Reductive mobilization of iron by electrons

Ferritin, an iron storage protein, plays an important role in iron homeostasis. The mechanism of reductive mobilization of iron from ferritin has not been clarified yet despite many studies. The aim of this study was to assess the mechanisms of the mobilization of iron from ferritin by NADPH P-450 reductase. Nucleotide-dependent flavoenzymes generated significant mobilization of iron from ferritin. The possibility of reductive mobilization of iron from ferritin by electrons released from flavin sites or heme site of two flavoenzymes was investigated to elucidate the mediator-independent mechanisms of such reductive mobilization. The mobilization by NADPH-P450 reductase in the presence of ferricyanide increased threefold, while in the presence of cytochrome C increased thirteen-fold. These results indicate that electrons released from both flavins of NADPH-P450 reductase contribute to the reductive mobilization of iron from ferritin. The mechanism of the mobilization of iron from ferritin is discussed

マスイ ト シュウジュツキ シンキン キョケツ

Prevention and adequate treatment of perioperative myocardial ischemia has been an important subject of anesthetic practice. Potent coronary vasodilators, including dipyridamole, have been shown to cause myocardial ischemia via a "coronary steal" mechanism, which is defined as marked redistribution of myocardial blood flow from ischemic to normal zones or from subendocardial to subepicardial areas during constant aortic perfusion pressure and heart rate. The hypothesis that inhalation agents, e.g., isoflurane and sevoflurane, may cause coronary steal in humans remained controversial. By using the myocardial contrast echocardiography, however, it was showed that sevoflurane did not cause transmural coronary steal or intercoronary steal in dogs with acute coronary artery stenosis and in patients with multivessel coronary artery disease. Ischemic preconditioning, which is defined as previous exposure to transient cardiac ischemia, provides protection from subsequent myocardial infarction. Administration of volatile anesthetics including sevoflurane also improves myocardial function and reduces myocardial infarct size after ischemia-reperfusion in vitro and in vivo. This phenomenon is called anesthetic-induced preconditioning. Activation of mitochondrial adenosine triphosphate-regulated potassium (KATP) channels and inhibition of the opening of the mitochondrial permeability pore, through multiple signaling pathways including protein kinase C, has been implicated as a pivotal mechanism mediating ischemic- and anesthetic-induced preconditioning. Several prospective, randomized, clinical trials provided evidence that perioperative beta-adrenergic receptor blockade reduced postsurgical mortality in patients at risk for myocardial ischemia and infarction. Consequently the American Heart Association and American College of Cardiology issued the guidelines that made appropriate perioperative beta-adrenergic receptor blockade a standard of care. In the heart, sublethal heat stress induces heat shock protein (Hsp) 70 synthesis. The resulting increased level of Hsp 70 has been shown to enhance myocardial tolerance to subsequent ischemia-reperfusion injury. It has been reported that administration of the anti-gastric ulcer drug geranylgeranylacetone (GGA) before ischemia induced Hsp 70 expression and resulted in myocardial protection against ischemia and reperfusion injury. This cardioprotective effect of GGA was negated by administration of 5-hydroxydecanoate. These results suggest that the mechanism of GGA-induced myocardial protection may involve mitochondrial KATP channels. A more detailed knowledge of different mechanisms in myocardial protection can allow effective strategy of cardioprotection in perioperative anesthetic protocols

