Maximum Rate Of Rise Research Articles

A compact solid-state high repetition rate trigger based on a spiral generator.

The trigger generator made with a spiral generator (SG) has the advantages of light weight, compact structure, and low cost and has promising applications in the pulsed power field. This paper introduces a compact solid-state high-voltage pulse trigger system based on an improved SG, which has improved repetition rate and lowered the demands for semiconductor switches' maximum current and current rise rate when compared with previous studies. The improvement is achieved by winding outward an additional layer of the passive layer and low-voltage metal strip, which realizes a significant reduction of the peak current and current rise rate of the discharge switch. The final dimension of the trigger is 25 × 10 × 10cm3, excluding the power supply. An experiment carried out in single shot mode shows that the peak value of the output pulse can reach 50kV with a leading edge of 57ns. Repetitive experiments were carried out up to 1kHz, with the peak voltage of the output pulse being 30.5kV, the leading edge being 48ns, and the jitter being 0.84ns. Finally, the generator is used to trigger a gas switch, and it works stably and reliably.

Experimental Estimation of Turbulent Flame Velocity in Gasoline Vapor Explosion in Multi-Branch Pipes

The overpressure characteristics of gasoline explosions in multi-branch pipes are caused by various factors, with flame velocity as a particularly significant determinant. Overlooking the impact of turbulent flow in the branch pipes can induce a significant discrepancy in the outcome when using laminar flame velocity to determine the maximum rate of overpressure rise. To quantify the impact of turbulent flame velocity on the rate of overpressure rise in the gasoline explosions within branch pipes, the laminar flame velocity was replaced with its turbulent counterpart. Additionally, modifications to the formula for calculating the maximum overpressure rise rate were implemented. Then, experimental data of peak explosion overpressure and overpressure rise rate under different numbers of branches were obtained. Finally, the empirical data were inputted into the modified formula to determine the maximum rate of overpressure rise, thus enabling the calculation of the turbulent flame velocity across varying numbers of branches. The findings reveal a positive correlation between the number of branches and the turbulent flame velocity during tube explosions. When the number of branch pipes increased from 0 to 4, the turbulent flame velocity was found to range from 8.29 to 13.39 m/s. The increase in the number of branches did not consistently enhance the turbulent flame velocity. As the number of branches increased from zero to three, the turbulent flame velocity rose accordingly. Differently, as the number of branches exceeds three, the turbulent flame velocity exhibits fluctuations and peaks at a level approximately 1.8 times higher. The research method of this paper can provide a reference for estimating the turbulent flame velocity in the combustion process of flammable gas explosions in multi-branch tunnels.

Exceptional Performance of Flame-Retardant Polyurethane Foam: The Suppression Effect on Explosion Pressure and Flame Propagation of Methane-Air Premixed Gas.

A self-built gas explosion testing platform was used to explore the quenching effect of flame-retardant polyurethane foam on a gas explosion. The effect of the foam's filling position and length on the explosion suppression performance was explored. The results demonstrate that polyurethane foam exhibits an excellent flame-quenching performance, with a minimum of a 5 cm length of porous material being sufficient to completely quench the flame during propagation. Furthermore, the attenuation function of this porous material on the pressure wave is insignificantly affected by the change in ignition energy. Compared with the explosive state of the empty pipeline, the best suppression effect is obtained when the polyurethane foam is 20 cm in length with a filling position at 1.8 m, and the maximum explosion pressure and maximum rise rate are attenuated by 86.2% and 84.7%, respectively. This work has practical significance for the application of porous materials in explosion suppression and explosion-proof technologies in the chemical industrial processing and oil (gas) storage fields.

