Implementation of Patient Blood Management in Orthotopic Heart Transplants: A Single Centre Retrospective Observational Review.

BACKGROUND: Blood transfusion in the perioperative cardiothoracic setting has accepted risks including deep sternal wound infection, increased intensive care unit length of stay, lung injury, and cost. It has an immunomodulatory effect which may cause allo-immunisation. This may influence long-term survival through immune-mediated factors. Targeting coagulation defects to reduce unnecessary or inappropriate transfusions may reduce these complications. METHODS: In 2012, an institution-wide patient blood management evidence-based algorithmic bleeding management protocol was implemented at The Prince Charles Hospital, Brisbane, Australia. The benefit of this has been previously reported in our lung transplant and cardiac surgery (excluding transplants) cohorts. This study aimed to investigate the effect of this on our orthotopic heart transplant recipients. RESULTS: After the implementation of the protocol, despite no difference in preoperative haemoglobin levels and higher risk patients (EuroSCORE 20 vs 26; p=0.013), the use of packed red blood cells (13.0 U vs 4.4 U; p=0.046) was significantly lower postoperatively and fresh frozen plasma was significantly lower both intra- and postoperatively (7.4 U vs 0.6 U; p<0.001, and 3.3 U vs 0.6 U; p=0.011 respectively). Concurrently, the use of prothrombin complex concentrate (33% vs 78%; p<0.001) and desmopressin (5% vs 22%; p=0.0028) was significantly higher in the post-protocol group, while there was less use of recombinant factor VIIa (15% vs 4%; p=0.058). Intraoperative units of cryoprecipitate also rose from 0.9 to 2.0 (p=0.006). CONCLUSIONS: We have demonstrated that a targeted patient blood management protocol with point-of-care testing for heart transplant recipients is correlated with fewer blood products used postoperatively, with some increase in haemostatic products and no evidence of increased adverse events.

Inhibition of tumorigenesis driven by different Wnt proteins requires blockade of distinct ligand-binding regions by LRP6 antibodies.

Disregulated Wnt/beta-catenin signaling has been linked to various human diseases, including cancers. Inhibitors of oncogenic Wnt signaling are likely to have a therapeutic effect in cancers. LRP5 and LRP6 are closely related membrane coreceptors for Wnt proteins. Using a phage-display library, we identified anti-LRP6 antibodies that either inhibit or enhance Wnt signaling. Two classes of LRP6 antagonistic antibodies were discovered: one class specifically inhibits Wnt proteins represented by Wnt1, whereas the second class specifically inhibits Wnt proteins represented by Wnt3a. Epitope-mapping experiments indicated that Wnt1 class-specific antibodies bind to the first propeller and Wnt3a class-specific antibodies bind to the third propeller of LRP6, suggesting that Wnt1- and Wnt3a-class proteins interact with distinct LRP6 propeller domains. This conclusion is further supported by the structural functional analysis of LRP5/6 and the finding that the Wnt antagonist Sclerostin interacts with the first propeller of LRP5/6 and preferentially inhibits the Wnt1-class proteins. We also show that Wnt1 or Wnt3a class-specific anti-LRP6 antibodies specifically block growth of MMTV-Wnt1 or MMTV-Wnt3 xenografts in vivo. Therapeutic application of these antibodies could be limited without knowing the type of Wnt proteins expressed in cancers. This is further complicated by our finding that bivalent LRP6 antibodies sensitize cells to the nonblocked class of Wnt proteins. The generation of a biparatopic LRP6 antibody blocks both Wnt1- and Wnt3a-mediated signaling without showing agonistic activity. Our studies provide insights into Wnt-induced LRP5/6 activation and show the potential utility of LRP6 antibodies in Wnt-driven cancer.

Evaluation of the Precision of Kinetic Stem Cell (KSC) Counting for Specific Quantification of Human Mesenchymal Stem Cells in Heterogeneous Tissue Cell Preparations.

