Climate drives the geography of marine consumption by changing predator communities.

The global distribution of primary production and consumption by humans (fisheries) is well-documented, but we have no map linking the central ecological process of consumption within food webs to temperature and other ecological drivers. Using standardized assays that span 105° of latitude on four continents, we show that rates of bait consumption by generalist predators in shallow marine ecosystems are tightly linked to both temperature and the composition of consumer assemblages. Unexpectedly, rates of consumption peaked at midlatitudes (25 to 35°) in both Northern and Southern Hemispheres across both seagrass and unvegetated sediment habitats. This pattern contrasts with terrestrial systems, where biotic interactions reportedly weaken away from the equator, but it parallels an emerging pattern of a subtropical peak in marine biodiversity. The higher consumption at midlatitudes was closely related to the type of consumers present, which explained rates of consumption better than consumer density, biomass, species diversity, or habitat. Indeed, the apparent effect of temperature on consumption was mostly driven by temperature-associated turnover in consumer community composition. Our findings reinforce the key influence of climate warming on altered species composition and highlight its implications for the functioning of Earth's ecosystems.

Discarded Human Thymus Is a Novel Source of Stable and Long-Lived Therapeutic Regulatory T Cells.

Regulatory T cell (Treg)-based therapy is a promising approach to treat many immune-mediated disorders such as autoimmune diseases, organ transplant rejection, and graft-versus-host disease (GVHD). Challenges to successful clinical implementation of adoptive Treg therapy include difficulties isolating homogeneous cell populations and developing expansion protocols that result in adequate numbers of cells that remain stable, even under inflammatory conditions. We investigated the potential of discarded human thymuses, routinely removed during pediatric cardiac surgery, to be used as a novel source of therapeutic Tregs. Here, we show that large numbers of FOXP3(+) Tregs can be isolated and expanded from a single thymus. Expanded thymic Tregs had stable FOXP3 expression and long telomeres, and suppressed proliferation and cytokine production of activated allogeneic T cells in vitro. Moreover, expanded thymic Tregs delayed development of xenogeneic GVHD in vivo more effectively than expanded Tregs isolated based on CD25 expression from peripheral blood. Importantly, in contrast to expanded blood Tregs, expanded thymic Tregs remained stable under inflammatory conditions. Our results demonstrate that discarded pediatric thymuses are an excellent source of therapeutic Tregs, having the potential to overcome limitations currently hindering the use of Tregs derived from peripheral or cord blood.

Real-time 3-dimensional echocardiography provides new insight into mechanisms of tricuspid valve regurgitation in patients with hypoplastic left heart syndrome.

BACKGROUND: Tricuspid regurgitation in hypoplastic left heart syndrome has an impact on outcome, but its mechanisms remain unclear. METHODS AND RESULTS: Real-time 3-dimensional echocardiography was performed in 35 patients with hypoplastic left heart syndrome (age, 1 month to 10 years; 10 after first-stage Norwood, 12 after superior cavopulmonary shunt, 13 after Fontan). From the 3-dimensional data set, we marked the annulus in systole and diastole. At mid systole, we marked the location of the papillary muscle tip and point of chordal attachment to the leaflet. We traced the surfaces of the tricuspid valve leaflets and measured the volume of leaflet prolapse, tethering, annular and septal leaflet areas, and papillary muscle position. Seventeen patients had moderate tricuspid regurgitation (prolapse, 7; tethered leaflets, 7) and 18 mild (prolapse, 0; tethered leaflets, 7). Multiple linear regression analysis revealed that moderate tricuspid regurgitation is associated with leaflet tethering and prolapse; that in hypoplastic left heart syndrome with tethered leaflets, the papillary muscle is displaced laterally and the tricuspid annulus is more planar; and that enlargement of the annulus at mid systole, small septal leaflet area, and age affect the degree of prolapse. CONCLUSIONS: In hypoplastic left heart syndrome, moderate tricuspid regurgitation may be associated with increasing age, geometrical changes of the annulus, leaflet prolapse, lateral papillary muscle displacement, and subsequent leaflet tethering, as well as a smaller septal leaflet.

Treating the right patient at the right time: access to heart failure care.

Heart failure affects over 500,000 Canadians, and 50,000 new patients are diagnosed each year. The mortality remains staggering, with a five-year age-adjusted rate of 45%. Disease management programs for heart failure patients have been associated with improved outcomes, the use of evidence-based therapies, improved quality of care, and reduced costs, mortality and hospitalizations. Currently, national benchmarks and targets for access to care for cardiovascular procedures or office consultations do not exist. The present paper summarizes the currently available data, particularly focusing on the risk of adverse events as a function of waiting time, as well as on the identification of gaps in existing data on heart failure. Using best evidence and expert consensus, the present article also focuses on timely access to care for acute and chronic heart failure, including timely access to heart failure disease management programs and physician care (heart failure specialists, cardiologists, internists and general practitioners).

