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Medical laser applications require knowledge about the optical properties of target tissue. In this study, the optical properties of selected native and coagulated human brain structures were determined in vitro in the spectral range between 360 and 1100 nm. The tissues investigated included white brain matter, grey brain matter, cerebellum and brainstem tissues (pons, thalamus). In addition, the optical properties of two human tumours (meningioma, astrocytoma WHO grade II) were determined. Diffuse reflectance, total transmittance and collimated transmittance of the samples were measured using an integrating-sphere technique. From these experimental data, the absorption coefficients, the scattering coefficients and the anisotropy factors of the samples were determined employing an inverse Monte Carlo technique. The tissues investigated differed from each other predominantly in their scattering properties. Thermal coagulation reduced the optical penetration depth substantially. The highest penetration depths for all tissues investigated were found in the wavelength range between 1000 and 1100 nm. A comparison with data from the literature revealed the importance of the employed tissue preparation technique and the impact of the theoretical model used to extract the optical coefficients from the measured quantities.

Myostatin (MSTN), a negative regulator of muscle growth and size, is increased after acute myocardial infarction (AMI) but timing of upregulation after injury is not known. In this study, we investigated the timing of the MSTN/AKT/p38 pathway activation in heart and skeletal muscle after AMI, as well as the potential effect of cardiac injury-related MSTN endocrine signaling on skeletal muscle and other circulating growth factors. Methods Coronary artery ligation was performed in C57BL/6 mice at age 8 weeks to induce AMI. Mice were sacrificed at different time points (10 m, 1 h, 2 h, 6 h, 12 h, 24 h, 1 week, 2 weeks, 1 months and 2 months) after surgery ( n = 3 per time point, n = 18 total). Results Cardiac and circulating MSTN upregulation occurred as early as 10 min after AMI. Two months after AMI, increased cardiac MSTN/SMAD2,3 and p38 together with decreased IGF-1/AKT signaling suggest an anti-hypertrophic profile. In skeletal muscle, an absence of local MSTN increase was accompanied by increased MSTN-dependent SMAD2,3 signaling, suggestive of paracrine effects due to cardiac-derived MSTN. Protein degradation by the ubiquitin–proteasome system in the skeletal muscle was also evident. Serum from 24 h post-MI mice effectively induced a MSTN-dependent increase in atrogin1 and MuRF1. Conclusion Our study shows that cardiac MTSN activation occurs rapidly after cardiac ischemia and may be involved in peripheral protein degradation in the skeletal muscle by activating atrogin1 and MuRF1.

Background: Ca2+/calmodulin-dependent protein kinase (CaMK)II has been implicated in impaired myocardial Ca2+ signaling and may play an important role in the development of heart failure (HF). The objective of this study was to characterize CAMKII signaling in patients with HF before and after prolonged left ventricular assist device (LVAD) support. Methods: LV apex tissue pairs were collected in patients with dilated cardiomyopathy (n=10) at LVAD implantation and explantation. Normal cardiac tissue was used as control (n=4). Total protein, as well as cytoplasmic and nuclear fractions, were analyzed by Western Blot analysis. Results: The duration of LVAD support ranged from 48 to 595 days (mean = 271±54) with no patient exhibiting myocardial recovery. Total CamKIIδ levels in failing hearts were significantly higher than normal hearts and increased after LVAD, mainly due to an increase in cytoplasmic CaMKIIδC, which regulates Ca2+ handling (Table 1). Nuclear CaMKIIδB, which regulates Ca2+ gene transcription, did not change. Calmodulin remained increased in the nuclear and cytoplasmic fractions after LVAD. CaMKII autonomous, non-CaM-dependent activity, reflected by phosphorylation in Thr207, was increased pre- and post LVAD in cytoplasmic CaMKIIδC. The CaMKII-dependent myocyte enhancer factor 2 (MEF2) was increased pre- and significantly further post LVAD in the nucleus while decreased in the cytoplasm, suggesting translocation into the nucleus after LVAD support. Class IIa HDACs 4 and 5 interact with MEF2, resulting in repression of MEF2-dependent genes. Phosphorylated levels of HDAC4 and HDAC5 were increased pre- and post LVAD, which would result in activated MEF2. Conclusions: This study shows for the first time an increase of the hypertrophic factor MEF2 associated with persistent activation of CamKIIδC after prolonged LVAD support, which may have implications for cardiac remodeling during mechanical support.