Kinetic stem cell (KSC) counting is a recently introduced first technology for quantifying tissue stem cells in vertebrate organ and tissue cell preparations. Previously, effective quantification of the fraction or dosage of tissue stem cells had been largely lacking in stem cell science and medicine. A general method for the quantification of tissue stem cells will accelerate progress in both of these disciplines as well as related industries like drug development. Triplicate samples of human oral alveolar bone cell preparations, which contain mesenchymal stem cells (MSCs), were used to estimate the precision of KSC counting analyses conducted at three independent sites. A high degree of intra-site precision was found, with coefficients of variation for determinations of MSC-specific fractions of 8.9% (p < 0.003), 13% (p < 0.006), and 25% (p < 0.02). The estimates of inter-site precision, 11% (p < 0.0001) and 26% (p < 0.0001), also indicated a high level of precision. Results are also presented to show the ability of KSC counting to define cell subtype-specific kinetics factors responsible for changes in the stem cell fraction during cell culture. The presented findings support the continued development of KSC counting as a new tool for advancing stem cell science and medicine.

Impact of Aortic Atresia After Fontan Operation in Patients With Hypoplastic Left Heart Syndrome.

BACKGROUND: Patients with aortic atresia have the worst prognosis in the spectrum of hypoplastic left heart syndrome. It remains unknown whether patients with aortic atresia continue to do poorly after Fontan operation. This study aimed to determine the association between aortic atresia and atrioventricular valve (AVV) function and clinical outcomes after Fontan operation in patients with hypoplastic left heart syndrome. METHODS: We performed a retrospective study of 1731 patients who survived the Fontan operation from the Australia and New Zealand Fontan Registry between 1975 and 2020. RESULTS: We identified 188 patients with hypoplastic left heart syndrome, including 99 (53%) with aortic atresia. Overall transplant-free survival and freedom from failure of Fontan circulation at 15 years was 91% (95% CI, 86%-96%) and 79% (95% CI, 71%-88%), respectively. The cumulative incidence of AVV operation at 15 years of age for patients with aortic atresia and aortic stenosis was 28% (95% CI, 19%-38%) and 14% (95% CI, 7%-22%; P = .03), respectively. The cumulative incidence of AVV failure (moderate or greater regurgitation or AVV operation) at 15 years of age for patients with aortic atresia and aortic stenosis was 50% (95% CI, 37%-61%) and 30% (95% CI, 19%-42%; P = .01). Patients with AVV failure were at increased risk of having moderately, or worse, decreased systolic ventricular function (odds ratio 6.7; 95% CI, 1.7-33; P = .01) and failure of Fontan circulation (hazard ratio 3.7; 95% CI, 1.5-9.1; P < .01). CONCLUSIONS: In patients with hypoplastic left heart syndrome, there is no significant difference in transplant-free survival after Fontan operation between patients with aortic atresia and patients with aortic stenosis. However, patients with aortic atresia have a much higher burden of AVV failure than patients with aortic stenosis. Atrioventricular valve failure is associated with failure of Fontan circulation.

CardioCel® for repair of congenital heart defects: nationwide results of over 1000 implants.

OBJECTIVES: To assess the mid-term performance of CardioCel for the repair of congenital heart defects. METHODS: Data were retrospectively collected from databases and hospital records in 3 congenital cardiac surgery centres in Australia. Kaplan-Meier curves and log-rank tests were used to test for associations between patient age, gender, patch type and site of implantation. Multivariable Cox regression was used to test whether any specific implantation site was associated with reintervention risk, after adjusting for age group, gender and patch type. RESULTS: A total of 1184 CardioCel patches were implanted in 752 patients under the age of 18 years. Median age at implant was 12 months [interquartile range (IQR) 3.6-84]. Median follow-up was 2.1 years (IQR 0.6-4.6). Probability of freedom from CardioCel-related reintervention was 93% [95% confidence interval (CI) 91-95] at 1 year, 91% (95% CI 88-93) at 3 years and 88% (95% CI 85-91) at 5 years, respectively. On multivariable regression analysis, aortic valve repair had a higher incidence of reintervention [hazard ratio (HR) = 7.15, P = 0.008] compared to other sites. The probability of reintervention was higher in neonates (HR = 6.71, P = 0.0007), especially when used for augmentation of the pulmonary arteries (HR = 14.38, P = 0.029), as compared to other age groups. CONCLUSIONS: CardioCel can be used for the repair of a variety of congenital heart defects. In our study, in patients receiving a CardioCel implant, reinterventions were higher when CardioCel was used to augment the pulmonary arteries in neonates and for aortic valve repair as compared to other sites.

Autoregulatory model comparison and optimisation methodology.