General commentary on access to cardiovascular care in Canada: universal access, but when? Treating the right patient at the right time.

In 2004, the Canadian Cardiovascular Society formed an Access to Care Working Group with a mandate to use the best science and information available to establish reasonable triage categories and safe wait times for common cardiovascular services and procedures through a series of commentaries. The present commentary is the first in the series and lays out issues regarding timely access to care that are common to all cardiovascular services and procedures. The commentary briefly describes the 'right' to timely access, wait lists as a health care system management tool, and the role of the physician as patient advocate and gatekeeper. It also provides advice to funders, administrators and providers who must monitor and manage wait times to improve access to cardiovascular care in Canada and restore the confidence of Canadians in their publicly funded health care system.

Treating the right patient at the right time: access to care in non-ST segment elevation acute coronary syndromes.

In 2004, the Canadian Cardiovascular Society formed an Access to Care Working Group with a mandate to use the best science and information available to establish reasonable triage categories and safe wait times for common cardiovascular services and procedures through a series of commentaries. The present commentary discusses the rationale for access benchmarks for urgent cardiac catheterization and revascularization, including hospital transfer in the setting of non-ST elevation acute coronary syndromes. The literature on standards of care, wait times, wait list management and clinical trials was reviewed. A survey of all cardiac catheterization directors in Canada was performed to develop an inventory of current practices in identifying and triaging patients. The Working Group recommended the following medically acceptable wait times for access to diagnostic catheterization and revascularization in patients presenting with acute coronary syndromes: for diagnostic catheterization and percutaneous coronary intervention, the target should be 24 h to 48 h for high-risk, three to five days for intermediate-risk and five to seven days for low-risk patients; for coronary artery bypass graft surgery, the target should be three to five days for high-risk, two to three weeks for intermediate-risk and six weeks for low-risk patients. All stakeholders must affirm the appropriateness of these standards and work continuously to achieve them. However, some questions remain around what are the best clinical risk markers to delineate the triage categories and the utility of clinical risk scores to assist clinicians in triaging patients for invasive therapies.

Canadian Cardiovascular Society commentary on implantable cardioverter defibrillators in Canada: waiting times and access to care issues.

The Canadian Cardiovascular Society is the national professional society for cardiovascular specialists and researchers in Canada. In the spring of 2004, the Canadian Cardiovascular Society Council formed an Access to Care Working Group in an effort to use the best science and information to establish reasonable triage categories and safe wait times for access to common cardiovascular services and procedures. The Working Group has elected to publish a series of commentaries to initiate a structured national discussion on this very important issue. Access to treatment with implantable cardioverter defibrillators is the subject of the present commentary. The prevalence pool of potentially eligible patients is discussed, along with access barriers, regional disparities and waiting times. A maximum recommended waiting time is proposed and the framework for a solution-oriented approach is presented.

The gold standard for atrial septal defect closure: current surgical results, with an emphasis on morbidity.

Device closure of atrial septal defects (ASDs) is rapidly becoming routine in children. Comparisons are often made to older surgical series with higher morbidities. However outcomes including reintervention, late failure, and the need for long-term follow-up must be considered and compared to those of a current surgical series. One hundred consecutive surgical closures of ASDs in children were reviewed. The mean age was 60.5 +/- 6.4 months; 6 patients underwent repair in the first year of life. Full clinical and echocardiographic follow-up was available on all patients. There was no mortality; there were no residual ASDs and no neurological complications. There were 3 cases of postpericardiotomy syndrome and 26 pericardial effusions. Median stay was 4 days; all patients have been discharged from follow-up. A review of the literature on the short-term follow-up of ASD devices revealed a number of problems. Their long-term durability is unknown. As such, it remains an experimental procedure and must be compared over the long-term to the current gold standard, surgical repair.

Prevention of allograft heart valve failure in a rat model.

