Koichi Morioka

Leukocyte and platelet depletion with a blood cell separator: Effects on lung injury after cardiac surgery with cardiopulmonary bypass

This study was undertaken to assess the effects of leukocyte and platelet depletion on postoperative lung injury in 42 patients who underwent heart operations. Blood was serially sampled before, during, and after cardiopulmonary bypass, and leukocyte count, platelet count, and thromboxane B2 6-keto-PGF1 alpha, leukocyte elastase, thrombin-antithrombin III complex, and D-dimer levels were determined. Postoperative respiratory function was assessed based on analyses of oxygenation and carbon dioxide elimination. Leukocyte and platelet depletion was performed in 21 patients (experimental group) but not in another (control group). In the experimental group, leukocytes and platelets were removed continuously by means of the blood cell separator CS-3000, beginning immediately after the start of the operation and ending 1 hour after the release of aortic occlusion. Leukocyte elastase, thromboxane B2, ratio of thromboxane B2 to 6-keto-PGF1 alpha, thrombin-antithrombin III complex, and D-dimer were significantly lower in the experimental group than in the control group. Of the various indexes of oxygenation, arterial oxygen tension was significantly higher in the experimental group and the alveolar-arterial oxygen pressure difference and respiratory index were significantly lower in the experimental group. The positive end-expiratory pressure needed to achieve an appropriate arterial oxygen tension was significantly lower in the experimental group. The elimination of carbon dioxide was lower in the experimental group. Depletion of leukocytes and platelets reduced respiratory dysfunction after heart operations with cardiopulmonary bypass. It was particularly effective in patients with a low preoperative oxygenation capacity and in those for whom an extended period of cardiopulmonary bypass was required.

Surgical outcome of infectious aneurysm of the abdominal aorta with or without SIRS

The surgical outcome of infectious abdominal aortic aneurysms was evaluated based on the preoperative presence or absence of systemic inflammatory response syndrome (SIRS). Nine patients were divided into two groups according to the criteria for SIRS such as body temperature, heart rate, respiratory rate, and white blood cell count. In the group with SIRS, rupture and impending rupture of aneurysms occurred in three of the four patients (75%). All aneurysms were resected with a small part as a remnant; two in situ and two extraanatomic reconstructions were performed. Three patients died after surgery: one after in situ (cerebral infarction) and two after extraanatomic reconstruction (sepsis and multiple organ failure). In the group without SIRS, closed en bloc resection in two patients and resection of the aneurysm with a small part as a remnant in three patients were performed. In situ reconstruction in all patients and omentum wrapping in two patients were performed. One of the five patients died of massive hematemesis 70 days after surgery. The overall mortality rate was 75% in the group with SIRS versus 20% in the group without SIRS. The surgical outcome of infectious abdominal aortic aneurysm depends upon the severity of underlying infection. A possibility exists that SIRS is a useful indicator for predicting the surgical outcome of patients.

Surgical treatment of infected thoracic and abdominal aortic aneurysms

Twelve patients with infected aneurysms of the thoracic and abdominal aorta were evaluated. Aneurysmal location, aetiology, bacteriology and treatment modality were analysed to determine the relationship between these factors and outcome. Patients were divided into two groups based on the preoperative states of their infections. Group 1 patients (n = 7) underwent resection after resolution of their active infection. The causative organisms included Staphylococcus epidermidis (two cases). Salmonella spp. (one). Acinetobacter (one), Mycobacterium tuberculosis (one) and unknown organisms (two). Group 2 patients (n = 5) required urgent surgery because of uncontrolled sepsis despite intensive treatment with antibiotics. The causative organisms included Staphylococcus aureus (two cases). Pseudomonas aeruginosa (two) and Salmonella spp. (one). In group 1, three patients underwent closed en bloc excision of the aneurysm with in-situ graft replacement, and four underwent partial resection with in-situ graft replacement. In group 2, three patients underwent resection of the aneurysm with ligation of aorta and extra-anatomic bypass, and two underwent in-situ graft replacement after débridement of infected tissue. Overall, patients in group 1 had a mortality rate of 14% compared with 80% in group 2. These results suggest that the operative approach and method chosen to restore arterial continuity have less of an impact on outcome. The primary determinants of outcome are virulence of the infecting organism and the preoperative state of the infection.

