David J. Schmeling

Histamine: A promoter of xanthine oxidase activity in intestinal ischemia/reperfusion

Xanthine oxidase (XO)-derived oxygen radicals are thought to play an important role in the intestinal injury resulting from ischemia and reperfusion. In vitro data shows enhanced XO activity in the presence of histamine. Histamine is known to be released during intestinal ischemia and reperfusion. The purpose of this study was to evaluate the relationship between histamine and XO in vivo in intestinal ischemia/reperfusion injury. Using an established model of gut ischemia and reperfusion, portal venous plasma was obtained and assayed for histamine levels, XO activity, and xanthine dehydrogenase (XD) activity following injury. Intestinal ischemia for 120 minutes resulted in a 200% increase in plasma histamine levels (263.4 +/- 36.9 nmol/mL control, v 548.7 +/- 35.1 nmol/mL experimental, P less than .05). Reperfusion for 15 minutes resulted in a further increase in plasma histamine (to 658.3 +/- 33.9 nmol/mL), compared with 120 minutes of ischemia alone. No significant change in plasma XO activity resulted after simple ischemia for 120 minutes. However, XO activity doubled within 15 minutes of reperfusion of the ischemic intestine (6.37 +/- 0.53 nmol O2- per milliliter per minute v 3.12 +/- 0.25 nmol O2- per milliliter per minute, P less than .05). Reperfusion for 60 minutes resulted in the maximal observed increase in plasma XO activity (9.49 +/- 0.67 nmol O2- per milliliter per minute). Analysis of XD activity demonstrated no significant decrease compared with controls until 120 minutes of ischemia and 60 minutes of reperfusion (1.62 +/- 0.49 nmol uric acid per milliliter per minute at 60 minutes of reperfusion, versus 5.02 +/- 0.52 nmol uric acid per milliliter per minute control, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cytoprotection by diclofenac sodium after intestinal ischemia/reperfusion injury.

Intestinal injury resulting from ischemia/reperfusion (I/R) is of fundamental importance in clinical pediatric surgery. I/R injury results from inadequate oxygen delivery as well as a secondary inflammatory response involving neutrophils and oxidants. This study was designed to evaluate a novel use for diclofenac sodium (DS), a nonsteroidal antiinflammatory agent, and to compare it with traditional antioxidants in this setting. Rats were subjected to intestinal ischemia followed by reperfusion. When killed, samples were obtained for measurement of intestinal myeloperoxidase (MPO), a measure of neutrophil sequestration, as well as for adenosine triphosphate (ATP) content, a marker of tissue injury. Animals exposed to I/R injury had significant neutrophil sequestration in the intestine by 120 minutes of ischemia, and this persisted after 60 minutes of reperfusion. DS pretreatment did not prevent neutrophil sequestration in the intestine. Analysis of intestinal ATP content demonstrated a decrease in intestinal ATP after 120 minutes of ischemia, and this did not change with 60 minutes of reperfusion. Pretreatment with DS significantly attenuated this intestinal ATP depletion. Furthermore, with 120 minutes of ischemia and 60 minutes of reperfusion, ATP preservation with DS pretreatment exceeded that obtained using the following conventional antioxidants: a xanthine-oxidase inhibitor (lodoxamide), deferoxamine, dimethysulfoxide, and superoxide dismutase plus catalase. DS has a significant cytoprotective effect for intestine subjected to I/R injury, exceeding that of conventional antioxidants. DS does not attenuate injury by preventing neutrophil influx into injured intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal and Metabolic Response to Operative Stress in the Neonate

It is evident from this review that newborns, even those born prematurely, are capable of mounting an endocrine and metabolic response to operative stress. Unfortunately, many of the areas for which a relatively well-characterized response exists in adults are poorly documented in neonates. As is the case in adults, the response seems to be primarily catabolic in nature because the combined hormonal changes include an increased release of catabolic hormones such as catecholamines, glucagon, and corticosteroids coupled with a suppression of and peripheral resistance to the effects of the primary anabolic hormone, insulin.

Experimental obliterative cholangitis : a model for the study of biliary atresia

Noninfectious obliterative cholangitis results from biliary tract inflammation in clinical conditions such as biliary atresia and sclerosing cholangitis. The purpose of this study was to develop an animal model of noninfectious biliary tract inflammation and fibrosis. An implantable osmotic pump was connected to a catheter placed into the gallbladder of hamsters. Phorbol myristate acetate (PMA) was infused into the biliary tract for periods of 6 hours to 28 days. After 7 days the animals developed neutrophil infiltration, cellular necrosis, and edema of the biliary ducts. After 14 days, the animals demonstrated intrahepatic cholestasis with bile duct fibrosis and acute and chronic inflammatory cell infiltration. By 28 days pronounced portal fibrosis was present, some of which created an early bridging cirrhosis pattern. In addition there was evidence of neocholangipgenesis. We conclude that long-term PMA infusion into the biliary tract generates an inflammatory response characterized by obliterative cholangitis and fibrosis, sharing many of the histologie features of human biliary atresia. This model may provide a relatively simple technique for investigating the process of nqnpyogehic biliary tract inflammation.

