Kupffer cells and neutrophils as paracrine regulators of the heme oxygenase-1 gene in hepatocytes after hemorrhagic shock.

Heme oxygenase (HO) plays a pivotal role for the maintenance of liver blood flow and hepatocellular integrity after hemorrhagic shock. We investigated the role of Kupffer cells and neutrophils as paracrine modulators of hepatocellular HO-1 gene expression in a rat model of hemorrhage and resuscitation. Male Sprague-Dawley rats (n = 6-10/group) were anesthetized (pentobarbital, 50 mg/kg intraperitonal) and subjected to hemorrhagic shock (mean arterial blood pressure: 35 mmHg for 60 min) or a sham protocol. Based on the time course of HO-1 gene expression, the effect of various antioxidants, Kupffer cell blockade [gadolinium chloride (GdCl3); 10 mg/kg; 24 h prior to hemorrhage or dichloromethylene diphosphonate (Cl2MDP); 1 mg/kg; 2 days prior to hemorrhage], or neutrophil depletion (vinblastine, 0.5 mg/kg, 5 days prior to hemorrhage) on induction of the HO-1 gene was assessed at 5 h of resuscitation, i.e., the time point of maximal induction. Kupffer cell blockade and antioxidants abolished HO-1 mRNA and protein induction after hemorrhage, while neutrophil depletion failed to affect hepatocellular HO-1 gene expression. In addition, Kupffer cell blockade aggravated hepatocellular injury. N-formyl-methionine-leucyl-phenylalanin (fMLP) induced a substantial influx of neutrophils into the liver but failed to induce hepatocellular HO-1 mRNA expression. These data suggest that Kupffer cells but not neutrophils induce an adaptive hepatocellular stress response after hemorrhage and resuscitation. Oxygen-free radicals released by Kupffer cells may serve as paracrine regulators of a hepatocellular stress gene which is necessary to maintain liver blood flow and integrity under stress conditions.

Moderate controlled hypotension with sodium nitroprusside does not improve surgical conditions or decrease blood loss in endoscopic sinus surgery.

UNLABELLED: STUDY OBJECTIVES To determine if moderate controlled hypotension can improve the dryness of the surgical field in endoscopic sinus surgery. STUDY DESIGN: Randomized, prospective study. SETTING: University-affiliated hospital. PATIENTS: 32 ASA physical status I and II adult patients undergoing endoscopic sinus surgery. INTERVENTIONS: All patients were premedicated orally with chlorazepate. Patients in Group H received 12.5 mg captopril orally prior to surgery. Anesthesia was provided using an intravenous (IV) technique supplemented with nitrous oxide (N(2)O); anesthesia was maintained with boluses of 2 mcg/kg fentanyl and a propofol infusion at rates between 3 and 9 mg/kg/h at the discretion of the anesthetist. In Group H, sodium nitroprusside was infused at a rate of 1 to 2.5 mcg/kg/min to maintain moderate controlled hypotension with mean blood pressure of 65 to 75 mm Hg. MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure was assessed via the radial artery. Readings were recorded prior to intubation, immediately after intubation, at the start of surgery, then at 5, 15, 30, 45, and 60 minutes intraoperatively, and at the end of surgery. Intraoperative blood loss, dryness of the surgical field, adrenocorticotropic (ACTH) hormone, arginin-vasopressin (AVP), cortisol, and the preoperative and postoperative psychomotoric function were examined. At the start of surgery and thereafter, MAP increased in Group N but not in Group H. Throughout surgery, MAP was significantly lower in Group H than in Group N. Blood loss, dryness of the surgical field, ACTH, AVP, and cortisol levels, and psychomotoric function were not significantly different between the groups. CONCLUSION: Intravenous anesthesia supplemented with N(2) is as effective as moderate controlled hypotension when blood loss, visibility in the surgical field, ACTH, AVP, and cortisol are examined.

[Prophylactic analgesia in functional endoscopic sinus surgery. Hemodynamics, surgical conditions, stress response]. / Prophylaktische Analgesie bei endoskopischen Nasennebenhöhleneingriffen. Hämodynamik, Operationsbedingungen, Stressantwort.

OBJECTIVE: Sufficient control of intraoperative bleeding in functional endoscopic sinus surgery is essential for obtaining adequate surgical results. The necessity of hypotensive anesthetic techniques is a controversial topic among anesthesiologists and ENT-surgeons. This prospective, randomized study compared N2O-supplemented intravenous anesthesia with propofol and fentanyl or sufentanil with respect to hemodynamic reactions, endocrine stress response, blood loss and surgical conditions, and recovery. METHODS: After obtaining informed consent, 32 patients undergoing endoscopic sinus procedures were anesthetized with N2O, propofol, and fentanyl or sufentanil (dosage ratio fentanyl:sufentanil = 7:1). Arterial blood pressure was measured via an arterial line, blood samples for ACTH, AVP, and cortisol were obtained pre-, intra-, and post-operatively, and a psychomotor function test was conducted pre- and postoperatively. The ENT-surgeon estimated the dryness of the surgical field on a numeric scale ranging from 1 to 5, and intraoperative blood loss was measured. RESULTS: Hemodynamic reactions to surgical simulation were blunted more sufficiently in the sufentanil group. Surgical conditions were satisfactory in all patients, but significantly better in the sufentanil group; differences in blood loss did not prove statistically significant. The endocrine stress response was efficiently blunted without significant differences between the groups. Post-operative psychomotor testing showed better recovery in the sufentanil group. CONCLUSIONS: N2O-supplemented intravenous anesthesia is suitable for functional endoscopic sinus procedure without any further need for induced hypotension; sufentanil seems to be superior in regard to hemodynamic stability, surgical conditions, and psychomotor recovery.