L-carnitine: Searching for New Therapeutic Strategy for Sepsis Management.

In this review, we discussed the biological targets of carnitine, its effects on immune function, and how L-carnitine supplementation may help critically ill patients. L-carnitine is a potent antioxidant. L-carnitine depletion has been observed in prolonged intensive care unit (ICU) stays, while L-carnitine supplementation has beneficial effects in health promotion and regulation of immunity. It is essential for the uptake of fatty acids into mitochondria. By inhibiting the ubiquitin-proteasome system, down-regulating the apelin receptor in cardiac tissue, and reducing ß-oxidation of fatty acid, carnitine may decrease vasopressor requirement in septic shock and improve clinical outcomes of this group of patients. We also reviewed animal and clinical studies that have been recruited for evaluating the beneficial effects of L-carnitine in the management of sepsis/ septic shock. Additional clinical data are required to evaluate the optimal daily dose and duration of L-carnitine supplementation.

Ventricular substrate identification using close-coupled paced electrogram feature analysis.

AIMS: Substrate based catheter ablation strategies are widely employed for treatment of scar-related ventricular tachycardia (VT). We analysed intracardiac electrograms (EGMs) from close-coupled paced extrastimuli extracted from the EnSite Precision mapping system. We sought to characterize EGM responses of ventricular myocardium to varying coupling intervals from the right ventricular apex (RVA) in both healthy individuals and patients presenting with VT for catheter ablation. METHODS AND RESULTS: Extrastimuli were delivered from the RVA after estimation of the ventricular effective refractory period. Electrograms were recorded from high-density mapping catheters in the left ventricle and exported for analysis to MATLAB. Observational data were collected from 14 patients with ischaemic VT (mean age 72.4 ± 6.3 years, one female) and five controls (mean age 59.4 ± 7.4 years, one female). These derived data were used to inform an interventional strategy on a further 10 patients (mean age 64.7 ± 10.0 years; two female). Significant differences were observed in EGM duration (ED) and latency (LT) at all coupling intervals between VT patients and controls. Significant increases in ED and LT with decreased RVA coupling interval were observed at VT isthmuses. Abnormal responses derived from control subject data were used to classify four types of ventricular EGM response. Targeting sites with abnormal LT and ED significantly reduced VT inducibility (5/14 derivation patients to 0/10 intervention patients; P = 0.03). CONCLUSION: Paced electrogram feature analysis is a novel tool to characterize the ischaemic substrate. Association with VT isthmuses and early ablation results suggest a possible role in substrate ablation for ischaemic VT.

Alleviation of Cyclophosphamide-induced Hemorrhagic Cystitis by Dietary Pomegranate: A Comparative Experimental Study With Mesna.

In this study, we investigated the effects of pomegranate on alleviating cyclophosphamide-induced hemorrhagic cystitis (HC). Initially, 16 Sprague-Dawley rats were allocated into 4 groups: group 1 (control), group 2 (CP) in which HC was induced by cyclophosphamide; group 3 (CP+M), HC-induced rats that received Mesna regimen, and group 4 (CP+P), which compromised rats that had been on a 14-day diet of pomegranate juice before HC induction. Cystometry was performed a few hours before euthanasia; after euthanasia, aortic blood samples and bladder tissue samples were obtained to perform TUNEL assay, and histopathologic and biochemical assessments. Urodynamic findings revealed that mean detrusor pressure in CP+P was significantly lower compared with that in CP and CP+M (P<0.05). Histopathologically, urothelium destruction and inflammation were lower in CP+P and CP+M compared with that in CP. Collagen destruction was less prominent in CP+P compared with that in CP and CP+M. Tissue and plasma levels of malondialdehyde were significantly lower in CP+P versus CP (P<0.05). Catalase activity and total protein thiol group levels in plasma and bladder tissue were higher in CP+P versus CP (P<0.05). The TUNEL positivity in CP+P was significantly weaker than that in CP, indicating less DNA fragmentation and apoptosis. Pomegranate's characteristics could significantly affect the inflammatory and destructive process of hemorrhagic cystitis.

Inflection point analysis: A machine learning approach for extraction of IEGM active intervals during atrial fibrillation.

OBJECTIVE: In this paper, we propose a novel algorithm to extract the active intervals of intracardiac electrograms during atrial fibrillation. METHODS: First, we show that the characteristics of the signal waveform at its inflection points are prominent features that are implicitly used by human annotators for distinguishing between active and inactive intervals of IEGMs. Then, we show that the natural logarithm of features corresponding to active and inactive intervals exhibits a mixture of two Gaussian distributions in three dimensional feature space. An Expectation Maximization algorithm for Gaussian mixtures is then applied for automatic clustering of the features into two categories. RESULTS: The absolute error in onset and offset estimation of active intervals is 6.1ms and 10.7ms, respectively, guaranteeing a high resolution. The true positive rate for the proposed method is also 98.1%, proving the high reliability. CONCLUSION: The proposed method can extract the active intervals of IEGMs during AF with a high accuracy and resolution close to manually annotated results. SIGNIFICANCE: In contrast with some of the conventional methods, no windowing technique is required in our approach resulting in significantly higher resolution in estimating the onset and offset of active intervals. Furthermore, since the signal characteristics at inflection points are analyzed instead of signal samples, the computational time is significantly low, ensuring the real-time application of our algorithm. The proposed method is also robust to noise and baseline variations thanks to the Laplacian of Gaussian filter employed for extraction of inflection points.