Urinary excretion of polyamines: importance of circadian rhythm, age, sex, menstrual cycle, weight, and creatinine excretion.

The urinary excretion of putrescine, spermidine, spermine, and N1- and N8-acetylspermidines was measured in 95 volunteers. The 24-h excretion, split in four consecutive periods, was analyzed for circadian rhythm in eight volunteers. Circadian rhythm was observed in total polyamine and in N1- and N8-acetylspermidine excretions. The excretion rates of these polyamines were highest in the morning. The normal values for 24-h urinary excretion of polyamines were determined in 87 volunteers. Men excreted significantly more spermidine (P less than 0.001), N8-acetylspermidine (P less than 0.05), and spermine (P less than 0.001) than did women; putrescine excretion was higher in women (P less than 0.001). This variation was only partially explained by differences between sexes in body or muscle mass because most differences remained significant even after normalization for creatinine excretion and body weight. No correlation between the polyamine excretions and age or menstrual cycle was found.

Gut luminal lactate release during gradual intestinal ischemia.

OBJECTIVES: Gut ischemia induced by occlusion of the superior mesenteric artery (SMA) results in release of lactate into the gut lumen. We studied the threshold of SMA flow reduction that leads to increased gut luminal lactate during stepwise reduction in SMA blood flow. DESIGN AND SETTING: A randomized, controlled animal experiment in a university experimental research laboratory. INTERVENTIONS: Anesthetized, normoventilated, normovolemic domestic pigs were randomized to ischemia ( n=7) and sham groups ( n=7). SMA blood flow was reduced stepwise at 15-min intervals by 22%, 44%, 66%, and 88% and kept constant thereafter for 60 min. MEASUREMENTS AND RESULTS: Jejunal luminal microdialysate lactate and mucosal pCO(2) were measured every 15 min. The luminal lactate increased over the upper normal limit of 0.2 mmol/l at a median SMA blood flow of 9.6 ml kg(-1) min(-1) (range 7.5-23.7). In five of seven animals the increase in luminal lactate was preceded by or accompanied by an increase in the mucosal-arterial pCO(2) gradient. CONCLUSIONS: There is a threshold of SMA blood flow below which gut luminal lactate increases, indicating mucosal anaerobic metabolism. Measurement of gut luminal lactate by microdialysis can be used to assess the adequacy of gut perfusion and the onset of anaerobic metabolism.

Urinary excretion of polyamines in patients with surgical and accidental trauma: effect of total parenteral nutrition.

Excretion of polyamines first increases and then decreases in patients with multiple trauma receiving total parenteral nutrition (TPN). To separate the effects of trauma and TPN on polyamine excretion, we studied 12 patients with multiple trauma and 14 patients after surgery for colorectal malignancy. Patients were randomized to receive either TPN or hypocaloric glucose infusion. Urinary excretion of total and free polyamines, putrescine (PU), spermidine (SPD), and spermine (SP), and their metabolites, N1-acetylspermidine (N1-AcSPD) and N8-acetylspermidine (N8-AcSPD), and energy and nitrogen balance were measured. Polyamine excretion, excluding SP, markedly increased after trauma and surgery, exceeding the normal values by twofold to 10-fold. In patients receiving TPN, the excretion of total polyamines was 48% higher (P < .01), PU was 34% higher (P < .05), SPD was 35% higher (P < .05), and SP was 350% higher (P < .05) than in patients receiving hypocaloric glucose. Urinary excretion of SP was only 17% of the reference value during hypocaloric glucose (P < .05), but was normal during TPN. The difference in polyamine excretion between nutrition groups was more pronounced when normalized for nitrogen or energy balance. Patients receiving TPN were more hypermetabolic than patients receiving hypocaloric glucose (resting energy expenditure, 1.36 +/- 0.06 [SE] and 1.16 +/- 0.04 times predicted values, respectively; P < .025). Statistically, energy expenditure could explain the difference in polyamine excretion between nutrition groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effects of sepsis and trauma on urinary excretion of polyamines.

