Acute gastric mucosal ulcerogenesis is dependent on the concentration of bile salt.

Studies on animals implicating reflux of bile salts in formation of "stress ulcer" often are suspect because of the inordinately high intragastric concentrations of bile salts used to induce experimental acute gastric mucosal damage. We studied reflux of bile salt in 11 patients after operation. Nine refluxed bile salts in a mean intragastric concentration of 1.87 +/- 0.24 mM. (range, 0.34 to 4.88 mM.). In the present study, therefore, the ulcerogenic potential of physiologic concentrations of bile salts was evaluated. With use of vascularized, chambered canine gastric mucosa, groups of animals were studied during three consecutive periods. Group A = topical acid test alone (ATS) during periods 1, 2, and 3; Group B = (1) ATS, (2) ATS, (3) ATS + vasopressin (VP = 0.1 U per Kg.-min. via the splenic artery); Group C = (1) ATS, (2) ATS + topical 1 mM. sodium taurocholate (TC), (3) ATS + 1 TC + VP; Group D = (1) ATS, (2) ATS + 2 TC, (3) ATS + 2 TC + VP; Group E = (1) ATS (2) ATS + 5 TC, (3) ATS + 5 TC + VP. Parameters evaluated were (1) net fluxes H+, Na+; (2) electrical potential difference (PD); (3) clearance of aminopyrine, a measure of mucosal blood flow (MBF); and (4) formation of lesions, graded zero to six by an independent observer who used photographs. In nonischemic mucosa, bile salts produced no ulcers, a significant concentration-dependent increase in H+ "back diffusion" and fall in PD, and a noncentration-dependent increase in MBF. In ischemic mucosa, the combination of topical acid, topical bile salts, and mucosal ischemia was acutely ulcerogenic. The severity of mucosal injury was dependent on the concentration of bile salt (y = 0.108 + 1.53x, r = 0.90, p less than 0.01). These data indicate that acute mucosal damage occurs in the presence of physiologic concentrations of bile salt, i.e., those routinely found in the gastric contents of postoperative patients.

Relationship of transmural electrical potential difference to changes in gastric mucosal permeability to H+ and blood flow.

Chambered in vivo wedges of proximal canine gastric mucosa were used to evaluate the relationship between PD, net H+ and Na+ fluxes, and gastric mucosal nutrient blood flow, as adjudicated by the ability of the mucosa to clear aminopyrine. Assuming that steady state conditions existed during the study, the results indicate that (1) the mean PD/15 minute period is a significant linear function of both net H+ and net Na+ flux and therefore, presumably, of changes in gastric mucosal permeability to cations, and (2) the mean PD/15 minute period is a significant exponential function of gastric mucosal nutrient blood flow, marked reductions in PD occurring at flows of 1 to 1.5 ml or less. If the thesis that acute posttraumatic hemorrhagic gastritis is a consequence of concomitant alterations in gastric mucosal permeability to H+ and reductions in mucosal blood flow is correct, the PD might represent a useful clinical tool for detecting, in susceptible patients, the evolutionary stages of this devastating complication of trauma.

Hemodynamic and metabolic alterations in peripheral tissue during hemorrhagic shock.

In dogs subjected to hypovolemic shock (modified Wiggers model) severe enough to decrease the arterial flow in an isolated hind limb by two-thirds, a marked hyperglycemia (three times control) and an increase in blood glucose AV difference (ten times control) occur. Despite the decreased arterial flow, glucose uptake by peripheral tissues increased by a factor of three within one-half hour of hemorrhage and remained elevated for several hours. Presumably, the increased glucose uptake reflects the need for more energy substrate during the hypoxic conditions of the decreased peripheral blood flow.

Pancreaticoduodenectomy in the treatment of congenital fibrosarcoma of the duodenum.

A 2-mo-old female with congenital fibrosarcoma causing duodenal obstruction had a pancreaticoduodenectomy. She is doing well with the aid of oral pancreatic enzyme supplements 14 mo after her pancreaticoduodenectomy with no evidence of tumor recurrence or pancreatic endocrine dysfunction.

Influence of isoproterenol and cholestyramine on acute gastric mucosal ulcerogenesis.

One thesis concerning the pathogenesis of "stress ulcer" states that the combination of (1) bile acid-induced H+ "back diffusion" and (2) gastric mucosal ischemia is acutely Hg) to induce ischemia, this thesis was further tested by selectively mitigating either the ischemic or the back diffusion components of the model. Vascularized wedges of proximal canine gastric wall mounted on Lucite chambers were studied. With the mucosa directly visualized, control group A (6 dogs) was subjected sequentially to (1) topical acid test solution alone (ATS), (2) ATS + S, and (3) ATS + S + topical 5 mM Na taurocholate (TC). Study group B (6 dogs): (1) ATS, (2) ATS + S + the beta adrenergic agonist, isoproterenol, 1.5 microng per kg-min infused into the splenic artery, and (3) ATS + S + TC + isoproterenol. Study group C (6 dogs): (1) ATS, (2) ATS + S + the bile acid binding resin, cholestyramine (C), 4 g per liter, and (3) ATS + S + TC + C. During each period the net flux of H+, the electrical potential difference, and the aminopyrine clearance (AC) were determined. Mucosal damage (intramucosal hemorrhage, erosions, and ulcers, graded 0 to 5) was assessed blindly by an independent observer using photographs. The results indicate (1) that, despite H+ back diffusion comparable to ATS + S + TC, intraarterial isoproterenol significantly protects against lesion formation by increasing AC, and (2) that, despite a reduction in AC comparable to ATS + S + TC, topical C significantly protects against lesion formation by preventing excessive back diffusion of H+.