Masato Kawakami

Preliminary clinical outcome study of mild resuscitative hypothermia after out-of-hospital cardiopulmonary arrest

The effects of mild hypothermia (MH) were investigated. From 1995 to 1996, 28 adult patients with out-of-hospital cardiopulmonary arrest (CPA) had return of spontaneous circulation and survived for more than two days. Thirteen patients were in the MH group. In the MH group, core temperature was maintained between 33 and 34 degrees C for 48 h, and then re-warmed to a temperature of 37 degrees C, at a rate of no greater than 1 degrees C per day. Fifteen patients, admitted before the MH protocol was instituted, were in the control group. Despite the fact that the number of witnessed arrests in the control group were greater than in the MH group, there were both more survivors (7/13 vs. 5/15) and more fully recovered patients (3/13 vs. 1/15) in the MH vs Control groups. Eleven of 13 MH patients, as compared to 6/15 controls developed pneumonia. Our study, although preliminary, suggests that MH might confer improved outcome, as has been shown in animal models, after CPA. This treatment is associated with an increase in pneumonic complications.

Measurement of interleukin-6, interleukin-10, and tumor necrosis factor-alpha levels in tissues and plasma after thermal injury in mice☆

BACKGROUND Cytokines are important modulators of physiologic alterations after thermal injury. Indeed, an increase in the level of circulating cytokines has been documented after thermal injury. However, the mechanism of the increase has not been clarified. We determined cytokine levels in local tissue after thermal injury to identify the tissues responsible for the increase. METHODS Female C57BL/6 mice each received a 20% full-thickness burn injury. Blood, burned skin, unburned skin, muscle underlying the burn, and muscle of the thigh, liver, spleen, and mesenteric lymph node were sampled at 1, 2, 4, 8, and 24 hours after injury. Uninjured control mice were treated similarly. The samples were cultured, and concentrations of tumor necrosis factor-alpha, interleukin-6 (IL-6), and IL-10 in the culture media were measured by using an enzyme-linked immunosorbent assay. RESULTS IL-6 levels in unburned skin were significantly increased at 1 hour and decreased at 24 hours, compared with the control. IL-6 levels in muscle underlying the burn were significantly decreased at 8 hours. No elevation of plasma IL-6 levels was observed after injury. Neither tumor necrosis factor-alpha IL-10 was detected in any tissue. CONCLUSIONS Results indicate that unburned skin may be a major source of IL-6 production after thermal injury and may contribute to the physiologic alterations occurring after such injury.

Permethrin Emulsion Ingestion: Clinical Manifestations and Clearance of Isomers

BACKGROUND Oral intoxication with permethrin, an insecticide which prolongs axonal sodium channel depolarization, has not been documented in humans. We treated a 59-year-old man who drank approximately 600 mL of 20% permethrin emulsion in a suicide attempt. METHODS Sequential blood samples were obtained to determine permethrin isomer levels using high-performance liquid chromatography. RESULTS Vomiting and diarrhea occurred after ingestion. On admission, loss of consciousness and metabolic acidosis were observed. On regaining consciousness, the patient complained of a burning sensation in the oral cavity. He received fluid therapy after gastric lavage and recovered without severe complications. Apart from initially impaired consciousness, no clinical neurotoxicity such as tremor, hyperexcitation, ataxia, convulsions, or paralysis occurred, though these have been reported in permethrin-intoxicated animals. Serum permethrin concentrations peaked 3-4 hours after ingestion at 868 ng/mL. Clearance of trans permethrin was more rapid than that of cis permethrin. CONCLUSION The unequal clearance of permethrin isomers paralleled findings in animal experiments. Vomiting and diarrhea probably limited absorption in the present case, resulting in a peak serum concentration and a degree of neurotoxicity far less than those seen in animals.

Rapid body cooling by cold fluid infusion prolongs survival time during uncontrolled hemorrhagic shock in pigs.

OBJECTIVE The purpose of this study was to examine whether cold fluid infusion could rapidly decrease the core temperature and prolong survival during uncontrolled hemorrhagic shock in pigs. METHODS Fourteen pigs under light halothane anesthesia and spontaneous breathing underwent initial blood withdrawal of 25 mL/kg over 15 minutes, followed by uncontrolled hemorrhage (5-mm aortotomy). Immediately after the aortotomy, the pigs were randomized to receive 500 mL lactated Ringers solution at either 4 degrees C (group 1, n = 7) or 37 degrees C (group 2, n = 7) over 20 minutes through the internal jugular vein and observed until their death or for a maximum of 240 minutes. RESULTS The pulmonary artery temperature of group 1 decreased to 35.5 degrees +/- 0.3 degrees C after the infusion, then remained at 35.5 degrees C during the observation period. Pulmonary artery temperature values of group 2 remained at around 37.5 degrees C throughout the experiment. The mean survival time was 220 +/- 45 minutes in group 1 versus 136 +/- 64 minutes in group 2 (p < 0.05, life table analysis). The additional intraperitoneal blood loss of group 1 was similar to that of group 2 (9 +/- 4 g/kg vs. 10 +/- 5 g/kg). CONCLUSION In lightly anesthetized pigs during uncontrolled hemorrhagic shock, infusion with 4 degrees C lactated Ringers solution (which seems to be feasible in the clinical setting) decreases the core temperature rapidly and prolongs survival.

