Post-ischemic Intravenous Administration of Allogeneic Dental Pulp-Derived Neurosphere Cells Ameliorated Outcomes of Severe Forebrain Ischemia in Rats.

BACKGROUND: Transplantation of bone marrow or adipose-derived mesenchymal stem cells (MSCs) for various neurological disorders has yielded promising results in models of focal cerebral ischemia. Dental pulp stem cells (DPSCs) are a type of MSC. In serum-free culture, they can form neurospheres that contain nestin-positive neuronal progenitor cells. We hypothesized that transplantation of dental pulp-derived neurosphere cells would ameliorate outcomes of global cerebral ischemia, the pathophysiology of which is known to resist conventional treatments. We also hypothesized that transplantation of dental pulp-derived cells would provide some neuroprotection in this pathology due to the presence of DPSCs. METHODS: Using adult rats, ischemia was induced by two-vessel occlusion of both carotid arteries in combination with systemic hypotension. Allogeneic dental pulp cells from juvenile rats were cultured in advance in serum-free medium to obtain neurospheres. Dental pulp-derived neurosphere cells or dental pulp-derived cells were intravenously administered at 3 h after ischemic insult, with normal saline as a control. Animals were observed for 14 days after ischemia. Neurological outcome was assessed using the water-maze test and neuromotor test. Histological outcome was measured by counting the percentage of dead neurons in the hippocampal CA1 and CA3 regions. RESULTS: Transplantation of both dental pulp-derived neurosphere cells and dental pulp-derived cells significantly improved survival rate and water-maze test results. Neurosphere cell transplantation was related to significantly better neuromotor test and histological outcomes, as indicated by the reduced percentage of dead neurons in CA1. CONCLUSIONS: Transplantation of dental pulp-derived neurosphere cells ameliorated outcomes of global cerebral ischemia. It was also demonstrated that dental pulp-derived cell administration provided some neuroprotection.

Dexmedetomidine sedation during the nighttime reduced the incidence of postoperative atrial fibrillation in cardiovascular surgery patients after tracheal extubation.

BACKGROUND: Dexmedetomidine (Dex) provides sedation and analgesia by acting on central alpha-2 receptors and is suitable for use after extubation because it has little respiratory depression. Considering the sympathoinhibitory and anxiolytic action of Dex, there is the possibility that Dex might reduce the incidence of atrial fibrillation (AF), which is recognized as a common complication after cardiovascular surgery. We investigated whether the postoperative incidence of AF decreased in patients who received Dex only during the nighttime in the intensive care unit (ICU). METHODS: We retrospectively reviewed ICU charts to determine the incidence of AF and associated factors during the 2-day period after tracheal extubation in patients who underwent cardiovascular surgery from November 2009 to November 2010. The patients were divided into a Dex group (n = 16) and a non-Dex group (n = 29). RESULTS: There were no differences in AF risk factors except for diabetes between the two groups. The average rate of Dex administration was 0.3 ± 0.2 µg/kg/h. There were also no differences between the groups in heart rate during the daytime, central venous pressure, body temperature, white blood cell count, serum level of C-reactive protein, catecholamine use, beta-blocker use, and amount of fentanyl. AF developed in one patient in the Dex group (6.3 %) and ten patients in the non-Dex group (34.5 %) during the observation period, and the difference was significant (p = 0.035). None of the risk factors for AF was significantly associated with AF in univariate analysis; however, multivariate logistic regression analysis using age, Dex use, and beta-blocker use, extracted because their p values in univariate analysis were not exceeding 0.15, showed that Dex use was the only factor associated with the development of AF (p = 0.045, odds ratio 9.75 [1.05-90.8]). CONCLUSIONS: The results suggest that adequate sedation with Dex during the nighttime can reduce the incidence of AF in cardiovascular surgery patients after extubation.

Height and drinking status in relation to risk of anemia in rural adult healthy Japanese men: the Nagasaki Islands study.

