Mismatch recovery of regional cerebral blood flow and brain temperature during reperfusion after prolonged brain ischemia in gerbils

BACKGROUND: Recovery of cerebral reperfusion after stroke or cardiac arrest can take a long time. We aimed to identify differences in the postischemic recovery of physiologic parameters between short and prolonged brain ischemia. METHODS: Eighteen Mongolian gerbils were assigned to one of three groups: 5-minute (G5), 15-minute (G15), or 30-minute (G30) ischemia. With the use of our original microspectroscopy system, global ischemic reperfusion was performed. We measured changes in regional cerebral blood flow (r-CBF), microvessel diameter, and brain temperature (BrT) simultaneously. We also monitored somatosensory evoked potentials (SEPs) to evaluate electrophysiologic response. RESULTS: Both G5 and G15 showed concurrent recovery of r-CBF and BrT with hyperemia and hyperthermia, respectively, 10 to 15 minutes after reperfusion. The increase in BrT was <1 degree C and recovered to baseline within 60 minutes after reperfusion. In G30, recovery of r-CBF was significantly delayed relative to that of BrT. The increase in BrT was >2 degrees C, peaking approximately 15 minutes after reperfusion, and then maintained increases of >1 degree C for 120 minutes. SEPs in G5 and G15 showed concomitant recovery with that of r-CBF, whereas SEP recovery in G30 was delayed relative to that of r-CBF, eventually disappearing. All except one of the G30 gerbils died within 24 hours, but all in G5 and G15 survived. CONCLUSIONS: These results suggest that mismatch recovery of r-CBF and BrT after prolonged ischemia initiates metabolic derangement in brain tissue, leading to the electrochemical dysfunction and mortality.     

Dynamic characteristics of a magnetically levitated impeller in a centrifugal blood pump

Centrifugal blood pumps that employ hybrid active/passive magnetic bearings to support noncontact impellers have been developed in order to reduce bearing wear, pump size, the power consumption of the active magnetic bearing, and blood trauma. However, estimates made at the design stage of the vibration of the impeller in the direction of passive suspension during pump operation were inaccurate, because the influence of both the pumping fluid and the rotation of the impeller on the dynamic characteristics was not fully recognized. The purpose of this study is to investigate the dynamic characteristics in a fluid of a magnetically levitated rotating impeller by measuring both the frequency response to sinusoidal excitation of the housing over a wide frequency range and the displacement due to input of a pulsatile flow during left ventricular (LV) assist. The excitation tests were conducted under conditions in which the impeller was levitated in either air or water, and with or without rotation. The experimental and analytical results indicate that vibration of the impeller due to the external force in water was decreased, compared with that in air due to the hydraulic force of water. The axial resonant frequency rose quadratically with rotational speed, and the tilt mode had two resonant frequencies while rotating due to the gyroscopic effect. With the pump inserted into a mock systemic circulatory loop, the dynamic stability of the impeller when pulsatile pressure was applied during LV assist was verified experimentally. The amplitudes of vibration in response to the pulsatile flow in the passively constrained directions were considerably smaller in size than the dimensions of initial gaps between the impeller and the pump housing.     

New Generation Extracorporeal Membrane Oxygenation With MedTech Mag‐Lev,a Single‐Use,Magnetically Levitated,Centrifugal Blood Pump: Preclinical Evaluation in Calves

We have evaluated the feasibility of a newly developed single‐use, magnetically levitated centrifugal blood pump, MedTech Mag‐Lev, in a 3‐week extracorporeal membrane oxygenation (ECMO) study in calves against a Medtronic Bio‐Pump BPX‐80. A heparin‐ and silicone‐coated polypropylene membrane oxygenator MERA NHP Excelung NSH‐R was employed as an oxygenator. Six healthy male Holstein calves with body weights of about 100 kg were divided into two groups, four in the MedTech group and two in the Bio‐Pump group. Under general anesthesia, the blood pump and oxygenator were inserted extracorporeally between the main pulmonary artery and the descending aorta via a fifth left thoracotomy. Postoperatively, both the pump and oxygen flow rates were controlled at 3 L/min. Heparin was continuously infused to maintain the activated clotting time at 200–240 s. All the MedTech ECMO calves completed the study duration. However, the Bio‐Pump ECMO calves were terminated on postoperative days 7 and 10 because of severe hemolysis and thrombus formation. At the start of the MedTech ECMO, the pressure drop across the oxygenator was about 25 mm Hg with the pump operated at 2800 rpm and delivering 3 L/min flow. The PO₂ of the oxygenator outlet was higher than 400 mm Hg with the PCO₂ below 45 mm Hg. Hemolysis and thrombus were not seen in the MedTech ECMO circuits (plasma‐free hemoglobin [PFH] < 5 mg/dL), while severe hemolysis (PFH > 20 mg/dL) and large thrombus were observed in the Bio‐Pump ECMO circuits. Plasma leakage from the oxygenator did not occur in any ECMO circuits. Three‐week cardiopulmonary support was performed successfully with the MedTech ECMO without circuit exchanges. The MedTech Mag‐Lev could help extend the durability of ECMO circuits by the improved biocompatible performances.     

