High levels of circulating epinephrine trigger apical cardiodepression in a ß2-adrenergic receptor/Gi-dependent manner: a new model of Takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy is an acute heart failure syndrome characterized by myocardial hypocontractility from the mid left ventricle to the apex. It is precipitated by extreme stress and can be triggered by intravenous catecholamine administration, particularly epinephrine. Despite its grave presentation, Takotsubo cardiomyopathy is rapidly reversible, with generally good prognosis. We hypothesized that this represents switching of epinephrine signaling through the pleiotropic ß(2)-adrenergic receptor (ß(2)AR) from canonical stimulatory G-protein-activated cardiostimulant to inhibitory G-protein-activated cardiodepressant pathways. METHODS AND RESULTS: We describe an in vivo rat model in which a high intravenous epinephrine, but not norepinephrine, bolus produces the characteristic reversible apical depression of myocardial contraction coupled with basal hypercontractility. The effect is prevented via G(i) inactivation by pertussis toxin pretreatment. ß(2)AR number and functional responses were greater in isolated apical cardiomyocytes than in basal cardiomyocytes, which confirmed the higher apical sensitivity and response to circulating epinephrine. In vitro studies demonstrated high-dose epinephrine can induce direct cardiomyocyte cardiodepression and cardioprotection in a ß(2)AR-Gi-dependent manner. Preventing epinephrine-G(i) effects increased mortality in the Takotsubo model, whereas ß-blockers that activate ß(2)AR-G(i) exacerbated the epinephrine-dependent negative inotropic effects without further deaths. In contrast, levosimendan rescued the acute cardiac dysfunction without increased mortality. CONCLUSIONS: We suggest that biased agonism of epinephrine for ß(2)AR-G(s) at low concentrations and for G(i) at high concentrations underpins the acute apical cardiodepression observed in Takotsubo cardiomyopathy, with an apical-basal gradient in ß(2)ARs explaining the differential regional responses. We suggest this epinephrine-specific ß(2)AR-G(i) signaling may have evolved as a cardioprotective strategy to limit catecholamine-induced myocardial toxicity during acute stress.

Research on AGV path tracking method based on global vision and reinforcement learning.

As the key to the movement of automated guided vehicle (AGV), the design of control algorithm directly affects whether AGV can follow the preset path. Aiming at the difficulty of AGV control, an AGV path tracking control method based on global vision and reinforcement learning is proposed. Firstly, the global view is obtained by the visual sensor, and the position information of obstacles and AGV is obtained by the target detection algorithm. Secondly, the path planning algorithm is used to obtain the driving path information which is used to establish a virtual environment. Thirdly, the position and pose of the physical AGV are introduced into the virtual environment by the visual sensor, and the virtual AGV is reset. Finally, the image obtained by virtual vehicle camera is input into the reinforcement learning model and the output action is sent to the physical AGV for execution. In the experimental part, this method can not only plan the driving path in different environments but also well control AGV to drive along the specified path, which proves that this method has strong robustness and feasibility.

Research on AGV trackless guidance technology based on the global vision.

With the change of manufacturing mode and the progress of science and technology, the traditional manufacturing industry has gradually developed to intelligent manufacturing and flexible manufacturing. To achieve factory transformation, Automatic Guided Vehicle (AGV) is indispensable. In this paper, an AGV trackless guidance technology based on global vision is proposed. Firstly, the global vision camera is used to obtain the image of the AGV driving area, and then the obstacle information and position information of the AGV are obtained by image processing technology. Secondly, the A* algorithm is used to intelligently plan the AGV driving path, and the wireless network communication is used to control the AGV driving according to the planned path. Experiments show that the method is feasible and has the advantages of high flexibility, high precision, low cost and strong expansibility, which is of great significance to the realization of intelligent warehouse and unmanned chemical plant.

Overexpression of sarcolipin decreases myocyte contractility and calcium transient.

OBJECTIVE: Sarcolipin (SLN) is a novel 31-amino-acid protein associated with the sarcoplasmic reticulum (SR) whose function in cardiac muscle is poorly defined. In this study, we tested the hypothesis that SLN is a regulator of SR Ca(2+) transport function by overexpressing SLN in adult rat ventricular myocytes which express low levels of SLN. METHODS: Expression of SLN mRNA in rat tissues was analyzed by Northern blot as well by RT-PCR analysis. To define the role of SLN in cardiac muscle contractility, we overexpressed SLN in adult rat ventricular myocytes using adenoviral gene transfer techniques. Localization of SLN in the adult rat ventricular myocytes was determined using confocal microscopy. Myocyte contractility and calcium transients were measured using edge detection and Fura 2AM. RESULTS: Our results demonstrate that overexpression of SLN decreased the cell shortening significantly when compared to control myocytes, whereas the time to peak contraction was not altered. In addition, SLN overexpression prolonged the time of 50% relaxation. Calcium transient analysis shows that time to 50% decay of [Ca(2+) ]i was markedly prolonged in SLN-overexpressing myocytes (control -245.0+/-3.78 vs. SLN -199.0+/-3.25 ms, p<0.001). However, there were no significant differences in peak amplitudes of [Ca(2+)](i) between SLN-overexpressing and control myocytes. We further demonstrate that SLN is localized within the SR membrane similar to PLB and SR Ca(2+) ATPase. Co-immunoprecipitation studies indicate that SLN can physically interact with phospholamban. CONCLUSIONS: We conclude that SLN may play an important role in regulating the SR calcium ATPase pump, possibly by interacting with phospholamban.