CONTROL OF END-TIDAL HALOTHANE CONCENTRATION: Part A: Anaesthesia Breathing System and Feedback Control of Gas Delivery

Conventional anaesthetic breathing systems are not designed to control end-tidal gas concentrations, nor can they be used to measure accurately the uptake of oxygen or of anaesthetic agent. We built and tested a leak-tight closed-loop anaesthetic breathing system with low solubility to volatile anaesthetic agents and with efficient gas mixing. The system included a water-sealed spirometer, a small carbon dioxide absorber, a coaxial tube to the patient a circulating pump and feedback controllers for system volume and anaesthetic concentration. Feedback control was implemented to adjust and control automatically the end-tidal anaesthetic concentration and the volume of the system with oxygen supplied through a mass flow controller and with halothane supplied by a titrating syringe. Controller gains, as a function of body weight, were found using a nine-compartment tissue uptake model. Stability was maintained with ±50% changes in alveolar ventilation and cardiac output. During subsequent investigations in an animal model, arterial, mixed venous and cerebral venous blood halothane concentrations were measured to show that the feedback-controlled halothane induction was optimized. We conclude that feedback control appears to be clinically applicable for adjusting the end-tidal Concentration and system volume to provide a rapid and optimized induction of anaesthesi

CONTROL OF END-TIDAL HALOTHANE CONCENTRATION: Part B: Verification in Dogs

Conventional anaesthetic techniques do not allow for the automatic control of end-tidal halothane concentration and, therefore, brain concentration cannot be predicted. In this study, eight dogs were ventilated with halothane in oxygen using a new closed-loop anaesthetic breathing system which provided a constant end-tidal concentration. During the first 60 min the end-tidal concentration was maintained at 0.87 vol% (1 MAC). Then followed 60 min of halothane wash-out and a further 120-min period of halothane at 1.74 vol% (2 MAC). Halothane concentrations were measured in the inspired and expired air, and in the arterial, cerebral venous and mixed venous blood. Haemodynamic and respiratory variables were measured. The system reached 95% of the target end-tidal concentration within 6 min without over-shooting. After 2 h of wash-in, significant gradients still persisted between end-tidal, arterial and cerebral venous blood concentrations. Measured uptake differed from theoretically calculated uptake by 18.3-57.6%, depending on the model used. Measured arterial and cerebral venous concentrations differed from theoretically calculated values by 7% and 17.5%, respectively. It was shown that the required end-tidal concentrations can be obtained rapidly and accurately, and that brain tissue concentrations can be predicted within certain limit

Evaluation of a Graphical Anesthesia Drug Display for Space Travel

As the frequency and duration of space travel increase, the potential need for emergency medical care in space grows, and with it the need for patient monitoring devices supporting therapeutic treatment. Providing emergency care to an injured astronaut may necessitate immediate surgery. During such events, the timely administration of anesthetic agents will need to be performed by someone who is not a formally trained anesthesiologist. The availability of usable real-time displays of intravenous anesthetic concentrations and effects could significantly enhance intraoperative clinical decision-making both in space and on earth. The effectiveness of the real-time anesthesia display on the management of total intravenous anesthesia was determined by 31 anesthesiologists participating in a simulation study. In the presence of the anesthesia drug display, clinicians maintained physiologic indicators such as blood pressure and heart rate closer to baseline levels. Participants also reported an increase in perceived performance when using the drug display. The results indicate that surgeries on earth and in orbit would benefit from the implementation of this display

Pulmonary Metaphor Design and Anesthesia Simulation Testing

Medical decision making is a crucial process to successfully treat a critical medical emergency. During an unexpected medical event, astronauts, like anesthesiologists, must react quickly in a complex environment. Tools, such as the pulmonary metaphor display, were created to aid the medical caregiver\u27s decision making process. The pulmonary metaphor display is designed to help the caregiver collect and integrate pulmonary data to provide a more accurate, quicker diagnosis and treatment. The following outline anesthesiology simulation study will provide the data to prove that the pulmonary metaphor display is beneficial to medical decision making

An Iceberg Model for Improving Mathematical Understanding and Mindset or Disposition: An Individualized Summer Intervention Program