Introduction: Adults with congenital heart disease (ACHD) are at increased risk for early adverse outcomes following heart transplantation (Htx). Despite the need for improved risk stratification, small cohorts have constrained identification of patient-specific factors associated with poor prognosis. We hypothesized that type of CHD, number of sternotomies and prior end-organ dysfunction would be associated with an increased risk for mortality post-HTx. Methods: We performed a retrospective, observational cohort study of all patients with ACHD who underwent HTx at our institution from 1/1997 to 1/2014. The primary endpoint was death. Exposures of interest included type of CHD, number of sternotomies and hepatic dysfunction secondary to passive congestion, measured as high Models for End-Stage Liver Disease Excluding INR (MELD-XI) score. Results: 48 ACHD patients were followed (mean age at HTx: 36±1.7 years). Diagnoses included: Tetralogy of Fallot (TOF)/pulmonary atresia/double outlet right ventricle in 15 (31%), D-transposition of the great arteries in 10 (21 %), tricuspid atresia/double inlet left ventricle in 9 (19%), VSD/ASD in 4 (8%), heterotaxy in 3 (6%), congenitally corrected transposition of the great arteries in 2 (4%), and 5 (10%) with other diagnoses. Pre-transplant cardiac surgeries included: Fontan operation in 12 (25%), Mustard/Senning repair in 9 (19%), TOF repair in 5 (11%), Rastelli repair in 5 (11%), VSD/ASD closures in 3 (6%), other another congenital heart surgery in 8 (17%) and no prior cardiac surgery in 5 (11%). Over a median follow-up time of 3.9 years, 14 patients died (29%) and 10 (71%) deaths occurred within 30 days of HTx. Survival at 1 and 5 years was 77%. Deaths within 30 days of surgery were secondary to hemorrhage in 4 (40%), graft failure in 3 (30%) and multi-system organ failure in 3 (30%). By multivariate analysis, ≥3 sternotomies (HR 8.5, p=0.02), MELD-XI score >18 (HR 6.2, p=0.009) and heterotaxy (HR 9.8, p=0.01), were significant predictors of mortality. Conclusion: In our cohort of patients with CHD undergoing Htx, ≥3 sternotomies, MELD-XI score >18 and heterotaxy syndrome were significantly associated with death. These findings may be important in patient selection and timing of Htx in this population.

Various treatment strategies have been developed to treat hypertension and affect its clinical outcome. These include early lifestyle modifications such as weight loss, nutritional changes, and exercise as well as pharmacological interventions that are based on diuresis, inhibition of the renin-angiotensin system, calcium channel blockade, central and peripheral sympatolysis, as well as α- and β-receptor blockade.1 In individuals with prehypertension and patients with established hypertension, initial treatment, before the administration of pharmacological therapies, focuses on lifestyle changes targeting nutrition and exercise.1 In particular exercise is an intervention that is widely prescribed and recommended. Multiple clinical trials have shown effects of exercise on blood pressure with an average reduction of −10 mm Hg systolic and −8 mm Hg diastolic.2 Unfortunately, exercise is notoriously difficult to observe, evaluate, and dose in an outpatient population with hypertension.2,3 Exercise is a physiological intervention with a broad variety of positive cardiovascular effects that include changes in lipid metabolism, insulin resistance, weight, arterial hypertension, inflammation, endogenous anabolism, and mood.2 It seems, in fact, reasonable to hypothesize that metabolic abnormalities associated with the primarily sedentary lifestyle in modern Western civilizations are not only counteracted but normalized by physical activity. Therefore, regular exercise would be a physiological correction rather than a medical treatment intervention. Exercise programs distinguish between primarily aerobic dynamic (eg, running and cycling) and resistance (eg, strength training) exercises. Dynamic exercise with alternating muscle contraction and relaxation results in a steady rise of systolic blood pressure when intensity increases, whereas the diastolic pressure varies minimally. In contrast, resistance exercise is characterized by prolonged isometric muscle contraction before relaxation with high interstitial pressure that causes collapse of arterioles and capillaries. Blood pressure increases in relation to intensity and duration of the contraction. Effects of exercise on the myocardium have been well established. …

