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回路内気化器を設置した通常の麻酔器を用いてASA I～IIの12名の成人にセボフルラン,亜酸化窒素と酸素を使用し,6時間の閉鎖循環式麻酔を行なった.麻酔ガスモニターは呼吸回路内に空気が侵入しないように工夫し,測定後の余剰ガスは呼吸回路に回収した.酸素と亜酸化窒素の流量とセボフルランの気化器の設定濃度を調節して,およそ2%の吸気セボフルランの濃度と0.3のFIO2を維持した.吸気セボフルラン濃度は15±3分で2%に同亜酸化窒素濃度は3±1分で25%に達した.麻酔経過は円滑でSpO2はつねに97%以上を維持した.酸素,亜酸化窒素およびセボフルランの和(総濃度)は吸入麻酔開始直後は97±2%(このときはFIO2に等しい)であったが1時間後には94±1%,3時間後には93±3%に減少した.この原因は体内の溶存窒素の呼吸回路内への拡散によるものと考えられた.1時間当たりの酸素投与量は経時的に漸増傾向を,亜酸化窒素の投与量は経時的に有意に減少した.Compound Aは終始32ppm以下で許容できる濃度であった.

回路内気化器を設置した通常の麻酔器を用いて10名の成人にセボフルランと酸素を使用し,6時間以上の閉鎖循環式麻酔を行なった.麻酔ガスモニターは呼吸回路内に空気が侵入しないように工夫し,セボフルランの気化器を0.5%に設定して麻酔を開始した.吸気セボフルラン濃度は14±3分で2%に達した.その直後に気化器を0.2%に,そしてその12±8分後に0.1%に設定して吸気濃度を2%に維持した.麻酔経過は円滑でSpO2はつねに97%以上を維持し,compound Aは検出されたが許容できる濃度であった.閉鎖循環式回路による吸入麻酔開始直後の吸気酸素濃度は94±2%であったが,1時間後には85±4%,3時間後には83±3%に減少した.この原因は体内の溶存窒素の呼吸回路内への拡散によるものと考えられた.閉鎖循環式麻酔ではMACが43%以下の麻酔薬が必要であると考えられた.

市販されている通常の麻酔器でも回路の工夫や,回路内の酸素や麻酔薬の濃度,回路内圧などの連続的な監視により,閉鎖麻酔や低流量麻酔が可能である1)が,麻酔科医の精神的疲労も大きい.今回われわれはこれらの問題点を解決し,安全性を高めるために通常の麻酔器に各種機能を付加し,閉鎖麻酔,低流量麻酔および機能的閉鎖麻酔を行なった.5～6時間の麻酔中に呼吸回路内の低酸素や異常圧を認めず,この麻酔器の有用性を認めた.

Cardiac surgery with cardiopulmonary bypass (CPB) is frequently associated with a complex array of post-operative clinical abnormalities, including low-output syndrome and pulmonary dysfunction. It has been reported that oxygen free radicals are one of the important factors causing reperfusion injury. To determine whether oxygen free radicals are produced during cardiac surgery, we studied nine patients anesthetized with high doses of fentanyl. Lipid peroxide (LPO) and leukotriene B4 (LTB4) levels increased significantly from 60 min after aortic ligation to 180 min after reperfusion (aortic declamping), compared with the levels before surgery, while superoxide dismutase (SOD) was not affected markedly. Creatine kinase (CK), CK muscle-brain (CK-MB), and neutrophils increased from 60 min after aortic declamping. Correlations were not observed between LPO and CK nor between LPO and CK-MB. These results suggest that free radicals are generated during cardiac surgery with cardiopulmonary bypass (CPB), but it is unclear whether free radicals cause tissue injury after cardiac surgery with CPB.

