Yoshihiro Kitamura

Elevated expression of inducible nitric oxide synthase and inflammatory cytokines in the alveolar macrophages after esophagectomy.

Objective To evaluate the role of inducible nitric oxide (NO) synthase (iNOS) and inflammatory cytokines in alveolar macrophages (AMs) after esophagectomy in the pathogenesis of acute lung injury. Design Prospective, exploratory, open-labeled clinical study. Setting Intensive care unit and operating room in a university hospital. Patients Thirteen patients receiving esophagectomy with carcinoma of the esophagus (postesophagectomy group), ten patients just before the surgery (preoperation group), and seven patients receiving surgery less invasive than esophagectomy (other surgery group) were selected. Interventions Bronchoalveolar lavage fluid (BALF) and blood samples were obtained from study groups. Measurements and Main Results The AMs in the BALF collected from each group were stained immunohistochemically with antibodies against iNOS, interleukin (IL)-6, and IL-8. The intensities of these expressions were determined by semiquantitative cytofluorometric system. NOx (NO2−+NO3−), IL-6, and IL-8 levels in the BALF and plasma were measured concurrently. The expressional intensities of iNOS, IL-6, and IL-8 in AMs obtained from the postesophagectomy group were maximal 24 hrs after the skin incision and significantly more evident than those from other groups. The IL-6, IL-8, and NOx levels in BALF and IL-6 and IL-8 levels in plasma in the postesophagectomy patients were also elevated. The intensities of iNOS and inflammatory cytokines expressions in AMs were closely related to postoperative respiratory failure. Conclusions The activation of topical alveolar macrophages may be involved in the pathogenesis of pulmonary complications in the postoperative period after esophagectomy.

Effect of amino acid infusion on central thermoregulatory control in humans.

BackgroundAdministration of protein or amino acids enhances thermogenesis, presumably by stimulating oxidative metabolism. However, hyperthermia results even when thermoregulatory responses are intact, suggesting that amino acids also alter central thermoregulatory control. Therefore, the authors tested the hypothesis that amino acid infusion increases the thermoregulatory set point. MethodsNine male volunteers each participated on 4 study days in randomized order: (1) intravenous amino acids infused at 4 kJ · kg−1 · h−1 for 2.5 h combined with skin-surface warming, (2) amino acid infusion combined with cutaneous cooling, (3) saline infusion combined with skin-surface warming, and (4) saline infusion combined with cutaneous cooling. ResultsAmino acid infusion increased resting core temperature by 0.3 ± 0.1°C (mean ± SD) and oxygen consumption by 18 ± 12%. Furthermore, amino acid infusion increased the calculated core temperature threshold (triggering core temperature at a designated mean skin temperature of 34°C) for active cutaneous vasodilation by 0.3 ± 0.3°C, for sweating by 0.2 ± 0.2°C, for thermoregulatory vasoconstriction by 0.3 ± 0.3°C, and for thermogenesis by 0.4 ± 0.5°C. Amino acid infusion did not alter the incremental response intensity (i.e., gain) of thermoregulatory defenses. ConclusionsAmino acid infusion increased the metabolic rate and the resting core temperature. However, amino acids also produced a synchronous increase in all major autonomic thermoregulatory defense thresholds; the increase in core temperature was identical to the set point increase, even in a cold environment with amble potential to dissipate heat. In subjects with intact thermoregulatory defenses, amino acid–induced hyperthermia seems to result from an increased set point rather than increased metabolic rate per se.

Upright Posture Reduces Thermogenesis and Augments Core Hypothermia

UNLABELLED We recently reported that baroreceptor-mediated reflexes modulate thermoregulatory vasoconstriction during lower abdominal surgery. Accordingly, we examined the hypothesis that postural differences and the related alterations in baroreceptor loading similarly modulate the thermogenic (i.e., shivering) response to hypothermia in humans. In healthy humans (n = 7), cold saline was infused IV (30 mL/kg at 4 degrees C) for 30 min to decrease core temperature. Each participant was studied on 2 separate days, once lying supine and once sitting upright. Tympanic membrane temperature and oxygen consumption were monitored for 40 min after each saline infusion. The decrease in core temperature upon completion of the infusion in the upright posture position was 1.24 degrees C +/- 0.07 degrees C, which was significantly greater than the 1.02 degrees C +/- 0.06 degrees C seen in the supine position. The core temperature was reduced by 0.59 degrees C +/- 0.07 degrees C in the upright position but only by 0.37 degrees C +/- 0.05 degrees C in the supine position when the increase in oxygen consumption signaling thermogenic shivering occurred. Thus, the threshold temperature for thermogenesis was significantly less in the upright than the supine position. The gain of the thermogenic response did not differ significantly between the positions (363 +/- 69 mL. min(-1). degrees C(-1) for upright and 480 +/- 80 mL. min(-1). degrees C(-1) for supine). The skin temperature gradient was significantly larger in the upright than in the supine posture, suggesting that the peripheral vasoconstriction was augmented by upright posture. Plasma norepinephrine concentrations increased in response to cold saline infusion under both conditions, but the increase was significantly larger in the upright than in the supine posture. Baroreceptor unloading thus augments the peripheral vasoconstrictor and catecholamine response to core hypothermia but simultaneously reduces thermogenesis, which consequently aggravated the core temperature decrease in the upright posture. IMPLICATIONS Upright posture attenuates the thermogenic response to core hypothermia but augments peripheral vasoconstriction. This divergent result suggests that input from the baroreceptor modifies the individual thermoregulatory efferent pathway at a site distal to the common thermoregulatory center or neural pathway.

Thermoregulatory Response to Intraoperative Head-Down Tilt

UNLABELLED Thermoregulation interacts with cardiovascular regulation within the central nervous system. We therefore evaluated the effects of head-down tilt on intraoperative thermal and cardiovascular regulation. Thirty-two patients undergoing lower-abdominal surgery were randomly assigned to the 1) supine, 2) 15 degrees -20 degrees head-down tilt, 3) leg-up, or 4) combination of leg-up and head-down tilt position. Core temperature and forearm minus fingertip skin-temperature gradients (an index of peripheral vasoconstriction) were monitored for 3 h after the induction of combined general and lumbar epidural anesthesia. We also determined cardiac output and central-venous and esophageal pressures. Neither right atrial transmural pressure nor cardiac index was altered in the Head-Down Tilt group, but both increased significantly in the Leg-Up groups. The vasoconstriction threshold was reduced in both leg-up positions but was not significantly decreased by head-down tilt. Final core temperatures were 35.2 degrees C +/- 0.2 degrees C (mean +/- SEM) in the Supine group, 35.0 degrees C +/- 0.2 degrees C in the Head-Down Tilt group, 34.2 degrees C +/- 0.2 degrees C in the Leg-Up group (P < 0.05 compared with supine), and 34.3 degrees C +/- 0.2 degrees C when leg-up and head-down tilt were combined (P < 0.05 compared with supine). These results confirm that elevating the legs increases right atrial transmural pressure, reduces the vasoconstriction threshold, and aggravates intraoperative hypothermia. Surprisingly, maintaining a head-down tilt did not increase right atrial pressure. IMPLICATIONS Intraoperative hypothermia is exaggerated when patients are maintained in the leg-up position because the vasoconstriction threshold is reduced. However, head-down tilt (Trendelenburg position) does not reduce the vasoconstriction threshold or aggravate hypothermia. The head-down tilt position thus does not require special perioperative thermal precautions or management unless the leg-up position is used simultaneously.