Influences of concentration gradients and ignition positions on unconfined inhomogeneous hydrogen explosion

This work aims at investigating the inhomogeneous hydrogen cloud explosion in unconfined spaces. The influences of concentration gradient and ignition position on the explosion were studied. Different initial inhomogeneous hydrogen clouds with vertical concentration gradients were prepared by controlling the injection rate and ignition time. Results show that the explosion flame at the equivalent concentration zone has higher temperature, faster propagation and more intense combustion reaction. With the decrease of the concentration gradient, the flame is faster and higher in temperature. The max explosion temperature increases from 905.9 °C to 1000.8 °C. The shapes of flame and temperature field in the gas cloud change from mushroom-shaped to ellipsoidal and then to spherical. The maximum overpressure (Pmax), maximum rise rate of overpressure ((dP/dt)max) and positive impulse (I) increase significantly with the decrease of concentration gradient. While ignited with different ignition positions, the flame propagation from the equivalent concentration zone to the flammability limit zone is inhibited by the concentration gradient. Central ignition induces the most intense and shortest explosion process and causes the highest temperature. Generally, central ignition induces larger Pmax and I in the vicinity of the cloud. Non-central ignition extends the impact areas of explosion.

Effects of pre-electroacupuncture on blood pressure and cardiac function in high-salt-induced hypertension rats

To observe the effects of pre-electroacupuncture at "Taichong"(LR3), "Neiguan"(PC6) and "Waiguan"(TE5) on blood pressure and cardiac function of high-salt-induced hypertension rats, so as to explore the possible mechanism of pre-electroacupuncture in improving hypertension. Twenty-four SD rats were randomly divided into control group, high-salt group and pre-electroacupuncture group, with 8 rats in each group. The hypertension model was established by feeding high-salt diet for 7 weeks. In the pre-electroacupuncture group, rats received electroacupuncture intervention at bilate-ral LR3, PC6 and TE5 (2 Hz/15 Hz, 2 mA) for 30 min, once a day, from the first day of modeling, for a total of 7 weeks. The blood pressure of rats was monitored by caudal artery noninvasive blood pressure measurement technique before and at the 1st, 3rd, 5th and 7th week of modeling. At the 8th week of the experiment, left ventricular catheterization was performed and biological signal acquisition system was used to detect left ventricular hemodynamics indexes and analyze left ventricular function, the car-diac mass ratio was measured to evaluate the degree of myocardial hypertrophy. The mRNA expressions of atrial natriuretic peptide(ANP), myosin heavy chain 7(MYH7), α-smooth muscle actin(α-SMA), interleukin(IL)-1β, and IL-6 of myocardial tissues were detected by quantitative real-time PCR. Sirius red staining was used to observe the degree of myocardial fibrosis. Compared with the control group, systolic blood pressure, diastolic blood pressure, mean arterial pressure, left ventricular end-diastolic pressure (LVEDP), cardiac mass ratio，and the mRNA expressions of ANP, MYH7, α-SMA, IL-1β, and IL-6, and sirius red staining area of myocardium were all significantly increased(P<0.01,P<0.05)，maximal rate of rise and descent of left ventricular pressure(LVP±dP/dtmax) were decreased (P<0.05,P<0.01) in the high-salt group. Compared with the high-salt group, rats in the pre-electroacupuncture group had lower systolic blood pressure, diastolic blood pressure, mean arterial pressure, LVEDP，cardiac mass ratio，higher LVP±dP/dtmax,down-regulated mRNA expressions of ANP, MYH7, α-SMA, IL-1β, IL-6, and smaller area of sirius red staining(P<0.05, P<0.01). Pre-electroacupuncture tends to lower blood pressure, improve cardiac function and reduce myocardial fibrosis in high-salt-induced hypertension rats, which may be associated with inhibiting inflammatory response.

The characteristics of ‘abrupt wave front’ floods on Pennine catchments, northern England, and their transmission downstream

Abstract Visible flood waves, described as abrupt wave front events (AWF), have been identified on rivers in northern England rising in the Pennines, from both historical and recent gauged data. The focus of this paper is on the characteristics of two gauged AWF events on the Rivers Wear and Tees in 1983 and their comparison to ‘normal’ floods. The description and analysis is based on contemporaneous photographs and observations and on digital level and flow records. The rapid 15-min rise in these events is compared with the maximum rate of rise in annual maximum peak floods by comparing flood hydrographs. The propagation of the flood wave downstream is illustrated. The 15-min increase in discharge is compared in relation to the peak flow for AWF and normal floods at different gauged locations down the catchments showing striking differences. The character of the AWF response in the vertical or near-vertical wave front and rapid increase in both level and discharge points to the occurrence of kinematic shock waves.

