Neural network imaging to characterize brain injury in cardiac procedures: the emerging utility of connectomics.

Cognitive dysfunction is a poorly understood but potentially devastating complication of cardiac surgery. Clinically meaningful assessment of cognitive changes after surgery is problematic because of the absence of a means to obtain reproducible, objective, and quantitative measures of the neural disturbances that cause altered brain function. By using both structural and functional connectivity magnetic resonance imaging data to construct a map of the inter-regional connections within the brain, connectomics has the potential to increase the specificity and sensitivity of perioperative neurological assessment, permitting rational individualized assessment and improvement of surgical techniques.

Anaortic, total-arterial, off-pump coronary artery bypass surgery: why bother?

Coronary artery bypass grafting (CABG) remains the standard of care for multi-vessel coronary disease. However, the increased rate of peri-operative stroke reported after surgery compared to percutaneous coronary intervention (PCI) remains of concern. Anaortic, total-arterial, off-pump coronary artery bypass (OPCAB) grafting is a technique that offers the main advantages of surgical revascularisation with a rate of stroke that is equivalent to that of PCI. Some recent trials comparing conventional on-pump CABG with OPCAB have questioned the efficacy of the off-pump technique - these are most often performed with manipulation of the ascending aorta. We review the potential benefits of the anaortic, total-arterial OPCAB technique to explain why it is being employed by an increasing number of surgeons.

Conformational activation of CD11b without shedding of L-selectin on circulating human neutrophils.

Membrane-activated complex 1 (Mac-1; CD11b/CD18) is a beta(2) integrin implicated in the pathophysiology of neutrophil-mediated tissue injury whose functional capacity is determined by stimulus-induced conformational activation rather than up-regulation. Mac-1 up-regulation and conformational activation, together with shedding of L-selectin, are reported after in vitro neutrophil activation. However, their regulation on circulating human neutrophils during acute inflammation is unclear. Using flow cytometry, we investigated neutrophil expression of Mac-1, its activation-reporter neo-epitope CBRM1/5, and L-selectin during the inflammatory stimulus of cardiac surgery. A subpopulation of circulating neutrophils expressed CBRM1/5 (CBRM1/5+) under basal conditions (6.28+/-2.59%) and was persistently expanded (9.95+/-4.0%-15.2+/-4.2%; P<0.0001) peri-operatively, whereas total CD11b expression increased only transiently, intra-operatively. L-selectin expression was unchanged on CBRM1/5+ neutrophils, and soluble L-selectin levels decreased intra-operatively (P<0.01), indicating that L-selectin was not shed. Increased CBRM1/5 expression without L-selectin loss or CD11b up-regulation was replicated in vitro by neutrophil stimulation with IL-8, C3a, and platelet-activating factor. Heparin, a known CD11b ligand, which is administered during cardiac surgery, markedly reduced neutrophil expression of conformationally active CD11b in vivo and in vitro, identifying a potential mechanism for its anti-inflammatory properties. We conclude that conformational activation of CD11b occurs on circulating neutrophils in vivo and can occur in the absence of CD11b up-regulation and L-selectin shedding.

Retrieval of critically ill adults using extracorporeal membrane oxygenation: the nine-year experience in New South Wales.

In New South Wales, a coordinated extracorporeal membrane oxygenation (ECMO) retrieval program has been in operation since 2007. This study describes the characteristics and outcomes of patients transported by this service. We performed a retrospective observational study and included patients who were transported on ECMO to either of two adult tertiary referral hospitals in Sydney, New South Wales, between February 28, 2007 and February 29, 2016. One hundred and sixty-four ECMO-facilitated transports occurred, involving 160 patients. Of these, 118 patients (74%) were treated with veno-venous (VV) ECMO and 42 patients (26%) were treated with veno-arterial ECMO. The mean (standard deviation, SD) age was 40.4 (15.0) years. Seventy-seven transports (47%) occurred within metropolitan Sydney, 52 (32%) were from rural or regional areas within NSW, 17 (10%) were interstate transfers and 18 (11%) were international transfers. Transfers were by road (58%), fixed wing aircraft (27%) or helicopter (15%). No deaths occurred during transport. The median (interquartile range) duration of ECMO treatment was 8.9 (5.2-15.3) days. One hundred and nineteen patients (74%) were successfully weaned from ECMO and 109 (68%) survived to hospital discharge or transfer. In patients treated with VV ECMO, age, sequential organ failure assessment score, pre-existing immunosuppressive disease, pre-existing diabetes, renal failure requiring dialysis and failed prone positioning prior to ECMO were independently associated with increased mortality. ECMO-facilitated patient transport is feasible, safe, and results in acceptable short-term outcomes. The NSW ECMO Retrieval Service provides specialised support to patients with severe respiratory and cardiovascular illness, who may otherwise be too unstable to undergo inter-hospital transfer to access advanced cardiovascular and critical care services.

