Published papers

This study was designed to evaluate the changes of endogenous catecholamine secretions in association with dopamine infusion (6.0 ± 1.9 μg/kg/min. mean ± S.D.) in man. In 18 patients undergoing gynecological abdominal surgery, epidural anesthesia combined with light general anesthesia was performed to suppress the physical and mental stress during surgery. Eleven of them were given dopamine during the operation (dopamine group) and the other 7 patients were not given dopamine (control group). Urine samples were collected before and during the operations, and the concentrations of dopamine, norepinephrine and epinephrine per 1 mg of creatinine were measured by high performance liquid chromatography using the native fluorescence detection method. In the dopamine group, norepinephrine excretion during the operations increased on average 66% compared with the preoperative value (p < 0.01). In contrast, in the control group, both norepinephrine and epinephrine excretion were unchanged. These results suggest that exogenous dopamine increases the plasma level of norepinephrine in man.

Background: The effects of inhalational anesthetics on the microcirculation, including leukocyte dynamics, remain to be clarified. The authors investigated halothane and sevoflurane anesthesia to determine if these agents evoked leukocyte adhesion through endothelial cell-dependent mechanisms involving such adhesion molecules. Methods: Rats were anesthetized with halothane or sevoflurane in 100% oxygen and the lungs were mechanically ventilated. Leukocyte behavior in mesenteric venules was recorded through intravital video microscopy under monitoring microvascular hemodynamics. To examine the mechanisms for leukocyte rolling and adhesion, these studies were repeated after animals were pretreated with a monoclonal antibody against P- selectin (MAb PB1.3) or against intracellular adhesion molecule-1 (ICAM-1; MAb IA29): P-selectin required for rolling of circulating leukocytes and ICAM-1 for firm adhesive interactions with leukocyte integrins. Results: Under baseline anesthetic conditions (1 minimum alveolar concentration [MAC]), venular wall shear rates, an index of the disperse force on marginating leukocytes, in the sevoflurane-treated rats were about two times higher than those with halothane. At 2 MAC, halothane caused a marked arteriolar constriction and decreasing shear rates concurrent with an increasing density of venular leukocyte adhesion. Sevoflurane at 2 MAC induced leukocyte rolling and adhesion, which were attenuated by PB1.3 and 1A29, without alterations in the wall shear rates. Halothane-induced leukocyte adhesion was not prevented by PB1.3 but it was by 1A29. Conclusions: Halothane or sevoflurane anesthesia induces venular leukocyte rolling and adhesion: P-selectin upregulation plays a crucial role in leukocyte rolling and adhesion during sevoflurane anesthesia, whereas low- flow perfusion is likely to evoke ICAM-1-dependent leukocyte adhesion during halothane anesthesia.

Purpose: To examine the hypothesis that epidural anesthesia throughout lower abdominal surgery would depress both postoperative pain and cortisol release. Methods: Forty adult patients undergoing abdominal total hysterectomy were studied. The patients were randomly assigned to two groups. Group G received general anesthesia alone (sevoflurane 1.5%-2.5%); group E received a combination of epidural anesthesia (1.5% mepivacaine) with a light plane of general anesthesia (sevoflurane<0.5%). Postoperative analgesia was obtained epidurally by patient-controlled analgesia. Postoperative pain at rest and during movement was assessed by a visual analogue scale (VAS) at 2, 24, and 48 h following surgery. The plasma concentration and urinary excretion of cortisol were measured during the perioperative period. Results: VAS values were lower in group E than in group G during movement at 24h (4.6±0.5 vs 6.1±0.4 cm). Urinary cortisol excretion on the first postoperative day was less in group E than in group G (192±34 vs 480±120μg). Conclusions: Epidural blockade prior to surgical stimuli and throughout lower abdominal surgery reduces the postoperative dynamic pain and stress response. © 1997 JSA.

Objectives: To determine the benefits of a human urinary protease inhibitor (ulinastatin) on postoperative pulmonary dysfunction associated with neutrophil activation during cardiopulmonary bypass. Design: A prospective, randomized, clinical study. Setting: The study was performed at Keio University Hospital, Tokyo. Participants: Eighteen adult patients scheduled for primary cardiac surgery. Interventions: The patients were randomly assigned either to the control group (n = 8) or to the group (n = 10) receiving ulinastatin (600,000 U in total). Measurements and Main Results: Human neutrophil ability to release elastase in response to N- formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) in vitro was measured before and after cardiopulmonary bypass, together with plasma levels of neutrophil elastase complex, interleukin-8, and C3a. Intrapulmonary shunt fraction was then calculated. Neutrophil elastase release in response to fMLP significantly increased in the control group, but remained unchanged in the ulinastatin group. In addition, ulinastatin minimized the increase of plasma neutrophil elastase, independently of the production of interleukin-8 or C3a. Simultaneously, ulinastatin ameliorated the increase of intrapulmonary shunt, which was correlated with extracellular elastase release. Conclusions: Ulinastatin attenuated the elevation of fMLP-induced elastase release, which was associated with the deterioration of gas exchange during cardiopulmonary bypass. The administration of this agent has a potential to lessen the risk of postperfusion lung injury.

We investigated the efficacy of preventive use of diltiazem to suppress supraventricular tachyarrhythmia such as paroxysmal atrial tachycardia (PAT) and atrial fibrillation (Af) in the patients who underwent transthoracic esophagectomy. We divided 52 patients into 2 groups; the diltiazem group (n=26) and the control group (n=26). In the diltiazem group continuous intravenous infusion of diltiazem (1-3mcg · kg-1 · min-1) was started when the patient's heart rate remained over 110 · min-1 without any predisposing factor. On the other hand, in the control group we did not use it preventively. In both groups, we did not restrict the use of antiarrhythmic agents if necessary. We recognized PAT or Af in the control group (54 %) more often than in the diltiazem group (19 %). PAT or Af seldom occurred after the 4th post-operative day in the both groups. Serum diltiazem concentrations of 9 patients after about 10 hours infusion showed great variation (between 30 and 250 ng · ml-1). In 7 of them the diltiazem concentration increased as the duration of infusion was prolonged. However, we did not observe bradyarrhythmia. We consider that the continuous diltiazem infusion is effective in suppressing supraventricular tachyarrhythmia after esophagectomy.