Cerebral pressure autoregulation (AR) is a process by which blood flow is kept constant over a specific cerebral perfusion pressure (CPP) range. There have been a number of advances in recent years in the monitoring and modelling of this physiological variable; however, there has been very little work done on the comparison or optimisation of some of the existing models in clinical use today: pressure reactivity index, highest modal frequency techniques and compartmental modelling. Presented here is a methodology for the comparison and optimisation results for these main AR models. By simple mathematical manipulation of the original modelling end points each model can be converted into a form that is directly comparable to the others. Using a standardised data set with known gold standard AR status indications, the models can then be readily assessed. As a consequence each of the models can then be optimised to maximise specificity and sensitivity.

Impact of Fontan Fenestration on Long-Term Outcomes: A Propensity Score-Matched Analysis.

Background The long-term impact of fenestration at the time of Fontan operation remains unclear. We aimed to review the early and long-term impact of Fontan fenestration in the Australia and New Zealand cohort. Methods and Results We reviewed 1443 patients (621 fenestrated, 822 nonfenestrated) from the Australia and New Zealand Fontan registry. Data were collected on preoperative demographics, operative details, and follow-up. Propensity-score matching was performed to account for the various preoperative and operative differences and risk factors. Primary outcomes were survival and freedom from failure. Median follow-up was 10.6 years. After propensity-score matching (407 matched pairs), there was no difference in survival (87% versus 90% at 20 years; P=0.16) or freedom from failure (73% versus 80% at 20 years; P=0.10) between patients with and without fenestration, respectively. Although patients with fenestration had longer bypass and cross-clamp times (P<0.001), there was no difference in hospital length of stay or prolonged pleural effusions (P=0.80 and P=0.46, respectively). Freedom from systemic and Fontan circuit thromboembolism was higher in the nonfenestrated group (89%; 95% CI, 88%-95%) than the fenestrated group (84%; 95% CI, 77%-89%; P=0.03). There was no difference in incidence of plastic bronchitis, protein-losing enteropathy, New York Heart Association Class III/IV symptoms, or Fontan takedown. Conclusions In the propensity score-matched analysis we have demonstrated no difference in long-term survival or freedom from Fontan failure in patients with and without fenestration. There was a higher incidence of long-term thromboembolic events in patients with fenestration. Overall, it appears that fenestration in Fontan circulation does not bring long-term benefits.

Outcomes of pulmonary valve leaflet augmentation for transannular repair of tetralogy of Fallot.

OBJECTIVE: To evaluate the midterm results of pulmonary valve leaflet augmentation in transannular repair of tetralogy of Fallot (TOF). METHODS: From 2007 to 2019, 131 patients underwent a transannular repair with pulmonary leaflet augmentation for TOF (n = 120) and double outlet right ventricle with pulmonary stenosis (n = 11). Patch material was expanded polytetrafluoroethylene (n = 76), glutaraldehyde-treated autologous pericardium (n = 47) and bovine pericardium (n = 8). RESULTS: Median age at repair was 8.9 months (interquartile range, 5.4-14.8). There was no operative mortality. Median follow-up was 6.25 years (interquartile range, 2.77-7.75). Freedom from severe pulmonary regurgitation (PR) was 85% (95% confidence interval [CI], 77%-90%) and 76% (95% CI, 66%-83%) at 1 and 5 years, respectively. Freedom from moderate or greater PR was 69% (95% CI, 60%-76%) and 30% (95% CI, 21%-39%) at 5 and 10 years, respectively. Three patients required pulmonary valve replacement for PR. Nine patients required pulmonary balloon valvuloplasty. Freedom from intervention for pulmonary valve stenosis was 98% (95% CI, 93%-99%) and 94% (95% CI, 87%-97%) at 1 and 5 years, respectively. One patient with severe PR had an indexed right ventricular volume >160 mL/m2. Use of expanded polytetrafluoroethylene resulted in a greater freedom from moderate or greater PR (log-rank test P < .001; Cox regression hazard ratio, 0.40; 95% CI, 0.25-0.63; P < .001). CONCLUSIONS: At midterm follow-up of transannular repair with pulmonary valve leaflet augmentation, severe PR occurs in less than 50% of patients. The expanded polytetrafluoroethylene patch performs better than pericardium.

The influence of coronary artery anatomy on mortality after the arterial switch operation.

