L E T T E R S T O T H E E D I T O R

ANTISECRETORY AND PROTECTIVE PROPERTIES OF PROSTAGLANDIN ANALOGS

IN MAN

To The Editor: Recent studies have shown that various natural

and synthetic prostaglandins can protect animal gastric mucosa from the damage induced by a variety of agents such as aspirin, bile salts, etc. (1). This phenomenon has been called cytoprotection and is separate from, and unrelated to, inhibition of gastric acid secretion because of the following two reasons:

Certain prostaglandins which are not antisecre- tory still prevent aspirin-induced lesions; further- more in the case of antisecretory prostaglandins, the dose inhibiting aspirin-induced lesions was much smaller than the threshold antisecretory dose.

Simultaneous demonstration of acid inhibition and gastric cytoprotection by a given prostaglandin analog is still lacking in man. We therefore tested the effects of 16,16-dimethyl-prostaglandin E2 and the thiaprostaglandin EMD 33290 (3-cis-hydroxy-2- trans-(3-methyl-3-hydroxy- 1 -heptyl-thio)-5-oxo- 1 - r-cyclopentylheptanoic acid-4-benzamidophenyles- ter) on basal acid secretion as well as on aspirin- and bile salt-induced fall of gastric transmucosal potential difference (PD) in man.

Basal acid output was tested over a time period of 6 hr by intragastric titration with 0.1 N NaOH (N = 6). Gastric potential difference was determined us- ing the method of Andersson and Grossman (2).

Both prostaglandin analogs prevent the drop in gastric potential difference (control values -42.4 -+ 2.8 mV) associated with 1000 mg aspirin and 50 ml of 4 mmol/liter sodium taurocholate. In control experiments both irritants caused a fall in PD of about 30% within 10-15 min (aspirin group -29.1 +-- 2.4 mV, sodium taurocholate group -28.3 -+ 1.9 mV). The protective doses against aspirin for 16,16- dimethyl-prostaglandin E2 and EMD 33290 were 0.0001 txg/kg body wt and 0.70 /xg/kg body wt, respectively. Against sodium taurocholate doses of 0.01 ~xg/kg body wt and 36 Ixg/kg body wt were effective.

By contrast, 20-100 times higher doses of both prostaglandin analogs were necessary to inhibit gastric acid secretion. Half-maximal inhibition of basal acid output was achieved by 0.1 ~g/kg body wt 16,16-dimethyl-prostaglandin E2 and by 20 ~g/kg body wt EMD 33290. Whereas the antisecretory effect of 16,16-dm-PGEa was still demonstrable

after 6 hr, the inhibition of basal acid output by EMD 33290 was of only short duration.

In analogy to animal findings, certain prostaglan- din analogs possess distinct cytoprotective and anti- secretory properties in the human stomach. The protective effects of EMD 33290 and 16,16-dm- PGE2 became apparent in doses far below the antisecretory threshold.

PETER MOLLER BERND SIMON

Medizinische Universitdtsklinik Heidelberg Gastroenterologische Abteilung

Bergheimerstr. 58, 6900 Heidelberg, F.R.G. H A N N S - G E R D DAMMANN

Medizinische Universitdtsklinik Hamburg Krankenhaus Eppendorf

Martinistrasse 52, 2000 Hamburg 20, F.R.G.

REFERENCES

1. Robert A: Cytoprotection by prostaglandins. Gastroenterol- ogy 77:761-767, 1979

2. Andersson S, Grossman MJ: Profile of pH, pressure and potential difference at gastroduodenal junction in man. Gas- troenterology 49:364-369, 1965

ESOPHAGEAL PERFORATION AND ENDOSCOPY

To The Editor: I wish to comment on the letter to the editor by

Dr. John Squire Kirkham in the September 1981 issue of Digestive Diseases and Sciences. [ agree with Dr. Kirkham that the diameter of the instru- ments, as well as other technical differences among scopes, are of little importance in determining the risk of perforation. Thus, there has been little change in the overall incidence of perforation coin- cident with the replacement of rigid endoscopes with flexible ones. According to the case I have published (Endoscopy 1: 60-62, (1979)) and to the experience of hundreds of upper endoscopies done since then, the most important means of avoiding perforations is to never overcome resistance by force. If one thinks the resistance is due to spasm, wait until it relaxes! If there is something else, withdraw the instrument and try again!

The most experienced endoscopist is the one who has done one perforation. If he has done more than one, he should consider being supervised again!

DR. E. SCAPA Mallory Institute of Pathology

Boston City Hospital Boston, Massachusetts

862 Digestive Diseases and Sciences, Vol. 27, No. 9 (September 1982) 0163-2116/82/0900-0862503.00/1 �9 1982 Digestive Disease Systems, Inc.