Ulf Haglund

Protection of the small intestine from nonocclusive mesenteric ischemic injury due to cardiogenic shock

In a pericardial tamponade model of cardiogenic shock in pigs, we had previously shown that acute reductions in cardiac output produce severe mesenteric ischemia due to disproportionate splanchnic vasoconstriction. In this study, we extended the period of cardiogenic shock in order to investigate the pathogenesis of ischemic injury to the small intestinal wall. Four hours of tamponade produced sustained changes in splanchnic hemodynamics, similar to those observed in the prior short-term experiments. The resultant mesenteric ischemia caused necrotic lesions of the small intestine which were characteristic of those seen in nonocclusive mesenteric ischemia in human subjects. Prior alpha-adrenergic blockade failed to prevent either sustained mesenteric vasospasm or ischemic injury. In contrast, prior blockade of the renin-angiotensin axis, whether by nephrectomy or angiotensin-converting enzyme inhibition, blocked the splanchnic vasoconstriction, and thereby protected the small intestine from ischemic injury. The primary hemodynamic and pathologic features of this model of nonocclusive mesenteric ischemia appear to be mediated by the renin-angiotensin axis.

Intestinal ischemia -- the basics.

Introduction: In this review the physiology of the intestinal circulation of importance for the understanding of intestinal ischemia is briefly outlined. Perspectives: The potential threat of massive intestinal vasoconstriction causing nonocclusive intestinal ischemia is discussed, as is the clinical importance of the reperfusion component of the ischemic injury. The clinical causes of intestinal ischemia are outlined. The delay in the usual clinical diagnostic process and its severe consequences are emphasized. Emphasis is made to discuss the special situation with sigmoid gangrene following surgery for ruptured aortic aneurysm. Laparotomy upon clinical suspicion of intestinal ischemia is generally recommended. The various therapeutic surgical measures available if diagnosis is made before massive intestinal gangrene are discussed.

The fundamental hemodynamic mechanism underlying gastric "stress ulceration" in cardiogenic shock.

Acute hemorrhagic ulceration of the gastric mucosa is seen frequently in patients with hypovolemic or cardiogenic shock. Although such lesions clearly are related to regional gastric ischemia, little attention has been directed at the underlying mechanism(s) mediating the ischemia itself. To this end, anesthetized pigs were subjected to sustained cardiogenic shock (mild hemorrhage and pericardial tamponade) such that cardiac output was reduced to 38 +/- 1% of the baseline level for 4 hours, followed by release of the tamponade, reinfusion of the shed blood, and resuscitation for 2 hours. During the period of shock, there was profound regional gastric ischemia, resulting from severe and disproportionate gastric vasoconstriction. Blinded gross and microscopic evaluation of the stomachs removed after the experiment revealed severe mucosal ischemic necrosis, hemorrhage, and ulceration, whereas sham-operated pigs showed no lesions. The characteristics of this model therefore mimic the essential features of the gastric stress ulceration syndrome. Prior confirmed total alpha-adrenergic blockade with phenoxybenzamine failed to alter these features significantly. In contrast, prior ablation of the renin-angiotensin axis, whether by angiotensin-converting enzyme inhibition with teprotide or by bilateral nephrectomy, significantly and substantially ameliorated the ischemia, vasospasm, and mucosal injury. In this model of cardiogenic shock, acute gastric mucosal stress ulceration is caused by a disproportionately severe regional gastric ischemia resulting from selective splanchnic vasospasm that is unaffected by sympathetic blockade but abolished by prior ablation of the renin-angiotensin axis. Like nonocclusive small bowel ischemia, ischemic colitis, and the shock liver syndrome, gastric stress ulceration is yet another component of the multiple splanchnic organ failure syndrome that appears to be mediated primarily by the remarkable sensitivity of the splanchnic vascular bed to the renin-angiotensin axis.

A cost-minimization analysis of laparoscopic cholecystectomy versus open cholecystectomy

BACKGROUNDnEarlier economic analyses have evaluated charges but not costs, and have not considered the cost of production losses associated with open and laparoscopic cholecystectomy. This study attempted to accomplish an economic evaluation of open versus laparoscopic cholecystectomy from the point of view of society.nnnMETHODSnA cost-minimization analysis, using a clinical decision model, was performed. The data used were taken from different clinical studies, Swedish national registers, local patient statistics, and hospital accounting systems. The direct and indirect costs were measured.nnnRESULTSnLaparoscopic cholecystectomy resulted in cost savings per patient amounting to about 2,400 SEK (as of 31 August 1994, Pound = 11.90 SEK;

Hemodynamic changes in the inferior caval vein during pneumoperitoneum : An experimental study in pigs

1 = 7.76 SEK) compared with open surgery.nnnCONCLUSIONSnFrom the point of view of society, laparoscopic cholecystectomy was a cost-saving strategy if at least 68 patients were operated on yearly. However, with regard to hospital costs, open cholecystectomy was less expensive than laparoscopic cholecystectomy.