Urinary excretion of polyamines increases in patients with trauma and infection. To separate the effect of infection from the general metabolic response to sepsis, we studied 7 patients with sepsis and 13 patients with multiple trauma in the intensive-care unit. Urinary excretion of total and free polyamines, putrescine, spermidine, spermine, and their metabolites N1-acetylspermidine (N1-AcSPD) and N8-acetylspermidine (N8-AcSPD), and energy and nitrogen balance were measured. The patients were randomized to receive either hypocaloric glucose alone or with amino acids for 2 days. The excretion of individual polyamines, except spermine, significantly exceeded normal values in both patient groups; the excretion of total polyamines was 530 and 323% higher than normal in patients with sepsis and trauma, respectively. The excretion of N1-AcSPD and total spermidine was 141 and 74% higher in patients with sepsis than in patients with trauma, respectively (p < 0.05), whereas the excretion of N8-AcSPD was equal in both patient groups. This was also reflected as a significantly increased urinary ratio of N1-AcSPD to N8-AcSPD in septic patients (6.37 +/- 1.61; mean +/- SE) compared with patients after injury (2.69 +/- 0.27, p < 0.01) or a healthy population (1.08 +/- 0.04, p < 0.001). Amino acid infusion had no effect on polyamine excretion. The mean energy balance was -17.0 +/- 1.1 and -19.1 +/- 1.1 kcal.kg-1.day-1, and the mean nitrogen balance was -0.17 +/- 0.03 and -0.15 +/- 0.02 g.kg-1.day-1 in patients with sepsis and trauma, respectively (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Polyamine excretion in depleted patients with gastrointestinal malignancy: effect of perioperative nutrition and tumor removal.

Polyamines, synthesized by all mammalian cells, are involved in protein and energy metabolism. We measured urinary excretion of polyamines, putrescine, spermidine, spermine, and their metabolites N1-acetylspermidine and N8-acetylspermidine, resting energy expenditure, and nitrogen excretion in 12 depleted patients with gastrointestinal malignancy during preoperative and postoperative parenteral nutrition and in 7 patients with multiple trauma receiving similar parenteral nutrition. During preoperative nutrition support, the excretion of putrescine (p less than .05) and total polyamines (p less than .01) increased by 420% and 60%, respectively. Increases in energy balance and resting energy expenditure during nutrition could entirely explain the observed changes in polyamine excretion. Preoperatively, the excretion of N1-acetylspermidine (p less than .05), N8-acetylspermidine (p less than .001) and total polyamines (p less than .05) was higher in patients with a surgically noncurable tumor than in those with a surgically curable tumor. The energy balance and resting energy expenditure could also explain the differences in polyamine excretion between patients with surgically curable and noncurable disease, excluding the increased N8-acetylspermidine. Postoperatively, the excretion of N8-acetylspermidine in patients with multiple trauma without malignancy and in patients with palliative operation was similar, and was higher than in patients with a totally resected malignancy (p less than .01). Our results suggest that the excretion of polyamines reflects the activity of energy metabolism in general and that polyamine excretion is not specific for any particular disease.

Comparison of monoglyceryl acetoacetate and glucose as parental energy substrate after experimental trauma.

The effects of ketone bodies and glucose on nitrogen balance and liver protein synthesis were studied in rat after experimental trauma. Energy was delivered intravenously as either monoglyceryl acetoacetate (MA; 87.5% of total energy input) or glucose (G). The isocaloric infusions (132 kcal/kg/day) were started after recovery from anaesthesia and continued for 2 days. The liver protein synthesis was then measured in vitro by perfusion with 14C-leucine. The infusion of MA resulted in a more negative cumulative nitrogen balance (MA: -2.31 +/- 0.26 g N/kg, G: -1.32 +/- 0.43 g N/kg/48 h; mean +/- SD) and liver protein synthesis (MA: 43.4 +/- 17.2, G: 71.1 +/- 15.2; arbitrary units, mean +/- SD). The results indicate no benefits from MA during the immediate post-traumatic period.

Use of resources and postoperative outcome.

OBJECTIVE: To characterise those surgical patients who consume one half of all hospital patient days, and to compare their outcome with that of low consumers. DESIGN: A retrospective cohort study. SETTING: Tertiary referral centre, Finland. PATIENTS: 13025 surgical patients who were admitted to a university hospital in Kuopio, Finland, during 1997. INTERVENTIONS: The length of stay below which half of all patient days fell was chosen as a cut-off value to divide patients into low and high consumers. MAIN OUTCOME MEASURES: Hospital and 12-month mortality and standardised mortality ratios (SMR: observed deaths/expected deaths based on the corresponding general population). RESULTS: The 2239 patients (17%) whose length of stay exceeded 9 days (high consumers) took up one half of all patient days. The pattern of resource use varied between operative specialities. At 12 months the SMRs showed excess mortality among high consumers (5.0, 95% confidence interval 4.4 to 5.7) compared with low consumers (2.1, 95% CI 1.9 to 2.3). CONCLUSIONS: Relating the length of stay to the proportion of resources consumed may provide a feasible tool for the recognition of different patterns of use of resources. SMRs may be more relevant measures of outcome than hospital mortality when assessing the efficacy of operative treatment.

Gut permeability in patients with acute pancreatitis.

