Kazuo Irita

Diacylglycerol, 1-oleoyl-2-acetyl-glycerol, stimulates superoxide-generation from human neutrophils

1-Oleoyl-2-acetyl-glycerol which activates Ca2+-activated phospholipid-dependent protein kinase, induced the superoxide-production of human neutrophils, while other diacylglycerols did not. The induction was independent of extracellular calcium and did not accompany the increase of the intracellular free calcium. The superoxide-release by the diacylglycerol was inhibited by retinal, the inhibitor of the protein kinase. The diacylglycerol stimulated the phosphorylation of at least 4 proteins in intact neutrophils, the phosphorylation of which was stimulated by phorbol 12-myristate 13-acetate, the activator of the protein kinase. These observations indicate the possible involvement of the kinase in the induction process.

Anesthesia‐related mortality and morbidity over a 5‐year period in 2,363,038 patients in Japan

Background:  Statistical data of mortality and morbidity related to anesthesia have not been reported in Japan since World War II. The need to comprehensively examine the events of cardiac arrest as well as mortality prompted the first national study in Japan.

Effects of Sevoflurane and Isoflurane on Electrocorticographic Activities in Patients With Temporal Lobe Epilepsy

To compare the neuroexcitatory effects of sevoflurane and isoflurane, we recorded electrocorticograms (ECoG) during wakefulness and during sevoflurane and isoflurane anesthesia in six patients with temporal lobe epilepsy (TLE). These patients had subdural grid electrodes chronically implanted in the temporal region. During sevoflurane anesthesia at 1.5 minimum alveolar concentration (MAC) of the combination with 67% nitrous oxide (N2O), a marked increase in interictal paroxysmal activities was observed in four patients. Two patients had a slight increase in paroxysmal activities. Activated areas were widely distributed, not being confined to the ictal onset zone of spontaneous seizures. However, isoflurane anesthesia at 1.5 MAC of the combination with 67% N2O was associated with less increased paroxysmal activity. While the neuroexcitatory properties of sevoflurane proved greater than those of isoflurane, the widespread irritative response to sevoflurane administration was not helpful in localizing the epileptogenic area.

Anesthesia-related mortality and morbidity in Japan (1999).

1 Department of Anesthesiology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan 2 Department of Anesthesiology and Critical Care Medicine, Jichi Medical School, Tochigi, Japan 3 Department of Anesthesiology and Resuscitology, Okayama University, Graduate School of Medicine and Dentistry, Okayama, Japan 4 Department of Anesthesiology and Critical Care Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan 5 Department of Anesthesiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan 6 Department of Anesthesiology, School of Medicine, Keio University, Tokyo, Japan 7 Department of Anesthesiology and Intensive Care Medicine, Kanazawa University, Graduate School of Medical Science, Kanazawa, Japan 8 Sapporo Ichijyo Clinic, Sapporo, Japan 9 Department of Anesthesiology and Critical Care Medicine, Gifu University School of Medicine, Gifu, Japan

Performance evaluation of a new pulse oximeter during mild hypothermic cardiopulmonary bypass.

UNLABELLED Newly developed pulse oximeters (POs) are designed to display accurate SpO(2) during motion and hypoperfusion. We compared the performance of a new PO, the Masimo SET Radical (M), with a conventional PO, the Nihon Kohden AY-900P (N), during hypothermic cardiopulmonary bypass. Eighteen patients were studied prospectively. PO failure was defined as failure to show no SpO(2) value or show incorrect SpO(2) values for longer than 3 min continuously. PO failure occurred in 4 and 14 patients with M and N, respectively (P = 0.0022). All 4 patients in whom PO failure developed with M were among the 14 patients with N. No SpO(2) was provided for 4% +/- 12% of the duration of aorta cross-clamping with M and 36% +/- 39% with N (P = 0.002). Skin temperature and mean arterial blood pressure when PO failure started to occur and ended were similar between M and N. PO failure easily developed in patients with preoperative diuretic therapy or with intraoperative hyperlactatemia in N, but not in M. M was able to display accurate SpO(2) values significantly more frequently and longer than N during mild hypothermic cardiopulmonary bypass with nonpulsatile flow, suggesting that M is more useful for monitoring SpO(2) during hypoperfusion. IMPLICATIONS We compared the performance of a new pulse oximeter with that of a conventional pulse oximeter during hypothermic cardiopulmonary bypass with nonpulsatile flow. The newly developed device displayed accurate SpO(2) significantly more frequently and longer than a conventional oximeter. Newly developed pulse oximeters seem to be more useful for monitoring SpO(2) during hypoperfusion.

