical significant prolongation of the survival time, although the difference with the polyunsaturated fatty acid group was very small and not statistically significant. It was concluded that stress and diets high in certain types of fatty acids depress the immune response in rats, possibly via a mechanism which has some common pathways. The adrenal glands could play an important role in this immune inhibition.