BACKGROUND: Several studies have reported that height is inversely associated with risk of cardiovascular disease but positively associated with cancer risk. On the other hand, evidence has been accumulating that anemia reflects poor health and increased vulnerability to poor outcomes in older persons. Moreover, alcohol consumption has also been reported to be associated with mortality. However, no studies have reported on a possible association between height and risk of anemia in relation to drinking status. METHODS: We conducted a cross-sectional study of 1287 men aged 40-89 years undergoing general health check-ups. RESULTS: Independent from classic cardiovascular risk factors, we found a significant inverse association between height and anemia for non-drinkers and a J-shaped association for drinkers. The multivariable odds ratio (ORs) of an increment of 1 SD (standard deviation) in height (6.68 cm) for anemia for non-drinkers was 0.59 (0.45-0.77). For drinkers, with the second quartile of height (Q2) as the reference group, the multivariable OR of anemia was 2.68(0.90-7.96) (p = 0.075) for the lowest height quartile (Q1), 2.73(0.92-8.08) for the third quartile (Q3) and 4.82(1.65-14.10) for the highest quartile (Q4) (p = 0.004). CONCLUSION: Height was found to be associated with anemia for rural Japanese men and drinking status is likely to affect those associations.

Preischemic Administration of Sevoflurane Does not Exert Dose-dependent Effects on the Outcome of Severe Forebrain Ischemia in Rats.

We previously showed that preischemic administration of high-dose isoflurane worsened the outcome from severe forebrain ischemia in rats. Conversely, high doses of sevoflurane have been reported to improve the outcome from forebrain ischemia when the insult is moderate. To clarify the dose-dependent effects of sevoflurane on severe forebrain ischemia, we performed an outcome study using an identical protocol to that in our previous study with isoflurane. Fasting male Sprague-Dawley rats underwent surgical preparation for forebrain ischemia under halothane anesthesia. Anesthesia was changed to fentanyl/nitrous oxide to eliminate the halothane, after which 30 minutes of 0.5, 1.0, 1.5, 2.0, or 2.5 minimum alveolar concentration sevoflurane was administered. Ten minutes of ischemia was induced by bilateral carotid occlusion plus systemic hypotension, in which cessation of electroencephalographic activity was confirmed. Sevoflurane was discontinued and anesthesia continued with fentanyl/nitrous oxide for an additional 100 minutes. Outcome evaluation at 5 days postischemia included seizure incidence, mortality rate, neuromotor score, and histologic injuries to the cerebral cortex and hippocampal CA1 and CA3. Different doses of sevoflurane did not statistically affect seizure incidence (10.0% to 18.2%), mortality rate (20.0% to 46.7%), cortical damage (mild to moderate degree), or hippocampal CA1 damage (93.7% to 96.7% neuronal necrosis) or CA3 damage (36.3% to 41.7%). Dose-dependent effects of sevoflurane were not observed for any of the outcome variables assessed in this rat model of severe forebrain ischemia.

Superior recovery profiles of propofol-based regimen as compared to isoflurane-based regimen in patients undergoing craniotomy for primary brain tumor excision: a retrospective study.

