Comparing physiological impacts of positive pressure ventilation versus self-breathing via a versatile cardiopulmonary model incorporating a novel alveoli opening mechanism.

Mathematical models can be used to generate high-fidelity simulations of the cardiopulmonary system. Such models, when applied to real patients, can provide valuable insights into underlying physiological processes that are hard for clinicians to observe directly. In this work, we propose a novel modelling strategy capable of generating scenario-specific cardiopulmonary simulations to replicate the vital physiological signals clinicians use to determine the state of a patient. This model is composed of a tree-like pulmonary system that features a novel, non-linear alveoli opening strategy, based on the dynamics of balloon inflation, that interacts with the cardiovascular system via the thorax. A baseline simulation of the model is performed to measure the response of the system during spontaneous breathing which is subsequently compared to the same system under mechanical ventilation. To test the new lung opening mechanics and systematic recruitment of alveolar units, a positive end-expiratory pressure (PEEP) test is performed and its results are then compared to simulations of a deep spontaneous breath. The system displays a marked decrease in tidal volume as PEEP increases, replicating a sigmoidal curve relationship between volume and pressure. At high PEEP, cardiovascular function is shown to be visibly impaired, in contrast to the deep breath test where normal function is maintained.

High levels of IgM against methylglyoxal-modified apolipoprotein B100 are associated with less coronary artery calcification in patients with type 2 diabetes.

OBJECTIVE: Advanced glycation end products (AGE) have been implicated in diabetic vascular complications through activation of pro-inflammatory genes. AGE-modified proteins are also targeted by the immune system resulting in the generation of AGE-specific autoantibodies, but the association of these immune responses with diabetic vasculopathy remains to be fully elucidated. The aim of this study was to determine whether antibodies against apolipoprotein B100 modified by methylglyoxal (MGO-apoB100) are associated with coronary atherosclerosis in patients with type 2 diabetes. METHODS: We measured antibodies against MGO-apoB100 in plasma from 497 type 2 diabetic patients without clinical signs of cardiovascular disease. Severity of coronary disease was assessed as coronary artery calcium (CAC) imaging. Immunoglobulin (Ig)M and IgG levels recognizing MGO-apoB100 were determined by enzyme-linked immunosorbent assay. RESULTS: Anti-MGO-apoB100 IgM antibody levels were higher in subjects with a low to moderate CAC score (≤400 Agatston units) than in subjects with a high score (>400 Agatston units; 136.8±4.4 vs. 101.6± 7.4 arbitrary units (AU), P<0.0001) and in subjects demonstrating no progression of CAC during 30 months of follow-up (136.4±5.7 vs. 113.9 ± 6.2 AU in subjects with progression, P<0.0001). Subjects with a family history of premature myocardial infarction had lower levels of anti-MGO-apoB100 IgM. Female subjects had higher levels of anti-MGO-apoB100 antibodies and lower CAC than men. Accordingly, high levels of IgM against MGO-apoB100 are associated with less severe and a lower risk of progression of coronary disease in subjects with type 2 diabetes. CONCLUSIONS: Although conclusions regarding causal relationships based on epidemiological observations need to be made with caution, our findings suggest the possibility that anti-MGO-apoB100 IgM may be protective in diabetic vasculopathy.

Associations between autoantibodies against apolipoprotein B-100 peptides and vascular complications in patients with type 2 diabetes.

AIMS/HYPOTHESIS: Oxidation of LDL in the arterial extracellular matrix is a key event in the development of atherosclerosis and autoantibodies against oxidised LDL antigens reflect disease severity and the risk of developing acute cardiovascular events. Since type 2 diabetes is associated with increased oxidative stress, we tested the hypothesis that autoantibodies against oxidised LDL antigens are biomarkers for vascular complications in diabetes. METHODS: We studied 497 patients with type 2 diabetes without clinical signs of coronary heart disease. Oxidised LDL autoantibodies were determined by ELISA detecting IgG and IgM specific for native and malondialdehyde (MDA)-modified apolipoprotein B-100 peptides p45 and p210. The severity of coronary disease was assessed as the coronary artery calcium score. RESULTS: Patients affected by retinopathy had significantly higher levels of IgG against MDA-p45 and MDA-p210. In contrast, high levels of autoantibodies against the corresponding native peptides were associated with less coronary calcification and a lower risk of progression of coronary disease. CONCLUSIONS/INTERPRETATION: Our observations suggest that LDL oxidation is involved in the pathogenesis of diabetic retinopathy and that autoantibodies against apolipoprotein B peptides may act as biomarkers for both micro- and macrovascular complications in diabetes.

Donation after cardiac death kidneys with low severity pre-arrest acute renal failure.

The widening gap between supply and demand for renal transplantation has prompted many centers to use donors after cardiac death. Some of these donors exhibit signs of acute renal failure (ARF) prior to cardiac arrest. Concern has been expressed about poor quality of graft function from such donors. In response to this perception, we reviewed 49 single renal transplant recipients from category III donors after cardiac death between 1998 and 2005, at our center. All kidneys but one had hypothermic machine perfusion and viability testing prior to transplantation. According to the RIFLE criteria, nine recipients had kidneys from donors with "low severity pre-arrest ARF". The remainder of the recipients were used as control group. There was no statistical significant difference in delayed graft function and rejection rates between these two groups. Recipients GFR at 12 months was 44.4 +/- 17.1 and 45.2 +/- 14.7 (mL/min/1.73m(2)) from donors with ARF and without ARF, respectively (p = 0.96). In conclusion, low severity ARF in kidneys from controlled after cardiac death donors can be a reversible condition after transplantation. Short-term results are comparable to the kidneys from same category donors without renal failure, providing that some form of viability assessment is implemented prior to transplantation.

Improved interpretation of dobutamine stress echocardiography following 4 months of systematic training in patients following acute myocardial infarction.

OBJECTIVES: Interpretation of stress echocardiography is subjective, and highly dependent on the experience of the interpreter. We sought to evaluate whether a cardiologist without any previous experience in stress echocardiography could adequately learn the skills of interpreting dobutamine stress echocardiograms (DSE) in post-infarct patients, after a period of systematic training. METHODS: A trainee in cardiology blindly reported 51 consecutive DSEs from a database of post-infarction studies, after 2 and 4 months of systematic training. We compared his interpretation with that of an expert. RESULTS: Agreement between the trainee and the expert improved significantly from 2 to 4 months of training in the left anterior descending artery territory for the overall scan interpretation (from kappa = 0.58 to kappa = 0.73; p = 0.03), wall thickening assessment in individual segments (from kappa = 0.40 to kappa = 0.55; p < 0.01) and the diagnosis of viable myocardium (from kappa = 0.11 to kappa = 0.43; p = 0.01). Similar improvement was observed in left circumflex, but not in the right coronary artery territory. Agreement in identifying inducible ischaemia also remained poor. CONCLUSION: This study suggests that systematic training can significantly reduce interobserver variability in a short time frame (4 months) and may improve the interpretation of DSE by a trainee. But improvements in image quality and use of predefined reading criteria are necessary to improve interobserver agreement further in myocardial regions where conformity in dobutamine stress echocardiographic interpretation is low.