OBJECTIVE: We sought to determine the influence of coronary artery anatomy on mortality in more than 1000 children undergoing the arterial switch operation. METHODS: All patients who underwent an arterial switch operation were identified from 2 hospital databases and reviewed retrospectively. Coronary anatomy was recorded from operative reports using the Leiden classification. RESULTS: An arterial switch operation was performed in 1033 children between 1983 and 2013. Coronary anatomy was normal in 697 patients (67%). The most common type of anomalous coronary anatomy was the circumflex coronary artery arising from sinus 2 (in 152 patients [15%]). Forty-seven patients (4.5%) had all coronary arteries arising from a single sinus. Of these 47 patients, 34 patients (3.3%) had a true single coronary artery. Fifty-two patients (5.0%) had an intramural coronary artery. Overall early mortality was 3.3% (34 out of 1033 patients) over the 30-year period. Early mortality was 3.0% (21 out of 697) for patients with normal coronary anatomy and 3.9% (13 out of 336) for any type of anomalous coronary anatomy. Early mortality was 3.3% (5 out of 152) for patients with the circumflex coronary artery arising from sinus 2, 6.4% (3 out of 47) for patients with all coronary arteries arising from a single sinus, and 5.9% (2 out of 34) for patients with a true single coronary artery. Early mortality for patients with intramural coronaries was 1.9% (1 out of 52). No coronary pattern was found to be a risk factor for mortality. CONCLUSIONS: Patients with anomalous coronary artery anatomy had higher rates of early mortality after the arterial switch operation but this was not statistically significant. Coronary artery reoperations were rare.

Reintervention and survival in 1428 patients in the Australian and New Zealand Fontan Registry.

OBJECTIVE: Patients undergoing single-ventricle palliation have experienced significant improvement in survival in the recent era. However, a substantial proportion of these patients undergo reoperations. We performed a review of the Australia and New Zealand (ANZ) Fontan Registry to determine the overall reintervention and reoperative burden in these patients. METHODS: A retrospective longitudinal cohort study was performed using data from patients who underwent a Fontan operation between 1975 and 2016 from the ANZ Fontan Registry. The data obtained included Fontan operation, reinterventions and most recent follow-up status. We examined the type and timing of reinterventions and survival. RESULTS: Of the 1428 patients identified, 435 (30%) underwent at least one reintervention after the Fontan operation: 110 patients underwent early reintervention and 413 underwent late reinterventions. Excluding Fontan conversion and transplantation, 220 patients underwent at least one interventional procedure and 209 patients underwent at least one reoperation. Fenestration closure and pacemaker-related procedures were the most common catheter and surgical interventions, respectively. The cumulative incidence of reintervention following Fontan was 23%, 37% and 55% at 10, 20 and 30 years, respectively. Survival and freedom from failure were worse in patients requiring later reintervention after Fontan surgery (51% vs 83% and 42% vs 69%, respectively at 30 years, p<0.001). This difference persisted after excluding pacemaker-related procedures (p<0.001). Operative mortality for non-pacemaker late reoperations after Fontan was 6%. CONCLUSIONS: A substantial proportion of Fontan patients require further intervention to maintain effective single-ventricle circulation. Patients undergoing reoperation after Fontan have higher rates of mortality and failure, despite intervention.

Assessment of cerebrovascular resistance with a model of cerebrovascular pressure transmission.

A method to assess continuous changes of cerebrovascular resistance based on a biomechanical model of cerebrovascular pressure transmission is developed. Such a method provides an end-point measure to assess new and/or existing management strategies during intensive-care management of patients with brain injury. Changes of both pial arteriolar resistance and cerebrovascular resistance derived by a physiologically based biomechanical model of cerebrovascular pressure transmission, the dynamic relationship between arterial blood pressure (ABP) and intracranial pressure (ICP), were compared to test the validity of the modeling procedure. Pressor challenge was administered to normoxic (N=5) and hypoxic (N=5) piglets equipped with closed cranial windows. Pial arteriolar diameters were used to compute arteriolar resistance. Percent change of pial arteriolar resistance (%DeltaPAR) and percent change of model-derived cerebrovascular resistance (%DeltasCVR) in response to pressor challenge were computed. During intact cerebrovascular regulation and during hypoxia-induced impairment of cerebrovascular regulation, changes in pial arteriolar resistance were accurately predicted by the proposed modeling method designed to assess changes of cerebrovascular resistance.

