EFFECTS OF ACUTE STRETCH ON CARDIAC ELECTRICAL PROPERTIES IN SWINE

Stretch is known to result in an electrically less stable ventricular substrate, yet the reported effects of stretch on measured electrophysiological parameters have been inconsistent and even contradictory. The goal of this study was to evaluate the effects of acute mechanical stretch on cardiac electrical features thought to be key in generation of arrhythmia, namely restitution of action potential duration (APD), electrical memory, and onset of alternans. Microelectrodes were used to record intracellular potentials pre, during, and post-stretch from isolated right ventricular tissues from swine. In separate experiments, the effects of two levels of stretch were quantified. Pacing protocols employing explicit diastolic interval (DI) control and cycle length (CL) control were used to obtain measures of restitution of APD, memory, and alternans of APD. Stretching the tissue had varying effects on APD, restitution and memory. Stretch increased APD, restitution slopes and memory by as much as 24, 30 and 53 % in some cases, while it decreased these by up to 18, 37 and 81 % in others. During stretch, alternans of APD were observed in some cases, which occurred at slower rates of activation than before stretch. Histology of tissue samples showed localized changes in orientation of cells relative to the direction of stretch. Our results show that among individual trials, stretch altered the measured electrophysiological properties, sometimes markedly. However, when pooled together, these changes cancelled each other and the averages showed no statistically significant difference after stretch. A potential mechanism that explains this divergent and inconsistent response to stretch is the presence of local, micron level, variation in orientation of myocytes. Upon stretch, these divergent effects likely increase dispersion of repolarization diffusely and might thus be the reason behind the consistently observed increase in arrhythmic substrate after stretch

Low-power current-mode ADC for CMOS sensor IC

A low-energy current-mode algorithmic pipelined ADC targeted for use in distributed sensor networks is presented. The individual nodes combine sensing, computation and communications into an extremely small volume. The nodes operate with very low duty cycle due to limited energy. Ideally these sensor networks will be massive in size and dense in order to promote redundancy. In addition the networks will be collectively intelligent and adaptive. To achieve these goals, distributed sensor networks will require very small,inexpensive nodes that run for long periods of time on very little energy. One component of such network nodes is an A/D converter. An ADC acts as a crucial interface between the sensed environment and the sensor network as a whole. The work presented here focuses on moderate resolution, and moderate speed, but ultra-low-power ADCs. The 6 bit current-mode algorithmic pipelined ADC reported here consumes 8 pJ/bit samples at 0.65V supply and 130 kS/s. The current was chosen as the information carrying quantity instead of voltage as it is more favorable for low-voltage and low-power applications. The reference current chosen was 150nA. All the blocks are using transistors operating in subthreshold or weak inversion region of operation, to work in low-voltage and low current supply. The DNL and INL plots are given in simulation results section. The area of the overall ADC was 0.046 mm2 only

Supernormal Conduction and Suppression of Spatially Discordant Alternans of Cardiac Action Potentials

Spatially discordant alternans (DA) of action potential durations (APD) is thought to be more pro-arrhythmic than concordant alternans. Super normal conduction (SNC) has been reported to suppress formation of DA. An increase in conduction velocity (CV) as activation rate increases, i.e., a negative CV restitution, is widely considered as hallmark of SNC. Our aim in this study is to show that it is not an increase in CV for faster rates that prevents formation of DA, rather, it is the ratio of the CV for the short relative to the long activation that is critical in DA suppression. To illustrate this subtlety, we simulated this phenomenon using two approaches; (1) by using the standard, i.e., S1S2 protocol to quantify restitution and disabling the slow inactivation gate j of the sodium current (INa), and (2) by using the dynamic, i.e., S1S1 protocol for quantification of restitution and increasing INa at different cycle lengths (CL). Even though both approaches produced similar CV restitution curves, DA was suppressed only during the first approach, where the CV of the short of the long-short action potential (AP) pattern was selectively increased. These results show that negative CV restitution, which is considered characteristic of SNC, per se, is not causal in suppressing DA, rather, the critical factor is a change in the ratio of the velocities of the short and the long APs

Supernormal Conduction and Suppression of Spatially Discordant Alternans of Cardiac Action Potentials

Spatially discordant alternans (DA) of action potential durations (APD) is thought to be more pro-arrhythmic than concordant alternans. Super normal conduction (SNC) has been reported to suppress formation of DA. An increase in conduction velocity (CV) as activation rate increases, i.e., a negative CV restitution, is widely considered as hallmark of SNC. Our aim in this study is to show that it is not an increase in CV for faster rates that prevents formation of DA, rather, it is the ratio of the CV for the short relative to the long activation that is critical in DA suppression. To illustrate this subtlety, we simulated this phenomenon using two approaches; (1) by using the standard, i.e., S1S2 protocol to quantify restitution and disabling the slow inactivation gate j of the sodium current (INa), and (2) by using the dynamic, i.e., S1S1 protocol for quantification of restitution and increasing INa at different cycle lengths (CL). Even though both approaches produced similar CV restitution curves, DA was suppressed only during the first approach, where the CV of the short of the long-short action potential (AP) pattern was selectively increased. These results show that negative CV restitution, which is considered characteristic of SNC, per se, is not causal in suppressing DA, rather, the critical factor is a change in the ratio of the velocities of the short and the long APs