To study whether neuronal regeneration occurs after laserinduced interstitial thermotherapy (LITT) of the brain, we examined lesions and their margins in adult Lewis rats with histological and immunohistochemical methods. We used the Bodian stain and antibodies against β-amyloid precursor protein (APP), which has been associated with trophic effects in neural regeneration and against heat-shock protein 72 (HSP 72) and neurofilament 68 (NF 68). The glial reaction was monitored with antibodies against glial fibrillary acidic protein (GFAP) and apolipoprotein E (Apo E). β-Amyloid precursor protein showed a distinct temporal profile in areas of lesion margins thought to be associated with neurite sprouting and regeneration. Axonal accumulation of APP started 1 h after LITT and reached a maximum after 3 days. Heat-shock protein 72 was weakly positive in isolated marginal neurons in the early postoperative period. Subsequent to GFAP expression, Apo E immunoreactivity was detected in reactive astrocytes but not in profiles thought to be axonal sprouts. The results showed that margins of LITT-induced lesions contain profiles which resemble sprouting neurites and are similar to those found after injury or ischemia but with differences in the time course of reactive proteins.

Objectives This study aimed to investigate the utility of serial tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) for monitoring right ventricular failure (RVF) after left ventricular assist device (LVAD) surgery. Background RVF post-LVAD is a devastating adverse event. Methods The authors prospectively studied 68 patients undergoing elective LVAD surgery. Echocardiograms were performed within 72 h before and 72 h after surgery. RVF was pre-specified as: 1) the need for salvage right ventricular assist device (RVAD); or 2) persistent need for inotrope and/or pulmonary vasodilator therapy 14 days after surgery. Patients were classified as Group RVF or Group Non-RVF. Results A total of 24 patients (35.3%) met criteria for RVF. Preoperative TDI-derived S’ was lower and RV E/E’ ratio was higher (3.7 ± 0.6 cm/s vs. 4.7 ± 0.9 cm/s, 12.0 ± 2.3 vs. 10.0 ± 2.5, both p l 0.001, respectively), and the absolute value of RV longitudinal strain (RV-strain) obtained from STE was lower (–12.6 ± 3.3% vs. –16.2 ± 4.3%, p l 0.001) in Group RVF vs. Group Non-RVF. Echo parameters within 72 h after surgery showed higher RV-E/E’, (13.9 ± 4.6 vs. 10.1 ± 3.0, p l 0.001) and lower RV-strain (–11.8 ± 3.5% vs. –16.7 ± 4.4%, p l 0.001) in Group RVF vs. Group Non-RVF. Preoperative S’l4.4 cm/s, RV-E/E’>10 and RV-strain l –14% discriminated patients who developed RVF at day 14 with a predictive accuracy of 76.5%. When we included postoperative RV-E/E’ and RV-strain, the predictive accuracy increased to 80.9%, with a sensitivity of 66.7% and a specificity of 88.7%. Conclusions Serial echocardiograms using TDI and STE before and soon after LVAD surgery may aid in identifying need to initiate targeted RVF specific therapy in this population.

Right ventricular failure (RVF) after left ventricular assist device (LVAD) placement is associated with increased morbidity and mortality. Echocardiography is a primary imaging method in the assessment of cardiac function; however, visualization of the right-sided heart is often technically difficult in patients with heart failure. We aimed to create a simple and generally applicable scoring system based on "left-sided echocardiographic parameters" to provide complementary information for predicting RVF after LVAD surgery. We reviewed 111 consecutive patients undergoing LVAD surgery from 2007 through 2010. Echocardiograms within 5 days before surgery were analyzed. RVF was defined as an unexpected RV assist devices requirement, nitric oxide inhalation48 hours, and/or inotropic support14 days. Thirty-five patients (32%) developed RVF. LV end-diastolic dimension (LVEDD) was smaller, LV ejection fraction was greater, and the left atrial diameter/LVEDD ratio was greater (p0.05 for all comparisons) in patients with RVF than in those without RVF. An RVF score (LV echocardiographic RVF score) was determined as a sum of points based on receiver operator characteristics analysis: LVEDD78, 79 to 70, and70 mm; LV ejection fraction ≤19%, 19% to 33%, and33%; and left atrial diameter/LVEDD0.63, 0.63 to 0.68, and0.68; each variable was associated with 0 and 1 point and 2 points, respectively. LV echocardiographic RVF score ≥3 was associated with RVF with a sensitivity of 88.6% and score ≥5 with a specificity of 80.3%. In conclusion, patients with relatively small LV size, preserved LV contraction, and dilated left atrium were at higher risk for RVF after LVAD surgery. In conclusion, LV echocardiographic RVF score provides a novel tool to predict RVF after LVAD surgery, which does not involve invasive or technically complicated procedures.