Elective use of veno-venous extracorporeal membrane oxygenation and high-flow nasal oxygen for resection of subtotal malignant distal airway obstruction.

We describe the use of peripheral veno-venous extracorporeal membrane oxygenation (VV ECMO) and high-flow nasal oxygen as procedural support in a patient undergoing debulking of a malignant tumour of the lower airway. Due to the significant risk of complete airway obstruction upon induction of anaesthesia, ECMO was established while the patient was awake, and was maintained without systemic anticoagulation to minimise the risk of intraoperative bleeding. This case illustrates that ECMO support with high-flow nasal oxygen can be considered as part of the algorithm for airway management during surgery for subtotal lower airway obstruction, as it may be the only viable option for maintaining adequate gas exchange.

Flow mixing during peripheral veno-arterial extra corporeal membrane oxygenation - A simulation study.

Peripheral veno-arterial extra-corporeal membrane oxygenation (ECMO) is an artificial circulation that supports patients with severe cardiac and respiratory failure. Differential hypoxia during ECMO support has been reported, and it has been suggested that it is due to the mixing of well-perfused retrograde ECMO flow and poorly-perfused antegrade left ventricle (LV) flow in the aorta. This study aims to quantify the relationship between ECMO support level and location of the mixing zone (MZ) of the ECMO and LV flows. Steady-state and transient computational fluid dynamics (CFD) simulations were performed using a patient-specific geometrical model of the aorta. A range of ECMO support levels (from 5% to 95% of total cardiac output) were evaluated. For ECMO support levels above 70%, the MZ was located in the aortic arch, resulting in perfusion of the arch branches with poorly perfused LV flow. The MZ location was stable over the cardiac cycle for high ECMO flows (>70%), but moved 5cm between systole and diastole for ECMO support level of 60%. This CFD approach has potential to improve individual patient care and ECMO design.

The expanding role of extracorporeal membrane oxygenation retrieval services in Australia.

Herein we detail the cases of three patients transferred on veno-arterial extracorporeal membrane oxygenation (VA ECMO) from a tertiary referral hospital to an ECMO centre. We highlight the benefits of such a transfer and offer this as a model of care for unwell patients likely to require a prolonged period of ECMO support.

Prediction of cyclosporine clearance in liver transplant recipients by the use of midazolam as a cytochrome P450 3A probe.

BACKGROUND: Interindividual differences in the kinetics of cyclosporine (INN, ciclosporin) result in part from variations in the activity of cytochrome P450 3A (CYP3A). The biotransformation of midazolam to 1'-hydroxymidazolam is also catalyzed by CYP3A. The objective of this study was to examine the usefulness of midazolam as a CYP3A probe to predict cyclosporine clearance. METHODS: Twenty-six stable liver transplant recipients receiving immunosuppressive therapy with oral cyclosporine (Neoral) were studied. Midazolam (0.015 mg/kg) was administered intravenously and a blood sample was obtained 1 hour later. The plasma concentration of midazolam and 1'-hydroxymidazolam was measured by gas chromatography-mass spectrometry. Blood concentration of cyclosporine was measured by a fluorescence polarization assay. Cyclosporine clearance was calculated as daily dose divided by trough level. RESULTS: There were large interindividual variations in cyclosporine clearance and in midazolam metabolism. Cyclosporine blood levels correlated poorly with dose (r = -0.016). However, there was a significant correlation between cyclosporine clearance and the plasma concentration of 1'-hydroxymidazolam (r = 0.559; P < .001) or the midazolam/1'-hydroxymidazolam plasma concentration ratio (r = 0.668; P < .001). CONCLUSION: Heterogeneity in CYP3A activity contributes to interpatient differences in cyclosporine dosage requirements after liver transplantation. Midazolam metabolism correlated with cyclosporine clearance, but it accounted for only about 40% of the variability in the apparent oral clearance of cyclosporine and this relationship is not tight enough to be useful in the prediction of cyclosporine dosage requirements in the clinical setting.