Phase Relationship between Alternans of Early and Late Phases of Ventricular Action Potentials

Background: Alternans of early phase and of duration of action potential (AP) critically affect dispersion of refractoriness through their influence on conduction and repolarization. We investigated the phase relationship between the two alternans and its effect on conduction. Methods and Results: Transmembrane potentials recorded from ventricles of eight swine and three canines during paced activation intervals of ≤300 ms were used to quantify alternans of maximum rate of depolarization (|dv/dt|max) and of action potential duration (APD). Incidence of APD alternans was 62 and 76% in swine and canines. Alternans of APD was frequently accompanied with alternans of |dv/dt|max. Of these, 4 and 26% were out of phase in swine and canines, i.e., low |dv/dt|max preceded long APD. Computer simulations show that out of phase alternans attenuate variation of wavelength and thus minimize formation of spatially discordant alternans. Conclusion: The spontaneous switching of phase relationship between alternans of depolarization and repolarization suggests that mechanisms underlying these alternans may operate independent of each other. The phase between these alternans can critically impact spatial dispersion of refractoriness and thus stability of conduction, with the in phase relation promoting transition from concord to discord while out of phase preventing formation of discord

External fixation versus plating in intra-articular distal end radius fractures

Background: Distal end radius fractures are one of the most common encountered fractures in Orthopaedics. Prompt intervention in terms of volar locking plate or external fixation can be performed. The purpose of this study was to derive a better outcome as to which type of fixation is a better choice for the treatment of intra-articular distal end radius fracture.Methods: A prospective randomized controlled study was conducted with 30 patients and comparison was made between the plating and external fixator group using the modified clinical-scoring system of Green and O'Brien and demerit point system at each follow-up.Results: In the plating group 14 patient’s fracture united in 6th week and 1 patient’s fracture united at 8th week this result was similar to the external fixator group were 14 patient’s fracture united in 6th week and 1 patient’s fracture united at 8th week. 1 patient each developed wrist joint stiffness and delayed union in the plating group as compared to the external fixator group were 1 patient each developed wrist joint stiffness, delayed union and broken implant in situ and pin tract infection.Conclusions: During the initial follow ups the functional outcome of the plating group were better than the external fixator group but as the time passed at the final follow up plating was only marginally better than the external fixator group. It was seen that radiologically plating lead to a better correction of all the parameters as compared to external fixator group

Efficacy and safety of tadalafil in ureteric stent related symptoms: a double blind, prospective, randomised study

Background: Is tadalafil effective and safe in ureteric stent related symptoms? The objective of this trial is to study the efficacy and safety of tadalafil and compare it with tamsulosin in relieving ureteric stent related symptoms by using ureteral stent symptom questionnaire.Methods: Total 144 patients with dj stent symptoms were randomized into two groups with 72 patients in each. Group A patients were given tadalafil 5mg and Group B, tamsulosin 0.4mg for 2 weeks. Ureteral stent symptom questionnaire was filled on 7th day and on 21st day after stent insertion. Statistically significant difference between groups was determined by the t-test, Mann-Whitney U-test, Pearson Chi-square test or Fisher's exact test. Comparison between quantitative time related variables was done by Wilcoxon Signed Rank test. All the statistical tests were two-sided and were performed at a significance level of α=.05.Results: Tamsulosin was found more effective then tadalafil in decreasing mean urinary index (p=0.004). Tadalafil caused significant decrease in body pain (p=0.006) and improvement in general health index score, work performance and sex score (P value= 0.041, <0.001 and <0.015 respectively) as compared to tamsulosin. Additional problems score improvement and analgesic use were found comparable in 2 groups (p value =0.193, 0.070 respectively). Adverse effect with both the drugs were minimal, mild to moderate and self-limiting.Conclusions: Tadalafil found more effective then Tamsulosin in relieving body pain, sexual symptoms and improving general health and work performance but less effective in improvement of urinary symptoms

Optical and electrochemical dual channel sensing of Cu2 + using functionalized furo[2,3-d]pyrimidines-2,4[1H,3H]-diones

Owing to their easy accessibility and high degree of structural and functional diversity, many multicomponent reactions (MCRs) have been a rich source of conjugate π-systems, functionalised chromophores (or fluorophore) and redox active molecules. Despite their high explorative potential and practical benefits, only a few MCR products have been so far investigated for their metal sensing abilities. In the present report, two furopyrimidinones (FPys) based molecular systems have been synthesized by [4 + 1] cycloaddition based MCR sequence. Designed chemosensors displayed optic (absorption spectra) as well as electroanalytical (ion selective electrode) response toward Cu2 + ion in solution and membrane phase respectively (dual channel sensing). Different aspects of both the sensing phenomena such as selectivity, association constants, detection limit, membrane composition etc. were studied in detail using UV–Vis spectroscopy, NMR titration and cell assembly. Both the compounds showed excellent performance characteristics such as high selectivity, acceptable affinity and low detection limits (10− 7 M) in both sensing assays with potential utility in the area of sample monitoring