BACKGROUND: The bacterial contamination of pancreatic necrosis in acute pancreatitis is supposed to occur through translocation of intestinal bacteria. Increased gut permeability may be the initial phenomenon in this process. To test the hypothesis that gut permeability is increased in acute pancreatitis a clinical study was made where gut absorption and permeability were assessed with multi-sugar probes in patients with acute pancreatitis within 2 days after admission to hospital and again after recovery of disease. METHODS AND RESULTS: Twenty-three patients with acute pancreatitis and 20 healthy controls were studied. According to Atlanta classification, 15 patients had mild and 8 patients severe pancreatitis. Gut absorption, assessed as the 5-h urine excretion of L-rhamnose, D-xylose and 3-O-methylglucose, was decreased in patients with acute pancreatitis and more pronounced in patients with severe pancreatitis (L-rhamnose and D-xylose: P < 0.001; 3-O-methylglucose: P < 0.05). Gut permeability, assessed as the ratio of lactulose/L-rhamnose, was increased in severe pancreatitis (0.16 +/- 0.13, 0.07 +/- 0.03, 0.04 +/- 0.04; severe pancreatitis, mild pancreatitis, controls, respectively; P < 0.001 between three groups, P < 0.05 between pancreatitis groups). CONCLUSIONS: Gut absorption capacity is decreased and gut permeability is increased in patients with acute pancreatitis. Patients with severe pancreatitis may be more exposed to impaired gut barrier function.

Gastric tonometry in assessing splanchnic tissue perfusion in acute pancreatitis.

BACKGROUND: Hypovolemia is typical early in acute pancreatitis. Despite fluid resuscitation splanchnic hypoperfusion may be present and may have a role in the course of pancreatitis. To test this hypothesis, we assessed gastric mucosal pH (pHi) and P(CO)2 during the first 48 h of hospitalization for acute pancreatitis. METHODS: Thirty-three patients were studied. A gastric tonometer was inserted on admission, and gastric mucosal pH and P(CO)2 were measured on admission and then every 12 h during next 48 h. RESULTS: On the basis of the Atlanta classification there were 22 cases of mild and 8 of severe pancreatitis. Three patients were excluded because of consent withdrawal. The groups were similar with regard to age, sex ratio, and etiology of pancreatitis. Independently of disease severity the gastric pHi decreased, and the gastric mucosal-arterial P(CO)2 difference and pH difference both increased over time as compared with base line. No difference was seen in these values between mild and severe pancreatitis. CONCLUSIONS: Moderate gastric mucosal hypoperfusion was found early in acute pancreatitis. However, gastric pHi measurement with tonometry has no obvious value as a screening tool to assess the severity of pancreatitis.

The effect of dopexamine on regional tissue oxygenation, systemic inflammation and amino acid exchange in major abdominal surgery.

BACKGROUND: Beta-adrenergic agents are frequently used to improve cardiac performance in surgical and intensive care patients. Beta-adrenergic agents have metabolic and anti-inflammatory effects in addition to their cardiovascular effects. Splanchnic metabolic activity increases in response to surgery and inflammation. Dopexamine is believed to favor blood flow distribution to the splanchnic region. METHODS: We investigated the effect of dopexamine, started before major abdominal surgery, on postoperative patterns of systemic and regional blood flow, metabolic response, and markers of inflammation. Twenty-one patients undergoing major abdominal surgery were studied. All patients were stabilized preoperatively to predefined hemodynamic endpoints with fluids. After preoperative measurement of systemic and splanchnic oxygen transport and splanchnic lactate, glutamine and alanine exchange and blood levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6), the patients were randomized to receive an infusion of dopexamine at 0.5 microg kg(-1) min(-1) (group 1) or 2.0 microg kg(-1) min(-1) (group 2) or placebo. Measurements were repeated at 6 h and 24 h after the end of the operation and the blood levels of cytokines also at 36 h postoperatively. RESULTS: Dopexamine evoked an increase in cardiac index preoperatively. Postoperatively, there was no difference between the groups in systemic and regional hemodynamics or oxygen transport: cardiac index, splanchnic blood flow and oxygen delivery increased similarly in each group. Accordingly, systemic oxygen extraction decreased. Glutamine, alanine and lactate exchange did not differ between the groups. The only metabolic change was an increased splanchnic uptake of alanine, which also was unaffected by dopexamine. There was no difference between the groups in TNF and IL-6 levels; TNF level did not change, while IL-6 level increased in response to surgery. CONCLUSIONS: Dopexamine, when added to a preoperative stabilization protocol with fluids, did not augment the postoperative hemodynamic response, and had no effect on postoperative metabolic and inflammatory responses.

Intestinal luminal microdialysis: a new approach to assess gut mucosal ischemia.

