Primary Human Lung Alveolus-on-a-chip Model of Intravascular Thrombosis for Assessment of Therapeutics.

Pulmonary thrombosis is a significant cause of patient mortality; however, there are no effective in vitro models of thrombi formation in human lung microvessels that could also assess therapeutics and toxicology of antithrombotic drugs. Here, we show that a microfluidic lung alveolus-on-a-chip lined by human primary alveolar epithelium interfaced with endothelium and cultured under flowing whole blood can be used to perform quantitative analysis of organ-level contributions to inflammation-induced thrombosis. This microfluidic chip recapitulates in vivo responses, including platelet-endothelial dynamics and revealed that lipopolysaccharide (LPS) endotoxin indirectly stimulates intravascular thrombosis by activating the alveolar epithelium, rather than acting directly on endothelium. This model is also used to analyze inhibition of endothelial activation and thrombosis due to a protease activated receptor-1 (PAR-1) antagonist, demonstrating its ability to dissect complex responses and identify antithrombotic therapeutics. Thus, this methodology offers a new approach to study human pathophysiology of pulmonary thrombosis and advance drug development.

Diabetes attenuates the minimum anaesthetic concentration (MAC) and MAC-blocking adrenergic response reducing actions of clonidine in rats.

BACKGROUND: It is well known that clonidine, an alpha2 agonist, reduces anaesthetic requirement and attenuates haemodynamic responses against noxious stimuli. However, the diabetic state is known to affect several functions of alpha2 adrenoceptors. We investigated the effects of streptozotocin (STZ)-induced diabetes mellitus (DM) on these beneficial actions of clonidine in halothane-anaesthetized rats. METHODS: The rats were randomly assigned to one of three groups: diabetes (n=24, induced by 50 mg x kg(-1) IV STZ), diabetes treated with insulin (n=24), or control (n=24). We evaluated the effects of clonidine on minimum anaesthetic concentration (MAC) and minimum concentration of halothane needed to suppress cardiovascular responses evoked by a noxious stimulus (MAC-blocking adrenergic responses: MAC-BAR) in each group. MAC and MAC-BAR of halothane were determined by the tail clamp method. MAC-BAR was defined as the MAC which attenuated haemodynamic responses within 10% following the tail clamp. RESULTS: The diabetic state decreased MAC of halothane by approximately 10%, while MAC-BAR of halothane had been little affected. In the diabetes group, MAC reducing action of clonidine (30 and 100 microg x kg(-1), IV) was completely abolished and MAC-BAR reducing action of clonidine was partially reduced (30 but not 100 microg x kg(-1), IV). Insulin treatment preserved these actions of clonidine. CONCLUSION: It is suggested that the diabetic state attenuates the beneficial actions of clonidine and that insulin treatment of diabetes preserves these actions of clonidine.

[Transthoracic radical esophagectomy after extensive myocardial infarction].

We experienced the perioperative management of a 47 year-old patient for transthoracic esophagectomy after myocardial infarction. He was admitted to our hospital and diagnosed as having advanced esophageal cancer and he developed extensive myocardial infarction on the day of admission. Revascularization with PTCA was not successful, and circulatory support (IABP) was required for 7 days. Complete occlusion of the right coronary artery and extensive akynesis of the right ventricle occurred. Two months later, transthoracic esophagectomy was scheduled. The patient was monitored with pulmonary artery catheter during perioperative period. The postoperative course was uneventful and the patient was discharged 64 th day after the operation.

[Monitoring of cerebral oxygenation status with near-infrared spectroscopy during inferior vena caval reconstruction under extracorporeal circulation].

We report two cases of anesthetic management with monitoring by near-infrared spectroscopy in patients with renal cell carcinoma and with adrenal cortical carcinoma, who had tumor thrombus invading into the inferior vena cava. In inferior vena caval reconstruction, extracorporeal circulation such as veno-veno bypass or cardiopulmonary bypass is frequently required. The hemodynamic unstability under extracorporeal circulation may lead to severe cerebral damage, especially in elderly patients. We monitored cerebral oxygenation state during reconstruction of the vena cava by near-infrared spectroscopy. One patient underwent surgery with veno-veno bypass and another patient with partial cardiopulmonary bypass. Oxygenated hemoglobin decreased during extracorporeal circulation, especially during the use of partial cardiopulmonary bypass compared with veno-veno bypass. However, these decreased oxygenated hemoglobin was restored rapidly at the end of extracorporeal circulation. Both patients showed no post-operative neurological complication. We concluded that near-infrared spectroscopy, which is continuous and non-invasive monitoring of cerebral oxygenation status, is one of the useful monitors during extracorporeal circulation.

A study of 13 patients with gastric tube in place after esophageal resection: use of omeprazole to decrease gastric acidity and volume.

STUDY OBJECTIVE: To investigate whether oral omeprazole 20 mg decreases the risk of aspiration pneumonia in patients with gastric tube reconstruction. DESIGN: Consecutive study. SETTING: Operation room of cancer center. PATIENTS: Thirteen patients with gastric tube reconstruction for esophageal cancer. INTERVENTIONS: Oral omeprazole 20 mg was given the night before surgery. A rapid-sequence induction with cricoid pressure was employed for induction of anesthesia. After tracheal intubation, a nasogastric catheter was inserted into the gastric tube and the contents were aspirated. MEASUREMENTS AND MAIN RESULTS: The pH and volume of the gastric contents were measured. The pH and volume of the gastric tube contents were 4.5 +/- 1.6 (range from 2.5 to 7.0) and 9.5 +/- 10.2 mL (range from 0 to 30 mL), respectively. Food residue was recognized in nine patients. There was no patient with a pH below 2.5 and a volume of 25 mL or greater. CONCLUSIONS: Omeprazole 20 mg decreased the acidity and volume of the gastric tube contents and reduced the risk of aspiration pneumonia in patients with a gastric tube in place.