Moderate hypothermia alters interleukin-6 and interleukin-1α reactions in ischemic brain in mice

Female C57BL/6 mice were decapitated and their brains were removed and cultured at either 37 or 33 degrees C for 48 h to investigate whether or not moderate hypothermia alters the cytokine reactions in the ischemic brain. The interleukin-6 and interleukin-1alpha levels in the culture media were significantly elevated in a time-dependent manner. The interleukin-6 levels after the incubation at 33 degrees C were significantly lower than those at 37 degrees C. The interleukin-1alpha levels at 33 degrees C were significantly higher than those at 37 degrees C. The interleukin-1alpha levels incubated with interleukin-6 antibody were significantly higher than those without IL-6 antibody. At 37 degrees C, the mRNA expression of interleukin-6 was observed from 2 to 48 h after incubation, but the same expression of interleukin-1alpha was only detected until 12 h. Accordingly, the ischemic brain incubated at 33 degrees C showed a decreased interleukin-6 production in comparison with that at 37 degrees C and the level of interleukin-6 showed negative feedback for the production of interleukin-1alpha. The temperature should, therefore, be carefully considered when evaluating the cytokine reaction for cerebral ischemia.

Characteristics of plasma extracellular SOD in burned patients

The aim of this study was to examine three types of superoxide dismutase (SOD) in plasma after burns, and especially to clarify the characteristics of plasma extracellular SOD (EC-SOD) in burned patients. A total of 71 blood samples were collected from 18 patients on arrival, day 1, day 3 and day 5 after burns. We measured three types of SOD (Mn, Cu/Zn, EC) in plasma using ELISA, and the relationships among the three types of SOD concentrations were examined. We next analyzed the characteristics of plasma EC-SOD using stepwise multivariate regression analysis. Any plasma SOD isoenzyme concentration measured after burns was beyond the normal range and EC-SOD accounted for the major part of plasma SODs. EC-SOD and Cu/Zn-SOD were positively correlated, whereas Mn-SOD was not related to the other SODs. Also, plasma EC-SOD was significantly related to existence of inhalation injury, %TBSA and age, respectively. The plasma EC-SOD might therefore play some roles in the pathophysiology of burned patients.

Changes of the Interleukin-6 Levels in Skin at Different Sites After Thermal Injury

OBJECTIVE To delineate the regulation of IL-6 production in unburned skin adjacent to a burn in an animal model. METHODS In C57BL/6 mice, at 15, 30, and 60 minutes after a 20% full-thickness burn, skin was removed from various sites. Control samples were obtained from unburned mice. Normal skins were incubated with tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1alpha), IL-1 beta, and IL-6. Unburned skin specimens were incubated with anti-TNF-alpha and IL-1alpha antibodies. Cytokine levels were measured by enzyme-linked immunosorbent assay. RESULTS The burn increased the IL-6 levels at 30 minutes (p < 0.05) and the IL-1alpha levels at 15 and 60 minutes in the unburned skin. TNF-alpha, IL-1alpha, and IL-1beta increased IL-6 production in normal skin (p < 0.05). Anti-IL-1alpha antibody decreased IL-6 production in the unburned skin (p < 0.05). CONCLUSIONS IL-1alpha modulates IL-6 production in unburned skin after injury. IL-6 and IL-1alpha might contribute to the alterations after a burn.

Catecholamines play a role in the production of interleukin-6 and interleukin-1α in unburned skin after burn injury in mice

ObjectiveTo investigate the effects of catecholamines on the production of interleukin (IL)-6 and IL-1&agr; in unburned skin after a burn injury. DesignRandomized, controlled study. SettingAnimal laboratory. SubjectsAnesthetized female C57BL/6 mice. InterventionsA full-thickness burn injury on 20% of total body surface area was produced on the clipped dorsum, which was followed by resuscitation with lactated Ringer’s solution (0.1 mL/g). Phentolamine mesylate (10 mg/kg) or propranolol hydrochloride (10 mg/kg) was administered intraperitoneally before the burn injury. Measurements and Main Results Epinephrine and norepinephrine increased the production of IL-6 but not of IL-1&agr; in normal abdominal skin, and these increases were reversed by a &bgr;-blocker (propranolol hydrochloride) but not an &agr;-blocker (phentolamine mesylate). A 20% full-thickness burn injury of the skin increased the plasma concentration of epinephrine 30 mins after the injury in female C57BL/6 mice, but not norepinephrine or dopamine. The burn also increased IL-6 production in unburned abdominal skin. The administration of a &bgr;-blocker before a 20% burn injury suppressed the increased IL-6 production in unburned abdominal skin as determined by both protein level and mRNA expression. Pretreatment with the &agr;-blocker was less effective. ConclusionsWe propose that the neuroendocrine system activated by a 20% burn injury participates in the increased IL-6 production in the unburned skin.

Plasma Activated Clotting Time as an Indicator of Dangerous Hypocoagulability in Warfarin-treated Trauma Patients: A Preliminary Study

This study was conducted to determine the possibility of detecting dangerous hypocoagulability in trauma victims given warfarin by measuring plasma activated clotting time (ACT). Sensitivity of the plasma ACT to warfarin was tested using lyophilized plasmas and plasma samples from nontraumatized but anticoagulated patients. Lyophilized plasmas were also used to evaluate the effect of defects in the intrinsic coagulation system on the plasma ACT. The plasma ACT, measured using a 4.4-mM calcium solution, showed satisfactory prolongation when the thrombotest of matched samples was within the therapeutic range for warfarin therapy. Conversely, the plasma ACT was not prolonged when the only abnormality of matched samples was mild to moderate prolongation of the activated partial thromboplastin time (APTT). These findings suggest that the plasma ACT could be a reliable indicator of dangerous hypocoagulability in trauma patients receiving warfarin therapy during the immediate postinjury period.