Lack of cardioprotection from metabolic support with glutamine or glutamate in a porcine coronary occlusion model

Objective Previous experimental studies indicate that glutamine or glutamate may provide cardioprotection by improving the oxidative metabolism in myocardial ischemia. We investigated the effect of glutamine or glutamate, given during reperfusion, on resulting infarct size and hemodynamic recovery.

Design A porcine coronary occlusion model was applied. Infusions were initiated 15 min before reperfusion and supplemented with intracoronary bolus doses at reperfusion. The primary outcome measure was infarct size in relation to area at risk determined by a standard tissue staining procedure. Secondary outcome measures were the hemodynamic variables.

Results The infarct sizes as a proportion of the area at risk (mean±SD) were: control group, 0.64±0.19 (n=9); glutamine group, 0.87±0.07 (p<0.05 vs control group) (n=8); glutamate group, 0.72±0.11 (n=9). Glutamine increased systemic vascular resistance, while glutamate preserved cardiac output during infusion.

Conclusion Substrate supplementation with the anaplerotic precursors glutamine and glutamate is ineffective as adjunctive therapy for severe myocardial ischemia. Beneficial effects documented in less complex experimental systems could not be transferred to a more pathophysiological relevant model.     

Percutaneous Transluminal Coronary Angioplasty versus Thrombolysis in Acute Myocardial Infarction: A Prospective,Matched, Controlled Study

The aim of this study was to evaluate the outcome of primary percutaneous transluminal coronary angiography (PTCA) in the treatment of acute myocardial infarction (AMI) The study included patients with electrocardiographic signs of transmural AMI, symptom duration of less than 12 h, and with no contraindications to thrombolytic therapy. Patients who had undergone primary PTCA were matched consecutively, for age, gender, infarct localization and duration of symptoms, to patients who had received thrombolytic therapy (82 patients to each group). Patients who were admitted to hospital during daytime had a primary PTCA, whereas those admitted outside daytime were given thrombolytic therapy. In the primary PTCA group, 9 patients had a combined endpoint compared with 22 patients in the thrombolysis group (p &lt; 0.02 ). In-hospital mortality was 3.7% in the PTCA group and 4.9% in the thrombolysis group (ns). At six months, a combined endpoint occurred in 23 patients in the primary PTCA group and in 50 patients in the thrombolysis group (p &lt; 0.00005). Six months' mortality was 4.9% in the PTCA group and 7.3% in the thrombolysis group (ns). Among patients in the PTCA group, left ventricular ejection fraction was significantly higher, stay in hospital was shorter and there were significantly fewer incidences of heart failure and severe arrhythmias than among patients in the thrombolysis group. The results of primary PTCA implemented in our departments are comparable with those reported in randomized trials from experienced centres. Our study indicates that patients treated with primary PTCA have fewer complications, a better left ventricular systolic function and a shorter hospital stay compared with patients treated with thrombolysis.     

99m Tc-Sestamibi SPECT is a Useful Technique for Viability Detection. Results of a Comparison with NH 3 /FDG PET

Objective - Assessment of myocardial viability by 99m Tc-Sestamibi Single Photon Emission Computerized Tomography (SPECT) has been suggested as a more readily available and cheaper alternative to Positron Emission Tomography (PET) with 13 N-ammonia (NH 3 ) and 18 F-fluoro-deoxy-glucose (FDG). We hypothesized that a semi-quantitative evaluation by SPECT could delineate myocardial viability with an acceptable concordance to PET. Design - Fifty patients (age 57 &#45 7 years; ejection fraction 28 &#45 8%), with ischemic cardiomyopathy, underwent SPECT and PET imaging in random order. Viability by SPECT was defined as a defect size <50% of the segment area, or a defect representing &#83 50% of the segment but with a mean activity &#83 50% of peak activity. PET viability was defined as a perfusion score >2 and FDG score &#104 2 (five-point scale, 0 = normal, 4 = absent activity). Results - By segmental comparison to PET, SPECT yielded a sensitivity and specificity of 87% and 82% for detection of viable myocardium. The positive and negative predictive values were 96% and 58%, respectively. Conclusion - In patients with severe ischemic cardiomyopathy 99m Tc-Sestamibi SPECT can delineate viable myocardium with an acceptable segmental concordance to NH 3 /FDG PET.     

Inverse Association Between Birth Weight,Birth Length and Serum Total Cholesterol in Adulthood

Objectives - To investigate whether impaired fetal growth, measured by low birth weight and short birth length, is linked with raised levels of serum lipids and increased risk and mortality of coronary heart disease. Design - The association between birth length, birth weight, Ponderal Index and total serum cholesterol was examined in 545 Danish men and women aged 31 to 51 years who participated in the Ebeltoft Health Promotion Project in Denmark. Results - No associations were found in women. For men, a negative association was found between birth weight and serum total cholesterol, with a fall in mean serum total cholesterol from 6.03 mmol/l at birth weight below 3300 g to 5.64 mmol/l at birth weight above 4000. A similar association was found between birth length and serum cholesterol, with a mean value of 6.23 mmol/l at birth length below 51 cm and a mean value of 5.56 mmol/l at birth length above 54 cm. No associations were found for Ponderal Index. Between 3% and 8% of the variance in serum total cholesterol could be explained by the statistical models used in this study. Conclusion - Our findings support the hypothesis of a negative association between birth weight, birth length and elevated serum cholesterol in adult life, but only in men.     