To investigate whether ulinastatin pretreatment (6000 U.kg-1 before CPB and before declamping of aorta) influenced the production of cytokines and adhesion molecules in the peripheral circulation.This prospective randomized study was performed in 22 patients undergoing cardiac surgery. They were divided into two groups. Patients in Group I were untreated and in Group II treated with ulinastatin. The soluble intercellular adhesion molecule-1 (S-ICAM-1), soluble endothelial leukocyte adhesion molecule-1 (S-ELAM-1), interleukin 8 and 6 (IL- 8, 6) were measured using ELISA kits.Serum S-ICAM-1 concentration in Group I increased from the preoperative value of 297 +/- 27 ng.kg-1 to 418 +/- 106 ng.kg-1 at 60 min after declamping of the aorta (P0.01) but did not change in Group II. Serum S-ELAM-1 concentration did not change in either group. Serum concentration of IL-8 and IL-6 in Group I (37 +/- 44 pg.kg-1, and 59 +/- 59 pg.kg-1, preoperatively) increased to 169 +/- 86 pg.kg-1 and 436 +/- 143 pg.kg-1 at 60 min after declamping of the aorta (P0.001, P0.001). The increases were greater than those from 25 +/- 6 pg.kg-1 and 30 +/- 26 pg.kg-1 to 56 +/- 36 pg.kg-1 and 132 +/- 78 pg.kg-1 in Group II (P0.001, P0.001). The levels of S-ICAM-1 correlated with those of IL-8 (r = 0.5, P0.001).These results suggest that ulinastatin may suppress the increase in IL-8 production and the expression of ICAM-1 during cardiac surgery.

It has been reported that interleukin 8 (IL-8) and interleukin 6 (IL-6) are two of the chemical mediators causing myocardial injury. It is not clear whether treatment with corticosteroids in vitro in these patients can prevent the production of interleukin 8 and 6. This prospective study was conducted to investigate whether methylprednisolone (MP) pretreatment (30 mg.kg-1 before CPB and before declamping of aorta) influenced the production of IL-8 and 6 in the peripheral circulation in 27 patients undergoing elective coronary artery bypass surgery. The IL-8 and IL-6 concentrations were measured by ELISA kit. We also studied the effect of MP pretreatment on postoperative cardiac function. Serum concentration of IL-8 in non-MP-treated patients (37 +/- 44 pg.ml-1 preoperatively) increased to 169 +/- 86 pg.ml-1 60 min after declamping of the aorta (P < 0.001). The increase was greater than the increase from 22 +/- 8.9 pg.ml-1 to 52 +/- 35 pg.ml-1 in the MP-treated patients (P < 0.01). Serum IL-6 concentration in non-MP-treated patients increased from the preoperative value of 59 +/- 30 pg.ml-1 to 436 +/- 143 pg.ml-1 60 min after declamping of the aorta (P < 0.001). The increase was greater than the increase from 36 +/- 15 pg.ml-1 to 135 +/- 85 pg.ml-1 in the MP-treated patients (P < 0.01). Furthermore, postoperative cardiac index in MP-treated patients (3.6 +/- 1.1 L.min-1.m-2) was higher than 2.3 +/- 0.8 L.min-1.m-2 of non MP-treated patients (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Serum lactate concentrations and the lactate/pyruvate (L/P) ratio were measured in two groups of patients undergoing radical esophagectomy, as an indicator of tissue hypoxia, and β-glucuronidase and granulocyte elastase as indicators of tissue damage. One group received prostaglandin E1 (PGE1) and the other group received nothing. Serum lactate concentrations and the L/P ratio increased significantly 30 min after starting thoracotomy in the patients who were not treated with PGE1. On the contrary, intravenous drip infusion of PGE1 (0.04 μg·kg(-1)·min(-1)) suppressed the increases in serum lactate concentratons and L/P ratios. Plasma granulocyte elastase activity increased significantly at the end of surgery in both groups. There was no change in serum β-glucuronidase activity in both groups. This study suggests that low doses of PGE1 maintain organ blood flow without affecting blood pressure. However, these low doses of PGE1 could not suppress granulocyte elastase release.

Laparoscopic cholecystectomy (LC) has been widely accepted as an alternative to laparotomy and has many advantages, including short hospital stay and very limited surgical invasion. However, this procedure may impair hepatic function in elderly patients because high pressure is maintained in the peritoneal cavity for an extended period. We observed the effect of pneumoperitoneum on the middle hepatic venous blood flow (MHVBF) in elderly patients undergoing LC. LC patients were anesthesized with inhaled and epidural anesthesia, after which MHVBF was continuously measured by transesophageal echocardiography. MHVBF decreased significantly during a period of high intraperitoneal pressure, and recovery of MHVBF after deflation was significantly lower in elderly patients (65-75 yr), but not in younger patients (24-62 yr). In contrast, MHVBF remained almost constant in elderly patients during open cholecystectomy, and thus was significantly different from that in patients who underwent LC with pneumoperitoneum. Laparoscopic cholecystectomy may impair hepatic function in elderly patients because high pressure is maintained in the peritoneal cavity for an extended period.