Thymidine Phosphorylase Gene Transfer Inhibits Vascular Smooth Muscle Cell Proliferation by Upregulating Heme Oxygenase-1 and p27KIP1

Objective—Thymidine phosphorylase (TP) reportedly promotes endothelial cell migration and induces heme oxygenase (HO)-1 expression. However, its effect on vascular smooth muscle cells (VSMCs) is poorly understood. In this study, we examined the effect of TP on VSMCs in vitro and in vivo. Methods and Results—Phagemid vector encoding human TP gene was transfected into rat VSMCs, and a clone overexpressing TP was selected (C2). C2 showed a slower migration and proliferation than VSMCs cloned with empty vector (pC) under basal, serum-stimulated, and hypoxic conditions. This decrease in proliferation correlated with TP-induced HO-1 expression and was reversed by inhibitors of either TP or HO activity. Furthermore, in C2, the cyclin-dependent kinase inhibitor (p27KIP1) was much more abundant than in pC, and the cell cycle was arrested at the G1 phase. TP or HO activity inhibitors decreased p27KIP1 expression in C2 to the level seen in pC. Adventitial TP gene delivery significantly reduced neointimal VSMC migration and neointima formation in balloon-injured rat carotid arteries. Conclusions—TP overexpression upregulated HO-1 expression and consequently increased p27KIP1 in cultured VSMCs, and inhibited VSMC migration and proliferation in vitro and in vivo. TP represents a promising target for treating vascular obstructive disease.

Hyperamylasemia and subclinical pancreatitis after cardiac surgery.

Hyperamylasemia after cardiac surgery is common but typically causes no clinical concern because it consists mainly of the salivary isoenzyme. In this study we evaluated the incidence, source, and time course of postoperative hyperamylasemia with special attention to the possibility of subclinical pancreatitis. In 88 patients prospectively tested for serum amylase and lipase concentrations, elastase 1 activity, and amylase isoenzyme characteristics, 57 (64%) showed hyperamylasemia during the early postoperative period. In most cases early hyperamylasemia was not of pancreatic origin, but two patients were diagnosed with subclinical pancreatitis. Among the last 23 patients, 5 of 10 patients with early hyperamylasemia exceeding 1000 IU/L showed late hyperamylasemia on the seventh postoperative day, when it represented mainly the pancreatic isoenzyme. Lipase concentrations and elastase 1 activities were elevated in these cases. Late hyperamylasemia following cardiac surgery may be of pancreatic origin and indicative of subclinical pancreatitis, even if early hyperamylasemia was of salivary origin.RésuméL’hyperamylasémie après chirurgie cardiaque est fréquente mais entraîne habituellement peu de soucis car il s’agit le plus souvent de l’isoenzyme salivaire. Dans cette étude, nous avons évalué l’incidence, la source et l’évolution dans le temps de l’hyperamylasémie postopératoire en tenant compte particulièrement de l’éventualité d’une pancréatite postopératoire infra-clinique. Chez 81 patients, analysés prospectivement pour l’amylase et la lipase sériques, l’activité en élastase l et les caractéristiques de l’isoenzyme, 57 (64%) avaient une hyperamylasémie en période postopératoire immédiate. Dans la plupart des cas, l’hyperamylasémie précoce n’était pas d’origine pancréatique, mais on a fait le diagnostic de pancréatite infraclinique chez deux patients. Parmi les 23 autres patients, 5 des 10 patients ayant une hyperamylasémie précoce au-dessus de 1000 IU/L avaient également une hyperamylasémie tardive au septième jour postopératoire, mais il s’agissait principalement d’enzyme d’origine pancréatique. Les concentrations en lipase et l’activité en élastase 1 étaient élevées dans ces cas. En conclusion, une hyperamylasémie tardive après chirurgie cardiaque peut être d’origine pancréatique et indique une pancréatite infra-clinique, même si l’hyperamylasémie précoce est d’origine salivaire.ResumenLa hiperamilasemia tras cirugia cardiaca es habitual pero no tiene repercusión clinica pues se trata sobre todo de la isoenzima salival. En este estudio evaluamos la frecuencia, el origen y la duración de la hiperamilasemia postoperatoria, prestando especial atención a la posible aparición de una pancreatitis subclinica. En 88 pacientes se determinó prospectivamente la concentración sérica de amilasa, lipasa, actividad de la elastasa l y las caracteristicas de la isoenzimas de la amilasa. 57 (64%) de los pacientes presentaron hiperamilasemia en el postoperatorio precoz. En la mayoria de los casos esta hiperamilasemia no reconocía una etiología pancreática, pero 2 pacientes fueron diagnosticados de pancreatitis subclínica. Entre los 23 últimos pacientes, en 5 de 10, que presentaron hiperamilasemia precoz superior a los 1,000 IU/L, se constató hiperamilasemia al séptimo día del postoperatorio, debido, sobre todo, a la isoenzima pancreática. La concentración de lipasa y la actividad de la elastasa l también estaban elevadas en estos casos. La hiperamilasemia tardía, tras cirugía cardiaca puede tener un origen pancreático reflejando una pancreatitis subclínica, incluso si la hiperamilasemia precoz reconoce un origen salival.

Long‐term effect of gene therapy for chronic ischemic myocardium using platelet‐derived endothelial cell growth factor in dogs

We previously reported the 2‐week benefits of platelet‐derived endothelial cell growth factor (PD‐ECGF) gene therapy in chronically ischemic myocardium. However, the long‐term effects and safety using this gene have not been reported.

