Effect of a smooth muscle antagonist on contraction of patched intestinal defects.

Growing new intestinal mucosa on serosal patches may potentially increase intestinal surface area but is limited by contraction of the serosal patch. Since this might be related to smooth muscle contraction or altered collagen metabolism, our aim was to determine whether the smooth muscle antagonist thiphenamil inhibits contraction. Fifty rabbits had two 2 x 5-cm full-thickness intestinal defects patched with adjacent cecum. Group I (n = 25) received saline and Group II (n = 25) 0.02 M thiphenamil at 10 cc/hr intraluminally. Animals were sacrificed at 1, 3, 5, 7, and 10 days. Group II had significantly less contraction of the proximal patch until the 10th day after patching (84 +/- 8 vs 66 +/- 20% Day 1, 67 +/- 4 vs 52 +/- 9% Day 5, 42 +/- 14 vs 42 +/- 7% Day 10). Epithelialization of patches was significantly less in Group II animals at 10 days (88 +/- 8 and 86 +/- 11% vs 47 +/- 20 and 50 +/- 16%, P less than 0.05) but crypt cell production rate and villus height were similar. The hydroxyproline content of regenerating tissue increased significantly 7 and 10 days after patching but was similar in the two groups (30.8 +/- 5.9 micrograms/mg tissue Day 10 vs 12.8 +/- 2.8 Day 1). Smooth muscle antagonism by thiphenamil inhibited contraction of serosal patches but had a deleterious effect on epithelialization and mucosal enzyme activity. The transient effect of thiphenamil and the associated increase of hydroxyproline content suggest that collagen may have the predominant role in contraction.