These results demonstrate that iptakalim could protect against IR-induced endothelial dysfunction, and ameliorate IR associated with hypertension, possibly via restoring the balance between NO and ET-1 signaling.

In the adaptive traffic signal control (ATSC), reinforcement learning (RL) is a frontier research hotspot, combined with deep neural networks to further enhance its learning ability. The distributed multiagent RL (MARL) can avoid this kind of problem by observing some areas of each local RL in the complex plane traffic area. However, due to the limited communication capabilities between each agent, the environment becomes partially visible. This paper proposes multiagent reinforcement learning based on cooperative game (CG-MARL) to design the intersection as an agent structure. The method considers not only the communication and coordination between agents but also the game between agents. Each agent observes its own area to learn the RL strategy and value function, then concentrates the Q function from different agents through a hybrid network, and finally forms its own final Q function in the entire large-scale transportation network. The results show that the proposed method is superior to the traditional control method.

The protective effects of lidoflazine and mioflazine against normothermic ischemia were evaluated in isolated rabbit hearts used in the working mode. Pretreatment with 0.125 mgl liter of these drugs improved recovery of cardiodynamic function during postischemic reperfusion. Functional recovery was preceded by less severe impairment of sarcolemmal structure and Ca2+ distribution at the end of the ischemic period, allowing the normalization of other substructures and the prevention of cellular Ca2+ overload during postischemic reperfusion. When cardiac output and semi-quantitative histology are taken as parameters, the protective effects of mioflazine were greater than that of lidoflazine.

In right atrial trabeculae from humans and in left atria from rat and guinea-pig hearts, the protective effects of mioflazine, lidoflazine, and verapamil against the accumulation of cellular calcium were investigated. Two consecutive, cumulative increases in the extracellular calcium concentration, [Ca2+]o (1-25 mmol/l), were induced, in between which the muscles were exposed for at least 30 minutes to solvent or drug. When using solvent in the 30-minute interval, the force of contraction was much lower during the second Ca2+ challenge, while the aftercontractions and the increase in passive tension at high [Ca2+]o tended to be larger. These signs of functional impairment were prevented by exposure to mioflazine or lidoflazine (3 mumol/l each) but not to verapamil (3 mumol/l). Muscles were fixed with glutaraldehyde at the end of the second Ca2+ challenge for morphological and cytochemical examination. After solvent treatment, more than half of the cells were severely damaged, showing cellular edema, contraction-band necrosis, mitochondrial swelling, and nuclear pyknosis; the sarcolemma was devoid of calcium deposits, damaged mitochondria contained either large deposits of calcium or flocculent densities, and in some cells, the cytoplasm was filled with calcium deposits. Following exposure to mioflazine and lidoflazine, but not to verapamil, the number of intact cells after the second Ca2+ challenge was not different from time-matched controls (80-90%). Furthermore, the shifts in cellular calcium distribution were prevented with mioflazine and lidoflazine, whereas verapamil was less effective. There were no species differences with respect to either morphological or contractile changes. In conclusion, exposure of atria to high [Ca2+]o induced similar ultrastructural and cytochemical changes as seen after ischemia-reperfusion induced damage. Indeed, under the mentioned conditions the sarcolemma lost its capacity to exclude Ca2+ after a challenge with high [Ca2+]o and allowed excessive Ca2+ entry. The pathway for this extra Ca2+ remains to be elucidated. L-type calcium channels are probably not involved, since verapamil cannot prevent the Ca2+ overload.