Kazutoshi Okada

Elevation of cytokines during open heart surgery with cardiopulmonary bypass : participation of interleukin 8 and 6 in reperfusion injury

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-α (TNF-α), 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 μl−1 preoperatively) peaked 60 min after declamping the aorta at 7432 ±4357 μl−1 (P < 0.01) and remained elevated 7136 ±5194 μl−1 at 180 min (P < 0.01). Plasma GEL level (168 ±71 μg sd L−1 preoperatively) peaked at 1134 ±453 μg · L−1 120 min after declamping of the aorta (P < 0.01) and remained elevated, 1062 ±467 μg · 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. Serum TNF-α was decreased at 60 min after aortic occlusion but otherwise did not change. Plasma GEL concentrations correlated with serum IL-8 levels (R = 0.7, P = 0.001) and the IL-6 and IL-8 concentrations correlated with the duration of aortic clamping (R = 0.64, P = 0.01, R = 0.7, P = 0.01). We conclude that the increases of IL-6 and IL-8 occur as a result of ischaemia, and suggest that these cytokines participate in reperfusion injury by activating neutrophils.RésuméL’ischémie myocardique est une des principales causes du syndrome de bas débit pendant la chirurgie à coeur ouvert. On pense que la lésion associée à l’ischémie et la reperfusion résulte en partie de l’action des neutrophiles, l’interaction des neutrophiles avec les cellules vasculaires endothéliales et l’activité de médiateurs, les cytokines qui induisent et modifient les réactions entre ces substances. Nous avons examiné la relation de la lésion cellulaire avec la concentration des interleukines 6 et 8 (IL-6 et IL-8), qui ont récemment attiré l’attention comme activateurs de neutrophiles. Chez 11 patients soumis à une chirurgie cardiaque ouverte avec circulation extracorporelle (CEC), on mesure en série le décompte des neutrophiles, l’élastase granulocytaire (GEL), l’IL-6 et l’IL-8, le facteur-α. de nécrose tumorale (TNF-α) et la concentration des CK et CK-MB. Le décompte des neutrophiles (moyenne ±SD: 2717 ±2421 μl−1 en préopératoire) atteint un maximum de 7432 ±435 μl−1 60 min après le déclampage de l’aorte (P < 0,01) et demeure élevé, 7136 ±5194 μl−1, à 180 min (P < 0,01). Le niveau de la GEL plasmatique (168 ±71 μg · L−1 en préopératoire) atteint un maximum de 1134 ±453 μg · L−1 après 120 min du déclampage de l’aorte (P < 0,01) et demeure élevé, 1062 ±467 μg · L−1 après 180 min de déclampage (P < 0,01). L’IL-6 sérique (118 ±59 pg · ml−1) atteint un maximum de 436 ±143 pg · ml−1 60 minutes après le déclampage de l’aorte (P < 0,01) et demeure élevé, 332 ±109 pg · ml−1 après 180 min. Le niveau sérique d’IL-8 (37 ±44 pg · ml−1 en préopératoire) atteint un maximum de 169 ±86 pg · ml−1 60 min après le déclampage de l’aorte (P < 0,01) et demeure élevé, 113 ±78 pg · ml−1 après 180 min. Le TNF-α décroît 60 min après le clampage aortique mais ne change plus par la suite. La concentration plasmatique de GEL est en corrélation avec le niveau sérique de l’IL-8 (R = 0,7, P = 0,001). Les concentrations d’IL-6 et d’IL-8 sont en corrélation avec la durée du clampage (R = 0,64, P = 0,01, R = 0,07, P = 0,01). Nous concluons que les augmentations d’IL-6 et d’IL-8 résultent de l’ischémie et nous suggérons qu’en activant les neutrophiles, ces cytokines participent à la genèse de la lésion de reperfusion.

Methylprednisolone inhibits increase of interleukin 8 and 6 during open heart 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 Junction. 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 ± 55 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). The levels of IL-8 max during surgery correlated negatively with postoperative cardiac index (γ = −0.67). These results suggest that methylprednisolone suppresses production of IL-8 and 6.RésuméOn a rapporté que l’interleukine 8 (IL-8) et que l’interleukine 6 (IL-6) étaient deux des médiateurs chimiques de la lésion cardiaque. Toutefois, on ne sait pas encore si le traitement aux corticostéroïdes in vivo prévient la production des interleukines 8 et 6. Cette étude prospective vise à déterminer si le prétraitement à la méthylprednisolone (MP) (30 mg · kg−1 avant le CEC et avant le déclampage de l’aorte) influence la concentration de l’IL-8 de l’IL-6 du sang veineux périphérique de 27 patients soumis à une chirurgie réglée de revascularisation myocardique. Les concentrations de l’IL-8 de l’IL-6 sont mesurée avec une trousse Elisa. Nous étudions aussi les répercussions du traitement à la MP sur la fonction cardiaque postopératoire. La concentration sérique de l’IL-8 des patients non traités (37 ± 44 pg · ml−1 en préopératoire) augmente à 169 ± 86 pg · ml−1 60 minutes après le déclampage de l’aorte (P < 0,001). Cette augmentation est plus importante que l’augmentation de 22 ± 8,9 pg · ml−1 à 52 ± 55 pg · ml−1 notée chez les patients traité à la MP (P < 0,01). La concentration serique de l’IL-6 chez les patients non traités à la MP augmente de la valeur préopératoire de 59 ± 30 pg · ml−1 à 436 ± 143 pg · ml−1 60 min après le déclampage de l’aorte (P < 0,001). Cette augmentation est plus importante que celle de 36 ± 15 pg · ml−1 à 135 ± 55 pg · ml−1 survenue chez les patients traités à la MP (P < 0,01). De plus, l’index cardiaque postopératoire des patients traités à la MP (3,6 ± 1,1 L · ml−1 · m−2) est plus élevé que celui des patients non traités 2,3 ± 0,8 L · ml−1 · m− 2 (P < 0,05). Les niveaux maximaux de 1’IL-8 sont en corrélation négative avec l’index cardiaque postopératoire (y = 0,67). Ces resultats suggèrent que la méthylprednisolone supprime la production de l’IL-8 et de l’IL-6.