PURPOSE: Studies comparing the recovery profiles of isoflurane- and propofol-based anesthesia for major intracranial surgery have reported contradictory results. The aim of our study was to clarify the emergence status in both regimens by investigating uniformly managed neuroanesthesia cases. METHODS: The anesthesia database at Yamagata University Hospital covering the period 2002-2005 was retrospectively investigated for adult patients who underwent craniotomy for primary brain tumor excision. General anesthesia was provided by an isoflurane- (ISO group) or propofol-based (PROP group) regimen. Times to extubation and operating room (OR) discharge, perioperative consciousness levels, and perioperative variables were compared. RESULTS: Of the 202 surgeries performed during the study period, 77 and 82 patients were anesthetized with isoflurane and propofol, respectively. Demographic data were comparable between the two groups, although the American Society of Anesthesiology grade was worse in the PROP group. Extubation times [39.5 ± 14.6 min (ISO) vs. 29.5 ± 14.9 min (PROP); P < 0.001] and OR discharge times [67.2 ± 18.0 (ISO) vs. 53.9 ± 17.6 min (PROP); P < 0.001] were significantly shorter in the PROP, with significantly better immediate consciousness levels. The differences in levels of consciousness persisted for several hours postoperatively. PROP patients had significantly higher urine outputs and lower body temperatures during anesthesia. The incidences of shivering, nausea, vomiting, and convulsions were not significantly different between the groups. The time to discharge was similar between the groups. CONCLUSIONS: Propofol was associated with a better recovery profile and neurological condition than isoflurane, as indicated by shorter extubation and OR discharge times and better postoperative consciousness.

Low-dose but not high-dose prostaglandin E(1) improves the histological outcome of severe forebrain ischemia in rats.

PURPOSE: Prostaglandin E(1) (PGE(1)) has been shown to provide short-term neuroprotection against various types of brain ischemia in a dose-dependent manner in mice. However, these findings were obtained from experiments performed without any control over physiological parameters. We performed an outcome study where physiological parameters were controlled in an attempt to confirm the dose-dependant neuroprotective effects of PGE(1). METHODS: A rat model of severe forebrain ischemia was used. Two doses of PGE(1) were administered during the pre-ischemic period, a low dose (LowPG group) and a high dose (HighPG group). Normotension was maintained in the LowPG group, while hypotension was induced in the HighPG group. In separate groups, normal saline (Control) or sodium nitroprusside (SNP) were infused to compare outcomes under similar blood pressure conditions. Histological outcomes in the hippocampal CA1 and entorhinal cortex were evaluated 5 days post-ischemia. RESULTS: HighPG resulted in hyperglycemia. The percentage of dead neurons in the hippocampal CA1 and entorhinal cortex were similar in the Control, SNP, and HighPG groups, the percentage being significantly attenuated in the LowPG group (CA1: Control = 92.8 +/- 2.4%, LowPG = 85.0 +/- 8.5%, HighPG = 95.3 +/- 2.4%, and SNP = 96.4 +/- 0.7%, P < 0.01; entorhinal cortex: Control = 73.8 +/- 4.0%, LowPG = 53.2 +/- 12.3%, HighPG = 72.1 +/- 12.6%, and SNP = 76.5 +/- 4.1%, P < 0.01). CONCLUSION: Pre-ischemic administration of low-dose PGE(1) in rats provided neuroprotection against severe forebrain ischemia. A dose dependency was not observed with PGE(1) dose and outcome.

Alteration of synaptic transmission in the hippocampal-mPFC pathway during extinction trials of context-dependent fear memory in juvenile rat stress models.

The medial prefrontal cortex (mPFC) has been proposed to be essential for extinction of fear memory, but its neural mechanism has been poorly understood. The present study examined whether synaptic transmission in the hippocampal-mPFC pathway is related to extinction of context-dependent fear memory in freely moving rats using electrophysiological approaches combined with behavioral analysis. Population spike amplitude in the mPFC was decreased during the first extinction trial by exposure to contextual fear conditioning. This synaptic inhibition was reversed by repeated extinction trials, accompanied by decreases in fear-related freezing behavior. These results suggest that alteration of synaptic transmission in the hippocampal-mPFC pathway is associated with the extinction processes of context-dependent fear memory. Further experiments were performed to elucidate whether early postnatal stress alters the synaptic response in the mPFC during extinction trials using a juvenile stress model, based on our previous findings that early postnatal stress affects the behavioral response to emotional stress. Adult rats that previously were exposed to five footshocks (FS) (shock intensity, 0.5 mA; intershock interval, 28 seconds; shock duration, 2 seconds) at postnatal day 21 to 25 (week 3; 3W-FS) exhibited impaired reversal of both inhibitory synaptic transmission and freezing behavior induced by repeated extinction trials. The neuronal and behavioral deficits observed in the 3W-FS group were prevented by pretreatment with the serotonin(1A) receptor agonist tandospirone (1 mg/kg, i.p.). These results indicate the possiblity that aversive stress exposure during the third postnatal week impaired extinction processes of context-dependent fear memory. The deficits in extinction observed in the 3W-FS group might be attributable to dysfunction of hippocampal-mPFC neural circuits involving 5-HT(1A) receptor mechanisms.