Numerical simulation of the effect of diaphragm orifice diameter in a flameproof enclosure with an interconnected structure during pressure piling

Combustible gas explosions are typically triggered at high temperatures by the generation of electric sparks on starting, stopping, or short circuiting of electrical equipment. Flameproof enclosures are widely installed in the petrochemical industry as safety equipment for eliminating ignition sources. Such enclosures are designed with a double-cavity structure, and a hole plate is used to connect the two cavities. However, pressure piling occurs in such double-cavity-connected structures, resulting in flameproof enclosures requiring to bear higher pressure than designed, which is a safety hazard. However, few studies have focused on the effect of the diaphragm orifice diameter of flameproof enclosures. Because the explosion of combustible gas in a flameproof enclosure is a complex process, numerical simulation was performed to study the process. Fluent was used for numerically simulating the ethylene/air premixed gas explosion characteristics of double-cavity-connected structure flameproof enclosures. The effects of an orifice hole diameter from 10 mm to 45 mm on flameproof characteristics, including the maximum explosion pressure, maximum explosion pressure rise rate, and maximum explosion index, were examined. The results are critical for the effective design of a double-cavity flameproof shell and provide theoretical support for fire suppression in a flameproof enclosure.

Heart sound–derived systolic time intervals for atrioventricular delay optimization in cardiac resynchronization therapy

Phonocardiography (PCG) can be used to determine systolic time intervals (STIs) from ventricular pacing spike to the first heart sound (VS1) and from the first to the second heart sound (S1S2). The purpose of this study was to investigate the relations between STIs and hemodynamics during atrioventricular (AV) delay optimization of biventricular pacing (BiVP) in animals and patients. Five pigs with AV block underwent BiVP, while PCG was collected from an epicardial accelerometer. In 21 patients undergoing cardiac resynchronization therapy device implantation, PCG was recorded with a pulse generator-embedded microphone. Optimal AV delays derived from shortest VS1 and longest S1S2 were compared with AV delays derived from highest left ventricular pressure (LVP), maximal rate of rise in LVP, and stroke work. In pigs, VS1 and S1S2 predicted the AV delays with optimal hemodynamics (highest LVP, maximal rate of rise in LVP, and stroke work) by a median error of 2-28 ms, resulting in a median loss of <2% of pump function. In patients, VS1 and S1S2 predicted the optimal AV delay by errors of 32.5 and 37.5 ms, respectively, resulting in 0.2%-0.9% lower LVP and stroke work, which were reduced to 21 and 24 ms in 8 patients with a full-capture AV delay of >180 ms. During BiVP with varying AV delays, close relations exist between PCG-derived STIs and hemodynamic parameters. AV delays advised by PCG-derived STIs cause only a minimal loss of pump function compared with those based on invasive hemodynamic measurements. ClinicalTrials.gov Identifier: NCT01832493.

Reverse Blocking Diode Thyristor With High Di/Dt Capability for Explosive Foil Initiator Applications

High-voltage switch with high current and high current rise rate capability is important in explosive foil initiator (EFI) applications because the current with high amplitude and short rise time is necessary in order to gasify the explosive foil. In this work, reverse blocking diode thyristor (RBDT) for this application is optimally designed and fabricated. The 2-D numerical model of RBDT is first established. Based on this model, the cathode layout and the doping concentration of P base layer of the device are carefully analyzed. The cell size and the length ratio of the emitter to the short-circuit point at cathode are analyzed. Samples of RBDT are developed in our laboratory, with the blocking voltage of 1600 V. The peak current of 2400 A is acquired in the pulse discharge experiment, with a maximum current rise rate as high as 18 kA/ <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\mu \text{s}$ </tex-math></inline-formula> , which is the highest <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\text{d}{i}/\text{d}{t}$ </tex-math></inline-formula> value reported for RBDT until now. This result makes the proposed RBDT a promising candidate for EFI applications.

