Effects of norepinephrine and phenylephrine on intestinal oxygen supply and mucosal tissue oxygen tension.

OBJECTIVES: To investigate effects of intravenous norepinephrine (NE) and phenylephrine (PE) on intestinal oxygen supply in an autoperfused, innervated jejunal segment. DESIGN AND SETTING: Prospective, randomized animal study in an animal research laboratory. MATERIALS AND METHODS: In 24 anesthetized and normoventilated pigs a segment of the jejunal mucosa was exposed by midline laparotomy and antimesenteric incision. Mucosal oxygen tension (PO2muc; Clark-type surface oxygen electrodes), microvascular hemoglobin oxygen saturation (HbO2, tissue reflectance spectrophotometry), and microvascular blood flow (perfusion units, PU; laser Doppler velocimetry), systemic hemodynamics, mesenteric-venous acid base and blood gas variables, and systemic acid base and blood gas variables were recorded after a resting period and at 20-min intervals during infusion of NE (0.01, 0.05, 0.1, 0.5, 1, 2 micrograms x kg-1 x min-1; n = 8) or PE (0.1, 0.5, 1, 2, 5, 10 micrograms x kg-1 x min-1; n = 8) and in controls (n = 8) without treatment. RESULTS: NE infusion led to significant tachycardia, an increase in cardiac output, and systemic oxygen delivery and consumption while PE progressively increased mean arterial pressure with only small effects on systemic blood flow. NE or PE infusion did not affect mesenteric venous oxygen tension (baseline: PE 53 +/- 5, NE, 52 +/- 4.2 mmHg), mesenteric oxygen extraction ratio (baseline: PE 0.29 +/- 0.08, NE 0.3 +/- 0.06), jejunal microvascular blood flow (baseline: PE 254 +/- 127, NE 282 +/- 72 PU), PO2muc (baseline: PE 31 +/- 9.1, NE 33 +/- 11 mmHg), and HbO2 (baseline: PE 52 +/- 9.6%, NE 58 +/- 11.6%). CONCLUSION: Despite major differences in systemic hemodynamics jejunal tissue oxygen supply is not affected by progressively increasing intravenous infusion of norepinephrine and phenylephrine.

Effects of epinephrine on intestinal oxygen supply and mucosal tissue oxygen tension in pigs.

OBJECTIVE: To study the effects of increasing dosages of epinephrine given intravenously on intestinal oxygen supply and, in particular, mucosal tissue oxygen tension in an autoperfused, innervated jejunal segment. DESIGN: Prospective, randomized experimental study. SETTING: Animal research laboratory. SUBJECTS: Domestic pigs. INTERVENTIONS: Sixteen pigs were anesthetized, paralyzed, and normoventilated. A small segment of the jejunal mucosa was exposed by midline laparotomy and antimesenteric incision. Mucosal oxygen tension was measured by using Clark-type surface oxygen electrodes. Microvascular hemoglobin oxygen saturation and microvascular blood flow (perfusion units) were determined by tissue reflectance spectrophotometry and laser-Doppler velocimetry. Systemic hemodynamics, mesenteric-venous acid-base and blood gas variables, and systemic acid-base and blood gas variables were recorded. Measurements were performed after a resting period and at 20-min intervals during infusion of increasing dosages of epinephrine (n = 8; 0.01, 0.05, 0.1, 0.5, 1, and 2 microg x kg(-1) x min(-1)) or without treatment (n = 8). In addition, arterial and mesenteric-venous lactate concentrations were measured at baseline and at 60 and 120 mins. MEASUREMENTS AND MAIN RESULTS: Epinephrine infusion led to significant tachycardia; an increase in cardiac output, systemic oxygen delivery, and oxygen consumption; and development of lactic acidosis. Epinephrine significantly increased jejunal microvascular blood flow (baseline, 267 +/- 39 perfusion units; maximum value, 443 +/- 35 perfusion units) and mucosal oxygen tension (baseline, 36 +/- 2.0 torr [4.79 +/- 0.27 kPa]; maximum value, 48 +/- 2.8 torr [6.39 +/- 0.37 kPa]) and increased hemoglobin oxygen saturation above baseline. Epinephrine increased mesenteric venous lactate concentration (baseline, 2.9 +/- 0.6 mmol x L(-1); maximum value, 5.5 +/- 0.2 mmol x L(-1)) without development of an arterial-mesenteric venous lactate concentration gradient. CONCLUSIONS: Epinephrine increased jejunal microvascular blood flow and mucosal tissue oxygen supply at moderate to high dosages. Lactic acidosis that develops during infusion of increasing dosages of epinephrine is not related to development of gastrointestinal hypoxia.