In patients undergoing Fontan completion, does a younger age at operation result in better long-term exercise capacity and prognosis?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'In [patients undergoing Fontan completion], does [a younger age at operation] result in [better long-term exercise capacity and prognosis]?'. Altogether, 304 papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Of these, 2 recent large reviews describe a better or a non-significant trend towards better outcomes when the Fontan procedure is performed at a younger age. This is supported by 4 studies demonstrating better long-term exercise capacity when patients undergo Fontan completion at a younger age. Additionally, 2 other studies describe increased rates of failure, adverse events and arrhythmias with older age at Fontan completion. Two publications describe non-inferior outcomes in patients with an older age at Fontan completion, although limited by the number of patients and follow-up. We conclude that the Fontan operation should be performed at an early age (<7 years) because the data show higher survival and fewer adverse events, and the gradual decline in exercise capacity in Fontan patients appears accelerated when the Fontan operation is performed at older age.

Outcomes of Patients Undergoing Surgical Management of Multiple Ventricular Septal Defects.

Surgical treatment of multiple ventricular septal defects (VSDs) has advanced significantly in recent years, yet remains technically challenging. With high rates of complications and reoperations, we sought to assess the outcomes of patients undergoing a variety of management techniques for multiple VSDs. From 1988 to 2015, 157 consecutive patients underwent surgical management of multiple VSDs at a median age of 2.2 months (2 days-16 years). Sixty-nine patients (44%) had exclusively multiple VSDs, 62 patients (39%) had multiple VSDs with concomitant intracardiac anomalies, and 26 patients (17%) had multiple VSDs with aortic arch anomalies. The predominant techniques used at the initial operations were patch closure (84 patients), pulmonary artery band (83 patients), suture closure (37 patients), and sandwich technique (13 patients). Eighteen patients underwent ventriculotomies. There were 3 hospital deaths (2%). Mean follow-up time was 8.6 ± 6 years (1 day-22 years). Four patients died during follow-up, whereas freedom from reoperations was 52% (95% confidence interval 42-61%) at 16 years. Freedom from reoperation was significantly lower in the 1988-2002 era than in the post-2002 era (38% vs 73%, P = 0.016). Pacemaker implantation was ultimately required in 9% (14 of 150) of patients. No deleterious impact of a ventriculotomy could be detected. Surgical treatment of multiple VSDs can be performed with excellent short- and long-term survival, and normal late functional outcome, however, carries a significant rate of reoperation. The recent inclusion of absorbable pulmonary artery bands and the sandwich technique appear safe and are useful adjuncts in these patients.

A comparison of pump-controlled retrograde trial off to arterio-venous bridging for weaning from venoarterial extracorporeal membrane oxygenation.

OBJECTIVES: The aim of the study is to compare a technique of pump-controlled retrograde trial off (PCRTO) to insertion of an arterio-venous (AV) bridge to conduct a trial from venoarterial extracorporeal membrane oxygenation (VA ECMO). METHODS: We studied all patients who were weaned from VA ECMO using either PCRTO or AV bridging from November 2014 to April 2018. Demographic data, indications for ECMO, duration of ECMO, duration of trial period off ECMO and survival were compared between the 2 groups. RESULTS: Seventy-nine patients were placed on VA ECMO from November 2014 to April 2018, of whom, 51 (65%) patients met the study inclusion criteria: 31 (61%) patients who had a trial period from VA ECMO using PCRTO and 20 (39%) patients who were weaned using an AV bridge. The indications for ECMO included cardiac (n = 16 and 11, respectively) and non-cardiac aetiologies (n = 15 and 9, respectively). There was 1 death in each group. The duration of the trial off VA ECMO was significantly shorter in the PCRTO group (median = 88.0 vs 196.6 min, P < 0.001). There were 2 conversions from PCRTO to AV bridging during the trial period off ECMO (2.9-kg neonate following a Norwood procedure and 2.2-kg patient following repair of ectopia cordis). CONCLUSIONS: PCRTO is a safe, simple and reproducible approach for enabling a trial period while preserving the circuit during weaning from VA ECMO. In our study, the duration of the trial period off VA ECMO was significantly shorter in the PCRTO group. PCRTO avoids manipulation of the ECMO circuit, provides a 'stress test' to evaluate cardiorespiratory reserve during the trial period off ECMO, is applicable for a wide variety of cardiac and non-cardiac indications and facilitates multiple attempts at weaning from ECMO.