Fast-track laparoscopic bariatric surgery: a systematic review

This study aimed to systematically evaluate the evidence-based literature on fast-track laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic adjustable gastric banding (LAGB) to determine the feasibility and safety of fast-track laparoscopic bariatric surgery. A literature search of PubMed, EMBASE and Cochrane Library using the MeSH terms “bariatric surgery”, “ambulatory surgical procedures” and related terms as keywords was performed. The study included articles that reported on intended next-day discharge for LRYGB and same-day discharge for LAGB. Data were extracted on study design and size, patient demographics, patient-selection criteria, patient preparation, perioperative management, operative details, clinical outcomes, and follow-up. The review included 13 studies classified as level 3b or 4 evidence. There were seven studies that investigated LAGB, five studies investigated LRYGB and one study detailed outcomes from both LRYGB and LAGB. Next-day discharge rate ranged from 81 to 100 % for LRYGB. Same-day discharge rate ranged from 76 to 98 % for LAGB. In LRYGB and LAGB complication, re-admission and mortality rates (≤10.5, ≤7.5, ≤0.1 %, respectively) were comparable with the conventional perioperative care. From our results, the fast-track management of patients undergoing LRYGB and LAGB is feasible. With careful patient selection and preparation within high-volume centres, and application of care pathways including close outpatient follow-up, outcomes for fast-track bariatric procedures can compare favourably with those reported in the literature for standard management, but with decreased cost. However, further studies from independent researchers are required to determine the safety of a generalised adoption of this approach outside of dedicated bariatric units, and to formally demonstrate the cost-benefit of fast-track bariatric surgery.     

In vivo imaging of system xc- as a novel approach to monitor multiple sclerosis

Purpose

Glutamate excitotoxicity contributes to oligodendroglial and axonal damage in multiple sclerosis pathology. Extracellular glutamate concentration in the brain is controlled by cystine/glutamate antiporter (system xc-), a membrane antiporter that imports cystine and releases glutamate. Despite this, the system xc^? activity and its connection to the inflammatory reaction in multiple sclerosis (MS) is largely unknown.

Methods

Longitudinal in vivo magnetic resonance (MRI) and positron emission tomography (PET) imaging studies with 2-[¹⁸F]Fluoro-2-deoxy-D-glucose ([¹⁸F]FDG), [¹¹C]-(R)-(1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl)-3-isoquinolinecarboxamide ([¹¹C]PK11195) and (4S)-4-(3-¹⁸F-fluoropropyl)-L-glutamate ([¹⁸F]FSPG) were carried out during the course of experimental autoimmune encephalomyelitis (EAE) induction in rats.

Results

[¹⁸F]FSPG showed a significant increase of system xc^? function in the lumbar section of the spinal cord at 14 days post immunization (dpi) that stands in agreement with the neurological symptoms and ventricle edema formation at this time point. Likewise, [¹⁸F]FDG did not show significant changes in glucose metabolism throughout central nervous system and [¹¹C]PK11195 evidenced a significant increase of microglial/macrophage activation in spinal cord and cerebellum 2 weeks after EAE induction. Therefore, [¹⁸F]FSPG showed a major capacity to discriminate regions of the central nervous system affected by the MS in comparison to [¹⁸F]FDG and [¹¹C]PK11195. Additionally, clodronate-treated rats showed a depletion in microglial population and [¹⁸F]FSPG PET signal in spinal cord confirming a link between neuroinflammatory reaction and cystine/glutamate antiporter activity in EAE rats.

Conclusions

Altogether, these results suggest that in vivo PET imaging of system xc^? could become a valuable tool for the diagnosis and treatment evaluation of MS.

     

Pitch Discrimination in Musicians and Non-Musicians: Effects of Harmonic Resolvability and Processing Effort

Musicians typically show enhanced pitch discrimination abilities compared to non-musicians. The present study investigated this perceptual enhancement behaviorally and objectively for resolved and unresolved complex tones to clarify whether the enhanced performance in musicians can be ascribed to increased peripheral frequency selectivity and/or to a different processing effort in performing the task. In a first experiment, pitch discrimination thresholds were obtained for harmonic complex tones with fundamental frequencies (F0s) between 100 and 500 Hz, filtered in either a low- or a high-frequency region, leading to variations in the resolvability of audible harmonics. The results showed that pitch discrimination performance in musicians was enhanced for resolved and unresolved complexes to a similar extent. Additionally, the harmonics became resolved at a similar F0 in musicians and non-musicians, suggesting similar peripheral frequency selectivity in the two groups of listeners. In a follow-up experiment, listeners’ pupil dilations were measured as an indicator of the required effort in performing the same pitch discrimination task for conditions of varying resolvability and task difficulty. Pupillometry responses indicated a lower processing effort in the musicians versus the non-musicians, although the processing demand imposed by the pitch discrimination task was individually adjusted according to the behavioral thresholds. Overall, these findings indicate that the enhanced pitch discrimination abilities in musicians are unlikely to be related to higher peripheral frequency selectivity and may suggest an enhanced pitch representation at more central stages of the auditory system in musically trained listeners.