マスイ ト シュウジュツキ シンキン キョケツ

Prevention and adequate treatment of perioperative myocardial ischemia has been an important subject of anesthetic practice. Potent coronary vasodilators, including dipyridamole, have been shown to cause myocardial ischemia via a "coronary steal" mechanism, which is defined as marked redistribution of myocardial blood flow from ischemic to normal zones or from subendocardial to subepicardial areas during constant aortic perfusion pressure and heart rate. The hypothesis that inhalation agents, e.g., isoflurane and sevoflurane, may cause coronary steal in humans remained controversial. By using the myocardial contrast echocardiography, however, it was showed that sevoflurane did not cause transmural coronary steal or intercoronary steal in dogs with acute coronary artery stenosis and in patients with multivessel coronary artery disease. Ischemic preconditioning, which is defined as previous exposure to transient cardiac ischemia, provides protection from subsequent myocardial infarction. Administration of volatile anesthetics including sevoflurane also improves myocardial function and reduces myocardial infarct size after ischemia-reperfusion in vitro and in vivo. This phenomenon is called anesthetic-induced preconditioning. Activation of mitochondrial adenosine triphosphate-regulated potassium (KATP) channels and inhibition of the opening of the mitochondrial permeability pore, through multiple signaling pathways including protein kinase C, has been implicated as a pivotal mechanism mediating ischemic- and anesthetic-induced preconditioning. Several prospective, randomized, clinical trials provided evidence that perioperative beta-adrenergic receptor blockade reduced postsurgical mortality in patients at risk for myocardial ischemia and infarction. Consequently the American Heart Association and American College of Cardiology issued the guidelines that made appropriate perioperative beta-adrenergic receptor blockade a standard of care. In the heart, sublethal heat stress induces heat shock protein (Hsp) 70 synthesis. The resulting increased level of Hsp 70 has been shown to enhance myocardial tolerance to subsequent ischemia-reperfusion injury. It has been reported that administration of the anti-gastric ulcer drug geranylgeranylacetone (GGA) before ischemia induced Hsp 70 expression and resulted in myocardial protection against ischemia and reperfusion injury. This cardioprotective effect of GGA was negated by administration of 5-hydroxydecanoate. These results suggest that the mechanism of GGA-induced myocardial protection may involve mitochondrial KATP channels. A more detailed knowledge of different mechanisms in myocardial protection can allow effective strategy of cardioprotection in perioperative anesthetic protocols

Intensive insulin therapy during cardiovascular surgery

Recent evidence in the fields of surgery, emergency and critical care medicine indicates that strict glycemic control results in lower mortality. Hyperglycemia occurs frequently in patients with and without diabetes during cardiovascular surgery, especially during cardiopulmonary bypass. However, strict glucose control is difficult to achieve during cardiovascular procedures. To establish effective intensive insulin therapy during cardiovascular surgery, we conduct continuous blood glucose monitoring and employ automatic control by using an artificial endocrine pancreas (the STGR-22, Nikkiso, Tokyo, Japan). In this review, we will outline the present status and problems of conventional glycemic control for perioperative cardiovascular surgery and introduce the new perioperative blood glucose management method that we are testing now. We will also discuss the importance of perioperative glycemic control for cardiovascular surgery as well as future prospects

Pathophysiology during ECC

Extracorporeal circulation, unlike pulsatile flow based on the beating heart, is the non-pulsatile flow through a blood pump, and the systemic circulation falls into non-physiological conditions. The living body shows various reactions to extracorporeal circulation. The pathophysiology of extracorporeal circulation includes changes in hemodynamics, coagulation, fibrinolysis, acid-base equilibrium, electrolytes, incretion, metabolism, and immune system. With advances in extracorporeal circulation technology, operability has been dramatically improved and safety has rapidly advanced as well. However, there are specific complications with extracorporeal circulation. We need to have a good knowledge of the pathophysiology and complications during extracorporeal circulation, as well as each component of the extracorporeal circulation system

Non-cardiac surgery applications of extracorporeal circulation

Although the efficacy of extracorporeal circulation (ECC) is well established for open-heart surgery, application of ECC in other surgical areas has not been given much attention. Advances in the related surgical technique and anesthetic management combined with refinements in the ECC procedure itself have encouraged several institutions to use ECC for complex non-cardiac surgeries. ECC is beginning to be used for circulatory support or tissue oxygenation during surgery on the lung, brain, liver, and kidney as well as in emergency situations. With ECC, difficult and complex surgeries can be performed more safely, and the success rate of certain surgeries has been positively affected. It is important that the surgeon, anesthesiologist, and perfusionist are trained in non-cardiac surgery applications of ECC. Thus, we review here non-cardiac uses that have emerged and summarize the related procedures

Minute distance obtained from pulmonary venous flow velocity using transesophageal pulsed Doppler echocardiography is related to cardiac output during cardiovascular surgery

Purpose. We studied the relationship between minute distance calculated from pulmonary venous flow (PVF) velocity tracing and cardiac output (CO)measured with thermodilution method in patients undergoing cardiovascular surgery. Methods. In 32 patients undergoing cardiovascular surgery, simultaneous measurements of hemodynamics including CO and transesophageal pulsed Doppler signals of PVF velocity were performed before and after surgical repair. Minute distance was calculated as the product of the heart rate and the sum of time-velocity integrals of PVF. Results. The minute distance after surgical intervention increased from 1121 ± 347 cm・sec-1to 1764 ± 538 cm・sec-1 (plt0.001 mean ± SD), while CO increased after surgical intervention from3.5 ± 0.9 L・min-1 to 5.3 ± 1.1 L・min-1. Simple linear regression analysis showed that minute distance was related with CO before and after surgical intervention (r=0.81 and r=0.76, respectively). The changes in minute distance were also related with those in CO (r=0.80). Conclusion. The present study demonstrated that minute distance obtained from the pulsed Doppler tracings of PVF velocity was related with CO during cardiovascular surgery in adults. These results suggest that the changes in CO could be estimated from minute distance in pulmonary vein