Esophageal and jejunal motor function after total gastrectomy and Roux-Y esophagojejunostomy

AbstractBackground: Laparoscopic procedures of increasing difficulty and duration are becoming more and more common. This may cause significant challenges to the circulatory system and possibly influence thrombogenicity.nn Methods: Experimental study of carbon dioxide pneumoperitoneum in pigs.nn Results: Inferior caval vein blood flow remained unchanged, whereas inferior caval vein pressure increased during pneumoperitoneum. Inferior caval vein, pulmonary, and systemic vascular resistance increased during pneumoperitoneum and remained increased after exsufflation.nn Conclusions: Pneumoperitoneum leads to an increased inferior caval vein pressure, which could cause a dilation of peripheral veins. The similar patterns of vascular resistance in the inferior caval vein, pulmonary artery, and systemic arteries (a gradual increase remaining elevated after exsufflation) suggest a common humoral factor or increased sympathetic nerve activity.n

Beneficial effect on intestinal anastomoses of S-2441, a synthetic kallikrein-kinin antagonist: Experimental studies in the rat☆

Emptying and peristaltic activity of the esophagus and proximal jejunum were studied using scintigraphy and fluoroscopy documented on videotape in 11 patients after total gastrectomy and Roux-Y loop reconstruction. Impaired esophageal motor function, as judged by both methods, was seen in five patients who were all 50 years of age or older. This was in contrast to the findings in a group of healthy control subjects, all over 50 years of age, in whom esophageal function appeared normal on scintigraphy in five of seven. Disturbed jejunal function, as judged by radiography, was found in eight patients, whereas the emptying rate according to scintigraphy was judged normal in all but two patients. Five of the patients complained of various adverse alimentary tract symptoms, but the scintigraphic and radiographic findings did not correlate with these symptoms.

The effect of dobutamine on distal colon ischaemia in the pig.

The effects of two protease inhibitors on breaking strength of an intestinal anastomosis were studied. The inhibitors tested were aprotinin and S-2441, a synthetic triple-peptide kallikrein-kinin antagonist. Rats were subjected to an end-to-end anastomosis in the small intestine. The breaking strength, or suture-holding capacity, was measured immediately after suture and after 24 hours. The loss of mechanical strength found in untreated rats was substantially, but not fully, prevented by S-2441. Aprotinin in the dose given was not effective.

An experimental porcine model of partial ischaemia of the distal colon

Objective: To test the hypotheses that dobutamine increases intestinal blood flow, it reduces mucosal acidosis and it prevents mucosal injury in an experimental porcine model of distal colonic ischaemia. And the hypothesis that mannitol prevents reperfusion injury.Design: Randomised animal experiment.Setting: University Hospital, Department of Experimental Research.Materials: Twenty-four pigs. Interventions: Twenty-one pigs were subjected to 7 h of controlled non-occlusive intestinal ischaemia of the distal colon, consisting of an occlusion of the inferior mesenteric artery (IMA) and a constriction of the superior mesenteric artery (SMA). At 3.5 h six pigs were treated with dobutamine, six with mannitol (0.18 g/kgBW), six with dobutamine and mannitol and three served as controls. Three non-ischaemic pigs were treated with dobutamine.Measurements and results: All animals were haemodynamically stable throughout the experiment. There was no difference in any variable between the animals treated with mannitol and those not treated. The ischaemic dobutamine-treated animals increased their cardiac output (CO) by 14 % compared to baseline and by 59 % compared to controls. The median final dosage of dobutamine was 13.2 µxg/kg per min (range 8.6–25.8). The blood flow in the restricted SMA, the intramucosal pH of the colonic mucosa (pHi) and the degree of histological mucosal injury were identical in animals treated with dobutamine and controls. The pH gap (pHa-pHi) correlated well (r=0.97) with the PCO2 gap (aPCO2-intestinal PCO2). The non-ischaemic animals treated with dobutamine increased CO by 37 % and blood flow of the SMA by 16 %.Conclusions: Dobutamine increased CO but did not ameliorate or deteriorate colonic ischaemia in this experimental model. The PCO2 gap correlated well with the pH gap.