Resistance to experimental peritonitis induced by local nonspecific stimulation of the reticuloendothelial system.

Zymosan, a yeast cell wall preparation from Saccharomyces cerevisiae, stimulates the reticuloendothelial system (RES) in animals. Pretreatment with zymosan induces resistance to several types of shock. We have shown evidence that zymosan given intraperitoneally (IP) induces greater protection than intravenous (IV) zymosan against E coli peritonitis in the rat. Moreover, IP zymosan has few systemic RES effects, which are commonly associated with IV zymosan. IV and IP zymosan stimulation were compared for effectiveness against experimental fibrinopurulent peritonitis in dogs (a peritonitis model quite similar to clinical peritonitis). Ten dogs received zymosan IV (10 mg/kg), ten dogs received zymosan IP (10 mg/kg), and eight dogs received an equal volume of saline IP on three consecutive days. On day 4, a 7.5 cm length of terminal ileum was isolated and its blood supply ligated to create an infarcted, blind loop of bowel. This loop was left in the peritoneal cavity for five days. Five-day survival was 80% (8/10) for the zymosan IP (P less than 0.05), 60% (6/10) for the zymosan IV and 12.5% (1/8) for the saline controls. All survivors were sacrificed at five days and found to have an intact enteric anastomosis with varying degrees of walled-off abscess at the site of the necrotic loop. Histologic evaluation of intraabdominal organs, peritoneum, and abscess wall was carried out. The IP zymosan had no significant systemic RES effects, whereas the IV zymosan produced a marked increase in liver and spleen weights. These findings reinforce the hypothesis that local nonspecific RES stimulation could have a major role in the preparation of certain high-risk patients for abdominal surgery where the chance of peritoneal soilage is high.

Effects of glucocorticosteroids in patients undergoing coronary artery bypass surgery.

Glucocorticosteroid, methylprednisolone sodium succinate (MPSS), 30 mg/kg of body weight, or dexamethasone sodium phosphate (DSP), 6 mg/kg of body weight, were given intravenously to 60 patients, divided into two groups of 30 45 minutes prior to cardiopulmonary bypass for coronary artery bypass. These two groups were compared with 30 patients in a control group receiving a placebo and undergoing the same surgery. The study was carried out in a double-lind fashion. Patients receiving MPSS had a significantly higher cardiac index in both the preoperative and postoperative periods. This was accompanied by a decreased peripheral resistance. Patients receiving either MPSS or DSP also showed some evidence for the "washout" phenomenon indicating the possibility of better microcirculatory flow. Gluconeogenesis may have been enhanced in both groups receiving MPSS or DSP, but the evidence was greater in thos patients receiving MPSS. There were no hospital deaths in any of the three groups totaling 90 patients.

Zymosan-induced resistance to endotoxin and hemorrhagic shock.

Improved surgical techniques and judicial use of available antibiotics have reduced the number of postoperative complications over the past decade. However, septic and hemorrhagic shock occur all too frequently, and each carries with it an appreciable morbidity and mortality. Endotoxins and hemorrhage are both known to suppress the phagocytic activity of the reticuloendothelial system (RES). On the other hand, zymosan, a yeast (Saccharomyces cerevisiae) cell wall preparation administered intravenously, results in temporary RES hyperplasia and increased phagocytic activity. Dogs were pretreated with zymosan to determine the degree of RES stimulation and protection against endotoxin and hemorrhagic shock attainable. Twenty-five dogs received intravenous zymosan (10 mg/kg) on days 1, 2, and 3. Another 24 dogs served as controls. On day four, one-half the animals in each group received E coli endotoxin (1.5 mg/kg) intravenously. The other animals underwent two hours of hemorrhagic shock at a mean blood pressure of 40 mm Hg. Seventy-two hour survival was as follows: Endotoxin treated, 66.7% (8/12); endotoxin control, 27% (3/11); hemorrhagic treated, 53.3% (8/15); and hemorrhagic control, 28.6% (4/14). Hemodynamic, metabolic, and lysosomal enzyme parameters were evaluated. No zymosan toxicity was observed. These findings suggest that an RES stimulant such as zymosan could be incorporated as preoperative adjunctive therapy to induce resistance to these shock syndromes in the elective surgical patient.

Reduction of experimental myocardial infarct size by combined treatment with methylprednisolone sodium succinate and betahistine hydrochloride.

This laboratory and others have shown that methylprednisolone sodium succinate and betahistine hydrochloride can each reduce the size of experimental myocardial infarct in dogs at six hours. In light of the fact that these two agents probably act via different mechanisms, a study was carried out to determine if there would be cumulative effects of using these two agents together. Using a left anterior descending coronary artery ligation model to create an experimental myocardial infarction and an intracellular lactic dehydrogenase (LDH) stain to measure the infarct size, 66 dogs were studied. Nineteen dogs served as controls with no therapy; 20 received a continuous intravenous infusion of betahistine hydrochloride (0.24 mg/kg/min) for six hours following ligation; 10 dogs received methylprednisolone sodium succinate intravenously 30 mg/kg at one hour postligation; and 17 other dogs received betahistine hydrochloride intravenously (0.24 mg/kg/min) over six hours following ligation, plus methylprednisolone sodium succinate intravenously (30 mg/kg) at one hour postligation. At six hours, the combined treatment demonstrated no significant improvement over betahistine HCl alone (control, 16.0%; betahistine HCl, 11.4%; combined, 11.2% P less than 0.05). At 24 hours, only the combined treatment group demonstrated a significant infarct size reduction (control, 15.5%; methylprednisolone, 13.1%; betahistine--HCl, 14.2%; combined, 9.7%; P less than 0.0025). Other parameters that were evaluated and analyzed include mean aortic pressure, left atrial pressure, cardiac index, total peripheral resistance, arterial and coronary sinus pH, pCO2, pO2, hematocrit, O2 consumption, O2 content difference, and coronary sinus lactate and creatine phosphokinase (CPK). These results suggest a significant cumulative effect in reducing infarct size over that achieved with one agent alone; however, further studies are needed to determine the appropriate dosage and temporal factors.

Endoscopic dilation of a gastric anastomotic stricture.

A stricture developed in a patient two months after undergoind a Billroth I gastroduodenal anastomosis. His mechanical gastric obstruction was relieved by dilation up to 37 F caliber under direct vision using a fiberendoscope. The patient became, and has remained, symptom free. Visualization of the area two months after dilation showed an adequately patent anastomosis.