OBJECTIVE To determine the influence of methylprednisolone on the cytokine balance during cardiac surgery. DESIGN Prospective, randomized, nonblinded study. SETTING University hospital. PATIENTS Twenty-one patients on cardiopulmonary bypass undergoing aortocoronary bypass surgery. INTERVENTIONS According to a randomized sequence, the patients either received methylprednisolone (30 mg/kg) [corrected] before cardiopulmonary bypass and before declamping of the aorta (MPS group, n = 11) or received nothing (control group, n = 10). MEASUREMENTS AND MAIN RESULTS Serum proinflammatory cytokines (interleukin [IL]-8, IL-6) and anti-inflammatory cytokines (IL-10, IL-1ra) were measured by enzyme-linked immunosorbent assays. Serum IL-6 and IL-8 concentrations in the control group (15.2 +/- 4.1 and 14.1 +/- 1.9 pg/mL, preoperatively) increased to 242 +/- 70.1 and 97.3 +/- 18.3 pg/mL at 60 mins after declamping of the aorta (p < .01, p < .01, respectively). The increases were greater than those from 2.5 +/- 0.6 and 2.5 +/- 0.5 pg/mL to 109.5 +/- 29.0 and 33 +/- 4.1 pg/mL in the MPS group for IL-6 and IL-8, respectively. Serum IL-10 concentrations increased significantly 60 mins after declamping of the aorta compared with its preoperative value in the two groups (the control group, from 1.0 +/- 0 to 537.9 +/- 61.7 pg/mL; the MPS group, from 0.3 +/- 0.2 to 654.9 +/- 24 pg/mL [p < .01, p < .01, respectively]). No difference was found between the two groups. Similarly, serum IL-1ra concentrations in the two groups increased the preoperative value in the control group from 304 +/- 120 to 44,374 +/- 14,631 pg/mL and in the MPS group from 616.5 +/- 109.6 to 35,598 +/- 9,074 pg/mL at 60 mins after declamping of the aorta (p < .01, p < .01, respectively). There was no difference between the two groups. CONCLUSIONS Methylprednisolone reduces the production of IL-6 and IL-8 but not that of IL-10 and IL-1ra. These results suggest that one of the mechanisms of the cytoprotective effect of methylprednisolone may be to make changes in the proinflammatory and anti-inflammatory cytokine balance.

It has been reported that inflammatory cytokines such as interleukin-8 and 6 (IL-8, IL-6) increase during cardiac surgery and caused postoperative cardiac dysfunction. Therefore, it is important to investigate changes of suppressive cytokines such as IL-10, interleukin-4 (IL-4) and interleukin-1 receptor antagonist (IL-1ra) during cardiac surgery.Serum levels of cytokines and IL-1ra were measured in 10 patients during cardiac surgery with cardiopulmonary bypass. Six blood samples were drawn after inducing anaesthesia. In each sample, serum IL-10, IL-4, IL-8, IL-6 and IL-1ra were measured by enzyme linked immunosorbent assay.Serum IL-6 and IL-8 concentration (19.1 +/- 8.8 pg.ml-1, and 13.4 +/- 5.2 pg.ml-1, preoperatively) increased to 227.5 +/- 191 pg.ml-1 and 81.0 +/- 56 pg.ml-1 at 60 min after declamping aorta (P0.01, respectively). Serum IL-10 concentration increased at 60 min after declamping the aorta compared with the preoperative value (from 1.0 +/- 0 pg.ml-1 to 552.0 +/- 158 pg.ml-1 P0.001]). Similarly, serum IL-1ra concentration increased from the preoperative value of 1331 +/- 896 pg.ml-1 to 43353 +/- 12812 pg.ml-1 at 60 min after declamping the aorta (P0.001). Positive correlations were obtained between IL-10 and IL-8, and between IL-10 and IL-6 (gamma = 0.7, gamma = 0.8, P0.001, respectively).These findings demonstrate that pro- and anti-inflammatory cytokines increase to maintain their balance during cardiac surgery.

