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Biomedical subjects

U Haglund

Publications and source records attributed to U Haglund.

At least 73 records · Page 4Linked to original sources
PubMed1993

Systemic mediators released from the gut in critical illness.

OBJECTIVE: To discuss the mediators released from the gut in critical states, with emphasis on the intestinal mucosal barrier function, mediators of bacterial origin, and myocardial depressant factors. DATA SOURCES: Relevant articles that have been published in the English language literature. STUDY SELECTION: No special study has been carried out for the present discussion. DATA EXTRACTION: Information from the literature has been used to illustrate important points in the discussion. DATA SYNTHESIS: Due to decreased mucosal blood flow, increased short-circuiting of oxygen in the mucosal countercurrent exchanger, and increased oxygen demand in sepsis mucosal injury develops rapidly in the gut after various forms of shock and splanchnic ischemia. In addition, due to increased generation of oxygen-derived radicals, injury may also occur with reperfusion. As a consequence of increased permeability of the intestinal mucosal barrier between the luminal content and the sterile interior milieu, increased translocation of bacteria and bacterial endotoxin occurs. In addition, cardiodepressant factors are released, as is evident from in vivo and in vitro studies. No such factor has been fully identified chemically. CONCLUSIONS: Intestinal mucosal injury, as seen in critical illness, may induce increased translocation of bacteria and endotoxin and release of myocardial depressant factors into the circulation.

Animals↗
PubMed1993

Goals for the resuscitation of shock.

OBJECTIVE: To remind practitioners of the conventional goals of resuscitation of overt hypotensive or uncompensated shock ("ABC," for airway, breathing, and circulation) and to introduce additional goals, represented by successive letters of the alphabet, to aid clinicians in recognizing the persistence of compensated shock in the splanchnic organs and in achieving more complete resuscitation by eliminating inadequate tissue perfusion in these organs. DATA SOURCES: Review and analysis of current medical literature on shock and organ failure, combined with the author's prior research and expertise in the areas of tissue oxygenation and tonometric monitoring in the critically ill. CONCLUSIONS: In traumatic and septic shock, multiple system organ failure is associated with a persistent state of compensated shock in which hypotension and oliguria are corrected, but in which inadequate perfusion persists in the splanchnic organs and especially in the mucosal lining of the gut. The additional goals recommended include "D" for increasing the delivery of oxygen to levels that meet the metabolic demand by all tissues in the body, especially those tissues within the splanchnic circulation, and "E" for ensuring extraction and utilization of oxygen by the tissues. Future needs for goals that address reperfusion injury, translocation of bacterial toxins, and the release of toxic mediators are also considered.

Animals↗
PubMed1993

Therapeutic potential of intraluminal oxygenation.

OBJECTIVE: To discuss the potential therapeutic value of intraluminal oxygenation of the gut in critical illness. DATA SOURCES: Relevant articles published in the English language literature. STUDY SELECTION: No special study has been carried out for the present presentation. DATA EXTRACTION: Information from the literature has been used to illustrate a potential way of preventing multiple organ failure. DATA SYNTHESIS: Animal experiments have demonstrated that oxygenation of the intestinal mucosa by providing gaseous oxygen to the mucosa or by perfusing the gut lumen with oxygenated fluids may prevent the development of mucosal injury that otherwise occurs in ischemic states. All available experience is based on experiments, and thus far, the clinical relevance of this observation is not tested. CONCLUSIONS: Intraluminal oxygenation may prevent the development of intestinal mucosal injury that is otherwise seen in conditions causing intestinal ischemia.

Animals↗
PubMed1993

Luminal release of hyaluronan (hyaluronic acid) in intestinal ischemia in the rat.

Hyaluronan (HA) is a glycosaminoglycan, the water-binding properties of which are suggested to be pivotal for an optimal hydration of tissues. The lamina propria of the intestinal villi is characterized by a high concentration of HA. Increased amounts of HA are observed in the intestinal lumen in patients with Crohn's disease. We have evaluated whether epithelial denudation as such is sufficient to increase the concentration of HA in the lumen of the small intestine. Epithelial damage was accomplished by reversible ischemia-reperfusion injury to the rat ileum and the concentration of HA was determined in luminal perfusate. The perfusate concentration of HA was increased from 26 +/- 8 micrograms/l before ischemia, to 68 +/- 13 and 41 +/- 12 micrograms/l 0-30 and 30-60 min after a 60-min period of subtotal ischemia without venous stasis (p < 0.05). In sham-operated animals, in contrast, the perfusate concentration of HA was virtually unchanged (31 +/- 18, 13 +/- 3 and 10 +/- 1 microgram/l, respectively). Specific staining for HA on sections revealed loss of HA from the villus tips after ischemia. The results show that epithelial denudation results in loss of HA from the villus interstitium to the intestinal lumen.