Simple deep hypothermia for open heart surgery in infancy

SummaryResults 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° C, and 18.9° 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.RésuméLes auteurs rapportent leur expérience de 121 enfants de moins de 10 kilos ( poids moyen: 7.8 kilos), opérés à cœur ouvert, sous hypothermie profonde, au cours des huit dernières années. Quatre-vingt-un de ces enfants étaient de moins ďun an (âge moyen: 12.3 mois).Ces enfants ont été opérés sous C.E.C., en hypothermie profonde permettant des arrêts circulatoires de 14 à 77 minutes (moyenne: 40 minutes 20 secondes).Ľhypothermie était produite par immersion en bain ďeau glacée sous ânes thésie profonde à ľéther et sous protection de bloqueurs sympathiques à hautes doses. La moyenne des températures œsophagiennes atteintes se situait à 20.8° C, et celle des températures rectales à 18.9° C.Aucun décès n’est relié à des causes anesthésiques ou à la réanimation du myocarde. Cependant, les soins post-opératoires respiratoires ont influencé significativement le pronostic. Dix-sept enfants (14 pour cent) sont morts en post-opératoire. p ]Les auteurs concluent que ľhypothermie profonde est une méthode simple pour la chirurgie ouverte des tout jeunes enfants.

Open-heart surgery without homologous blood transfusion in infants and children under simple deep hypothermia

PurposeTo investigate the hematological changes during the perioperative period of open-heart surgery without homologous blood transfusion under simple deep hypothermia in infants and small children, and to define the limits of body weight for open-heart surgery without homologous blood transfusion under simple deep hypothermia.MethodsWe performed open-heart surgery without homologous blood transfusion under simple deep hypothermia on eight children, four infants, and a neonate with diagnoses of atrial septal defect, ventricular septal defect, on total anomalous pulmonary venous return (TATVR). All patients except for one with TAPVR were surface-cooled with ice water under deep ether anesthesia. Hematological examinations were performed seven times during the perioperative period.ResultsThe body weight of the patients ranged from 2.5 to 15.0 kg (mean±SD, 9.5±3.5 kg) and the blood loss from 0.7 to 7.1g·kg−1 (4.6±2.0g·kg−1) The lowest values of the hematological findings in each case after surgery were as follows: Hb ranged from 7.6 to 10.9g·dl−1 (8.8±1.0g·dl−1), blood platelet count from 158×103 to 337×103 cells·µℓ−1-agonist (271±88 ×103 cells·µℓ−1-agonist, and total protein from 4.3 to 5.5 g·dl−1 (5.0±0.4g·dl−1)ConclusionSevere anemia and hypoproteinemia were not detected in any case, and, in particular, the reduction of the platelet count was slight. No events occurred as a result of decreased Hb concentration, serum protein, or both.

Simple deep hypothermia for repair of congenital tracheal stenosis: a case report

Congenital tracheal stenosis (CTS) is a rare disease that is frequently accompanied by cardiovascular malformations such as pulmonary artery sling (PA sling). It is difficult to make the diagnosis soon after birth, and death may occur before surgery. Anesthetic management for surgical repair is technically difficult, and the prognosis is particularly poor when the stenotic lesion is extensive or close to the tracheal carina [1-4]. The present report describes tracheal repair of CTS using a costal cartilage graft under simple deep hypothermia.

Functional closed-system anesthesia using a function-equipped anesthesia machine and time-cycled ventilator

Closed-system anesthesia is a very economical method, but it is technically complicated by the requirement for balanced supply and consumption of both anesthetic agents and oxygen. Low-flow anesthesia (LFA) is technically simple, and we studied modifications to further reduce the volume of anesthetic agents supplied. A device that automatically shut off delivery of nitrous oxide, depending on the oxygen concentration in the respiratory circuit, was attached to a standard anesthesia machine. The anesthesia machine was connected to a time-cycled artificial ventilator by a tube of 31 capacity (using three breathing tubes in series) that far exceeded the tidal volume. We performed functional closed-system anesthesia (FCA) using this system, and examined the changes in concentration and delivered volume of anesthetics in the respiratory circuit during anesthesia for 5 h.

Lipid peroxide and leukotriene B3 production in patients undergoing cardiopulmonary bypass

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.

The effect of prostaglandin E1 on the increase of serum lactate and plasma granulocyte elastase activity during radical surgery for esophageal cancer

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.