Prolongation of total permissible circulatory arrest duration by deep hypothermic intermittent circulatory arrest

OBJECTIVE We determined whether the duration of permissible circulatory arrest could be prolonged by deep hypothermic intermittent circulatory arrest. METHODS Twenty-five beagles were cooled on bypass to 18 degrees C to initiate deep hypothermia that was maintained for 3 hours. Five protocols were then studied: group 1, uninterrupted bypass during hypothermia; group 2, arrest for 40 minutes during hypothermia; group 3, arrest for 60 minutes during hypothermia; group 4, arrest for 80 minutes during hypothermia; and group 5, intermittent circulatory arrest, consisting of six cycles of 20 minutes of arrest followed by 10 minutes of systemic recirculation during hypothermia (total, 120 minutes of arrest). The oxyhemoglobin concentration in the brain was measured with near infrared spectrophotometry. RESULTS In groups 2, 3, and 4, the oxyhemoglobin concentration in the brain decreased continuously after arrest, finally reaching a plateau after 24.9 +/- 1.2 minutes. This finding suggested that the available cerebral oxyhemoglobin was depleted. In contrast, the available cerebral oxyhemoglobin was not depleted during hypothermic intermittent arrest in group 5. The mitochondrial respiratory control index was significantly lower in group 4 than in the other groups (p < 0.05). However, there were no significant differences in the respiratory control index for groups 1, 2, 3, and 5. Moreover, the formation of brain edema was significantly lower in group 5 than in the other groups (p < 0.05). CONCLUSIONS These results indicate that deep hypothermic intermittent arrest can increase the duration of total permissible circulatory arrest and will be a useful modality when prolonged arrest is anticipated.

Experimental determination of the safe minimum perfusion flow rate for low-flow hypothermic cardiopulmonary bypass.

This study investigated the safe minimum perfusion flow rate for low-flow hypothermic cardiopulmonary bypass in a canine model. The adequacy of cerebral oxygenation was determined from the adenosine concentration, the oxygen saturation of cerebral venous blood and brain oxyhemoglobin level. In experiment 1, nine beagles were cooled on bypass to a nasopharyngeal temperature of 18 degrees C and the perfusion flow rate was reduced in a stepwise fashion every 30 min from 100 to 50, 30, 20 and 10 ml/kg per min. In experiment 2, six beagles were cooled on bypass as in experiment 1, and flow was maintained at 30 ml/kg per min for 120 min. At a perfusion flow rate of 30 ml/kg per min, adequate cerebral oxygenation was maintained for 120 min. In contrast, perfusion flow rates of 20 and 10 ml/kg per min were associated with cerebral ischemia.

Thrombosed abdominal aortic aneurysm associated with an extensively "shaggy" aorta repaired anatomically via a thoracoabdominal approach with supraceliac aortic clamping: report of a case.

A 76-year-old man with a history of multiple laparotomies and severe coronary artery disease was referred to our hospital after the sudden development of pain and numbness in the lower extremities. Computed tomography showed a thrombosed abdominal aortic aneurysm and diffuse aortic atherosclerosis; compatible with a “shaggy aorta.” A good response to thrombolytic therapy permitted elective scheduling of abdominal aortic surgery after coronary artery bypass grafting. We operated via an extended left retroperitoneal approach through a thoracoabdominal incision. Epiaortic ultrasonography revealed that only the supraceliac aorta was free of mobile thrombi and had minimal plaque; we therefore placed a proximal aortic cross-clamp there. Anatomic aortic reconstruction was then performed successfully using an aorto-biiliac graft to restore adequate distal blood flow. There were no vital-organ ischemic complications, and the postoperative course was satisfactory.

Measurement of glucose metabolism in rat spinal cord slices with dynamic positron autoradiography

We attempted to measure the regional metabolic rate of glucose (MRglc) in sliced spinal cords in vitro. The thoracic spinal cord of a mature Wister rat was cut into 400-mum slices in oxygenated and cooled (1-4 degrees C) Krebs-Ringer solution. After at least 60 min of preincubation, the spinal cord slices were transferred into double polystyrene chambers and incubated in Krebs-Ringer solution at 36 degrees C, bubbled with 5% O(2)/5% CO(2) gas. To measure MRglc, we used the dynamic positron autoradiography technique (dPAT) with F-18-2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) and the net influx constant of [(18)F]FDG as an index. Uptake curves of [(18)F]FDG were well fitted by straight lines for more than 7 h after the slicing of the spinal cord (linear regression coefficient, r=0.99), indicating a constant uptake of glucose by the spinal cord tissue. The slope (K), which denotes MRglc, is affected by tetrodotoxin, and high K(+) (50 mM) or Ca(2+)-free, high Mg(2+) solution. After 10 min of hypoxia, the K value following reoxygenation was similar to the unloaded control value, but after 45 min of hypoxia, the K value was markedly lower than the unloaded control value, and after >90 min of reoxygenation it was nearly 0. Our results indicate that the living spinal cord slices used retained an activity-dependent metabolism to some extent. This technique may provide a new approach for measuring MRglc in sliced living spinal cord tissue in vitro and for quantifying the dynamic changes in MRglc in response to various interventions such as hypoxia.