Effect of Cecectomy and Succinylsulfathiazole on Vitamin K Synthesis. ∗

Great interest is centered on the synthesis of essential nutrients by microörganisms of the digestive tract. 1 , 2 , 3 , 4 , 5 , 6 The cecum, aptly referred to as a “fermentation vat,” 6 is generally regarded as the principal site of this important function in the rat.

Although quite a few reports have been made concerning the inhibitory effects of certain sulfonamides on the enteric synthesis of various vitamins very little experimental work has been done on the role of the cecum as a favorable site for such activity. The latter studies have been concerned only with the synthesis of B-complex vitamins 7 , 8 , 9 and the utilization of phytin phosphorus. 10

During the past year our investigation of factors affecting vitamin K synthesis in the intestinal tract 11 has included observations on cecectomized rats. The timeliness of certain of our findings prompts this short communication.

Stock rats about 35 days old were started on a vitamin K-free diet of the following composition: casein (Smaco, vitamin-free) 18, glucose (Cerelose) 66, salt mixture 4, etherextracted brewer's yeast 7, corn oil 3, cod liver oil 2, and choline chloride 0.04. After one week these animals were cecectomized and two days after the operation succinylsulfathiazole was added to the vitamin K-free diet at a level of 1% replacing an equal amount of glucose. Four weeks after cecectomy determination of the plasma prothrombin clotting time was started at biweekly intervals using a modification of Quick's method. 12 The blood was obtained by cardiac puncture under ether anesthesia.

Severe hypoprothrombinemia occurred in 14 out of 17 cecectomized animals fed the vitamin K-free diet containing succinylsuflathiazole. Within 3 months nearly all had died from hemorrhage due to severe hypoprothrombinemia. Seven to severe hypoprothrombinemia. Seven out of 9 littermates cecectomized at the same time and fed the diet without succinylsulfathiazole had normal prothrombin clotting times. The remaining 2 showed only a slight increase in prothromibin time. Similarly, unoperated (not cecectomized) rats fed the vitamin K-free diet containing succinylsulfathiazole had only an occasional and very mild hypoprothrombinemia.