Numerical simulation on influence of initial pressures on gas explosion propagation characteristics in roadway

In order to investigate the influence of initial pressures on the propagation characteristics of gas explosion in roadway, the physical model of gas explosion under different initial pressures in roadway is established by the fluid-structure interaction algorithm of ANSYS/LS-DYNA. The pressure of shock wave, the rise rate of pressure and the flame propagation velocity are analyzed when the initial pressure is 0.08, 0.09, 0.10, 0.11, and 0.12 MPa, respectively. The results reveal that the maximum pressure of shock wave at the same position in the roadway increases significantly with the increase of initial pressure, which presents a quadratic function relationship. The time to reach the maximum pressure of shock wave is extended comparatively. In addition, the maximum rise rate of shock wave pressure increases with the increase of the initial pressure, which means that the explosion hazard increases. The flame propagation velocity in the roadway decreases linearly with the increase of initial pressure. When the initial pressure increases by 0.01 MPa, the flame propagation speed will decrease by 2.6%.

Fire and explosion characteristics of vent gas from lithium-ion batteries after thermal runaway: A comparative study

The combustion and explosion of the vent gas from battery failure cause catastrophe for electrochemical energy storage systems. Fire extinguishing and explosion proof countermeasures therefore require rational dispose of the flammable and explosive vent gas emitted from battery thermal runaway. However, the fire and explosion nature of the multiphase vent gas remains unclear. This paper comparatively investigates the fire and explosion hazards of the vent gas emitted by different kinds of lithium-ion batteries after thermal runaway. Hazard data are collected for batteries with cathode LiNixCoyMnzO2 (x from 0.33 to 0.8) and LiFePO4, which are prevailingly used or to be used in energy storage scenarios. The composition and content of the vent gas were analyzed using a pressurized container and gas chromatography. A 1-liter explosion sphere was used to determine the explosion limits, explosion pressure, and maximum rise rate of explosion pressure for five cell chemistries at 298 K and 101 kPa absolute pressure. The laminar burning velocities of the five vent gases were measured by Bunsen burner. The minimum concentration of fire extinguishing agent was tested using a cup burner. The results show that the fire and explosion hazards posed by the vent gas from LiFePO4 battery are greater than those from Li(NixCoyMn1-x-y)O2 battery, which counters common sense and sets reminders for designing electric energy storage stations. We may need reconsider the choice of cell chemistries for electrical energy storage systems, and care more about the safety design against the fire and explosion disaster that may occur at system level. The explosion characteristics of the vent gases from five cell chemistries and the minimum fire extinguishing concentration can enlighten future risk assessments of electrochemical energy storage systems.

Influence of DSRD Operation Cycle on the Output Pulse Parameters

Drift step recovery diodes (DSRDs) are semiconductor opening switches designed for the forming of high-voltage nanosecond pulses. DSRD-based circuit includes inductive energy storage and works as a high-efficient compression stage of the tens to hundreds of nanoseconds input pulse down to nanosecond or subnanosecond range output pulse. Despite the well-investigated physical principles, a lot of published DSRD simulations, and practical DSRD-based pulsers, the fundamental research aimed at optimization of DSRD circuit has not been conducted yet. The present letter shows the result of extensive experiments elucidating the maximum voltage rise rate, pulse compression ratio, energy losses, and prepulse amplitude in DSRD circuits. The explicit definitions of DSRD pulse parameters, which are vital for the optimization process, are suggested for the first time. It is demonstrated that optimizations of different parameters contradict each other, and there is no universal optimal solution. The compromise should be found for each application using the recommendations presented in the letter.

Left Ventricular Pressure Estimation Using Machine Learning-Based Heart Sound Classification.

