Motomu Kobayashi

Quantitative evaluation of the neuroprotective effects of thiopental sodium, propofol, and halothane on brain ischemia in the gerbil: effects of the anesthetics on ischemic depolarization and extracellular glutamate concentration.

Although propofol and thiopental are commonly used as neuroprotective agents, it has not been determined which is more neuroprotective. This study was designed to quantitatively evaluate the neuroprotective effects of thiopental, propofol, and halothane on brain ischemia by determining P50, ischemic time necessary for causing 50% neuronal damage. Gerbils were anesthetized with thiopental, propofol, or halothane and underwent 2-vessel occlusion (0, 3, 5 or 10 min). Direct current potentials were measured in bilateral CA1 regions, in which histologic evaluation was performed 5 days later. In some animals, extracellular glutamate concentrations (microdialysis) were measured during 7.5 minutes of ischemia. P50 in the thiopental, propofol, and halothane groups were estimated to be 8.4, 6.5 (P<0.05, vs. thiopental), and 5.1 (P<0.05) minutes, respectively. Durations of ischemic depolarization were equally reduced in the thiopental and propofol groups compared with that in the halothane group. Severity of neuronal damage with identical duration of ischemic depolarization was attenuated by thiopental compared with the effect of propofol. Maximum glutamate concentrations in the thiopental and propofol group were significantly reduced compared with that in the halothane groups but were comparable. By using P50, we found that the neuroprotective effect of thiopental was greater than that of propofol. Although duration of ischemic depolarization was equally reduced in thiopental and propofol groups, thiopental has a greater suppressive effect on neuronal injury during identical duration of ischemic depolarization than propofol does. Glutamate concentration during brain ischemia tended to be attenuated more by thiopental than by propofol, but it was not statistically significant.

Effect of nitrous oxide on neuronal damage and extracellular glutamate concentration as a function of mild, moderate, or severe ischemia in halothane-anesthetized gerbils.

Background:The effect of nitrous oxide on ischemic neuronal damage was quantitatively evaluated by use of logistic regression curves. Methods:Seventy-two gerbils were anesthetized with 1% halothane and randomly assigned to receive 70% nitrous oxide or 70% nitrogen. Forebrain ischemia was performed for 3, 5, or 7 min, and direct-current potential in the hippocampal CA1 region was recorded. Histologic outcome was evaluated 5 days later. Relations of neuronal damage with ischemic duration and duration of ischemic depolarization were determined by logistic regression curves. In some animals, extracellular glutamate concentration was measured every 60 s during forebrain ischemia. Results:Nitrous oxide increased neuronal damage only with 5 min of ischemia (nitrous oxide vs. nitrogen: 78.5 ± 23.0 vs. 37.3 ± 12.2%; P < 0.01). The percentages of neuronal damage with 3 and 7 min of ischemia were not different with or without nitrous oxide. Logistic regression curves indicated that nitrous oxide significantly increased neuronal damage during the period from 3.07 to 6.63 min of ischemia. Logistic regression curves also indicated that nitrous oxide increased neuronal damage in the condition of the same duration of ischemic depolarization. Nitrous oxide shortened the ischemic duration necessary for causing 50% neuronal damage by 0.82 min. Dynamic change in extracellular glutamate concentration was not different (mean maximum dialysate glutamate concentration: 4.29 ± 3.09 vs. 4.63 ± 1.83 &mgr;m). Conclusion:Administration of nitrous oxide caused an increase in ischemic neuronal damage, but a significant adverse effect was observed with a limited range of ischemic intervals.

Reverse Right Ventricular Remodeling After Lung Transplantation in Patients With Pulmonary Arterial Hypertension Under Combination Therapy of Targeted Medical Drugs