Usefulness of continuous blood glucose monitoring and control for patients undergoing liver transplantation

Background : The purpose of this study was to evaluate the usefulness of the closed-loop system (STG-22 ; Nikkiso, Tokyo, Japan), a type of artificial endocrine pancreas for the continuous monitoring and control of intraoperative blood glucose in patients undergoing liver transplantation. Methods : Sixteen patients undergoing livingdonor liver transplantation were enrolled in this study. Glucose levels were controlled with either a manual injection of insulin based on a commonly used sliding scale (manual insulin group, n=8) or a programmed infusion of insulin determined by the control algorithm of the artificial endocrine pancreas (programmed insulin group, n=8). The target glucose level range was set at 80-150 mg/dl. Results : The mean and SD of blood glucose concentration during surgery (Glu-Ave and Glu-SD, respectively) for the programmed insulin group were lower than for the manual insulin group. The coefficient of variability (Glu-CV=Glu-SD×100 /Glu-Ave) for the programmed insulin group was also lower than for the manual insulin group (20.1±4.9% vs. 26.9±6.1% ; mean±SD). No hypoglycemia was detected in either group. Conclusion : The STG-22 closed-loop system is effective for maintaining strict blood glucose control during liver transplantation with minimal variability in blood glucose concentration

Tissue oxygenation index reflects changes in forearm blood flow after brief ischemia

Whether the near-infrared spectroscopy (NIRS) technology correctly detects the changes in oxygenation related to ischemia and reperfusion of organs and tissues other than brain remains unclear. The present study examined how different tissue oxygenation parameters derived from NIRS reflect the changes in the forearm blood flow (FBF) according to the brief ischemia and the subsequent reperfusion, and whether values of these parameters move in parallel with the medial and lateral sides of FBF. Thirteen volunteers underwent the prospective observational study. The tissue oxygenation index (TOI), regional saturation of oxygen (rSO2), skin tissue oxygenation (StO2), and FBF values were evaluated in the forearm. Medial rSO2 values at 1 to 3 minutes after the termination of brief ischemia were higher than lateral rSO2 and respective TOI values. FBF and StO2 values quickly increased according to the cessation of brief ischemia, whereas the medial and lateral values did not differ during and after the brief ischemia. TOI and StO2, but not rSO2, reflected changes in FBF of both medial and lateral sides simultaneously in response to the reperfusion after brief ischemia. Themuscle tissue oxygenation during reperfusion favors the use of TOI and StO2, but not rSO2, as the surrogate parameter

イワユル ビョウビョウ レンケイ ガ ソウコウ シタ ショウガイシャ ニ タイスル シュウガクテキ シカ チリョウ ニツイテ

In recent years, the oral environments of disabled people are well maintained by dental specialists for the disabled; however, because serious conditions requiring dental therapy do occur in disabled patients, we created a referral system for multidisciplinary dentistry for the disabled. In this report, we describe the successful implementation of this referral system and the treatment outcomes of disabled patients who underwent therapy by dental specialists. The patients were 12 disabled people, comprising 9 males and 3 females, who had been undergoing dental treatment in Tokushima Red Cross Hinomine Rehabilitation Center for People with Disabilities and had visited Tokushima University Hospital between January 2010 and March 2013. Their ages ranged from 14 to 71 years old, with a mean of 32.5 years old. The most common types of disabilities were hypophrenia: 7 patients (58.3%); cerebral palsy: 4 patients (33.3%), autism: 3 patients (25.0%), malformation syndrome: 2 patients (16.7%), etc. were found. The most frequent complications were epilepsy: 5 patients (41.7%); cured patent ductus arteriosus, laryngomalacia, asthma, hypertension, and ventilatory impairment were found in 1 patient (8.3%). Regarding oral diseases, chronic periodontitis and dental caries: 11 cases (91.7%), impacted wisdom teeth and persistence of deciduous teeth: 2 cases (16.7%) and oral cancer: 1 case (8.3%), were found. Concerning treatment, tooth extraction: 11 cases (91.7%), crown restoration: 5 cases (41.7%), pulpectomy: 2 cases (16.7%) and tumor resection: 1 case (8.3%), were safely performed. The procedures were performed under intravenous sedation in 6 cases, and under general anesthesia in the other 6 cases. Our referral system may contribute to the development of low-risk dentistry for the disabled