[Airway and respiratory management for anesthesia in the patients with severe motor and intellectual disabilities].

BACKGROUND: For the management of general anesthesia in the patients with severe motor and intellectual disabilities, airway and respiratory disorders are severe and may cause fatal events. We retrospectively examined these risk factors. METHODS: We assessed adverse airway and respiratory events associated with anesthesia from perioperative and anesthetic records of these patients retrospectively. RESULTS: Forty-one cases (31 were for fundoplication, and 10 were for gastrostomy or jejunostomy) were involved. On anesthetic introduction, in 9 cases tracheal intubation was difficult (failed in 1 case). These and other 4 cases had developed pharyngeal and laryngeal edema. Manual ventilation by facemask was successful in all cases. During the postoperative period, pneumonia (5 cases), pleural effusion (1 case), and apnea (2 cases) occurred unexpectedly. CONCLUSIONS: Patients with severe motor and intellectual disabilities belong to the group with high risk for general anesthesia.

[Perioperative administration of prostaglandin E1 inhibits post-operative serum bilirubin increase and preserves prothrombin time in patients with hepatocellular carcinoma and cirrhosis after laparoscopic microwave coagulation therapy].

BACKGROUND: Laparoscopic microwave coagulation therapy (LMCT) is indicated for the patients with hepatocellular carcinoma, especially when hepatic function is compromised. We retrospectively investigated the effects of perioperative administration of prostaglandin El on post-operative hepatic function in patients receiving LMCT. METHODS: Patients receiving LMCT for the treatment of hepatocellular carcinoma associated with compensated cirrhosis were included. Prostaglandin El administration was commenced after the induction of general anesthesia, with infusion rate at 0.01-0.02 microg x kg(-1) min(-1). Post-operative changes of serum albumin, serum total bilirubin, ALT, AST, lactate dehydrogenase, serum cholinesterase, platelet count, and percent prothrombin time were serially measured in patients with and without prostaglandin E1 administration. RESULTS: Perioperative prostaglandin El administration inhibited post-operative serum bilirubin increase and preserved prothrombin time compared to non-treated group. CONCLUSIONS: It was suggested that prostaglandin El possessed hepatoprotective property in compensated cirrhosis patients with hepatocelluar carcinoma receiving LMCT.

The dose-dependent effects of isoflurane on outcome from severe forebrain ischemia in the rat.

Isoflurane improves outcome against cerebral ischemia in the rat. However, the optimal neuroprotective concentration has not been defined. We examined the effects of different isoflurane concentrations on outcome from severe forebrain ischemia in the rat. Fasted rats were subjected to 0.5, 1.0, 1.5, 2.0, or 2.5 minimum alveolar concentration (MAC) isoflurane during 10 min bilateral carotid occlusion plus systemic hypotension. Each isoflurane concentration was administered only before ischemia. Arterial blood pressure was not pharmacologically manipulated. After ischemia, the anesthetic regimen was changed to fentanyl/nitrous oxide and maintained for 2 h. Pericranial temperature was maintained normothermic during the experiment. Neuromotor score, % dead hippocampal CA1 neurons, and cortical injury were measured 5 days postischemia. Preischemic arterial blood pressure decreased as MAC was increased. Animals administered >1.0 MAC frequently exhibited postischemic seizures resulting in increased mortality. There was no difference among MAC conditions for % dead CA1 neurons (93 approximately 95%). In the cortex, neuronal necrosis was less severe with 0.5 MAC and 1.0 MAC isoflurane relative to >1.0 MAC values. The neuromotor score in the 1.0 MAC isoflurane group was superior to the 2.5 MAC group. Dose-dependent effects of preischemic administration of isoflurane on histologic and behavioral outcome after severe forebrain ischemia were observed. Isoflurane MAC values <1.5 provided superior overall outcome relative to larger isoflurane concentrations.