BACKGROUND Patients with pulmonary arterial hypertension (PAH) are currently treated with combination therapy of PAH-targeted drugs. Reverse right ventricular (RV) remodeling after lung transplantation (LTx) in patients with end-stage PAH despite combination therapy of PAH-targeted drugs has not been fully elucidated.Methods and Results:A total of 136 patients, including 32 with PAH, underwent LTx from 1998 to 2014. We enrolled 12 consecutive patients with PAH treated with combination therapy of PAH-targeted drugs who underwent LTx and retrospectively analyzed the temporal and serial changes in hemodynamics and echocardiography before LTx and at 3 and 12 months after LTx. Before LTx, the RV was markedly dilated with substantially reduced RV fractional area change (RVFAC). At 3 months after LTx, pulmonary artery pressure, pulmonary vascular resistance and RV stroke work index were significantly decreased, while left ventricular stroke work index was increased. RV size assessed by echocardiography also significantly decreased and RVFAC improved. At 12 months after LTx, RVFAC was further increased and RV wall thickness was decreased significantly. CONCLUSIONS Although severe RV dysfunction and dilation were observed in patients with end-stage PAH despite combination therapy of PAH-targeted drugs, RV function and morphology were improved after reduction of RV pressure load by LTx.

Prolonged administration of twice-daily bolus intravenous tacrolimus in the early phase after lung transplantation

BACKGROUND Although administration of tacrolimus, whether by the enteric, sublingual, or continuous intravenous routes, has some limitations, twice-daily bolus intravenous tacrolimus administration has been shown to be beneficial in optimizing efficacy and safety after lung transplantation. However, at present, the duration of bolus intravenous tacrolimus administration is limited, and the effects of prolonged bolus intravenous tacrolimus administration remain unknown. Our study was aimed at assessing the safety and efficacy of prolonged twice-daily bolus intravenous tacrolimus administration in the early phase after lung transplantation. MATERIAL AND METHODS We retrospectively investigated the data of 62 recipients of lung transplantation who had received twice-daily bolus intravenous administration of tacrolimus, followed by oral tacrolimus, after lung transplantation at our institution between January 2011 and October 2015. RESULTS The median duration of bolus intravenous tacrolimus administration was 19 days (4-72 days). The target trough level was achieved in 89% of the patients by day 3. Acute kidney injury occurred in 27% of the patients during bolus intravenous tacrolimus. Two patients (3%) had neurotoxicity, necessitating discontinuation of tacrolimus. Suspected acute rejection requiring steroid pulse therapy occurred in 21% of patients during the follow-up period. Eight patients (13%) developed chronic lung allograft dysfunction during the follow-up period. The 1-year and 5-year survival rates after lung transplantation were 95% and 76%, respectively. CONCLUSIONS These results suggest that prolonged bolus intravenous tacrolimus administration in the early phase after lung transplantation is a safe and effective alternative to enteric, sublingual, or continuous intravenous administration.

Use of extended-criteria lungs on a lobe-by-lobe basis through ex vivo lung perfusion assessment

Initially rejected and extended-criteria lungs were partially used through an ex vivo lung perfusion (EVLP) assessment that was first clinically applied in Asia. The truly injured lobe (left lower lobe) was identified during 89-minute normothermic EVLP and was excised, and the remaining lobes were successfully transplanted into a patient with lymphangioleiomyomatosis. The lung lobes showed heterogeneous changes on the ex vivo rig, and a brief duration of EVLP helped differentiate lung quality on a lobe-by-lobe basis.

Airway complications have a greater impact on the outcomes of living-donor lobar lung transplantation recipients than cadaveric lung transplantation recipients

PurposeAirway complications (ACs) after living-donor lobar lung transplantation (LDLLT) could have different features from those after cadaveric lung transplantation (CLT). We conducted this study to compare the characteristics of ACs after LDLLT vs. those after CLT and investigate their impact on outcomes.MethodsWe reviewed, retrospectively, data on 163 recipients of lung transplantation, including 83 recipients of LDLLT and 80 recipients of CLT.ResultsThe incidence of ACs did not differ between LDLLT and CLT. The initial type of AC after LDLLT was limited to stenosis in all eight patients, whereas that after CLT consisted of stenosis in three patients and necrosis in ten patients (p = 0.0034). ACs after LDLLT necessitated significantly earlier initiation of treatment than those after CLT (p = 0.032). The overall survival rate of LDLLT recipients with an AC was significantly lower than that of those without an AC (p = 0.030), whereas the overall survival rate was comparable between CLT recipients with and those without ACs (p = 0.25).ConclusionACs after LDLLT, limited to bronchial stenosis, require significantly earlier treatment and have a greater adverse impact on survival than ACs after CLT.