BACKGROUND: The authors developed a microdialysis method for sampling lactate from the gut lumen to evaluate the metabolic state of the intestinal mucosa. The aim of the study was to evaluate the method in vivo during nonischemic systemic hyperlactatemia and gut ischemia. METHODS: Microdialysis capillaries were inserted in the lumen of jejunum, in the jejunal wall, and in the mesenteric artery and vein in anesthetized, normoventilated pigs. In the first experiment, infusion of lactate was used to clamp the arterial blood lactate at 5 mM and 10 mM (n = 6). In the second experiment, 90 min of intestinal ischemia was induced by total (n = 6) or partial (n = 6) occlusion of the superior mesenteric artery followed by 60 min of reperfusion. Sham-operated animals were used as controls (n = 6). RESULTS: Gut luminal lactate increased only slightly during the nonischemic hyperlactatemia: from a median baseline value of 0.10 (range, 0.06-0.28) to 0.50 (range, 0.15-1.18) and 0.86 (range, 0.35-2.05) mM. Total occlusion of superior mesenteric artery increased luminal lactate from a median of 0.09 (range, 0.06-0.17) to 2.37 (range, 1.29-2.98) and further up to 3.80 (range, 2.55-6.75) mM during reperfusion. Partial occlusion of superior mesenteric artery induced an increase from a median of 0.09 (range, 0.06-0.51) to 1.66 (range, 0.07-3.97) mM. Gut wall microdialysate lactate in deep and superficial layers followed the arterial and mesenteric vein microdialysate lactate. CONCLUSIONS: Luminal lactate concentration, as measured by microdialysis, increases substantially during gut ischemia but does not respond to systemic hyperlactatemia per se. In contrast, gut wall microdialysis cannot distinguish between gut ischemia and systemic hyperlactatemia. Gut luminal microdialysis provides a method for the assessment of intestinal ischemia with a potential for clinical application.

Splanchnic tissue perfusion in acute experimental pancreatitis.

BACKGROUND: Gut hypoperfusion may have a role in the pathogenesis of multiple organ failure, which is a the main cause of death in severe acute pancreatitis. We hypothesized that gut hypoperfusion is present early in acute pancreatitis and that supporting the systemic hemodynamics by fluid resuscitation would prevent this. METHODS: In a pig model of randomized, controlled experimental hemorrhagic pancreatitis induced by Na-taurocholate the animals were divided into four groups (n = 6 for each): 1) pancreatitis, 2) control, 3) pancreatitis and fluid resuscitation to keep the pulmonary capillary wedge pressure at 5 to 6 mmHg, and 4) control and fluid resuscitation as in group 3. Splanchnic perfusion was assessed by means of local PCO2 gap with intestinal tonometer, oxygen delivery and consumption, lactate production, and blood flow. The follow-up time was 6 h. RESULTS: The Pco2 gap increased in pancreatitis (1.72+/-0.17, 1.94+/-0.29, 1.75+/-0.22, 2.32+/-0.33; 9.40+/-2.16, 3.72+/-1.78, 0.84+/-0.39, 1.11+/-0.21 kPa, respectively; P < 0.05). Oxygen delivery in portal-drained organs decreased in pancreatitis (2.5+/-0.3, 2.6+/-0.2, 2.8+/-0.4, 2.3+/-0.2; 1.7+/-0.3, 2.3+/-0.3, 2.4+/-0.5, 2.3+/-0.3 ml/min x kg, respectively; P < 0.05). Regional oxygen consumption did not change. Arterial plasma lactate increased (1.20+/-0.19, 1.33+/-0.16, 1.14+/-0.15, 1.43+/-0.33; 3.81+/-1.31, 1.48+/-0.48, 1.12+/-0.18, 1.18+/-0.35 mmol/l, respectively; P < 0.05). The portal venous blood flow decreased 50% in pancreatitis, but with fluid resuscitation it increased 50%. CONCLUSIONS: Splanchnic hypoperfusion is present early in acute hemorrhagic pancreatitis. The signs of hypoperfusion can be prevented with fluid resuscitation.

Lipid peroxidation products and antioxidant capacity in portal venous and systemic arterial plasma during gradual intestinal ischemia and reperfusion in pigs.

Intestinal ischemia may evoke an inflammatory response and eventually multiple organ failure. We investigated whether intestinal ischemic injury induces systemic lipid peroxidation and changes in the plasma antioxidant capacity in a pig model. Together with cardiovascular parameters, arterial and portal venous blood of 7 pigs were measured for thiobarbituric acid-reactive material diene conjugates, fluorescent chromolipids and plasma antioxidant capacity during graded occlusion of superior mesenteric artery and reperfusion. Plasma levels of lipid peroxidation products did not change significantly during graded ischemia and reperfusion. Portal venous plasma antioxidant capacity increased slightly during reperfusion (from 96.16 +/- to 3.91 to 142.49 +/- 12.01 mumol/l, p < 0.05). Although elevated levels of free radical reaction products have been found in ischemia-reperfusion, we found no evidence of systemic lipid peroxidation in our intestinal ischemia model.