Resection of the Colon Simultaneously with Pancreaticoduodenectomy for Tumors of the Pancreas and Periampullary Region: Short-term and Long-term Results

Simultaneous resection of the colon with pancreaticoduodenectomy (PD) is occasionally inevitable to accomplish curative resection in instances when a periampullary tumor involves the mesentery of the colon. However, there is little information regarding short- and long-term outcomes of this aggressive surgery. Among 95 consecutive patients who underwent PD for periampullary malignant tumors, 12 had simultaneous resection of the right colon (group 1) and 83 underwent PD alone (group 2). Intraoperative variables, postoperative morbidity and mortality, and the length of the hospital stay were comparatively analyzed. Survival was also compared between the groups in a subset of 36 pancreatic adenocarcinoma patients. Group 1 included more patients with pancreatic cancer, and portal vein resection was more frequently performed, which seemed to be associated with a significantly longer operating time (640 vs. 510 minutes) and increased total blood loss (1965 vs. 1220 ml). However, morbidity and mortality rates did not differ between the groups (50,0% and 0%, respectively, in group 1; 44.6% and 1.2%, respectively, in group 2). The median hospital stays were 67 and 48 days in groups 1 and 2, respectively. In a subset of 36 pancreatic adenocarcinoma patients, the median progression-free survivals were 6 months in both groups 1 and 2; the median overall survivals were 14 months in group 1 and 12 months in group 2. There was no statistically significant difference in survival between the groups. Simultaneous right hemicolectomy with curative intent at the time of PD could thus be performed safely and may offer a survival benefit even for individuals who have advanced pancreatic cancers with involvement of the transverse mesocolon.     

Endoscopic treatment or surgery for undifferentiated early gastric cancer?

BACKGROUND: Although almost all (96%) the surgical cases of undifferentiated intramucosal early gastric cancer (EGC) have been found not to have lymph node metastasis (LNM), local treatment by endoscopic mucosal resection (EMR) is not accepted as an alternative treatment to surgery for this type of EGC. If a subgroup of patients with undifferentiated EGC with negligible risk of LNM can be defined, unnecessary surgery can be avoided. This study was conducted to determine this subgroup among undifferentiated EGC patients in whom the risk of LNM can be highly ruled out in an attempt to identify candidates who can be treated by EMR. METHODS: Data from 175 patients surgically resected for undifferentiated EGC were retrospectively collected, and clinicopathological factors were multivariately analyzed to identify predictive factors for LNM. RESULTS: Multivariate logistic regression analysis identified two independent risk factors for LNM, namely, a large tumor (>/=20 mm, P = 0.011) and presence of lymphatic involvement (P = 0.0005). Using these two risk factors as the predictive factors, LNM was observed in 5.8% of patients who had neither of the two predictive factors, whereas 23.1% or 13.1% of patients with one or two predictive factors had LNM, respectively. In contrast, the LNM rate was calculated to be 60% in patients who had both factors. Lymph node metastasis was not found in any of 6 patients with small intramucosal lesions (<10 mm) without lymphatic involvement. CONCLUSIONS: An intramucosal undifferentiated EGC that is smaller than 10 mm without lymphatic involvement can safely be treated by EMR alone, given the negligible possibility of LNM. When histological examination of endoscopically resected specimens shows lymphatic involvement or unexpectedly larger tumor size than that determined at pre-EMR endoscopic diagnosis, an additional surgical procedure should be considered.     

Effects of iterative reconstruction on image contrast and lesion detection in gamma camera coincidence imaging in lung and breast cancers.