Veno-venous extracorporeal membrane oxygenation bridged living-donor lung transplantation for rapid progressive respiratory failure with pleuroparenchymal fibroelastosis after allogeneic hematopoietic stem cell transplantation

Cases of extracorporeal membrane oxygenation (ECMO) bridged lung transplantation (LTx) are rare in Japan because an allocation system to prioritize patients based on urgency remains to be established. For critically ill patients who cannot wait for a brain-dead donor LTx, ECMO bridge to living-donor LTx may be the only practical option. A 21-year-old woman with pleuroparenchymal fibroelastosis after hematopoietic stem cell transplantation was admitted to our hospital with rapidly progressive respiratory failure. She was waitlisted for 6 months before admission, but veno-venous ECMO was initiated. She was transported under ECMO support via a jet plane and underwent successful living-donor LTx.

High Frequency of Acute Adverse Cardiovascular Events After Lung Transplantation in Patients With Pulmonary Arterial Hypertension Receiving Preoperative Long-Term Intravenous Prostacyclin

Adverse cardiovascular events after lung transplantation (LT) increase the mortality in patients with pulmonary arterial hypertension (PAH). Long-term intravenous prostacyclin is the usual treatment in severe patients with PAH, but it may increase the risk of hemorrhage due to its antiplatelet aggregation effect or thrombocytopenia. We investigated the impact of length of intravenous prostacyclin therapy on acute adverse cardiovascular events including hemorrhagic complication after LT. We retrospectively compared the incidence of adverse events (death, intrathoracic hematoma and bleeding, cardiac congestion or shock, cerebral infarction and pulmonary embolism) within 30 days after LT between no/short-term (median 0.6 years, n = 13) and long-term (median 3.7 years, n = 15) intravenous prostacyclin groups. There were no differences in the dose of intravenous prostacyclin and pulmonary artery pressure between the two groups. Among 22 adverse events (0.8 ± 1.1 events/patient), 4 events occurred in the no/short-term intravenous prostacyclin group and 18 occurred in the long-term intravenous prostacyclin group. The event rate per patient in the long-term intravenous prostacyclin group (1.2 ± 1.3 events/patient) was significantly higher than that in the no/short-term intravenous prostacyclin group (0.3 ± 0.5 events/patient) (P < 0.05). Intrathoracic hematoma and bleeding was the most frequent adverse event (9 events, 41%). Preoperative long-term intravenous prostacyclin therapy increases acute adverse cardiovascular events after LT in patients with PAH.

Pregnancy and delivery after myelomeningocele repair, ventriculoperitoneal shunt implantation, and augmentation cystoplasty

IntroductionManagement of pregnancy and delivery of a patient with a history of myelomeningocele requires a multidisciplinary team approach.Case reportWe report a case of pregnancy and delivery by a patient who had a history of myelomeningocele surgical repair, ventriculoperitoneal (VP) shunt, and bladder augmentation enterocystoplasty. Regarding types of delivery style, anesthesiologists recommended a Cesarean section under general anesthesia. However, urologists recommended a vaginal delivery because they were concerned that she would require a nephrostomy because of severe adhesion between her uterus and the neobladder if she had a Cesarean section.DiscussionIn a pregnant myelomeningocele patient with a VP shunt, neurosurgeons are expected to manage the VP shunt during pregnancy and delivery. The possible types of delivery style and the best options based on the neurological deficit should be discussed together with a medical team.

Successful Lung Transplantation Using a Deceased Donor Mechanically Ventilated for Ten Months

A successful outcome after lung transplant was achieved using lungs donated from a teenage boy who underwent prolonged mechanical ventilation. The donor experienced hypoxic brain damage and was declared brain dead 324 days after tracheal intubation. At the time of referral, the donors lungs revealed diffuse radiologic infiltration and atelectasis but excellent function, with a PaO2/FiO2 ratio of 450. The lungs were transplanted to a 10-year-old girl with bronchiolitis obliterans. She developed grade 2 primary graft dysfunction, but recovered quickly. She is doing well and has not experienced any other critical adverse events 12 months after lung transplantation.