PubMed HealthSearch

Biomedical subjects

U Haglund

Publications and source records attributed to U Haglund.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

Effects of positive end-expiratory pressure on splanchnic circulation and function in experimental peritonitis.

Splanchnic and central hemodynamic effects of positive end-expiratory pressure (PEEP) were studied in anesthetized pigs using mechanical ventilatory assistance, with or without sepsis (fecal peritonitis). One hour after sepsis, PEEP (10 cm H2O) was applied (n = 6). Another group (n = 6) had sepsis without PEEP. In one group (n = 6) without sepsis, PEEP was applied after 1 hour, while a fourth group (n = 5), without sepsis or PEEP, served as a control. The group with PEEP and sepsis had reduced cardiac index, portal venous blood flow, and liver surface blood flow. The group with PEEP alone had reduced splanchnic circulation by increasing gastrointestinal vascular resistance, while the group with sepsis alone had increased portal vascular resistance. In a separate series with sepsis, intermittent PEEP, and vigorous fluid resuscitation, it was demonstrated that avoiding hypovolemia did not seem to protect from the PEEP effects on the splanchnic circulation. The combination of sepsis and PEEP was not additive on portal blood flow reduction but reduced bile production.

Animals

Tissue oxygenation in hemorrhagic shock measured as transcutaneous oxygen tension, subcutaneous oxygen tension, and gastrointestinal intramucosal pH in pigs.

BACKGROUND AND METHODS: Tissue oxygenation, measured in peripheral tissue as transcutaneous PO2 (PtCO2) and subcutaneous PO2, was compared with the oxygenation in GI mucosa, which was measured as intramucosal wall pH (pHi), during experimental hemorrhagic shock and resuscitation in pigs. The pigs were hemorrhaged stepwise to a BP of 80 and 45 mm Hg, followed by retransfusion. PtCO2 was measured in the groin and subcutaneous PO2 was measured in the hip region. Intraluminal PCO2 was measured in the stomach, in the small intestine, and the sigmoid colon using silicone catheters. A simultaneous determination of arterial blood HCO3 concentration allowed pHi to be calculated using Henderson-Hasselbalch equation. Cardiac output was determined by thermodilution, and oxygen delivery (DO2) was calculated. RESULTS: Early indications of shock were decreases in PtCO2 and intestinal pHi (p less than .01). All measured variables decreased at the second step of bleeding. PtCO2 and subcutaneous PO2 was correlated to DO2 through the entire experiment (r2 = .25 and .49, respectively). Also, the pHi of the small intestine and the sigmoid colon correlated with DO2 (r2 = .36 and .25, respectively). PtCO2 and subcutaneous PO2 correlated with pHi in the small intestine and sigmoid colon. CONCLUSIONS: PtCO2 and pHi in the small intestine and sigmoid colon were the variables that most rapidly indicated blood volume loss. Subcutaneous PO2 and PtCO2, and small intestine and sigmoid colon pHi were correlated to total body oxygen transport. Peripheral tissue perfusion followed intestinal perfusion to some extent.

Animals

Involvement of neutrophils in postischaemic damage to the small intestine.

Haemorrhagic mucosal lesions are produced during intestinal ischaemia and after reperfusion probably mediated by oxygen radicals. Oxygen radicals react with cell membrane lipids and induce cell damage by peroxidation and induce accumulation of polymorphonuclear leucocytes in the tissue. The aim of the study was to elucidate the involvement of polymorphonuclear leucocytes in post-ischaemic intestinal damage. Intestinal ischaemia was induced in cats by partial occlusion of the superior mesenteric artery. Samples from the small intestine were excised before and at the end of the two hour hypotensive period as well as 10 minutes and 60 minutes after reperfusion. Conjugated dienes, myeloperoxidase, and the purine metabolites were determined in the samples. The tissue was also examined histologically. Seven cats were treated before reperfusion with a monoclonal antibody (IB4) which inhibits leucocyte adherence to endothelial cells and its subsequent activation. After reperfusion myeloperoxidase activity increased and the ischaemic mucosal lesions worsened significantly. IB4 treatment prevented an increase in post-hypotensive myeloperoxidase activity and attenuated the normally observed severe mucosal lesions. We conclude that the severe post-ischaemic lesions are induced by polymorphonuclear leucocytes. Such mucosal injury may be appreciably reduced by blocking leucocyte adherence with IB4.

Animals

Cold ischemic and reperfusion injury in a model of small bowel transplantation in the rat.

Following 0, 5, or 18 h of cold ischemia in the University of Wisconsin or Sacks' solution syngenic small bowel transplantation was performed to the renal vessels. Mucosal injury during ischemia or at reperfusion was evaluated microscopically using a grading scale from 0 to 8. The series subjected to small bowel transplantation without cold ischemia showed superficial damage to the tips of the villi (median grade 2) with no further exacerbation at reperfusion and complete healing 24 h thereafter. Moderate villous injury (median grade 3) was demonstrated following 5 h of cold ischemia. This injury was exacerbated to grade 4 (p less than 0.05) following reperfusion but was almost completely healed 24 h later. Grade 4 tissue injury was seen following 18 h of cold ischemia without further exacerbation at reperfusion and no clear tendency to healing 24 h later.

Animals

Visceral and peripheral tissue perfusion after cardiac surgery.

Visceral and peripheral tissue perfusion and oxygenation were studied in ten patients in the early phase after coronary artery bypass grafting. Visceral perfusion was assessed indirectly, by determining gastric intramucosal pH. As parameters of peripheral tissue perfusion and oxygenation, subcutaneous tissue PO2 (PscO2), transcutaneous PO2 (PtcO2). PtcO2 index (PtcO2/PaO2), laser-Doppler skin red-cell flux (RCF) and fingertip temperature (Tft) were recorded in the upper extremity. Central haemodynamics, rectal temperature and blood gases were also measured. The inspired oxygen concentration was maintained at 30 v/v%. Gastric intramucosal pH declined progressively during the first 3 hours in the intensive care unit, reached its minimum at 5 hours and thereafter slowly increased. The peripheral vascular bed was shut down on admission to the ICU, as indicated by low values of PscO2, PtcO2, PtCO2 index, RCF and Tft. These parameters began to rise after the next 2-4 hours and peaked by the end of the 8-hour study period, indicating complete opening of the peripheral vascular bed.

Body Temperature

Oxygen-free radicals (OFR) and circulatory shock.

During the past decade a large body of information has been collected showing that formation of short-lived highly reactive metabolites (i.e., radicals) constitutes an important principle of tissue injury. There are several sources of information which suggest that radicals are formed in connection with tissue ischemia and shock, and they may then cause damage to cells and contribute to the pathophysiology of ischemia and shock. In the present review we attempt to discuss how radicals damage tissue as well as the data which suggest that radicals are causing tissue injury in shock.

Animals