Cardiac surgery with cardiopulmonary bypass (CPB) is frequently associated with a complex array of post-operative clinical abnormalities, including low-output syndrome and pulmonary dysfunction. It has been reported that oxygen free radicals are one of the important factors causing reperfusion injury. To determine whether oxygen free radicals are produced during cardiac surgery, we studied nine patients anesthetized with high doses of fentanyl. Lipid peroxide (LPO) and leukotriene B

Myocardial ischaemia is one of the major causes of low output syndrome during open heart surgery. Injury associated with ischaemia and reperfusion has been considered to result, in part, from the action of neutrophils, the interaction of neutrophils with vascular endothelial cells, and the effects of cytokines which are mediators that induce and modify reactions between these substances. We investigated cell injury in relation to the concentrations of interleukins 6 and 8 (IL-6 and IL-8), which have recently received attention as neutrophil activators. Neutrophil counts, granulocyte elastase (GEL), IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha), CK, and CK-MB concentrations were determined serially in 11 patients undergoing open heart surgery with cardiopulmonary bypass (CPB). Neutrophil counts (mean +/- SD 2717 +/- 2421 microliters-1 preoperatively) peaked 60 min after declamping the aorta at 7432 +/- 4357 microliters-1 (P < 0.01) and remained elevated 7136 +/- 5194 microliters-1 at 180 min (P < 0.01). Plasma GEL level (168 +/- 71 micrograms.L-1 preoperatively) peaked at 1134 +/- 453 micrograms.L-1 120 min after declamping of the aorta (P < 0.01) and remained elevated, 1062 +/- 467 micrograms.L-1, after 180 min (P < 0.01). Serum IL-6 level (118 +/- 59 pg.ml-1 preoperatively) peaked at 436 +/- 143 pg.ml-1 60 min after declamping of the aorta (P < 0.01) and remained elevated, 332 +/- 109 pg.ml-1, after 180 min. Serum IL-8 level (37 +/- 44 pg.ml-1 preoperatively) peaked at 169 +/- 86 pg.ml-1 at 60 min after declamping of the aorta (P < 0.001) and remained elevated at 113 +/- 78 pg.ml-1 180 min after declamping of the aorta.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of a novel benzodiazepine derivative, Ro 16–6028 on rat brain dopamine system were examined under stress and non-stress conditions. Thirty minutes restraint stress increased dopamine synthesis in two dopamine neuron regions, prefrontal cortex and nucleus accumbence. Ro 16–6028 inhibited potently dopamine synthesis in prefrontal cortex, nucleus accumbens and striatum in dose dependent manner under non-stress condition. Furthermore, Ro 16–6028 reverses the stress-induced augmentation of the synthesis in prefrontal cortex. These findings indicate that Ro 16–6028 has an anxiolytic profile and that central dopamine system plays an important role in stress reaction.

Changes in granulocyte elastase (GLE) and Beta-gluculonidase (Beta-gl) were observed during open heart surgeries which were performed under deep hypothermia with surface cooling. In addition, the effect of urinary trypsin inhibitor, urinastatin, on the activities of these enzymes was studied. The patients were divided into three groups, namely group U-I with intravenous injection of 6000 u.kg(-1) of urinastatin before cooling, group U-II administered with an additional 6000 u.kg(-1) after warming to 30 degrees C, and an untreated group (Group C). The plasma level of GLE increased significantly in the three groups compared with the level before cooling respectively. In the group U-II, the GLE level after the warming was lower than that in the control group. The serum level of Beta-gl increased significantly in the three groups at the end of rewarming (36 degrees C). The release of GLE from lysosomes in granulocytes was inhibited in the group U-II. The insufficient inhibition of GLE release in the group U-I is probably due to relatively short half-life of urinastatin. Therefore double administration of 6000 u.kg(-1), before and after the cooling, may be required to achieve the therapeutic effect. Consequently, urinastatin appears to be useful in open heart surgery under deep hypothermia with surface cooling.