Phosphorylation of myosin light chain in intact pig leukocytes stimulated by phorbol 12-myristate 13-acetate

Phosphorylation of myosin light chain was investigated in intact pig polymorphonuclear leukocytes. The labeling of the myosin light chain (Mr = 21000) was increased by exposure of the cells to phorbol 12-myristate 13-acetate. Two-dimensional gel electrophoresis revealed three forms of Mr = 21000 light chain, of which two were phosphorylated. The phosphorylation of the myosin light chain was inhibited by neither N-(6-aminohexyl)-5-chloro-1-naphthalene sufonamide nor trifluoperazine, suggesting that calmodulin is not involved in the phosphorylation.

Dibucaine and tetracaine inhibit the activation of mitogen-activated protein kinase mediated by L-type calcium channels in PC12 cells.

BACKGROUND An elevation of the intracellular calcium level, which is mediated by N-methyl-D-aspartate receptors and L-type Ca2+ channels both, activates the mitogen-activated protein (MAP) kinase signaling pathway involved in synaptic modification. It has recently been suggested that MAP kinase plays a role in coupling the synaptic excitation to gene expression in the nucleus of postsynaptic neurons. Because the effects of local anesthetics on cellular signal transduction in neuronal cells are not well-known, the authors investigated whether they affect the MAP kinase signaling pathway using PC12 cells. METHODS The cells were stimulated with either 50 mM KCl or 1 microM ionomycin, and activated MAP kinase was thus immunoprecipitated. The immunocomplexes were then subjected to an Elk1 phosphorylation assay. Both the phosphorylation of MAP kinase and the induction of c-Fos were detected by immunoblotting. RESULTS Pretreatment of the cells with 1 mM (ethylenedioxy)-diethyl-enedinitrilotetraacetic acid or 5 micron nifedipine blocked the MAP kinase activation induced by 50 mM KCl, whereas pretreatment with 2 microM omega-conotoxin GIVA did not. The expression of c-Fos induced by potassium chloride was also suppressed by dibucaine, tetracaine (concentrations that inhibited 50% of the activity of positive control [IC50s] were 16.2+/-0.2 and 73.2+/-0.7 microM, respectively), and PD 98059, a mitogen-activated/extracellular receptor-regulated kinase inhibitor. Higher concentrations of dibucaine and tetracaine were needed to suppress the activation of MAP kinase induced by ionomycin (the IC50 values of dibucaine and tetracaine were 62.5+/-2.2 and 330.5+/-32.8 microM, respectively) compared with potassium chloride (the IC50 values of dibucaine and tetracaine were 17.7+/-1.0 and 70.2+/-1.2 microM, respectively). Although probable targets of these local anesthetics might be L-type Ca2+ channels or components between Ca2+ and Ras in MAP kinase pathway, the possibility that they directly affect MAP kinase still remains. CONCLUSIONS Dibucaine and tetracaine at clinical concentrations were found to inhibit the activation of MAP kinase and the expression of c-Fos mediated by L-type Ca2+ channels in PC12 cells. The suppression of MAP kinase pathway may thus be a potential target site for the actions of dibucaine and tetracaine, including the modification of the synaptic functions.

Effects of olprinone, a new phosphodiesterase inhibitor, on gastric intramucosal acidosis and systemic inflammatory responses following hypothermic cardiopulmonary bypass

Background: Phosphodiesterase (PDE) III inhibitors have both an inotropic and a peripheral vasodilatory effect, and also inhibit the activation of macrophages. Thus a newly developed PDE III inhibitor, olprinone, could modify gastric intramucosal pH (pHi), systemic oxygen consumption, and systemic inflammatory responses in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).

Detection of retroperitoneal hemorrhage by transesophageal echocardiography during cardiac surgery.

PurposeTo present a case of massive retroperitoneal hemorrhage during cardiopulmonary bypass (CPB) which was detected using transesophageal echocardiography (TEE).Clinical featureA 50-yr-old man suffering from severe mitral regurgitation (MR) was admitted for mitral valvuloplasty. After the beginning of CPB, the volume in the reservoir was noticed to be gradually decreasing. Although venous cannulation had been properly performed, TEE showed an echo free space around the liver, the spleen and in front of the abdominal aorta showed intraabdominal hemorrhage. After cardiac surgery, emergency laparotomy revealed about 5,000 ml of blood in the retroperitoneal space probably as a result of femoral artery cannulation prior to CPB. Hemostasis was achieved, and the patient made complete cardiac and neurological recovery. Retrospective review of the TEE imaging revealed that the kidneys were surrounded by blood bilaterally confirming the diagnosis of retroperitoneal hemorrhage.ConclusionRetroperitoneal hemorrhage during CPB is rare, but may be lethal. Transesophageal echocardiography is a useful monitor not only to evaluate cardiac performance, but also to detect unexpected intraabdominal bleeding during cardiac surgery.RésuméObjectifPrésenter le cas d’une hémorragie rétropéritonéale massive pendant la circulation extracorporelle (CEC), détectée à l’aide de l’échocardiographie transoesophagienne (ETO).Éléments cliniquesUn homme de 50 ans, souffrant de régurgitation mitrale sévère, a été admis pour une valvuloplastie mitrale. Après le début de la CEC, on a noté que le volume du réservoir baissait graduellement. Bien qu’on ait correctement réalisé la mise en place d’une canule veineuse, l’ETO a montré un espace libre d’écho autour du foie, de la rate et, en avant de l’aorte abdominale, indiquant la présence d’une hémorragie intra-abdominale. Après la cardiochirurgie, la laparotomie d’urgence a révélé la présence d’environ 5 000 ml de sang dans l’espace rétropéritonéal, le résultat probable de l’introduction d’une canule dans l’artère fémorale avant la CEC. L’hémostase a été rétablie et le patient a connu une récupération cardiaque et neurologique complète. Létude rétrospective des images de l’ETO a révélé que les reins étaient bilatéralement entourés de sang, ce qui confirme le diagnostic d’hémorragie rétropéritonéale.ConclusionL’hémorragie rétropéritonéale est rare pendant la CEC, mais elle peut être fatale. L’échocardiographie transoesophagienne est un moniteur utile non seulement pour évaluer le rendement du coeur, mais aussi pour détecter des saignements intra-abdominaux inattendus pendant la cardiochirurgie.