The hormonal and metabolic response to stress in the neonate

ConclusionsIt is apparent that adult patients demonstrate a catabolic response to the stresses induced by operative or accidental trauma. It seems that the degree of this catabolic response may be quantitatively related to the extent of the trauma or the magnitude of associated complications such as infection. The host response to infection, traumatic injury, or major operative stress is characterized by such events as fever, pituitary and stress hormone elaboration, mineral redistribution, and increased acute-phase protein synthesis [21].The beneficial effects of this stress response consist in providing alternate energy sources to meet metabolic demands and essential building blocks for synthetic activities occuring in the postoperative period. It has been suggested that the hyperglycemic response is essential for supplying the increased glucose requirements of injured tissue [81]. In addition, the proteolytic component of the stress response provides the necessary amino acid elements for reparative protein synthesis and production of acute-phase reactants by the liver. The changes in metabolic patterns induced by the stress response are satisfied in part by increased lipolysis and ketogenesis to provide an alternate source of metabolic fuel for tissues such as the brain and skeletal muscle. Additionally, the observed gluconeogenesis may aid in maintaining the glucose supply for vital organs principally dependent on glucose [52, 160].This metabolic response has also been shown to potentiate many adverse conditions in the postoperative period and to further exacerbate the stress response. Examples include a hypermetabolic state with attendant increased VO2, increased energy requirements, increased temperature, elevated cardiac output, and altered or impaired inflammatory or immune-responsiveness. Numerous investigators have demonstrated that adult patients exposed to severe degrees of traumatic stress are subjected to greatly increased rates of complications such as cardiac or pulmonary insufficiency, myocardial infarction, impaired hepatic and/or renal function, gastric stress ulcers, and sepsis. Furthermore, evidence exists to suggest that this response may be life-threatening if the induced catabolic activity remains excessive or unchecked for a prolonged period. Moyer et al. were able to identify with a great degree of certainty the patients who were likely to die based on a single analysis of a variety of plasma-borne substrates obtained up to 9 days prior to death [103].It is apparent that modulating or blunting the catabolic response induced by the stress state may have beneficial effects. In studies of postoperative pain management, improved pain control resulted in reduction of postoperative nitrogen loss and shortened periods of convalescence following operation [28, 88].It is evident from this review that human newborns, even those born prematurely, are capable of mounting an endocrine and metabolic response to operative stress. Unfortunately, many of the areas for which a relatively well-characterized response exists in adults are poorly documented in neonates. As is the case in adults, the response seems to be primarily catabolic in nature because the combined hormonal changes include an increased release of catabolic hormones such as catecholamines, glucagon, and corticosteroids coupled with suppression of and peripheral resistance to the effects of the primary anabolic hormone, insulin.The catecholamines may be the agents of primary importance in this response, and thus may modulate the remaining components of the hormonal response to stress as well as the metabolic changes, including inhibition of insulin release, marked hyperglycemia, and breakdown of the neonates stores of nutrients (carbohydrate, protein, and fat). These reactions ultimately result in the release of glucose, NEFA, ketone bodies, and amino acids. Although these metabolic by-products are necessary to meet the bodys altered energy needs in a time of increased metabolic demands, it is not difficult to imagine that a severe or prolonged response would be very detrimental to a previously ill neonate with limited reserves of nutrients and already high metabolic demands imposed by rapid growth, organ maturation, and adaptation to the postnatal environment. Preliminary investigations by Anand et al. outlined in this review indicate that alterations in anesthetic technique with the addition of agents such as halothane and fentanyl may be able to significantly blunt this catabolic response. In addition, it appears that modulation of the immune response may also greatly affect the postoperative catabolic response. It is hopeful that future developments and the acquisition of more detailed knowledge o the response will allow us to modify the stress response in neonates in order to further decrease their mortality and morbidity.

Extracorporeal life support (ECLS) for pediatric trauma: experience with five cases

Extracorporeal life support (ECLS) was used to treat five pediatric trauma patients (ages 1 to 17 years) with respiratory failure unresponsive to conventional mechanical ventilation. Diagnoses in these patients that resulted in respiratory failure included hydrocarbon aspiration (one patient), multiple trauma with pulmonary contusion (two patients), bronchopleural fistula (one patient), and neardrowning (one patient). Time on ECLS bypass averaged 328 h (range 140–527 h). Physiologic complications included bleeding, cardiac arrest, cardiac tamponade, hypoxemia, and hypotension. Mechanical complications involving the bypass circuit included roller-pump raceway rupture, roller-pump failure, and membrane oxygenator failure. All complications were managed without mortality. Three of the five patients were decannulated from ECLS and survived. Support was terminated in the remaining two due to irreversibility of the pulmonary injury. ECLS may provide life-saving support to pediatric patients with respiratory failure after trauma when conventional means of ventilatory support have failed.

Transanal wading pool suction-drain injury resulting in complete evisceration of the small intestine: case report and review of the literature

Suction evisceration from a pool drain is a rare injury. This child presented with what appeared to be isolated perineal trauma. Ultimately, the patient was found to have complete transanal small bowel evisceration. Reported herein are the specifics of this case, along with a review of the relevant literature relating to this case.

Metabolism of the Neonate Requiring Surgery

Postoperative or posttraumatic morbidity and mortality in the high risk adult patient have been correlated with, and may be participated by, the magnitude and duration of the metabolic response to the stressful event. Complications such as severe weight loss, cardiopulmonary insufficiency, thromboembolic disorders, gastric stress ulcers, impaired immunological function, prolonged convalescence, and death have been related to aspects of the metabolic response to surgical or traumatic stress.1,2