ObjectiveA method to estimate absolute left ventricular (LV) pressure and its maximum rate of rise (LV dP/dtmax) from epicardial accelerometer data and machine learning is proposed.MethodsFive acute experiments were performed on pigs. Custom-made accelerometers were sutured epicardially onto the right ventricle, LV, and right atrium. Different pacing configurations and contractility modulations, using isoflurane and dobutamine infusions, were performed to create a wide variety of hemodynamic conditions. Automated beat-by-beat analysis was performed on the acceleration signals to evaluate amplitude, time, and energy-based features. For each sensing location, bootstrap aggregated classification tree ensembles were trained to estimate absolute maximum LV pressure (LVPmax) and LV dP/dtmax using amplitude, time, and energy-based features. After extraction of acceleration and pressure-based features, location specific, bootstrap aggregated classification ensembles were trained to estimate absolute values of LVPmax and its maximum rate of rise (LV dP/dtmax) from acceleration data.ResultsWith a dataset of over 6,000 beats, the algorithm narrowed the selection of 17 predefined features to the most suitable 3 for each sensor location. Validation tests showed the minimal estimation accuracies to be 93% and 86% for LVPmax at estimation intervals of 20 and 10 mmHg, respectively. Models estimating LV dP/dtmax achieved an accuracy of minimal 93 and 87% at estimation intervals of 100 and 200 mmHg/s, respectively. Accuracies were similar for all sensor locations used.ConclusionUnder pre-clinical conditions, the developed estimation method, employing epicardial accelerometers in conjunction with machine learning, can reliably estimate absolute LV pressure and its first derivative.

Impact of Lightning Channel Base Current (CBC) Function Modeling on Computed Lightning Induced Overvoltage Waveshapes

Adverse effects of lightning strike are studied through the modeling of the lightning-induced over-voltage (LIOV) using the channel-base current (CBC) functions. A lightning current is characterized by the parameters like current peak value (Im), time-taken by the current to reach Im (tm), maximum rise-rate of the current (di/dt)max (steepness), and charge transferred at the contact point of the strike (Q). Using the CBC functions, the lightning electromagnetic fields (LEMFs) are calculated to compute the LIOV using a coupling model. Since the choice of CBC function plays an important role in LIOV computation, the present work studies its effect on the computed LIOV for matching and zero load impedance. As a case study, two functions: Heidlers and NCBC functions were examined. It was shown that a-sort-of delay characteristic from the NCBC function is reflected in the computed LIOV and also the tripolar nature of the LIOV for the case of imperfect ground. The difference between the LIOV computed using NCBC and Heidler?s function shows space-time reflections of the order of <formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex>$10^4$</tex></formula> magnitude.

Ignition sensitivity and explosion behaviors of micron-sized aluminum powder: Comparison between flake aluminum powder and spherical aluminum powder

The addition of aluminum powder can increase the energy of the combustion system. The spherical aluminum powder can be flaked by the ball milling technology, which can remove the oxide layer on the particle surface and improve the reaction activity. However, the ignition sensitivity and thermal behavior of flake aluminum powder should arouse extensive attention. In this paper, experimental measurements and statistical analysis are carried out for the ignition characteristics and explosion mechanism of micron-sized flake and spherical aluminum powder. Because the oxide layer is an important component in the oxidation process of aluminum powder, a theoretical model to calculate its equivalent thickness and fracture conditions is proposed. Moreover, the surface effect has a significant impact on intensifying the explosion hazard. For micron-sized aluminum powder, the relationship between ignition temperature and particle size is as follows: Ti∝d320.2. The maximum rise rate of explosion pressure for flake aluminum powder is 4.19 times than that for large spherical aluminum powder. Furthermore, the MEC results corresponding to the ignition probability are obtained by using the Logistic regression model. Present work recommends that the safety design should be based on the MEC prediction result of p = 0.5.

