Postoperative changes in collagen synthesis in intestinal anastomoses of the rat: differences between small and large bowel.

Abstract

Collagen synthesis is an essential feature of anastomotic healing in the intestine. Postoperative collagen synthesis, measured in vitro in intestinal anastomoses was studied from three hours to 28 days after operation. For this purpose, an ileal and a colonic anastomosis were constructed within the same animal and the results in both intestinal segments were compared. In the ileum, coliagen synthesis was significantly increased, with respect to unoperated controls, three hours after operation. It remained raised during the period of study, with a maximal 10-fold stimulation four days after operation, and had nearly returned to the preoperative level after four weeks. The general pattern was the same in the colon, although quantitatively different: the increase in synthetic activity was delayed in comparison with the ileum. Maximal stimulation was approximately six-fold. In addition, we calculated the ratio for each rat between anastomotic coliagen synthesis and the average value found in non-operated control animals. Postoperative stimulation in the ileum was higher than in the colon in almost every animal examined. The results show that the ileum responds more quickly and strongly to wounding than the colon, at least as far as the production of new coliagen is concerned. Possibly, this phenomenon contributes to the lower failure rate apparent for anastomoses in the smali bowel. The strength of the intact and the anastomosed bowel wall is derived from collagen fibrils, located predominantly in the submucosa,2 3 which connective layer forms the backbone of the intestine. During the first postoperative days anastomotic strength is low and anastomotic collagen levels change massively.4 It is generally assumed that the transiently lowered collagen concentrations, observed during normal healing, are the result of early, although limited, collagen degradation followed by considerable collagen synthesis. While early anastomotic strength depends on the suture holding capacity of existing collagen fibrils, newly formed collagen is needed to bridge the gap and restore the original strength of the bowel wall. Thus, the progress of collagen synthesis plays a central role in the healing sequence: disturbance ofits regulation will affect anastomotic strength and might enhance chances for dehiscence.The occurrence of collagen synthesis around experimental intestinal anastomoses has been shown in vivo, in the ileum5 and in the colon6 from two days after operation onwards. The methodology used for such experiments requires administration of large amounts of radioactive proline to animals and precludes the measurement of synthesis in the immediate postoperative period as the precursor needs to be injected at least 24 hours before death.6 A system to measure collagen synthesis in intestinal explants has recently been established.7 This in vitro system allows measurement immediately after operation and appears suitable to initiate research on the effects ofpotentially regulatory factors. Here, we report on the postoperative...

Intraperitoneal cytostatics impair early post-operative collagen synthesis in experimental intestinal anastomosesP6

“…In vivo measurements have established the occurrence of increased synthetic activity around experimental anastomoses in ileum (Jonsson et al, 1987) and colon (Jiborn et al, 1980). We have recently confirmed and extended these observations (Martens & Hendriks, 1991), using an in vitro technique for measuring collagen synthesis (Martens & Hendriks, 1989) also employed in the present study.…”

“…We have established a technique to measure collagen synthesis in intestinal explants (Martens & Hendriks, 1989). Using this technique, it can be demonstrated that anastomotic collagen synthesis increases shortly after operation and remains strongly elevated during the first postoperative week (Martens & Hendriks, 1991 Operative techniques Surgery was performed under semi-sterile conditions using a Zeiss operating microscope. The rats were anaesthetised by an intraperitoneal injection of sodium pentobarbital.…”

The effects of 5-fluorouracil and interferon-α on early healing of experimental intestinal anastomoses

“…It remains to be determined how exactly interferon-i interferes with the healing sequence. The strength of both the uninjured and the sutured bowel wall depends to a large extent on collagen and anastomotic construction leads very quickly to an increased collagen synthetic capacity within the wound area (Martens and Hendriks, 1991). Interferons are known to be able to inhibit collagen synthesis (Granstein et al.…”

Doxycycline-coated sutures improve mechanical strength of intestinal anastomoses

“…This is probably because MMP induction and activation after resection and suturing occur immediately, while de novo matrix synthesis does not begin until the third-fourth postoperative day [22,23]. Thus, early suture holding capacity is dependent on the pre-existing collagen-rich matrix of the submucosa, which is rapidly degraded by MMPs, while later the anastomosis is supported by newly deposited extracellular matrix.…”