Augmentation of vascular endothelial barrier function by heparin and low molecular weight heparin.

Glycosaminoglycans (GAGs) are an important component of endothelial barrier function. Early passage human umbilical vein endothelial cells were grown to confluence on transparent micropore filters and barrier function assessed as transendothelial electrical resistance (TEER) and permeability to albumin and sucrose. Unfractionated heparin and the LMW heparin Clexane decreased endothelial permeability to both sucrose and albumin and increased TEER. Chondroitin 6-sulphate also augmented barrier function, but other GAGs had no effect. Interleukin-1 increased permeability to albumin and sucrose and decreased TEER. Although heparin attenuated the effect of IL-1 on TEER and sucrose permeability, it could not restore the barrier to albumin transfer. Denuded endothelial matrix presented a negligible barrier, which was not enhanced by heparin. When sulphation of endogenous GAGs was inhibited by chlorate, barrier function was compromised and was not restored by exogenous heparin. Thus heparin enhances the barrier function of resting endothelium, but cannot completely overcome the increased permeability resulting from exposure to IL-1 or substitute for endogenous GAGs.

Two new peptides to improve post-operative gastric ileus in dog.

Peptides can influence gastrointestinal motility, and from data obtained earlier in rats, we hypothesized that MTL-RP/Ghrelin, as well as CGRP receptor antagonist 8-37, could improve gastric post-operative ileus in dog. Dogs submitted to laparotomy were perfused with or saline or CGRP 8-37 or MTL-RP/Ghrelin on days 1-4 post-operatively while gastric emptying was estimated by measuring the postprandial increase in plasma acetaminophen ingested with a meal. As expected, in saline-treated animals the gastric emptying function was impaired post-operatively. The total amount of acetaminophen emptied (AUC over 150 min) on post-operative days 1-4 reached respectively 31+/-5%, 65+/-8%, 60+/-8% and 62+/-8% of the normal emptying capacity. CGRP antagonist increased the total emptying of acetaminophen to 52+/-5% on day 1, 95+/-2% on day 2 and 103+/-3% (P<0.05) on day 3. The delayed emptying of acetaminophen seen post-operatively in saline-treated animals could be completely reversed by MTL-RP/Ghrelin (P<0.01) whether it was given at 100 microg/kg on day 2 (102+/-7% of the normal emptying capacity), 4 microg/kg on day 3 (106+/-7%) or 20 microg/kg on day 4 (132+/-8%). As found earlier in rodents, CGRP receptor antagonist 8-37 as well as MTL-RP/Ghrelin are potent prokinetics to improve post-operative gastric ileus in dog.

Composite graft replacement of the aortic root after previous cardiac surgery: a 20-year experience.

BACKGROUND: An aging population and prolonged survival of patients after cardiac operations has meant that composite aortic root replacement after previous cardiac operation is being performed with increasing frequency. METHODS: From January 1979 to July 1999, 32 patients underwent "reoperative" composite replacement of the aortic root at our institution. Previous operations were 16 aortic valve replacement, 9 coronary artery bypass grafting, 5 repair aortic dissection, and 7 others. Indications for operation included ascending aortic aneurysm in 16 patients, ascending aortic dissections in 10 patients, and other in 6 patients. RESULTS: The unit elective mortality was 3 of 26 (11.5%). One surgeon's elective mortality was 1 of 22 (4.6%). The unit emergent mortality was 6 of 6 (100%). There has been one late death. Morbidity was low. CONCLUSIONS: Reoperative aortic root replacement is a technically demanding procedure, but expertise in the area achieves low elective mortality. Consideration should be given to aortic root replacement at the initial procedure. Close follow-up of postcardiac operation patients is necessary to proceed with elective aortic root replacement if indicated. Emergent presentation in the reoperative setting has a very poor prognosis.

EMIT antiepileptic drug assays adapted to an Abbott-VP Analyzer and compared with a gas-chromatographic procedure.

