The Study Objective was to investigate the effect of vaccinia virus complement control protein (VCP) on ischemia reperfusion (I/R) injury in the kidney. Methods Long Evans rats weighting 345–418g were subjected to laparotomy, clamping of the right renal artery for 60 minutes followed by 24 hours reperfusion. The rats were randomly allocated to receive VCP or phosphate buffered-saline (PBS) or sham groups (n = 6 each). Blood was collected at various intervals for urea and creatinine studies, and the kidneys harvested for histopathological and immunohistochemical studies. Results The creatinine study indicated a 1.2-fold increase in the PBS group. The histopathological study revealed focal necrosis of the tubular epithelial cells in the VCP treated rats compared to the markedly elevated field scores in the PBS controls. The immunohistochemical study showed significant C3 deposition in the renal tubules of the PBS controls. Conclusion The results suggest that VCP plays a role in reducing ischemia/reperfusion induced renal injury possibly by inhibiting the biosynthesis of C3. Source of Research Support: GJK is currently a Senior International Wellcome Trust Fellow in Biomedical Sciences in South Africa. YTG is a recipient of the Poliomyelitis Research Foundation & the University of Cape Town Scholarships.
It has been shown previously that liver regeneration after partial hepatectomy in rats is delayed if the liver is subjected to either concurrent ischaemia, flushing with cold solution, or grafting. We have shown recently that treatment with CsA preoperatively overcomes the suppressive effect of flushing and returns the regenerative response to a normal time scale. The present study was designed to investigate whether administration of FK506 would also return the observed delayed regenerative response to normal.Long-Evans rats weighing 250–350 g were subjected to standard 68% partial hepatectomy. Group 1 had no further treatment; in group 2, the liver remnant was flushed with 10 ml cold (4°C) Ringers lactate solution, and in group 3, FK506 (1 mg/kg/day) was administered by intramuscular injection for 3 days before the partial hepatectomy and flushing as in group 2; a final dose was given after completion of the procedures. Animals were killed in sets of 6 per group at 4, 24, 48, 72, and 96 hr after surgery and blood samples were taken for measurement of plasma aspartate aminotransferase. Liver biopsies were analyzed for measurement of thymidine kinase and ornithine decarboxylase activity and for counting of mitotic figures. While the highest recorded thymidine kinase activity occurred in group 1 at 24 hr, this was delayed to 48 hr in both groups 2 and 3 and counts remained high up to 96 hr in group 3. Mitotic indices were only significantly elevated (compared with group 1 at 96 hr), while ornithine decarboxylase activity did not correlate with these changes being significantly lower than in groups 2 and 3 at 4 hr and in group 3 also at 24 hr. Plasma aspartate aminotransferase was also significantly higher in group 3. It is concluded that the administration of FK506 preoperatively to rats subjected to partial hepatectomy and flushing did not restore the delayed regenerative response to normal but enhanced the response (as measured by thymidine kinase but not by mitotic indices) which commenced at 48 hr and was still present at 96 hr.
The continuous suture technique for end-to-end vascular anastomosis is cautioned against because of the risk of vessel constriction. A modified method of continuous suture for end-to-end venous microanastomosis is presented in which vessel constriction does not occur. This technique was compared with the conventional interrupted suture technique in the rat femoral vein, with each rat serving as its own control. Forty-eight Long-Evans rats were used. The mean time taken to complete the anastomosis was 9.8 minutes (range, 8-14 minutes) for the modified continuous technique and 17.7 minutes (range, 14-24 minutes) for the conventional interrupted technique (p < 0.05, independent t-test). In addition, the veins were examined under the microscope for patency and the milk test was performed on each anastomosis 30 minutes postanastomosis, and 1 week and 1 month postoperatively. Two groups of rats were sacrificed, one at 1 week and one at 1 month, and the two different anastomoses were compared using vessel morphometry in 40 rats and corrosion casts in 8 rats. All veins were patent postoperatively, as well as at 1 week and 1 month postoperatively. Vessel morphometry confirmed a similar luminal surface area in all veins examined at 1 week and 1 month. A two-way analysis of variance of vessel morphometry indicated no significant interaction between the methods used and the postoperative time (p = 0.60). The modified continuous technique is twice as quick as the conventional interrupted technique for end-to-end microvenous anastomosis and does not lead to vessel constriction.