Absence of anti-trifluoroacetate antibody after halothane anaesthesia in patients exhibiting no or mild liver damage.

It has been shown that the circulating antibodies, which bind to rat hepatic microsomal proteins obtained after in vivo exposure to halothane, are detectable by immunoblotting in patients with “halothane hepatitis (HH),” and that rabbit immunized anti-sera against trifluoroacetylated rabbit serum albumin (TFA-RSA) recognizes rat microsomal distorted polypeptides in almost the same way as do sera from patients with HH. In this paper, we report first the development of a novel method of synthesizing TFA-RSA using p-nitrophenyl TFA, and second the results of tests for circulating anti-TFA antibodies in the serum of 86 patients who had received halothane anaesthesia and developed no (67 patients) or mild (19 patients, the maximum activity of serum alanine aminotransaminase 519 IU · L−1) liver damage. Serum was selected from stored sera of post-transfusion patients. The new method of synthesizing TFA-RSA was convenient and was able to be done at neutral pH. Rabbit sera obtained after immunization with the newly synthesized TFA-RSA recognized the same polypeptides (109 kDa, 92 kDa, 80 kDa, 76 kDa, 64 kDa and 59 kDa) as the established anti-sera against TFA-RSA, and these reactions were inhibited in the presence of TFA-lysine. Circulating antibodies were not detected in our patients who had developed no or mild liver damage. The present finding supports the hypothesis that the appearance of circulating antibodies against microsomal distorted proteins are specific to patients with HH. Furthermore, we have shown here that the halothane-induced mild increase in ALT activity is not associated with the appearance of those circulating antibodies, supporting the pathophysiological difference between HH and halothane-induced mild hepatic damage.RésuméOn a montré que les anticorps circulants qui se lieńt au protéines microsomiques hépatiques du rat après une exposition in vivo à l’halothane peuvent être détectés par immunotransfert chez les patients atteints d’« hépatite à l’halothane (HH) ». On a montré aussi que les anti-sérums de lapins immunisés contre l’albumine sérique trifluoroacétylée (TFA-RSA) reconnaissaient les polypeptides microsomaux déformés de rat de façon presque identique au serums de patients atteints d’HH. Dans cet article, nous rapportons d’abord le développement d’une nouvelle technique de synthèse de TFA-RSA à partir du p-nitrophényl TFA, et deuxièmement le résultat d’épreuves de détection des anticorps anti-TFA dans le sérum de 86 patients qui ont été anesthésiés à l’halothane et n’ont pas présenté (67 patients) ou ont présenté une lésion hépatique légère (19 patients dont l’activité de l’analine aminotransaminase n’a pas dépassé 519 UI · L−1). Le sérum a été choisi parmí des sérums stockés après transfusions. La nouvelle méthode de synthèse de la TFA-RSA est pratique et réalisable avec un pH neutre. Les sérum de lapins obtenus après immunisation avec la nouvelle TFA-RSA de synthèse ont reconnu les mêmes polypeptides (109 kDa, 92 kDa, 80 kDa, 76 kDa, 64 kDa et 59 kDa) que les anti-sérum TFA-RSA éprouvés, et ces réactions ont été inhibées en présence de TFA-lysine. Les anticorps circulants n’ont pas été décelés chez nos patients sans atteinte ou avec légère atteinte hépatique. Ces données supporte l’hypothèse selon laquelle l’apparition d’anticorps circulants contre les protéines microsomi-ques déformées sont spécifiques aux patients atteints de HH. Nous avons montré de plus, que la légère augmentation de l’activité de l’ALT n’est pas associée avec l’apparition de ces anticorps circulants, ce qui supporte la différence physiopathologique entre l’HH et la lésion hépatique légère induite par l’halothane.