A hybrid optimization strategy of electrical efficiency about cooling PEMFC combined with ultra-thin vapor chambers

The fan's cooling is critical to the overall safety and efficiency of an open-cathode proton exchange membrane fuel cell (PEMFC). The power of the fan directly determines the temperature, parasitic power, and electrical efficiency. Existing experimental research and simulations are still insufficient for the optimization of the electrical efficiency by adjusting the power of the fan in an open-cathode PEMFC. This paper develops a hybrid optimization strategy based on the team-designed open-cathode PEMFC combined with ultra-thin vapor chambers (UTVC) to search for the optimal fan power at a specific temperature and maximize the stack's electrical efficiency. The dynamic model of the PEMFC-UTVC system is established and validated by experiments by analyzing the heat dissipation structure of the PEMFC-UTVC system and combining the electrochemical principle with the thermodynamic theory. To maximize the electrical efficiency of the PEMFC-UTVC stack, a neural network method is integrated with a meta-heuristic algorithm with mutation. The penalty function method is used to transform the problem constraints throughout the optimization process. The optimization strategy demonstrates the advantages of a powerful optimal capacity, high precision, and high robustness. The results of optimization show that the electrical efficiency of PEMFC-UTVC can be maximized by adjusting the power of the fan. Under the current conditions of 20A, 30A, and 40A, the maximum rates of rise in electrical efficiency are 2.65%, 3.29%, and 4.35%, respectively. The proposed hybrid optimization strategy is expected to provide insights into the control and optimization of the open-cathode PEMFC system.

Experimental analysis of overpressure characteristics of gasoline–air mixture explosion in multi-branch tubes

Taking the multi-branch structure pipelines common in the field of energy and chemical industry as the research object, the combined experimental pipeline was used to control the constant total length of the pipeline, and the experimental analysis was carried out on the characteristics of oil and gas explosion overpressure under different distribution forms, distribution locations, length and number of branch tubes. The results showed that: Compared with straight pipelines, multi-branch pipelines have great influence on the peak value and rise rate of overpressure. Under the relative arrangement, the maximum overpressure and the maximum overpressure rise rate are less than those of the one-line arrangement and staggered arrangement, and the time to reach the maximum overpressure and the maximum overpressure rise rate is also delayed. The relationship of the maximum explosion overpressure rising rate at different branches of the tube is as follows: far from the ignition end > near the ignition end > evenly distributed along the main tube. With the increase of branch pipe length, both the peak value of overpressure and the rise rate of the maximum overpressure show a trend of decreasing first and then increasing. When the branch length is 1.5 m, the peak value of overpressure and the rise rate are smaller than the straight pipe condition. The increase in the number of branches does not lead to a continuous increase in the peak and maximum rate of overpressure rise. When the number of branches is less than 3, the peak value and the rate of rise of the maximum overpressure increase with the increase of the number of branches, while when the number of branches is more than 3, both the peak value and the rate of rise of the maximum overpressure decrease.

Effect of aging and sex on cardiovascular structure and function in wildtype mice assessed with echocardiography

This study employed traditional and advanced echocardiographic techniques to assess comprehensively age- and sex-related changes in cardiovascular structure and function in wildtype (WT) mice. Forty-five normal adult wildtype mice were apportioned to groups based on age and sex: 2-month (young) male or female, and 24-month (old) male or female (n = 13, 13, 13, and 6, respectively). Each underwent 2-dimensional (2D) imaging echocardiography, Doppler, tissue Doppler imaging echocardiography, and speckle-tracking echocardiography (STE) for comparison of cardiovascular structure and function parameters. Compared to the young mice, the old had significantly higher body weight (BW), and lower diastolic and mean arterial pressure. The left ventricular (LV) end-diastolic and end-systolic volumes, and left ventricular mass, were significantly higher in the old mice. Within each sex, the cardiac diastolic and systolic function parameters were comparable between the young and old. Isovolumetric relaxation time (IVRT)/diastolic time interval (DT) and the maximum drop rate of pressure in LV (− dP/dtmax) were significantly lower in the old mice, while the LV relaxation time constant (Tau) was significantly higher. Spearman’s rank correlation showed a positive association between IVRT/DT and − dp/dtmax (male r = 0.663; female r = 0.639). Among the males, the maximum rise rate of pressure in LV (+ dp/dtmax), and systolic global longitudinal strains and rates (S-GLS, S-GLSR) were significantly different between the young and old. Spearman’s rank correlation showed positive association between S-GLS, S-GLSR and + dp/dtmax (r = 0.709 and r = 0.499). Regarding vascular structure, the ascending aorta systolic and diastolic diameters were significantly higher in the old mice compared with the young. The male mice had progressive, age-related aortic stiffness. Ageing in mice leads to changes in cardiovascular structure and cardiac diastolic function, but systolic function is relatively well preserved in females. Changes in cardiac function and arterial stiffness were more significant in males than females. Traditional ECG is better than STE for evaluating LV diastolic function; STE is better for LV systolic function.