We have demonstrated in previous papers that prolonged nitrous oxide exposure suppresses murine hemopoiesis more in the spleen than in the bone marrow and that this is caused by the suppression of the hemopoietic supportive activity of the microenvironment. In the present study, we used splenectomized mice as an experimental model to investigate the direct effect on bone marrow function of prolonged nitrous oxide inhalation. All of the experimental mice were splenectomized at the age of 4 wk. Half of the experimental mice were continuously exposed to 50% nitrous oxide, and the remainder were continuously exposed to air as controls, starting 3 wk after splenectomy and lasting 14 days, and the numbers of pluripotent hemopoietic stem cells (CFU-S) and granulocyte-macrophage progenitor cells (GM-CFC) in bone marrow were counted. The numbers of pluripotent hemopoietic stem cells and granulocyte-macrophage progenitor cells in the bone marrow of mice exposed to air showed no significant change. The numbers of these two types of cells found in nitrous oxide-exposed mice were approximately 60% of control levels. These data are almost the same as our previously reported bone marrow data obtained in nonsplenectomized mice exposed to nitrous oxide for 14 days. The present results suggest that the marked decrease in the number of splenic hemopoietic stem cells in our previous data is not a result of migration of the cells to bone marrow, and that nitrous oxide directly affects murine bone marrow hemopoiesis.

Carbonic anhydrase in the red blood cell and in the pulmonary endothelium facilitates the elimination of CO2 in the lungs. Although a carbonic anhydrase inhibitor, such as acetazolamide which is frequently used in patients with glaucoma or with metabolic alkalosis, is known to impair the CO2 elimination in the lungs, the dose-response curve of CO2 elimination with acetazolamide has not been well documented in CO2 homeostasis. In the present study, the effects of inhibited carbonic anhydrase were tested in 8 anesthetized dogs; various dosages of acetazolamide were used. When the administered clinical dosage of acetazolamide increased from 5 to 20 mg/kg, PaCO2, PVCO2, arterial-alveolar PCO2 difference (a-ADCO2), and physiological VD/VT ratio increased progressively to 52.0 +/- 2.1 Torr, 58.0 +/- 3.0 Torr, 23.4 +/- 1.2 Torr, and by 19.2 +/- 1.8% (S.E.) respectively, whereas inhibition rate of red blood cell carbonic anhydrase (RCA) activity increased progressively to 73.1 +/- 2.1% (S.E.). On the other hand, PACO2 decreased to 27.1 +/- 1.8 Torr (S.E.) upon the first injection of 5 mg/kg of acetazolamide, but PACO2 did not change further upon 3 additional 5 mg/kg injections. Mixed venous-arterial PCO2 difference [V-a)PCO2), VCO2, and anatomical VD/VT ratio were unchanged by the administration of any doses of acetazolamide.

Taki, K., Takamura, M., Sotani, H. and Wakusawa, R. Management of the Acid-Base Balance by the Red Blood Cell Carbonic Anhydrase (RCA). I. Correlation of the RCA Activity and Acid-Base Balance in the in Vitro and in Vivo Experiments. Tohoku J. exp. Med., 1983, 139 (4) 339-348 - Changes in RCA activity are known to affect the acid-base balance, but a clear relationship between RCA activity and acid-base balance has not yet been established. The relationship between RCA activity and acid-base balance was studied in tonometry with 4 mixed gases for 6-9hr, in healthy adults at rest, in halothane anesthesia and in hypothermia. RCA activity increases when pH and HCO3-/PCO2 ratio increase and PCO2 decreases in vitro. It also increases when pH and HCO3-/PCO2 ratio decrease and the range of PCO2 broadens in vivo. The relationship between RCA activity and the HCO3-/PCO2 ratio is a fan shape, because a change of the HCO3-/ PCO2 ratio precedes the change of RCA activity. Some factor which increases the RCA activity may be produced secondarily in the body under the influence of high PCO2. Probably the acid-base balance is corrected by reduction of the RCA activity in the case of alkalosis, and the acid-base balance may be corrected by an increase in RCA activity in the case of acidosis