Purpose Galectin-3 (gal-3) is a novel biomarker implicated in cardiac fibrosis and is shown to correlate with the severity of heart failure (HF) and to independently predict mortality in HF. We investigated if hemodynamic improvement after left ventricular assist device (LVAD) implantation affects gal-3 levels. Methods and Materials Plasma samples were acquired from patients at time of LVAD implantation (HMII or Heartware, n=57), at 3 (n=17) and 6 months post-LVAD (n=14), and at explantation (n=23), as well as from healthy age and gender matched controls (n=30). Gal-3 was measured using a commercially available ELISA assay (BG Medicine, Waltham, MA). Data was analyzed with Prism 5. Events rates were calculated using the Kaplan-Meier method. Results At time of LVAD implantation, HF patients had significantly higher gal-3 levels compared to controls (29.2±14 ng/ml vs. 13±9 ng/ml; p figure 1 ] Conclusions Gal-3 levels are associated with HF state and predict survival on LVAD support. Distinct dynamics in gal-3 levels occur in patients following LVAD implantation with an initial decrease but subsequent increase. Gal-3 may serve as a new biomarker for risk assessment of patients before LVAD implantation.

Metabolic abnormalities leading to a catabolic syndrome with progressive muscular atrophy are a common final stage of various chronic diseases. Proinflammatory cytokines have been suggested both to induce and mediate local catabolic mechanisms. This review focuses on the role of proinflammatory cytokines in the development of muscular abnormalities resulting in a loss of muscle mass and function. In addition, the underlying molecular signaling pathways, their transcriptional regulation, and the cellular systems contributing to enhanced muscular protein breakdown are discussed.Using transcriptional screening techniques, specific changes in gene expression have been identified that are characteristic of muscular wasting processes. Of particular interest is the atrophy-related and cytokine-inducible expression of a number of E3 ligases (e.g. atrogin-1, muscle ring finger protein 1), highly specific regulators of the ubiquitin-proteasome pathway, which target proteins for proteolytic breakdown by the proteasome. Furthermore, the activity of several transcription factors (e.g. nuclear factor kappa B) has been involved in specific transcriptional mechanisms of local inflammation and muscular atrophy. Finally, proinflammatory cytokines suppress the expression and function of the local anabolic growth factor insulin-like growth factor 1.Pronounced catabolic effects of proinflammatory cytokines in various tissues contribute to local catabolism, with progressive atrophic alterations of the skeletal muscle in chronic disease states. Recent developments in this field have explored the underlying pathways of muscular wasting and have already resulted in the description of new molecular targets that might lead to new therapeutic options for the treatment of muscular atrophy.

In the advanced stages of chronic heart failure (CHF) the expression of inducible nitric oxide synthase (iNOS) in skeletal muscle (SM) may contribute to exercise intolerance and early fatigue. Cell culture studies and promoter analysis demonstrated that the transcription factor nuclear factor kappa B (NF-kappaB) is essential for iNOS-expression. The aim of this study was to assess whether NF-kappaB is activated in skeletal muscle of patients with CHF and linked to the expression of iNOS.Skeletal muscle biopsies were obtained from seven CHF patients and seven healthy controls (HC). Nuclear proteins were isolated and the content of activated NF-kappaB was analysed by electrophoretic mobility shift assay (EMSA). Inducible nitric oxide synthase expression in SM was determined by real time polymerase chain reaction (PCR).The expression of iNOS (1.4 +/- 0.2 versus 0.5 +/- 0.08 arbitrary units, P=0.001) and the activation of NF-kappaB in the SM (0.5 +/- 0.1 versus 0.1 +/- 0.04 arbitrary units, P=0.009) was significantly increased in CHF patients as compared to healthy controls. Furthermore, a linear correlation was observed between NF-kappaB activation and iNOS expression (r=0.78, P0.001).The results of this study indicate for the first time that in the skeletal muscle of patients with chronic heart failure the activation of the transcription factor NF-kappaB is increased and may represent one important regulatory factor for the expression of iNOS in patients. Nevertheless, due to the small sample size this observation has to be confirmed in subsequent studies with more patients.