[Tension pneumothorax manifested after extubation in a patient who underwent total gastrectomy].

A patient developed tension pneumothorax immediately after extubation. The patient was a 53-year-old man, who underwent total gastrectomy under general anesthesia combined with epidural anesthesia. The posterior mediastinum drainage tube was placed near the site of esophago-jejunum anastomosis. Surgeons reported that they might have injured left diaphragmatic pleura during the procedure. Postoperative chest X-ray showed no abnormal findings in the both lung fields. Patient's trachea was extubated when he emerged from anesthesia. However, Spo2 rapidly dropped from 100 to 88. Re-intubation was performed, and positive pressure ventilation was resumed. The Spo2 returned quickly to 100 without hemodynamic change. Auscultation revealed reduced respiratory sound from the left lung. Diagnosis of tension pneumothorax was made from emergency chest X-ray. Patient's respiration improved when chest tube was inserted, but a large amount of air was continuously drained. Air leakage decreased significantly when the mediastinum drainage tube was tentatively occluded. The possible mechanism of the positive pressure in the thoracic cavity was assumed that air was introduced with spontaneous inspiration from the drainage tube, and damaged pleura played as a check valve.

[Perioperative cerebral ischemia and the possibility of neuroprotection by inhalational anesthetics].

Deteriorated neurological outcome is not rare after major surgeries. With aging of the surgical population in Japan, an increasing frequency of perioperative cerebral ischemia is expected. To avoid neurological deterioration after surgery and general anesthesia, especially in high-risk patients, it is important to provide appropriate CNS-oriented anesthesia management. Controlling factors such as cerebral perfusion pressure, arterial blood gases, blood glucose concentration and body temperature may influence brain metabolism and neurological outcome. Inhalational anesthetics may also play an important role in perioperative neurological management, because numerous studies have demonstrated some degree of neuroprotective effect with halothane, sevoflurane, desflurane and isoflurane. Among these inhalational anesthetics, isoflurane has been most extensively studied regarding neuroprotection against cerebral ischemic insult. Although no clinical outcome trials have been performed, both in vivo and in vitro studies have consistently shown that the isoflurane provides neuroprotection. However, it is also suggested that factors such as sympathetic reactivity, brain temperature, anesthetic dosage, timing of anesthetic administration, and co-administration of nitrous oxide might affect the neuroprotective effect of isoflurane.

[A case of postoperative palsy of the brachial plexus and facial nerve caused by use of cervical collar during lung surgery].

We report a case of palsy of the brachial plexus and facial nerve manifested after surgery for lung cancer in a 77-year-old female who also had a retroodontoid pseudotumor. Lobectomy was conducted with the patient in a left lateral position. For the purpose of cervical stabilization, the orthopedic surgeon recommended the use of a cervical collar. During the operation, both of her arms were abducted at nearly 80 degrees. On the second postoperative day, the patient complained of sensory disturbances in the lateral area of her left brachium and forearm, which are innervated by the 5th and 6th cervical spinal nerves from the brachial plexus. She also complained that she could not abduct and flex her left shoulder, and could not flex her left elbow at all. Simultaneously, facial nerve palsy was observed in her left lower lip. During the operation, her shoulders were forcibly rotated internally and were extremely abducted, resulting in a narrowed distance between the lower jaw and the shoulder and stretching of the brachial plexus. Under this situation, the cervical collar was pressing strongly upon her neck and lower jaw, which might have produced the brachial plexus complication and facial nerve palsy.