Abstract P405: Cardioprotective Actions Of Nitroxyl Donor Angeli's Salt Are Preserved In The Diabetic Heart And Vasculature In The Face Of Nitric Oxide Resistance

Introduction: The risk of fatal cardiovascular events is increased in patients with type 2 diabetes mellitus (T2DM). A major contributor to poor prognosis is impaired nitric oxide (NO•) signalling at the level of tissue responsiveness, termed NO• resistance. Nitroxyl (HNO) induces positive inotropic and lusitropic effects in healthy and failing hearts. Hypothesis: We hypothesised that in a rodent model, T2DM will promote, and HNO will circumvent, NO• resistance in the myocardium and coronary vasculature. Methods: At 8 weeks of age, male Sprague-Dawley rats commenced a high-fat diet. After two weeks, the rats received low-dose streptozotocin (two intraperitoneal injections, 35 mg/kg, over two consecutive days), and continued the diet. Twelve weeks later, hearts were Langendorff-perfused to assess responses to the NO• donor diethylamine NONOate (DEA/NO) and the HNO donor Angeli’s salt. Results: Inotropic, lusitropic and coronary vasodilator responses to DEA/NO were impaired, and responses to Angeli’s salt were preserved or enhanced, in T2DM hearts compared with non-diabetic hearts. Conclusions: This is the first evidence that inotropic and lusitropic responses are preserved, and NO• resistance in the coronary vasculature is circumvented, by the HNO donor Angeli’s salt in T2DM. These findings highlight the cardiovascular therapeutic potential of HNO donors, especially in cardiac emergencies such as acute ischaemia or heart failure. Figure 1. Dose-response curves and maximal responses to DEA/NO or Angeli's salt in diabetic or non-diabetic hearts. (A-C) LV+dP/dt, (D-F) LV-dP/dt and (G-I) coronary flow rate. Data expressed as change from baseline (denoted by Δ), mean ± SEM. Data analysed by two-way RM ANOVA with Sidak's post-hoc test. *P&lt;0.05 vs. non-diabetic. LV, left ventricular; LV+dP/dt, maximal rate of rise in LV pressure; LV-dP/dt, maximal rate of fall in LV pressure.

NaV1.5 knockout in iPSCs: a novel approach to study NaV1.5 variants in a human cardiomyocyte environment

Cardiomyocytes derived from patient-specific induced pluripotent stem cells (iPSC-CMs) successfully reproduce the mechanisms of several channelopathies. However, this approach involve cell reprogramming from somatic tissue biopsies or genomic editing in healthy iPSCs for every mutation found and to be investigated. We aim to knockout (KO) NaV1.5, the cardiac sodium channel, in a healthy human iPSC line, characterize the model and then, use it to express variants of NaV1.5. We develop a homozygous NaV1.5 KO iPSC line able to differentiate into cardiomyocytes with CRISPR/Cas9 tool. The NaV1.5 KO iPSC-CMs exhibited an organized contractile apparatus, spontaneous contractile activity, and electrophysiological recordings confirmed the major reduction in total Na+ currents. The action potentials (APs) exhibited a reduction in their amplitude and in their maximal rate of rise. Voltage optical mapping recordings revealed that the conduction velocity Ca2+ transient waves propagation velocities were slow. A wild-type (WT) NaV1.5 channel expressed by transient transfection in the KO iPSC-CMs restored Na+ channel expression and AP properties. The expression of NaV1.5/delQKP, a long QT type 3 (LQT3) variant, in the NaV1.5 KO iPSC-CMs showed that dysfunctional Na+ channels exhibited a persistent Na+ current and caused prolonged AP duration that led to arrhythmic events, characteristics of LQT3.