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Objective: The goal of this investigation was to determine the role of calcitonin gene-related peptide (CGRP) in gastric mucosal resistance to ulceration., Summary Background Data: CGRP is a 37-amino acid peptide found in the peripheral ends of afferent gastric neurons. CGRP is known to inhibit acid secretion, stimulate mucosal blood flow, and stimulate release of somatostatin., Methods: The release of CGRP in response to intragastric and intra-arterial administration of capsaicin in the isolated, vascularly perfused rat stomach was measured by radioimmunoassay. The molecular forms of CGRP released were analyzed by gel filtration chromatography. The effect of intravenous CGRP or intragastric capsaicin on gastric ulceration induced by 100 mmol/L HCl and indomethacin was studied in intact and endogenous CGRP-depleted rats., Results: Intra-arterial capsaicin (concentration range, 10(-7) to 10(-5) mol/L) stimulated a prompt and sustained release of immunoreactive CGRP, of which 84% coeluted with rat 1-37 CGRP I by gel filtration. Intragastric capsaicin (range, 10(-5) to 10(-4) mol/L) failed to release CGRP into the vascular perfusate. In intact rats, intragastric capsaicin (10(-6) mol/L) or intravenous CGRP I (10 micrograms/kg/hr) reduced the number and area of mucosal lesions caused by HCl and indomethacin compared with the findings in control rats. Rats depleted of endogenous CGRP were more susceptible to gastric ulceration than were normal rats. Intragastric capsaicin failed to protect the mucosa of CGRP-depleted rats, whereas exogenous intravenous CGRP was effective., Conclusions: These data support the hypothesis that CGRP released from gastric enteric neurons mediates gastric mucosal resistance to ulceration by noxious agents.

The value of the amylase--creatinine clearance ratio (ACCR) in the diagnosis of postoperative pancreatitis was prospectively assessed. In 77 patients undergoing operations known to have a significant incidence of postoperative pancreatitis (gastric, biliary or pancreatic) i.e. "high risk" group, the ACCR was abnormally elevated postoperatively in 36 patients (47%). However, overt clinical pancreatitis occurred in only eight patients (10%). In 60 other patients undergoing nonabdominal operations (orthiipedic, head and neck, varicose vein surgery etc.) i.e. "low risk" group, the ACCR was abnormally elevated postoperatively in 23 patients (38%). No patient in this group developed clinical pancreatitis. We conclude, therefore, the ACCR is often abnormally elevated nonspecifically following any type of surgery, and cannot be used as evidence of postoperative pancreatitis. These data do suggest, however, that a normal ACCR, especially on successive daily determinations, might help to exclude the diagnosis of postoperative pancreatitis.

This study examines the effect of graded antral distension with acid (0.1 M HCl) or alkali (0.1 M NaHCO3) on pentagastrin-stimulated acid secretion in two groups of dogs. Group A consisted of six dogs provided with innervated antral pouch. In these dogs, the vagal branches to the fundus, as well as the extragastric vagal divisions (hepatic and celiac), were preserved. All of these animals had a gastric fistula in the main stomach, and in two a denervated fundic pouch or Heidenhain pouch was constructed in addition. Group B consisted of four dogs with an innervated antral pouch and gastric fistula. In this latter group, however, parietal cell vagotomy as well as extragastric vagotomy (division of the hepatic and celiac branches) was performed so that the only vagal communication was between the antrum and the CNS. Antral distension with acid caused significant inhibition of pentagastrin-stimulated acid secretion from both the gastric fistula and the Heidenhain pouch in Group A dogs. Antral acidification without distension did not inhibit. Alkaline antral distension in this group caused much less inhibition of acid secretion, but did cause significant increase in circulating immunoreactive gastrin. In Group B dogs, antral distension with neither acid nor alkali caused inhibition of pentagastrin-stimulated acid secretion, indicating that intact vagal supply to the oxyntic mucosa and/or to the extragastric abdominal organs is necessary for the inhibitory mechanism to operate. The results of this study suggest that: a) antral acidification per se does not inhibit pentagastrin-stimulated acid secretion; and b) antral distension with acid, and to a lesser extent with alkali, is inhibitory only if vagal innervation to the fundus and other abdominal viscera is preserved. The observations are compatible with the hypothesis that antral distension activates a neurohumoral inhibitory mechanism releasing the inhibitor reflexly from sites other than the antrum or CNS.

The effect of somatostatin (SS-14) was tested in an anesthetized rabbit model of closed-loop ileal obstruction. Experimental groups included (1) immediate treatment (N = 6) receiving SS-14 2,000 pmol X kg-1 X h-1 intravenously (I.V.) beginning at the time of ileal obstruction, (2) delayed treatment (N = 5) receiving SS-14 beginning 6 hours following ileal obstruction, and (3) control (N = 6) receiving only hydration. After 24 hours, all rabbits were killed. Significantly decreased intestinal luminal volume and sodium and potassium output was observed with both immediate and delayed SS-14 treatment when compared to control. Additionally, the gross and microscopic pathologic features of intestinal distension, inflammation, and necrosis seen in control rabbits were absent in rabbits treated with SS-14. The known broad spectrum of physiologic activity of SS-14 on the gastrointestinal tract appeared beneficial in this rabbit model of intestinal obstruction.