This study describes 3 years of mathematics intervention research examining the effectiveness of a summer individualized tutoring program for rising fourth-, fifth-, and sixth-grade students with low mathematics achievement. Based on an iceberg model of learning, an instructional framework was developed that identified and targeted students’ specific mathematical needs, developed number sense flexibility, and encouraged positive mindset or disposition. Students participated in eight one-on-one tutoring intervention sessions. Pre- and posttest results indicated that students made moderate to large effect size gains in each targeted area of instruction. Additionally, the intervention proved to produce positive results across three different contexts for delivering tutoring instruction

Potassium channel gene mutations rarely cause atrial fibrillation

BACKGROUND: Mutations in several potassium channel subunits have been associated with rare forms of atrial fibrillation. In order to explore the role of potassium channels in inherited typical forms of the arrhythmia, we have screened a cohort of patients from a referral clinic for mutations in the channel subunit genes implicated in the arrhythmia. We sought to determine if mutations in KCNJ2 and KCNE1-5 are a common cause of atrial fibrillation. METHODS: Serial patients with lone atrial fibrillation or atrial fibrillation with hypertension were enrolled between June 1, 2001 and January 6, 2005. Each patient underwent a standardized interview and physical examination. An electrocardiogram, echocardiogram and blood sample for genetic analysis were also obtained. Patients with a family history of AF were screened for mutations in KCNJ2 and KCNE1-5 using automated sequencing. RESULTS: 96 patients with familial atrial fibrillation were enrolled. Eighty-three patients had lone atrial fibrillation and 13 had atrial fibrillation and hypertension. Patients had a mean age of 56 years at enrollment and 46 years at onset of atrial fibrillation. Eighty-one percent of patients had paroxysmal atrial fibrillation at enrollment. Unlike patients with an activating mutation in KCNQ1, the patients had a normal QT(c )interval with a mean of 412 ± 42 ms. Echocardiography revealed a normal mean ejection fraction of 62.0 ± 7.2 % and mean left atrial dimension of 39.9 ± 7.0 mm. A number of common polymorphisms in KCNJ2 and KCNE1-5 were identified, but no mutations were detected. CONCLUSION: Mutations in KCNJ2 and KCNE1-5 rarely cause typical atrial fibrillation in a referral clinic population

VEGF regulates local inhibitory complement proteins in the eye and kidney

10.1172/JCI86418Journal of Clinical Investigation1271199-21

Selective vulnerability of the intermediate retinal capillary plexus precedes retinal ganglion cell loss in ocular hypertension

Introduction: Glaucoma, a disease of retinal ganglion cell (RGC) injury and potentially devastating vision loss, is associated with both ocular hypertension (OHT) and reduced ocular blood flow. However, the relationship between OHT and retinal capillary architecture is not well understood. In this project, we studied microvasculature damage in mice exposed to mild levels of induced OHT.Methods: Mild OHT was induced with the microbead model for 2 weeks. At this time point, some retinas were immunostained with CD31 (endothelium), Collagen IV (basement membrane), and RBPMS (RGCs) for z-stack confocal microscopy. We processed these confocal images to distinguish the three retinal capillary plexi (superficial, intermediate, and deep). We manually counted RGC density, analyzed vascular complexity, and identified topographical and spatial vascular features of the retinal capillaries using a combination of novel manual and automated workflows. Other retinas were dissociated and immunopanned to isolate RGCs and amacrine cells (ACs) for hypoxia gene array analysis.Results: RGC counts were normal but there was decreased overall retinal capillary complexity. This reduced complexity could be explained by abnormalities in the intermediate retinal capillary plexus (IRCP) that spared the other plexi. Capillary junction density, vessel length, and vascular area were all significantly reduced, and the number of acellular capillaries was dramatically increased. ACs, which share a neurovascular unit (NVU) with the IRCP, displayed a marked increase in the relative expression of many hypoxia-related genes compared to RGCs from the same preparations.Discussion: We have discovered a rapidly occurring, IRCP-specific, OHT-induced vascular phenotype that precedes RGC loss. AC/IRCP NVU dysfunction may be a mechanistic link for early vascular remodeling in glaucoma