Influence of hypercapnic vasodilation on cerebrovascular autoregulation and pial arteriolar bed resistance in piglets.

Changes in both pial arteriolar resistance (PAR) and simulated arterial-arteriolar bed resistance (SimR) of a physiologically based biomechanical model of cerebrovascular pressure transmission, the dynamic relationship between arterial blood pressure and intracranial pressure, are used to test the hypothesis that hypercapnia disrupts autoregulatory reactivity. To evaluate pressure reactivity, vasopressin-induced acute hypertension was administered to normocapnic and hypercapnic (N = 12) piglets equipped with closed cranial windows. Pial arteriolar diameters were used to compute arteriolar resistance. Percent change of PAR (%DeltaPAR) and percent change of SimR (%DeltaSimR) in response to vasopressin-induced acute hypertension were computed and compared. Hypercapnia decreased cerebrovascular resistance. Indicative of active autoregulatory reactivity, vasopressin-induced hypertensive challenge resulted in an increase of both %DeltaPAR and %DeltaSimR for all normocapnic piglets. The hypercapnic piglets formed two statistically distinct populations. One-half of the hypercapnic piglets demonstrated a measured decrease of both %DeltaPAR and %DeltaSimR to pressure challenge, indicative of being pressure passive, whereas the other one-half demonstrated an increase in these percentages, indicative of active autoregulation. No other differences in measured variables were detectable between regulating and pressure-passive piglets. Changes in resistance calculated from using the model mirrored those calculated from arteriolar diameter measurements. In conclusion, vasodilation induced by hypercapnia has the potential to disrupt autoregulatory reactivity. Our physiologically based biomechanical model of cerebrovascular pressure transmission accurately estimates the changes in arteriolar resistance during conditions of active and passive cerebrovascular reactivity.

Hydraulic responses to environmental perturbations in Tsuga canadensis and Betula lenta.

Eastern hemlock (Tsuga canadensis (L). Carr.) is a late-successional species found across the northeastern United States of America that is currently threatened by the exotic pest, hemlock woolly adelgid (Adelges tsugae Annand). Because whole-tree physiological characteristics may scale to influence ecosystem processes, we considered whole-tree hydraulic controls in eastern hemlock and the replacement species black birch (Betula lenta L.). Through a series of misting perturbations, whole-tree resistances (R), capacitances (C) and time constants (tau) were determined from time series sap flux data in eastern hemlock and black birch. Black birch trees responded more rapidly to environmental perturbations than eastern hemlock. Utilizing the step function after applied treatments, whole-tree tau ranged between 9.4 and 24.8 min in eastern hemlock trees compared with 5.9 to 10.5 min in black birch. Species was not a significant predictor of R or C when controlling for tree size. In both species, R decreased with sapwood area and C increased. Our tau results indicate that the loss and replacement of eastern hemlock by black birch will decrease the lag between transpiration and absorption of water from the soil and potentially alter the diurnal pattern of carbon and water uptake.

Water use and carbon exchange of red oak- and eastern hemlock-dominated forests in the northeastern USA: implications for ecosystem-level effects of hemlock woolly adelgid.

Water use and carbon exchange of a red oak-dominated (Quercus rubra L.) forest and an eastern hemlock-dominated (Tsuga canadensis L.) forest, each located within the Harvard Forest in north-central Massachusetts, were measured for 2 years by the eddy flux method. Water use by the red oak forest reached 4 mm day(-1), compared to a maximum of 2 mm day(-1) by the eastern hemlock forest. Maximal carbon (C) uptake rate was also higher in the red oak forest than in the eastern hemlock forest (about 25 versus 15 micromol m(-2) s(-1)). Sap flux measurements indicated that transpiration of red oak, and also of black birch (Betula lenta L.), which frequently replaces eastern hemlock killed by hemlock woolly adelgid (Adelges tsugae Annand.), were almost twice that of eastern hemlock. Despite the difference between species in maximum summertime C assimilation rate, annual C storage of the eastern hemlock forest almost equaled that of the red oak forest because of net C uptake by eastern hemlock during unusually warm fall and spring weather, and a near-zero C balance during the winter. Thus, the effect on C storage of replacing eastern hemlock forest with a forest dominated by deciduous species is unclear. Carbon storage by eastern hemlock forests during fall, winter and spring is likely to increase in the event of climate warming, although this may be offset by C loss during hotter summers. Our results indicate that, although forest water use will decrease immediately following eastern hemlock mortality due to the hemlock woolly adelgid, the replacement of eastern hemlock by deciduous species such as red oak will likely increase summertime water use over current rates in areas where hemlock is a major forest species.