The Abbott-VP Bichromatic Analyzer was used for the determination of four antiepileptic drugs (phenobarbital, phenytoin, carbamazepine, primidone) in serum by means of a modified EMIT homogeneous enzyme immunoassay procedure. The main objective of the work was to examine the precision and the accuracy of the results obtained with this system and its cost effectiveness in comparison to the manual method. Day-to-day precision for all four drugs is excellent with coefficients of variation averaging around 5% in the therapeutic range of concentrations. Results for sera analyzed by this procedure and by a gas chromatographic method do not show any significant difference for phenytoin and phenobarbital. There are however slight differences between the two methods for carbamazepine and primidone. These small differences do not modify significantly the clinical interpretation of the results. The procedure is simple and rapid, and requires only one third of the reagents needed in the recommended manual EMIT procedure using the Gilford Stasar III, thus greatly reducing the operation costs.

Comparison of three methods for the elimination of the labile fraction of HbA1.

Three different procedures were used to remove the "labile" fraction in the chromatographic quantitation of hemoglobin A1 (HbA1) by a minicolumn assay: (a) preincubation of the erythrocytes at 37 degrees C in isotonic saline for 4 h, (b) preincubation in the presence of semicarbazide-aniline at pH 5.0 for 30 min, and (c) preincubation in acetate buffer at pH 5.5 for 30 min. The results show that the two latter methods are not only more rapid but are also slightly more effective. The use of the acetate buffer is preferred because this reagent is more easily prepared and also because the presence of semicarbazide and aniline did not markedly accelerate the dissociation of Hb pre-A1c at pH 5.5. The procedure relies simply on the greater instability of Schiff base in acidic solution. There is a significant correlation between the "labile" fraction and the plasma glucose concentration at sampling time. The results support the view that the elimination of the "labile" precursor is essential to preserve the utility of the assay.

Intra-aortic balloon counterpulsation for cardiogenic shock due to cardiac contusion in an elderly trauma patient.

Blunt thoracic trauma may cause cardiac contusion and cardiogenic shock resistant to inotropic support. The use of intra-aortic balloon counterpulsation (IABCP) as a mechanical means of augmenting cardiac function following cardiac contusion is rare with case reports largely limited to its use in young trauma patients. We describe the case of a frail, 80-year-old woman who suffered cardiac contusion in a motor vehicle crash. She developed cardiogenic shock with electrocardiograph changes, elevated troponin T and severe global dysfunction on echocardiography. She was successfully managed with invasive monitoring, inotropic support and IABCP. This case provides support for aggressive resuscitation even in the very elderly as recovery from severe cardiac contusion may be possible.

Coronary artery bypass grafting (CABG) after initially successful percutaneous transluminal coronary angioplasty (PTCA): a review of 17 years experience.

OBJECTIVE: Patients who undergo successful percutaneous transluminal coronary angioplasty (PTCA) may subsequently require operative myocardial revascularization. This review examines whether prior successful PTCA alters outcomes following subsequent coronary artery bypass grafting (CABG). The costs of interventional cardiology procedures and definitive surgery were also examined. METHODS: From January 1981 through December 1997, 361 patients underwent CABG following initially successful PTCA (interval group). This group was compared with 11,909 patients who underwent CABG as the primary intervention for coronary artery disease (control group). RESULTS: The average time interval to CABG following initial PTCA was 13.7 months. The post-CABG myocardial infarction rate was 4% for patients in the interval group and 3% for patients in the control group. The 30-day mortality was similar for both patient groups (2%). For the interval group, the average cost of total interventional management was 24,220 dollars per patient. This included average costs of 13,873 dollars for CABG and 10,347 dollars for all preoperative interventional cardiology procedures. CONCLUSION: There is little doubt that PTCA procedures may provide successful myocardial revascularization. However, these procedures often need to be repeated over time and may serve only to delay coronary surgery, at substantial financial and personal cost.

Harmful effects of near-ultraviolet radiation used for polymerization of a sealant and a composite resin.

An electronic device used to polymerize a sealant and a composite resin has been found to emit 365-nanometer radiation at levels sufficient to kill the bacterium Escherichia coli rapidly (greater than 14,000 ergs per square millimeter per second). Because of the absence of shielding on the probe, significant amounts of energy (up to 45% of that at the probe tip) were measured at the sides of the probe. These findings--supported by the well-documented findings of biological damage caused by near-ultraviolet radiation, including skin cancer, damage to the lens of the eye, and mutagenic effects--suggest that clinicians take appropriate precautions to avoid potential hazards to themselves and their patients.