Objective: The intracellular pathway and the regulation of inducible nitric oxide synthase (iNOS) expression in skeletal muscle is incompletely understood. In vitro studies, using different cell types, suggest that inflammatory cytokines are potential triggers to induce iNOS expression. Methods: To analyze intracellular pathways leading to iNOS induction, rat skeletal myoblasts were incubated with inflammatory cytokines and assessed for iNOS expression by Western blot and Griess reaction. To confirm the in vitro findings, local cytokine levels were determined in skeletal muscle biopsies of patients with chronic heart failure (CHF) and correlated with iNOS expression. Results: Nitrite accumulation in the myoblast culture supernatant or iNOS protein in the cell pellet was significantly increased after incubation with IL-1β in combination with γ-IFN. Priming experiments revealed that γ-IFN elevated the expression of IL-1β receptor mRNA, whereby IL-1β was able to induce iNOS expression. The cytokine-mediated iNOS induction was significantly reduced by blocking ERK1/ERK2 activation and completely abolished by the inhibition of NFκB. In skeletal muscle biopsies of CHF patients the local content of IL-1β was significantly increased as compared to healthy controls. Furthermore, a linear correlation between IL-1β content and iNOS expression in the skeletal muscle was detected. Conclusions: These data demonstrate that IL-1β, together with the priming effect of γ-IFN, induces iNOS expression in skeletal muscle via activation of ERK1/ERK2 and NFκB.

OBJECTIVES We sought to assess the role of insulin-like growth factor-I (IGF-I) in muscle wasting in chronic heart failure (CHF), serum concentrations and local muscular IGF-I expression were determined in patients with severe CHF. BACKGROUND Chronic heart failure is associated with progressive muscle atrophy, leading to cardiac cachexia. Skeletal muscle disuse and inflammatory activation with elevated cytokine levels have been implicated; however, the pathomechanism involved remains largely unknown. METHODS Serum levels of IGF-I were measured by competitive solid phase immunoassay in 47 patients with severe CHF (left ventricular ejection fraction 30%) and 15 age-matched healthy subjects (HS). Insulin-like growth factor-I and IGF-I receptor expression were assessed in vastus lateralis biopsies by real-time PCR and Western blot analysis. RESULTS Although serum IGF-I was not significantly different (175 10 ng/ml in CHF vs. 170 12 ng/ml in HS, p NS), local muscle IGF-I mRNA expression was reduced by 52% in CHF (6.7 0.4 vs. 14.0 0.9 arbitrary units in HS, p 0.001). This was accompanied by an increase in IGF-I receptor mRNA expression (86.8 5.4 in CHF vs. 23.1 1.8 arbitrary units in HS, p 0.001). Local IGF-I expression was significantly correlated with muscle cross-sectional area (R 0.75, p 0.01). Chronic heart failure patients with a body mass index of 25 kg/m 2 showed signs of peripheral growth hormone (GH) resistance, as indicated by elevated serum GH, and reduced IGF-I levels. CONCLUSIONS In CHF patients, muscle IGF-I expression is considerably reduced in the presence of normal serum IGF-I levels, possibly contributing to early loss of muscle mass. These findings are consistent with a potential role of IGF-I for skeletal muscle atrophy in CHF. (J Am Coll Cardiol 2002;39:1175– 81) © 2002 by the American College of Cardiology Foundation In recent years it has become widely accepted that the catabolic syndrome associated with advanced stages of chronic heart failure (CHF) is more than a symptom of disease progression; cardiac cachexia has been shown to be correlated with lower exercise tolerance and reduced survival (1). However, the process leading to progressive loss of muscle mass and exercise capacity, finally resulting in cardiac cachexia, is still not completely understood. Muscle wasting starts long before the clinical signs of overt cachexia become apparent. It has already been documented that noncachectic patients with CHF show reduced leg lean tissue compared with healthy subjects (HS) (2), suggesting that the factors responsible for the initiation of the catabolic process may be present at early stages of the heart failure syndrome. Until now a number of different humoral factors have been accused of being responsible for the catabolic process in CHF, among them elevated serum cytokines (3) and catecholamines (4), cortisol/dihydroepiandrosterone imbalance (5) and growth hormone (GH) resistance (5). A possible causal relationship between these factors and the catabolic syndrome was inferred based on the presumption that serum hormone levels are representative of local concentrations in target organs—most notably the skeletal muscle. However, this presumption has not been validated. In the context of the present study we focused on the GH/IGF-I axis (GH/IGF-I)—a key system involved in regulation of normal cell growth, hypertrophy and atrophy. It has been shown that, in patients with CHF, low levels of systemic IGF-I are associated with a decreased leg muscle cross-sectional area and strength (6). We therefore hypothesized that the GH/IGF-I axis may be involved in the pathogenesis of skeletal muscle catabolism and dysfunction in CHF. Insulin-like growth factor-I exerts its functions via both autocrine and paracrine pathways. In order to assess the relation between local and systemic concentrations of IGF-I and GH the serum IGF-I and GH levels were measured and compared to the local expression of IGF-I and IGF-I receptor in the quadriceps muscle and noncachectic patients with CHF and of HS.