[Usefulness of a simple expiratory gas monitor during sedation under spinal anesthesia].

We introduce a simple expiratory gas monitor during sedation under spinal anesthesia. A small extension tube for infusion used as a gas sampling line is placed in the nasal vestibule. It is necessary to make it sure that the point of the tube should not contact with the mucous membrane of the nose. Our method needs no special equipments such as Capnoxygen or Nazorcap, but a cheap extension tube available in any operating room. Therefore this is a simple method. Expiratory gas monitor can detect apnea early, airway obstruction and stenosis and predict PaCO2 during sedation. The change of fractional concentration of oxygen in inspired gas predicts the change of tidal volume. Increase in the former reflects a decrease in the latter under the administration of oxygen. It is possible to evaluate whether sedation became steady with analysis of respiratory pattern. However, nasal discharge may interrupt monitoring expiratory gas. Our simple method to monitor expiratory gas is useful during sedation under regional anesthesia.

Premedication modifies the quality of sedation with propofol during regional anesthesia.

PURPOSE: To determine the effects of diazepam or clonidine on the quality of sedation with propofol during regional anesthesia. METHODS: In a prospective randomised, controlled, double-blinded study, 60 patients undergoing elective gynecological surgery were studied. They were given premedication with 0.15-mg clonidine (Group-CL, n=20), 5-mg diazepam (Group-DZ, n = 20), or placebo (Group-P, n = 20) po. After spinal anesthesia was established, sedation was provided with propofol and controlled using a five-point sedation score at 3, "eyes closed but rousable to command", and 4, "eyes closed but rousable to mild physical stimulation". During sedation, blinded anesthesiologist recorded occurrence of complications. At two hours after end of sedation, patients were asked if they had intraoperative dream and memory. RESULTS: The loading dose, steady-state infusion rate, and overall mean infusion rate in Group-CL were 0.80 mg x kg(-1), 2.35 mg x kg(-1) x hr(-1) and 2.89 mg x kg(-1) x hr(-1), compared with 0.97 mg x kg(-1), 3.13 mg x kg(-1) x hr(-1) and 3.59 mg x kg(-1) x hr(-1) in Group-DZ, and 1.38 mg x kg(-1), 4.10 mg x kg(-1) x hr(-1) and 4.36 mg x kg(-1) x hr(-1) in Group-P, respectively. Indices of both Group-CL (P < 0.001) and Group-DZ (P < 0.05) were smaller than those of Group-P Moreover, clonidine reduced the incidence of uncontrolled movement (P < 0.01), while diazepam reduced the incidence of intraoperative memory and increased the incidence of dream (P < 0.05). Premedication did not affect the incidence of other complications. CONCLUSION: Both premedicants reduced propofol requirements and exerted beneficial effects on the incidence of some complications during sedation with propofol as an adjunct to regional anesthesia.

Arrhythmogenic effect of hypercapnia in ducks anesthetized with halothane.

OBJECTIVE: To determine effects of hypercapnia on arrhythmias in ducks anesthetized with halothane. ANIMALS: 12 ducks, 6 to 8 months old, weighing 1.1 to 1.6 kg. PROCEDURES: Each duck was anesthetized with a 1.5% mixture of halothane in oxygen, and anesthetic depth was stabilized during a 20-minute period. We added CO2 to the inspired oxygen to produce CO2 partial pressures of 40, 60, and 80 mm Hg in the inspired gas mixture.The CO2 partial pressure was increased in a stepwise manner. When arrhythmias were not evident during inhalation of the gas mixture at a specific CO2 partial pressure, the CO2 partial pressure was maintained for 10 minutes before a sample was collected for blood gas analysis. When arrhythmias were detected, a sample for blood gas analysis was collected after the CO2 partial pressure was maintained for at least 2 minutes, and CO2 inhalation then was terminated. RESULTS: During the stabilization period, PaCO2 (mean +/- SD) was 33 +/- 5 mm Hg,and arrhythmias were not detected. In 6 ducks, arrhythmias such as unifocal and multifocal premature ventricular contractions developed during inhalation of CO2. Mean PaCO2 at which arrhythmias developed was 67 +/- 12 mm Hg. In 5 of 6 ducks with arrhythmias, the arrhythmias disappeared after CO2 inhalation was terminated. CONCLUSION AND CLINICAL RELEVANCE: Analysis of data from this study indicated that hypercapnia can lead to arrhythmias in ducks during halothane-induced anesthesia. Thus, ventilatory support to maintain normocapnia is important for managing ducks anesthetized with halothane.

[Perioperative management for radical esophagectomy in a patient with polycythemia vera].

We experienced perioperative management of a 75 year-old patient with polycythemia vera (PV) who underwent transthoracic esophagectomy. After treatment for 14 days of ranimustine and hydroxycarbamid, the preoperative hemoglobin, hematocrit values and platelet count were 17.9 g.dl-1, 58% and 54 x 10(4).mm-3 respectively. During the perioperative period, phlebotomy, elastic stockings, intermittent pneumatic compression, infusion of nafamostat, and early extubation (the day of operation) were performed to prevent deep venous thrombosis. The postoperative course was uneventful and the patient was discharged 34 days after the operation.