To investigate the effects of iterative reconstruction in 18F-fluorodeoxyglucose (FDG) gamma camera coincidence imaging (GCI), image contrast and visual detection obtained by using the iterative ordered-subsets expectation maximization (OSEM) reconstruction, in a phantom and in patients with lung cancer and breast cancer, were compared with those obtained by using the conventional filtered backprojection (FBP) reconstruction. Images of a cylindrical phantom containing hot spheres of various sizes (10-38 mm) were acquired by positron emission tomography (PET) and GCI at various sphere-to-background activity ratios. Forty-one consecutive patients with biopsy-proven cancer of lung (n = 20) and breast (n = 21) underwent PET and GCI on the same day after intravenous injection of 370 MBq of FDG. GCI images reconstructed by the OSEM and the FBP were compared. FDG PET was considered as the standard of reference. In GCI phantom images, OSEM yielded better contrast and signal-to-noise ratio (SNR) than FBP over the range of sphere sizes. Attenuation correction improved both the image measures and sphere detection obtained by the OSEM in GCI. In the study involving patients, FDG PET depicted 41 primary tumours and 25 metastatic lymph nodes. All of the tumours >2 cm in diameter (n = 25), six of the nine tumours 1.5-2.0 cm in diameter (67%), two of seven tumours <1.5 cm in diameter (29%), and 20 metastatic lymph nodes (80%) were detected in attenuation uncorrected GCI reconstructed by the OSEM as well as the FBP. The undetected lesions in GCI were identical between the OSEM and the FBP reconstructions. OSEM yielded significantly greater tumour-to-background (T/B) ratios and lower noise than FBP in GCI (T/B ratios, 4.1+/-3.2 vs 3.7+/-2.7, P = 0.02; noise, 0.09+/-0.04 vs 0.14+/-0.05, P<0.0001). In conclusion, OSEM yielded better image contrast and less noise than the FBP in GCI, but the lesion detection obtained by the OSEM and the FBP in attenuation uncorrected GCI in patients with lung cancer and breast cancer were similar. Phantom data suggest the potential of OSEM for improving lesion detection in GCI after attenuation correction.     

Simultaneous blockade of co-stimulatory signals, CD28 and ICOS, induced a stable tolerance in rat heart transplantation

An inducible co-stimulator (ICOS), a recently identified co-stimulatory receptor with a close structural homology of CD28 and CTLA4, is expressed on activated T cells. Anti-ICOS antibody was demonstrated to be effective on prolongation of graft survival after liver transplantation in rats. In this study, we investigated the potency of tolerance induction using the antibody combined with a recombinant adenovirus vector containing CTLA-4Ig cDNA (AdCTLA-4Ig) in rat heart transplantation model. Using a DA-to-Lewis rat heart transplantation model, an anti-rat ICOS antibody and AdCTLA-4Ig were simultaneously administered i.v. into recipients. The tissue specimens from the grafts were removed on various days after transplantation for histological evaluation. Donor-strain skin and heart grafts, and third-party heart allografts were challenged in the recipients with a long-term surviving graft. Splenocytes from the tolerance-induced recipients were used for adoptive transfer study. Anti-ICOS antibody alone did not prolong the survival of heart allograft. AdCTLA-4Ig monotherapy significantly prolonged the survival of heart allograft (Group 4). With a combination of Anti-ICOS antibody and AdCTLA-4Ig, all recipients were resulted in a long-term allograft acceptance for more than 200 days (Group 8). When challenged donor-strain skin grafts in the tolerant rats of Group 4, the skin was rejected, which also lead to a rejection of primary heart allografts. The recipients in Group 8 also rejected donor-strain skin grafts with no rejection of the primary heart grafts. These recipients accepted secondary heart grafts from donor-strain but not third-party. In Group 8 long-term survival recipients showed a high population of CD4+CD25+ regulatory T cell in peripheral blood, and in adoptive transfer study subtraction of these CD4+CD25+ T cells accelerate the rejection of heart graft in secondary irradiated recipients. The present results demonstrated that anti-ICOS antibody combined with AdCTLA-4Ig potently induces a stable immune tolerance after heart allografting in rat, which is mediated by the induction of CD4+CD25+ regulatory T cells. This strategy may be attractive for clinical employment to induce transplantation tolerance.     

Pancreas preservation by the 2-layer cold storage method before islet isolation protects isolated islets against apoptosis through the mitochondrial pathway

BACKGROUND: Apoptosis in isolated islets has been implicated in primary nonfunction or early graft failure after islet transplantation. Recently, pancreas preservation by the 2-layer method (TLM) before islet isolation has been proved to improve the islet yield, quality, and transplant results not only in experimental models, but also in clinical settings. We examined the influence of TLM on apoptosis of isolated islets. METHOD: Rat islets freshly isolated and after pancreas preservation by TLM or conventional cold storage in University of Wisconsin solution (UW) were examined and compared. Islet apoptosis was assessed by TUNEL and annexin V assays. The apoptosis pathways involved were investigated by measurement of caspase 3, 8, and 9 activities and by immunoblotting for total and phosphorylated c-Jun NH2-terminal kinase (JNK) and p38. RESULTS: Islet apoptosis in the UW group was significantly increased compared with the fresh and TLM groups. Both caspase 3 and 9 activities in the UW group were higher than in the fresh and TLM groups with an approximate increase of 2- to 3-fold. On the other hand, there was no significant difference in caspase 8 activity among these 3 groups. JNKs were strongly activated both in the TLM and UW groups; although they were not activated in the fresh group, p38 was activated to almost the same levels in these 3 groups. CONCLUSIONS: Pancreas preservation by TLM before islet isolation protects isolated islets against apoptosis mainly through the mitochondrial pathway. Pancreas storage before islet isolation even with TLM triggers activation of JNKs in isolated islets.