[Intestinal ischemic reperfusion syndrome: pathophysiology, clinical significance, therapy]. / Das Ischämie-Reperfusionssyndrom des Darmes: Pathophysiologie--klinische Relevanz--Therapie.

Gut ischemia-reperfusion injury is a serious condition in intensive care patients. Activation of immune cells within the huge endothelial surface area of gut microcirculation may initiate a systemic inflammatory response with secondary injury to distant organs. Translocation of bacteria and toxins through a leaky gut mucosa may amplify or perpetuate systemic inflammation, leading to multiple organ dysfunction syndrome and death in critically ill patients. Gut ischemia promotes regional production of inflammatory mediators, expression of cell adhesion molecules on endothelial and immune cell surfaces and increases the procoagulatory properties of vascular endothelial cells. During reperfusion, gut injury may be amplified by increased production of oxygen radicals and exhaustion of endogenous antioxidant defence mechanisms. Although several therapeutic strategies to interrupt the pathophysiology of ischemia-reperfusion have been shown to be beneficial in animal experiments, none of these interventions has gained clinical relevance. After initial hemodynamic and respiratory stabilisation of critically ill patients, strategies to prevent secondary gut injury by increasing splanchnic oxygen delivery or augment mucosal cell regeneration may be the only therapeutic options for intensive medical specialists at the present time. Early enteral nutrition and treatment with specific vasoactive drugs may reduce morbidity and costs of treatment in certain critically ill patients. However definitive evidence of a reduction in mortality with these therapies has still not be provided.

[Immunoglobulin A in saliva of children: age dependence and effect of respiratory tract diseases]. / Immunglobulin A im Speichel von Kindern: Altersabhängigkeit und Einfluss von Atemwegserkrankungen.

Immunoglobulin A (IgA) plays an essential role in the local defence mechanism and is part of the immunologic system. It is transported to the endothelial surface either as a monomer or as a dimer of two molecules of IgA connected by a j-chain and attached to a secretory component. The aim of the present study was to assess the relation of salivary IgA to the age of children and to assess a possible influence by acute and chronic respiratory diseases. IgA was measured in the saliva of altogether 230 children by means of radial immunodiffusion (LC-IgA Partigen, Behring) following a standardised protocol. Relation to age was measured in 159 healthy children aged one month to 15 years. The median of IgA was 36 mg/l with a range of 3.5-291 mg/l. There was no statistically significant relationship between salivary IgA and the age of the children. Median IgA in the saliva of children without any respiratory disorders (n = 169) was 36 mg/l (3.5-291 mg/l), of children with acute respiratory diseases (n = 33) 51 mg/l (3.5-257 mg/l) and of children with chronic respiratory diseases (n = 28) 47 mg/l (3.5-165 mg/l). There was no statistically significant difference between these three groups. In conclusion, the results of this study show that IgA in the saliva of children may not be related to age or influenced by acute or chronic respiratory diseases.

[Secretory immunoglobulin A in childhood: does the saliva value reflect the bronchial value?]. / Sekretorisches Immunoglobulin A im Kindesalter: Spiegelt der Speichelwert den Bronchialwert wider?

Immunoglobulin A (IgA) can be found in different body secretions and plays a major role in the local immune response. It inhibits bacterial adherence, neutralizes toxins and protects the mucosa from penetrating antigens and allergens. Whereas measurement of IgA in saliva mostly does not show any problems, difficulties in assessing IgA in bronchial fluids often occur mainly due to variable dilutional effects. Aim of the present study was to find out whether saliva IgA predicts bronchial IgA. In 15 children aged 4 months to 14 years (mean 53.5 months; SEM 12.3) with chronic cough (n = 10), mediastinal mass (n = 1), recurrent airways obstructions (n = 2) and inspiratory stridor (n = 2) we performed a diagnostic rigid bronchoscopy and assessed IgA by means of bronchial lavage (BL). We attempted to control for uncertain dilution by the use of albumin as a denominator and to present our data as ratios of IgA to albumin. As various disease states alter the integrity of the alveolar-capillary membrane and influence the concentration of albumin in the epithelial lining fluid we developed an optical score to describe the state of the bronchial mucosa. Measurement of saliva IgA is easy and can be done without dilutional effects. The mean value of IgA in saliva was 65.49 mg/l (SEM 14.75; range 3.5-227), the one of IgA in bronchial lavage fluid 30.75 mg/l (SEM 7.11; range 3.5-100). IgA-albumin ratio ranged from 0.006 to 1.46 (mean 0.36, SEM 0.12). Saliva IgA did neither significantly correlate with bronchial IgA nor with bronchial IgA-albumin ratio.(ABSTRACT TRUNCATED AT 250 WORDS)