OBJECTIVE: Allograft heart valves are commonly used in cardiac surgery. Despite mounting evidence that these valves are immunogenic, leading to premature failure, current clinical practice does not attempt to minimize or control such a response. The objective of this study was to evaluate immune modulatory approaches to ameliorate allograft valve failure in a rat model. METHOD: Aortic valve grafts were implanted infrarenally into Lewis rat recipients (n = 32). There were 4 transplant groups: syngeneic grafts (Lewis to Lewis), untreated allografts (Brown Norway to Lewis), allograft recipients treated with cyclosporine (INN: ciclosporin) (10 mg/kg per day for 7 or 28 days), and allograft recipients treated with anti-alpha4 integrin and anti-beta2 integrin monoclonal antibodies for 7 days. At 7 and 28 days the valves were examined for structural integrity and cellular infiltration. RESULTS: Both cyclosporine and anti-alpha4/beta2 integrin treatment resulted in significant reduction in leaflet infiltration by macrophages (ED1(+)), T cells (CD3(+)), and CD8(+) T cells at 7 days with preservation of structural integrity when compared with control allografts. Twenty-eight days after implantation, daily treatment with cyclosporine preserved leaflet structural integrity and inhibited cellular infiltration. However, a short course of cyclosporine (7 days) failed to prevent destruction of the valves at 28 days. CONCLUSIONS: Immune modulatory approaches aimed at T-cell activation or trafficking decrease leaflet cellular infiltration and prevent allograft valve structural failure. However, short-course therapy does not appear to be sufficient and must be maintained to allow long-term preservation of leaflet structural integrity (28 days).

Long-term results of relief of subaortic stenosis in univentricular atrioventricular connection with discordant ventriculoarterial connections.

BACKGROUND: We set out to examine the long-term results of relief of subaortic stenosis by enlargement of ventricular septal defect in patients with univentricular atrioventricular connection to a dominant left ventricle and discordant ventriculoarterial connections. METHODS: Twenty-four patients underwent enlargement of ventricular septal defect between 1985 and 1998 at a median age of 3.2 years (range, 3 weeks to 14 years). Ten patients were younger than 1 year of age. Eighteen had undergone previous banding of the pulmonary trunk, 9 of whom also required repair of coarctation of the aorta. The median subaortic gradient before enlargement was 46 mm Hg. Twenty-three patients had a patch to enlarge the rudimentary right ventricle. RESULTS: Five patients (21%) died in the early postoperative period. The overall survival at 1 and 3 years was 73%, and at 5 and 10 years was 68% and 60%, respectively. Complete heart block requiring insertion of a pacemaker occurred in 2 patients (8%). A Fontan operation was performed in 10 patients, 5 underwent a bidirectional Glenn procedure, and 2 required cardiac transplantation. Follow-up was complete in all survivors at a median time of 6.7 years (range, 8 months to 13 years). From the earlier part of the series, 3 patients experienced aortic insufficiency and 2 had recurrent obstruction. Factors adversely affecting survival were age younger than 1 year at operation and presence of obstruction within the aortic arch. CONCLUSIONS: Our experience shows that, in patients with univentricular atrioventricular connection to a dominant left ventricle and subaortic stenosis, enlargement of the ventricular septal defect provides satisfactory relief of obstruction except in those younger than 1 year of age, and those who have associated obstruction in the aortic arch.

T lymphocytes mediate leaflet destruction and allograft aortic valve failure in rats.

BACKGROUND: Allograft heart valves are commonly used in cardiac surgery but ultimately fail. This situation is most acute in children. This study addresses the role of T cell-mediated immune damage in allograft valve failure. METHODS: Syngeneic (Lewis to Lewis) or allogeneic (Brown Norway to Lewis) aortic valve grafts were implanted infrarenally into Lewis rat recipients (n = 24). Allogeneic valve grafts were also implanted into T cell-deficient rats (nude; n = 12). At 7, 14, and 28 days the valves were explanted and examined for structural integrity and cellular infiltration. RESULTS: Syngeneic grafts maintained normal leaflet structure with little leaflet immune infiltration. Allografts showed leaflet infiltration (7 days), significant leaflet thickening, progressively decreased cellularity (14 days), and leaflet destruction (28 days). Infiltrates contained CD43+, CD3+, and CD8+ cells. Allografts in T cell-deficient rats showed none of the above changes and maintained normal structural integrity. CONCLUSIONS: Allograft heart valves in the rat model undergo T cell-mediated immune rejection, resulting in structural failure.

Cryopreservation of rat aortic valves results in increased structural failure.