Background and Objectives Laser-induced thermotherapy (LITT) is an approach to the treatment of brain tumors especially in poorly accessible regions. Its clinical applicability with tumor cell destruction has been shown in several studies. However, no data are known about specific effects on tumors cells due to LITT in the time course of the lesion. Study Design/Materials and Methods LITT was performed in adult Lewis rats with implanted glioma cells in the brain using a standard exposure of 3 W for 30 seconds. Before and following LITT, neoplastic lesions were monitored by MRI. Proliferation of implanted cells and gliosis were assessed by several histological techniques and immunohistochemistry. Apoptosis was detected by TUNEL staining. Results Our experiments show a destruction of neoplastic cells by LITT but surviving tumor cells at the margin of the lesion. Apoptosis was detected following LITT restricted to residual neoplastic cells. Marginal survival of tumor cells lead to a secondary outgrowth into the necrotic lesion adjacent to sprouting capillaries. Conclusions LITT is a suitable technique for the treatment of brain neoplasms. However, further investigations are necessary to prevent tumor recurrences after LITT. Lasers Surg. Med. 30:227-232, 2002. © 2002 Wiley-Liss, Inc.

This editorial refers to ‘Detrimental effect of fractalkine on myocardial ischemia and heart failure’ by W. Xuan et al ., pp. 385–393, this issue. The endothelium plays a central role in maintaining cardiovascular integrity, function, and the response to injury. A multitude of bioactive molecules is known to be expressed in and secreted from the endothelium under both physiological and pathophysiological circumstances. Xuan et al. 1 uncover a unique role for fractalkine (FKN), a novel membrane-bound chemokine that is mainly expressed in endothelial cells in myocardial ischaemia and heart failure (HF). FKN, also known as CX3CL1, is an atypical chemokine that exists in either a membrane-bound form or as a cleaved soluble chemokine.1 The membrane-bound form acts as an adhesion molecule and can enable leucocyte adhesion via binding to CX3CR1, expressed on monocytes, NK cells, and a small subset of T cells.2,3 Under inflammatory conditions, the membrane-bound form can be cleaved to release a soluble chemokine that functions as a chemoattractant for monocytes and T cells.4 FKN has been implicated in a number of disease states, including atherosclerosis,5 glomerulonephritis,6 and cerebral ischaemia.7 Although also expressed in cardiomyocytes, very little is known about …

Chronic heart failure is defined as the inability of the heart to meet the circulatory demands of the organism. While cardiac injury, e.g. of ischaemic, toxic, metabolic, or genetic cause, is the initial abnormality, secondary changes occur over the course of the disease affecting most organ systems. This leads to a variety of pathologic changes including endothelial, pulmonary, hepatic, renal, endocrine and skeletal muscle abnormalities, and the state of multi-organ impairment in chronic heart failure is now considered the syndrome of chronic heart failure.1 A neuroendocrine activation has been described early in the stages of heart failure research with the demonstration of elevated levels or norepinephrine and epinephrine in patients with dilated and ischaemic cardiomyopathy.1 While initially thought to be a compensatory and protective mechanism, it has been shown that it in fact leads to increased myocardial oxygen demand, structural damage, myocardial apoptosis, and results in the suppression of myocardial β-adrenergic receptors which through a negative feed-back mechanisms leads to further increase in circulating levels of norepinephrine and epinephrine. Blockade of β-adrenergic receptors, initially highly controversial, has been shown to be one of the most effective … *Corresponding author. E-mail address : christian.schulze{at}bmc.org