Relationship of a cerebral autoregulatory index with outcome in head injured patients.

BACKGROUND: Cerebral autoregulation is the process by which cerebral blood flow (CBF) is maintained constant over a specific cerebral perfusion pressure (CPP) range. We have reworked a version of the Ursino and Lodi autoregulation model to derive an index of autoregulation (G), and compared it to a number of other autoregulatory models as well as a gold standard measure of autoregulation obtained from an animal model study (6 piglets with a cranial window preparation and ICP, ABP sampled at 250 Hz). The results of that study have shown that this index G correlates well with the "Bouma" index of autoregulation. METHODS: In this study this new autoregulatory index has been calculated for a sample of 12 head injury patient's data over multiple time points and then used to firstly investigate if this index in conjunction with other clinical prognostic factors may give a better indication of outcome and then analyse its trend with time to quantify how the level of autoregulation changes post-injury. FINDINGS: The index correlates well with dichotomised GOSe outcome (p = 0.03) and the trend in the result between middle and late time periods shows early signs of being predictive of outcome as well. CONCLUSIONS: Though more work is needed these results warrant further investigation with larger numbers of patients.

Assessment of cerebrovascular resistance with model of cerebrovascular pressure transmission.

BACKGROUND: A two step modeling method of cerebrovascular pressure transmission, the dynamic relationship between arterial blood pressure (ABP) and intracranial pressure (ICP) has been developed as a means to continuously assess cerebrovascular regulation and resistance. Initially, system identification modeling was used to construct a numerical model of cerebrovascular pressure transmission. Next, the modal frequencies of the numerical model and the actual ABP recording were used to manipulate the parameters of a physiologically-based biomechanical model such that: (1) the actual and simulated ICP; and (2) the numerical and biomechanical model modal frequencies match. MATERIALS AND METHODS: This study was designed to compare changes of cerebrovascular resistance of the biomechanical model with the expected changes of cerebrovascular resistance associated with the occurrence of either a plateau wave or refractory intracranial hypertension. Pressure recordings from five patients with plateau waves and five patients with intracranial hypertension were used. FINDINGS: Vascular resistance decreased significantly during the plateau wave and was inversely related to CPP, indicating active vasoreactivity. In contrast, vascular resistance increased significantly during intractable intracranial hypertension and was directly related to CPP, indicating impaired cerebrovascular regulation. CONCLUSIONS: Such results support the use of the modeling method as a means to continuously assess changes of cerebrovascular regulation and resistance.

Stroke with subarachnoid hemorrhage: assessment of cerebrovascular pressure regulation and simulated cerebrovascular resistance.

BACKGROUND: Monitoring methods designed to assess cerebrovascular regulation and increased cerebrovascular resistance (CVR) of patients with subarachnoid hemorrhage (SAH) would facilitate therapeutic intervention and potentially reduce secondary complications. The aim of this study was to assess changes of cerebrovascular regulation and CVR by evaluating changes of cerebrovascular pressure transmission in patients with SAH. METHODS: Admission Hunt-Hess grades, Fisher scores, Glasgow Outcome Scores (GOS) at 6 months, and pressure recordings were obtained from 20 patients. Biomechanical models of cerebrovascular pressure transmission were constructed over one-minute intervals for the initial and final two hours of post-hemorrhage monitoring. FINDINGS: Classified according to the GOS score at 6 months, eight patients died (GOS 1), five were severely disabled (GOS 3), and seven patients were moderately disabled (GOS 4). During the initial monitoring period 100%, 80%, and 28.6% of groups with GOS 1, 3, and 4 demonstrated impairment of cerebrovascular regulation; whereas, in the final monitoring period 100%, 100%, and 14.3% respectively demonstrated impairment. Between monitoring periods, simulated CVR (sCVR) significantly increased (p < 0.001) for patients with GOS 1 and 3 and decreased for those with GOS 4 with mean resistance for the latter group significantly lower (p < 0.001) than other means. CONCLUSIONS: Loss of cerebrovascular regulation and increased sCVR were observed in SAH patients with poor outcome.