c-Jun N-Terminal Kinases (JNKs) in Myocardial and Cerebral Ischemia/Reperfusion Injury

In this article, we review the literature regarding the role of c-Jun N-terminal kinases(JNKs) in cerebral and myocardial ischemia/reperfusion injury. Numerous studiesdemonstrate that JNK-mediated signaling pathways play an essential role in cerebraland myocardial ischemia/reperfusion injury. JNK-associated mechanisms are involved inpreconditioning and post-conditioning of the heart and the brain. The literature and ourown studies suggest that JNK inhibitors may exert cardioprotective and neuroprotectiveproperties. The effects of modulating the JNK-depending pathways in the brain andthe heart are reviewed. Cardioprotective and neuroprotective mechanisms of JNKinhibitors are discussed in detail including synthetic small molecule inhibitors (AS601245,SP600125, IQ-1S, and SR-3306), ion channel inhibitor GsMTx4, JNK-interactingproteins, inhibitors of mixed-lineage kinase (MLK) and MLK-interacting proteins, inhibitorsof glutamate receptors, nitric oxide (NO) donors, and anesthetics. The role of JNKs inischemia/reperfusion injury of the heart in diabetes mellitus is discussed in the contextof comorbidities. According to reviewed literature, JNKs represent promising therapeutictargets for protection of the brain and the heart against ischemic stroke and myocardialinfarction, respectively. However, different members of the JNK family exert diversephysiological properties which may not allow for systemic administration of non-specificJNK inhibitors for therapeutic purposes. Currently available candidate JNK inhibitors withhigh therapeutic potential are identified. The further search for selective JNK3 inhibitorsremains an important task

Digital Technologies in Providing Development of Algorithms Surgical Treatment of Supraventricular Arrhythmias

The aim of the study was the development and clinical application of patient selection algorithm for surgical treatment of longlasting persistent atrial fibrillation. The study included 235 patients with acquired heart disease and coronary artery disease, which in the period from 1999 to 2015 performed surgical treatment of long-term persistent atrial fibrillation (RF “MAZE III” procedure) in conjunction with the correction of the underlying heart disease. The patients were divided into 2 groups according to the method of operation: the group 1 – 135 patients (76 women and 59 men) who have applied an integrated approach to surgery for atrial fibrillation, including penetrating method of RF effects on atrial myocardium and the study of the function of the sinus node before and after the operation (these patients were operated on from 2008 to 2015). The group 2 – 100 patients (62 women and 38 men) with a “classical” method of monopolar RF “MAZE III”, which the sinus node function was not studied. We used the combined (epi- and endocardial) method of RF "MAZE". This algorithm is decreasing of possible permanent pacemaker postoperatively. The initial sinus node function in these patients, measured using the original method, the basic line of this algorithm was taken. The results showed that use this algorithm for selection of patients allows significantly reduce the possibility of pacemaker implantation in the postoperative perio

Protective Effects of a New C-Jun N-terminal Kinase Inhibitor in the Model of Global Cerebral Ischemia in Rats

C-Jun N-terminal kinase (JNK) is activated by various brain insults and is implicated in neuronal injury triggered by reperfusion-induced oxidative stress. Some JNK inhibitors demonstrated neuroprotective potential in various models, including cerebral ischemia/reperfusion injury. The objective of the present work was to study the neuroprotective activity of a new specific JNK inhibitor, IQ-1S (11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt), in the model of global cerebral ischemia (GCI) in rats compared with citicoline (cytidine-5?-diphosphocholine), a drug approved for the treatment of acute ischemic stroke and to search for pleiotropic mechanisms of neuroprotective effects of IQ-1S. The experiments were performed in a rat model of ischemic stroke with three-vessel occlusion (model of 3VO) affecting the brachiocephalic artery, the left subclavian artery, and the left common carotid artery. After 7-min episode of GCI in rats, 25% of animals died, whereas survived animals had severe neurological deficit at days 1, 3, and 5 after GCI. At day 5 after GCI, we observing massive loss of pyramidal neurons in the hippocampal CA1 area, increase in lipid peroxidation products in the brain tissue, and decrease in local cerebral blood flow (LCBF) in the parietal cortex. Moreover, blood hyperviscosity syndrome and endothelial dysfunction were found after GCI. Administration of IQ-1S (intragastrically at a dose 50 mg/kg daily for 5 days) was associated with neuroprotective effect comparable with the effect of citicoline (intraperitoneal at a dose of 500 mg/kg, daily for 5 days).The neuroprotective effect was accompanied by a decrease in the number of animals with severe neurological deficit, an increase in the number of animals with moderate degree of neurological deficit compared with control GCI group, and an increase in the number of unaltered neurons in the hippocampal CA1 area along with a significant decrease in the number of neurons with irreversible morphological damage