Animals↗
PubMed1993

Inhibition of CD18-dependent adherence of polymorphonuclear leukocytes does not affect liver oxygen consumption in fecal peritonitis in pigs.

We tested the hypothesis that circulating polymorphonuclear leukocytes (PMNs), adhering to endothelium of the liver vascular bed are involved in the alterations of the liver oxygen delivery (DO2) and consumption (VO2) that is a result of fecal peritonitis in pigs. Twenty-two pigs were divided into three groups. Animals in group I (n = 7) served as controls. Fecal peritonitis was induced in groups II (n = 7) and III (n = 8). Animals in group III were pretreated with IB4, a monoclonal anti-CD18 antibody inhibiting adherence of PMNs to the endothelium. Peritonitis increased liver VO2 in groups II and III in spite of decreased liver DO2. In group I, circulating PMNs increased during the experimental period. Sepsis caused a decrease in the number of circulating PMNs in group II, an effect that was fully counteracted in group III, where the number of PMNs rose to control level. Myeloperoxidase activity and morphometric determination of PMN infiltration in liver biopsies virtually paralleled the circulating PMN count. Although fecal peritonitis is followed by a CD18-dependent leukopenia that can be counteracted by pretreatment with an anti-CD18 antibodies, this treatment does not affect the alteration in liver VO2 and DO2 observed.

Animals↗
PubMed1993

Hepatic oxygen consumption and cytochrome P450 activity in experimental faecal peritonitis.

OBJECTIVE: To study hepatic oxygen consumption and cytochrome P450 activity in pigs with septic shock induced by faecal peritonitis. DESIGN: Controlled experimental study. ANIMALS: 12 pigs weighing 19-27 kg. INTERVENTION: The animals were divided into a control group (n = 6) and a peritonitis group (n = 6). Peritonitis was induced by intraperitoneal instillation of a standard amount of autologous faeces. The animals were then observed for 300 minutes. Liver biopsy specimens were taken at 0 and 300 minutes. MAIN OUTCOME MEASURES: Hepatic oxygen delivery (DO2) and consumption (VO2). Cytochrome P450 activity was studied by measuring O- and N-demethylation of codeine at 0 and 300 minutes. RESULTS: Hepatic DO2 was reduced, whereas VO2 was increased during sepsis. There were no significant changes in the N- and O-demethylation of codeine. CONCLUSIONS: Hepatic VO2 did increase during sepsis, possibly because of the increased metabolic demand. Cytochrome P450 activity was unaffected by the septic challenge.

Animals↗
PubMed1992

Pancreatic proteases and intestinal mucosal injury after ischemia and reperfusion in the pig.

Intraluminal pancreatic proteases have been proposed to play a pathogenic role in the injury seen after ischemia and reperfusion of the small intestinal mucosa. Intestinal ischemia can be detected by indirect intramucosal pH measurements using tonometry. In this study, pigs were subjected to laparotomy and ligation of the pancreatic duct (n = 10) or a sham procedure (n = 10). Three weeks later, a standardized hemorrhagic shock was induced followed by retransfusion. Central hemodynamics, portal venous flow, and duodenal and small intestinal mucosal intramucosal pH were monitored. Samples were obtained from the small intestine for microscopic examination. A typical superficial mucosal injury developed in both groups of animals after reperfusion. However, the injury developed significantly later in the duct-ligated animals. No major differences in survival, splanchnic hemodynamics, or intramucosal pH between the groups were seen during hemorrhagic hypotension or after reperfusion. These data favor the concept that intraluminal pancreatic proteases are important for the rapid development of the mucosal reperfusion injury.

Animals↗
PubMed1992

Cost-effectiveness of misoprostol in Sweden.

Based on an American multicenter study, an economic evaluation of prophylactic misoprostol was undertaken in Sweden. The study included 420 patients with osteoarthritis and nonsteroidal anti-inflammatory drug (NSAID)-associated abdominal pain, but no gastric ulcer at inclusion. The frequency of ulcer development with and without prophylactic misoprostol was assessed at 21.7% and 5.6%, respectively, for a 3-month period. All costs for drugs, ambulatory care, hospital care, loss of production, as well as other factors such as dosage and compliance, were transferred to Swedish conditions. It was concluded that in patients with osteoarthritis and NSAID-induced abdominal pain, prophylaxis with misoprostol is cost-effective in Sweden, which is similar to what is found for other countries. A prerequisite for this result is a frequency of ulcer development of 15%. A patient compliance to prophylactic treatment of more than 60% is also presupposed (79% was observed in the above study). Due to the high age of the osteoarthritis patient population, the cost-effectiveness is influenced to only a minor extent by whether indirect costs are included in the calculation.

Adult↗
PubMed1992

Regeneration of small bowel mucosa after intestinal ischemia.