The laser-induced interstitial thermo-therapy of brain tumors requires an exact therapy planning. Therefore, the knowledge of the optical properties of native (na) and coagulated (co) tissue structures is important. In this study the optical properties of native and thermally coagulated (2 h, 80 degree Celsius) human white (n equals 14; na equals 7, co equals 7) and gray matter (n equals 14; na equals 7, co equals 7) were investigated (spectral range equals 360 - 1100 nm, spectral resolution 20 nm) in vitro using the integrating sphere technique combined with the inverse Monte-Carlo method. The (mu) a of the native gray matter decreased from 0.333 plus or minus 0.219/mm (360 nm) to 0.054 plus or minus 0.069/mm (1100 nm). The (mu) s varied between 14.13 plus or minus 4.26/mm (360 nm) and 5.53 plus or minus 1.80/mm (1100 nm). The g-value increased from 0.818 plus or minus 0.093 (360 nm) to 0.904 plus or minus 0.051 (1100 nm). Coagulation increased (mu) a and (mu) s by a factor up to 3 and g up to 16%. White matter exhibited a (mu) a between 0.253 plus or minus 0.055/mm (360 nm) and 0.100 plus or minus 0.052/mm (1100 nm) and a (mu) s between 40.20 plus or minus 9.18/mm (360 nm) and 28.65 plus or minus 6.83/mm (1100 nm). The g-value varied between 0.702 plus or minus 0.093 (360 nm) and 0.886 plus or minus 0.012 (1100 nm). Coagulation increased (mu) a up to a factor of three and the g-value up to 14% while the increase (approximately 1.25 fold) of (mu) s was not significant. We conclude the optical properties of human brain tissue change significantly due to thermal denaturation.

Purpose Liver abnormalities have prognostic impact on the outcome of patients with advanced heart failure.We evaluated the Model of End-stage Liver Disease (MELD) score and its modified versions, established measures of liver dysfunction, as a tool to evaluate HTx urgency in ambulatory HF patients. Methods and Materials We retrospectively evaluated 343 patients undergoing HTx evaluation between 2005 and 2009. The prognostic effectiveness of MELD/MELDNa/MELD-XI for endpoint events defined as death/HTx/ventricular assist device (VAD) requirement was evaluated in our cohort and in subgroups of patients on and off oral anticoagulation. Results The MELD and MELDNa score were excellent predictors for 1 year endpoint events (AUC: 0.71 and 0.73, respectively). High scores (>12) were strongly associated with poor survival at one year (MELD: 69.3% vs. 90.4%, p Conclusions Assessment of liver dysfunction using the MELD scoring system provides additional risk information in patients with ambulatory heart failure.

Purpose Hemolysis is a well-known complication of left ventricular assist device (LVAD) implantation that contributes to hemodynamic derangement and end-organ damage. Micro-RNAs (miRs) are non-coding RNA species that control gene expression by targeting specific messenger RNAs for degradation. MiR-451 is specifically expressed in erythrocyte precursors and mature red blood cells. The goal of this study was to evaluate changes in circulating miR-451 levels before and after LVAD implantation and whether these changes associate with measures of hemolysis. Methods and Materials Blood samples were obtained from healthy volunteers and from patients with advanced heart failure at the time of LVAD implantation and at the time of explantation. Absorbance at 414 nm (ABS 414 ), the maximum absorbance of hemoglobin, was measured in plasma. RNA was extracted from plasma and RT-PCR specific for miR-451 was performed. Results The mean duration of LVAD therapy was 488 ± 179 days. Plasma ABS 414 correlated with the degree of hemolysis of blood that was mechanically disrupted in vitro. The mean plasma ABS 414 was increased 3.4-fold after LVAD implantation compared to paired pre-implantation samples (P=0.05), which had a mean plasma ABS 414 comparable to non-hemolyzed control samples. Lactate dehydrogenase and bilirubin, commonly used tests for hemolysis, each correlated poorly with plasma ABS 414 among these patients (R2=0.20 and 0.22, respectively; each P nonsignificant) and did not differ between pre- and post-LVAD samples. Compared to control plasma, miR-451 levels were roughly 40% higher in samples from heart failure patients before LVAD placement. Plasma miR-451 levels increased 164-fold after LVAD implantation compared to paired pre-implant samples (Mann-Whitney P= 0.002). Conclusions Micro-RNAs hold promise as biomarkers in heart failure. MiR-451 may be a new marker of hemolysis related to LVAD implantation that performs favorably compared to traditional markers.