BACKGROUND: The cause of valve allograft failure is most likely multifactorial and may include mechanical, immunological, and other factors. Cryopreservation of these valves is often used to extend storage times. However, there has been considerable confusion as to the effects of cryopreservation on valve durability. Our objective was to determine the effects of cryopreservation on histopathological changes in rat aortic valve grafts. METHODS AND RESULTS: Syngeneic rat aortic valve grafts (Lewis to Lewis; n=24) and allogeneic rat aortic valve grafts (Brown Norway to Lewis; n=24) were implanted infrarenally, either fresh or after cryopreservation. At 7, 14, and 28 days, the valves were explanted, and histological and immunohistochemical examinations were performed in a blinded fashion. Fresh syngeneic graft leaflets retained their normal structure for the 28-day period of observation. Cryopreserved syngeneic grafts showed retrovalvar thrombus formation, with leaflet destruction at 7, 14, and 28 days. Fresh allogeneic graft leaflets showed significant leaflet thickening and progressive destruction at 14 and 28 days. Cryopreserved allogeneic grafts had evidence of retrovalvar thrombus formation with leaflet destruction at 7, 14, and 28 days. Cryopreserved syngeneic grafts resulted in significant infiltration of mononuclear (ED1(+)) cells not seen with fresh syngeneic grafts but similar to fresh allogeneic grafts. All allogeneic grafts resulted in significant infiltration of T-lymphocytes (CD3(+), CD8(+), CD43(+)). CONCLUSIONS: Cryopreservation appears to predispose syngeneic and allogeneic rat aortic valve leaflets to accelerated injury and destruction. This mode of failure resembles that of fresh allogeneic valve grafts.

Simple modified ultrafiltration.

After reviewing all available methods of modified ultrafiltration (MUF), an attempt was made to develop a more simplified approach to this beneficial method of post-bypass fluid removal by withdrawing blood from the right atrium and reinfusing into the aortic cannula (venoarterial). The simplicity of operation, ease of setup and analysis of hemoglobin, hematocrit, total proteins and colloid osmotic pressure, and fluid removed were examined in 12 consecutive neonatal and pediatric patients undergoing cardiac surgery. Results indicate that this simplified modified ultrafiltration (SMUF) is comparable to all other methods of MUF by achieving dramatic improvements in all parameters measured. In addition, SMUF provides the perfusionist with the ability to run conventional ultrafiltration throughout the bypass procedure, using this one circuit design. As well as finding the learning curve for SMUF to be very short, this method was found to be superior in its simplicity of operation, ease of setup, reduced risk of complications and acceptance by the surgeon and anesthetist.

Aortic valve graft implantation in rats: a new functional model.

BACKGROUND: Allograft heart valves used in cardiac surgery often fail at an unacceptable rate. Immune mechanisms contribute to this failure, but adequate and functional small-animal valve models to characterize this phenomenon are lacking. The objective of this study was to create native aortic valve insufficiency in recipient rats to provide for a functional abdominal aortic valve graft implant. METHODS: Lewis recipient rats underwent single-leaflet injury of their native aortic valve through a right carotid catheter injury. Animals were allowed to recover for 28 days, at which time a Lewis aortic valve graft was implanted infrarenally. Echocardiography with color flow Doppler scanning was performed before aortic injury, 1 week after aortic injury, and after abdominal implantation of a valve graft in animals with native aortic insufficiency. RESULTS: After aortic valve injury, all animals had moderate-to-severe aortic insufficiency with a significant increase in diastolic and systolic left ventricular dimensions. Color flow Doppler scanning revealed diastolic aortic flow reversal from the aortic valve extending to the infrarenal abdominal aorta. Aortic valve grafts were then implanted infrarenally in animals with created aortic valve insufficiency and resulted in 100% patency and preservation of leaflets at 4 weeks after implantation. Leaflet motion of the abdominal graft was visualized by means of M-mode echocardiography. CONCLUSION: Compensated native aortic insufficiency results in aortic diastolic flow reversal distal to the infrarenal aorta, thus allowing normal motion of the infrarenal allograft leaflets. This functional model will provide an opportunity to investigate the role of immunologic valve injury in the failure of valve allografts.

Traumatic coronary artery fistula management.

Traumatic coronary artery-cameral fistulas (TCAF) are uncommon sequelae of trauma that require early surgical intervention to prevent complications. The etiology of traumatic coronary artery-cameral fistulas may be classified as accidental or iatrogenic and have distinctly different courses depending on the etiology. The two operations described for definitive surgical closure of a traumatic coronary-cameral fistula are external ligation/obliteration of the fistula (with or without bypass grafting to the coronary artery distal to the fistula) and direct repair of the fistula from within the recipient chamber. The technique of fistula closure from within the recipient chamber is associated with a reduced incidence of fistula recurrence. A case report and a collective literature review are presented.

Hepatic vein to the azygous vein anastomosis for pulmonary arteriovenous fistulae.

Pulmonary arteriovenous fistulae after a cavopulmonary anastomosis have been reported to resolve after hepatic venous return is included in the pulmonary circulation. We report a case in which the hepatic veins were redirected to the pulmonary circulation by connecting them directly to the azygous continuation of the inferior vena cava that had previously been connected to the right pulmonary artery. The patient's arterial saturation of 71% increased to 92% after 6 months.