BACKGROUND AND METHODS: The objective of this study was to evaluate the histologic reconstitution of the small intestinal mucosa after a standardized ischemic injury and to determine if the early repair process takes place by cell renewal or migration of existing mucosal cells. Therefore, male Wistar rats, weighing 190 to 320 g, were subjected to total warm intestinal ischemia by means of a hydrostatic pressure clamp for 45 or 90 mins. These rats were compared to sham-operated controls. Intestinal biopsies were obtained just before reperfusion and at various times up to 48 hrs thereafter. Mucosal injury was evaluated microscopically by a blinded examiner. RESULTS: Variable mucosal reconstitution occurred within 3 hrs, after 45 mins of ischemia, whereas mucosal repair required up to 18 hrs after 90 mins of ischemia. In a second series of experiments, 45 or 90 mins of ischemia and 5 hrs of reperfusion were followed by the iv administration of radioactively labeled thymidine. Intestinal biopsies were taken 1 hr later and prepared for autoradiography. No increase in mucosal mitoses was observed. CONCLUSIONS: The mucosal reconstitution occurred rapidly after 45 mins and 90 mins of total warm intestinal ischemia and primarily through mucosal cell migration.

Animals↗
PubMed1992

Duodenal mucosal pH as a reperfusion indicator in pancreatic-duodenal transplantation in the pig.

We have studied differences in reperfusion between the pancreas and the duodenum after 6 hr of cold storage in a porcine whole-organ pancreaticoduodenal allograft transplantation model. Two different flush-out and storage solutions, Perfadex and EuroCollins, were compared. Graft duodenal mucosal pH (pHi) was measured as an indicator of duodenal mucosal reperfusion. Pancreatic reperfusion was estimated indirectly using a ratio between the release of immunoreactive cationic trypsin (irCT) to serum 10 and 60 min following reperfusion. Twelve pigs (Perfadex n = 6, EuroCollins n = 6) were transplanted and all showed preserved endocrine and exocrine function postoperatively. Our data support the concept that reperfusion of a pancreaticoduodenal graft can be estimated using duodenal pHi and that the ratio of irCT at 10 and 60 min gives an indirect estimate of pancreatic reperfusion. The results also show that grafts stored in EuroCollins reperfuse more slowly than grafts stored in Perfadex.

Animals↗
PubMed1992

Splanchnic and total body oxygen consumption in experimental fecal peritonitis in pigs: effects of dextran and iloprost.

Tissue oxygenation in the gastrointestinal tract and in the liver was studied in a porcine model where septic shock was induced by fecal peritonitis. The effects of different fluid regimes were compared. In one group (n = 8) a moderate amount of crystalloid fluids was given, in another (n = 7) crystalloids and colloids, and in a third group (n = 6) iloprost, a prostacyclin analogue, was administered intra-arterially (10 ng x kg-1 b.w. x min-1) in combination with the crystalline and colloid fluid regime. Septic shock induced by fecal peritonitis reduced cardiac index and oxygen supply to splanchnic organs. Iloprost improved the hepatic arterial blood flow, and tended to attenuate the reduction in liver oxygen delivery. Oxygen consumption (VO2) in the gastrointestinal tract and the liver was significantly increased in the group given crystalloids. These animals developed a hypovolemic/hypodynamic septic shock. Liver VO2 in these animals became flow dependent reflected by increasing hepatic venous lactate values and inversion of lactate turnover by the liver. In the two other groups gastrointestinal and liver VO2 remained constant during the observation period. Oxygen extraction over the liver increased when oxygen delivery decreased. The increased liver VO2 is suggested to be secondary to impaired microcirculation and accumulation of macrophages and leukocytes in the septic liver.

Animals↗
PubMed1992

Early gut ischemia in experimental fecal peritonitis.

Tissue oxygenation in the gastrointestinal tract was studied in a porcine model in which septic shock was induced by fecal peritonitis. The oxygen delivered was estimated by measuring the portal venous blood flow and the calculated arterial oxygen saturation. The oxygen consumption of the gut, including the pancreas and spleen, was monitored by measuring the portal venous blood flow and the difference between the calculated arterial oxygen and the measured portal venous oxygen saturation. In addition, the oxygenation of the gut mucosa was followed via the tonometric technique. Furthermore, lactate was measured in arterial and portal blood. The experimental animals were divided into two groups, one control (n = 6) and one experimental (n = 6). Peritonitis was introduced by installation of a standardized amount of autologous feces into the abdominal cavity. The animals were followed for 5 hr. Very early during the course of sepsis there was a fall in gut intramucosal pH (pHi), and this was evident before any reduction in splanchnic DO2. Furthermore, an early increase in splanchnic VO2 was evident simultaneously with the fall in pHi. Arterial pH and lactate were not able to detect the inadequate regional tissue oxygenation. It is concluded that pHi measured with the tonometric technique is sensitive in detecting gut mucosal ischemia, and it is therefore highly likely that tonometry would be a valuable method in monitoring severe ill patients.

Animals↗