Purpose Heart failure (HF) is associated with abnormal metabolism and lipotoxicity. Fatty acids (Fas) and fatty acyl-CoAs may act as important mediators of lipotoxicity but their composition in human HF is unclear. We analyzed acyl-CoA and FA species in patients with HF before and after implantation of a ventricular assist device (LVAD) and controls. Methods and Materials Serum and myocardium were collected from 20 pats before and 15 pats after LVAD placement and 10 controls (con). FA and fatty acyl-CoA content were measured by LC/MS. Results Myocardial total fatty acyl-CoA (2.0±0.4 vs. 4.8±0.4 nmol/g in con, p 0.05) compared to con indicating reduced cardiac lipid uptake. Myocardial fatty acyl-CoA species C14, C16, C18, C16:1, C18:2, C18:1 and C20:4 were lower in HF compared to con (all p Conclusions HF is associated with decreased cardiac Fas and fatty acyl-CoA content. Mechanical unloading improves myocardial and skeletal metabolism with increased fatty acyl-CoAs and increased unsaturated fatty acyl-CoAs, suggesting increased lipid uptake. Thus, impaired lipid metabolism in HF can be corrected by LVAD therapy and potentially with pharmacologic therapies.

judged as signs of possible LVAD indication. Lastly, in-hospital and 1-year outcome was analyzed and compared with outcome of LVAD implanted from 2007 to 2010 (C-LVAD). Results: 1244 pts were hospitalized for HF in one year. 191 were excluded due to age and 270 for other causes. 59 out of the remaining 783 pts had LVEF 0.35 and received inotropes, but only 38 (3%) were considered appropriate potential LVAD candidates after hospital chart review. Inhospital mortality was 5/38 (13%). Within 1-year, 8 pts underwent to heart transplant and 3 to LVAD with 10 surviving; 8/16 (50%) of medically managed pts died. In-hospital mortality after 2007-2010 C-LVAD implantation was 5/27 (18.5%). In 1-year, 3 pts were transplanted and only 1/20 pts remaining on LVAD died. Conclusions: Pts with HF characterized by low LVEF and the need for inotropes have a poor 1-year prognosis on medical therapy and would probably benefit from LVAD. The proportion of pts potentially candidates for LVAD is low with respect to the total population of HF, but the absolute number is high due to the prevalence of this syndrome.

The Prevalence of Chronic Kidney Disease before and after Orthotopic Heart Transplant: Does the Degree of eGFR Decline Proportionally Translate into Poorer Patient Outcomes? J. Jiang, A. Almehmi, M. Ji, H. Yerebakan, M.A. Farr, M. Argenziano, C.R. Smith, H. Takayama, D.M. Mancini, Y. Naka, P.C. Schulze, F.H. Cheema. Department of Cardiothoracic Surgery, Columbia University Medical Center, New York, NY; Department of Cardiology, Columbia University Medical Center, New York, NY; Division of Nephrology, University of Tennessee College of Medicine, Memphis, TN.

New Onset Atrial Fibrillation and Atrial Flutter after Cardiac Transplant Is Associated with High Mortality and Cardiac Allograft Vasculopathy L.K. Soni, J. Jiang, M. Ji, S. Cheung, E. Heng, H. Yerebakan, C.R. Smith, M.A. Farr, H. Takayama, M. Argenziano, D.M. Mancini, Y. Naka, P.C. Schulze, F.H. Cheema. Department of Cardiothoracic Surgery, Columbia University Medical Center, New York, NY; Department of Cardiology, Columbia University Medical Center, New York, NY.