Acetazolamide, a carbonic anhydrase (CA) inhibitor, was used to normalize metabolic alkalemia. A dosage of acetazolamide for normalizing metabolic alkalemia has not yet been experimentally determined. The dosage of acetazolamide for this purpose is experimentally calculated in this paper. The correlation between various concentration of acetazolamide mixed with blood and the base excess (BE) levels in blood at the start of normalizing metabolic alkalosis was studied in vitro. The change rate of the BE level was calculated from BE levels noted before and after tonometry of the blood with and without acetazolamide. A dosage of acetazolamide which can cause the change rate of the BE level to decrease is considered to be an effective dosage. Metabolic alkalosis in vitro was produced by adding bicarbonate into the blood. An effective dosage of acetazolamide for metabolic alkalemia of which the BE range was from 0 to + 30 mEq/liter was calculated. CA activities in the kidney and the blood of dogs administered acetazolamide were examined. The effective dosage of acetazolamide obtained from in vitro experiments inhibited the CA activities not only in the blood but also in the kidneys. An effective dosage of acetazolamide to normalize a BE of + 10 mEq/liter in vitro was converted into about 7-12 mg/kg in vivo. This dosage inhibited the red blood cell carbonic anhydrase (RCA) activity to 20-40%, whereas the normal physiological variation range is 25%. An effective dosage of acetazolamide in the blood did not proportionally increase with an increase of HCO3- during severe alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)

星状神経節ブロックと硬膜外ブロックに抵抗性を示した reflex sympathetic dystrophy の1型である Shoulder Hand Syndrome の1症例にグアネチジンを用いた局所静脈内交感神経ブロックを行い, 良好な結果を得たので報告した.

人工呼吸で気道内圧が異常に高くなり, 人工呼吸によっても血液ガスの正常化が困難と判断された2症例に extra-corporeal lung assist (ECLA) を施行し, 気道内圧を下げて肺の安静と正常化を試みた.人工透析用回路と人工心肺用回路でECLAを施行して, 気道内圧を安全に下げることが出来たが, 何れの症例も1週間後に呼吸器以外の原因(症例I: 麻痺性イレウスと右下肢循環不全, 症例II: DIC) で死亡した. これらの経験と文献をもとに, ECLAの施行について若干の考察を行った.

The effects of prolonged exposure to nitrous oxide on the hemopoietic progenitor cells in bone marrow and spleen in mice were investigated. Fifty percent nitrous oxide caused a marked decrease in the number of pluripotent stem cells (CFU-S) and granulocyte-macro-phage progenitor cells (GM-CFC) in the spleen, whereas it caused only a slight decrease in these cells in the bone marrow. These results suggest that prolonged exposure to nitrous oxide induces damage in the splenic hemopoiesis in mice.

In order to clarify the mechanism of hemopoietic depression induced by nitrous oxide inhalation, effects of prolonged nitrous oxide exposure on the settlement of transplanted bone marrow cells were investigated. Mice were continuously exposed to mixed gas containing 50% nitrous oxide, 21% oxygen and 29% nitrogen for 7 days and then they were irradiated with 850 rads. By the irradiation, endogenous pluripotent hemopoietic stem cells (CFU-S) almost disappeared in the mice. Normal syngenic murine bone marrow cells were injected intravenously and the numbers of CFU-S, which settled in the bone marrow and spleen 2 hr after injection, were measured. There was no difference of the numbers of CFU-S settled in the bone marrow between nitrous oxide and control gas exposed mice. In contrast, the numbers of CFU-S in the spleen of nitrous oxide exposed mice were approximately 60% of the control. These results and our previous data suggest that hemopoietic inhibitory effects of nitrous oxide in mice are due to a damage of splenic hemopoietic microenvironment, that supports the settlement of hemopoietic stem cells.

Results of open cardiac surgery under deep simple hypothermia in 121 infants with body weight of less than 10 kg are reported. Deep ether anaesthesia combined with large quantities of ganglion blocking agents (triflupromazine 3 mg/kg) constitutes the anaesthetic management of choice for deep surface-induced hypothermia. The mean lowest oesophageal temperature was 20.8 degrees C, and 18.9 degrees C rectally. The mean circulatory arrest time was 40 minutes. Seventeen infants (14.0 per cent) died post-operatively. There were no operative deaths attributable to failure of cardiac resuscitation. This technique widens the scope of open heart surgery in small infants. Most of the surgically correctable malformations should be operable by this method. More than the potential hazards of hypothermia, which we believe are solved by our technique, the major problem posed by surgery in these small infants is the trans and post-operative respiratory management.