Myography of isolated blood vessels: Considerations for experimental design and combination with supplementary techniques

The study of the mechanisms of regulation of vascular tone is an urgent task of modern science, since diseases of the cardiovascular system remain the main cause of reduction in the quality of life and mortality of the population. Myography (isometric and isobaric) of isolated blood vessels is one of the most physiologically relevant approaches to study the function of cells in the vessel wall. On the one hand, cell-cell interactions as well as mechanical stretch of the vessel wall remain preserved in myography studies, in contrast to studies on isolated cells, e.g., cell culture. On the other hand, in vitro studies in isolated vessels allow control of numerous parameters that are difficult to control in vivo. The aim of this review was to 1) discuss the specifics of experimental design and interpretation of data obtained by myography and 2) highlight the importance of the combined use of myography with various complementary techniques necessary for a deep understanding of vascular physiology

Pannexin 1 facilitates arterial relaxation via an endothelium-derived hyperpolarization mechanism

AbstractPannexin 1 (Panx1) is involved in endothelium-dependent vasodilation in large arteries, but the exact mechanistic role remains poorly understood. We hypothesized that Panx1 facilitates large vessel relaxations regulating endothelium-derived hyperpolarization (EDH)-like mechanisms. The EDH-like component of acetylcholine-induced relaxation of saphenous arteries studied in isometric myograph after inhibition of NO-synthase and cyclooxygenase was significantly impaired in mice with genetically ablated Panx1 (KO) relative to that in the wild type (WT) mice. Application of P1-receptor antagonist and apyrase significantly reduced this component in WT, but not in KO mice, indicating participation of ATP released via Panx1 in the EDH-like relaxation

Remodeling of arterial tone regulation in postnatal development: focus on smooth muscle cell potassium channels

Maturation of the cardiovascular system is associated with crucial structural and functional remodeling. Thickening of the arterial wall, maturation of the sympathetic innervation, and switching of the mechanisms of arterial contraction from calcium-independent to calcium-dependent occur during postnatal development. All these processes promote an almost doubling of blood pressure from the moment of birth to reaching adulthood. This review focuses on the developmental alterations of potassium channels functioning as key smooth muscle membrane potential determinants and, consequently, vascular tone regulators. We present evidence that the pattern of potassium channel contribution to vascular control changes from K(ir)2, K(v)1, K(v)7 and TASK-1 channels to BK(Ca) channels with maturation. The differences in the contribution of potassium channels to vasomotor tone at different stages of postnatal life should be considered in treatment strategies of cardiovascular diseases associated with potassium channel malfunction

TWIK-related acid-sensitive potassium channels (TASK-1) emerge as contributors to tone regulation in renal arteries at alkaline pH

Aim: TASK-1 channels are established regulators of pulmonary artery tone but their contribution to the regulation of vascular tone in systemic arteries is poorly understood. We tested the hypothesis that TASK-1 channel functional impact differs among systemic vascular beds, that this is associated with differences in their expression and may increase with alkalization of the extracellular environment. Therefore, we evaluated the expression level of TASK-1 channels and their vasomotor role in mesenteric and renal arteries. Methods: Pulmonary, mesenteric and renal arteries from male Wistar rats were used for TASK-1 channel mRNA (qPCR) and protein content (Western blotting) measurements. The functional role of TASK-1 channels was studied by wire myography using the TASK-1 channel blocker AVE1231. In some experiments, the endothelium was removed with a rat whisker. Results: Expression levels of both mRNA and protein of the TASK-1 channel pore-forming subunit were highest in pulmonary arteries, lowest in mesenteric arteries and had an intermediate value in renal arteries. Blockade of TASK-1 channels by 1 µM AVE1231 increased U46619-induced contractile responses of pulmonary arteries but did not affect basal tone and contractile responses to methoxamine of mesenteric and renal arteries at physiological extracellular pH (pHo = 7.41). At alkaline extracellular pH = 7.75 (increase of NaHCO3 to 52 mM) AVE1231 evoked the development of basal tone and increased contractile responses to low concentrations of methoxamine in renal but not mesenteric arteries. This effect was independent of the endothelium. Conclusion: In the rat systemic circulation, TASK-1 channels are abundant in renal arteries and have an anticontractile function under conditions of extracellular alkalosis

MAPKs are highly abundant but do not contribute to α1-adrenergic contraction of rat saphenous arteries in the early postnatal period

Previously, the abundance of p42/44 and p38 MAPK proteins had been shown to be higher in arteries of 1- to 2-week-old compared to 2- to 3-month-old rats. However, the role of MAPKs in vascular tone regulation in early ontogenesis remains largely unexplored. We tested the hypothesis that the contribution of p42/44 and p38 MAPKs to the contraction of peripheral arteries is higher in the early postnatal period compared to adulthood. Saphenous arteries of 1- to 2-week-old and 2- to 3-month-old rats were studied using wire myography and western blotting. The α(1)-adrenoceptor agonist methoxamine did not increase the phosphorylation level of p38 MAPK in either 1- to 2-week-old or 2- to 3-month-old rats. Accordingly, inhibition of p38 MAPK did not affect arterial contraction to methoxamine in either age group. Methoxamine increased the phosphorylation level of p42/44 MAPKs in arteries of 2- to 3-month-old and of p44 MAPK in 1- to 2-week-old rats. Inhibition of p42/44 MAPKs reduced methoxamine-induced contractions in arteries of 2- to 3-month-old, but not 1- to 2-week-old rats. Thus, despite a high abundance in arterial tissue, p38 and p42/44 MAPKs do not regulate contraction of the saphenous artery in the early postnatal period. However, p42/44 MAPK activity contributes to arterial contractions in adult rats

The effects of acidosis on eNOS in the systemic vasculature: a focus on early postnatal ontogenesis

The activity of many vasomotor signaling pathways strongly depends on extracellular/intracellular pH. Nitric oxide (NO) is one of the most important vasodilators produced by the endothelium. In this review, we present evidence that in most vascular beds of mature mammalian organisms metabolic or respiratory acidosis increases functional endothelial NO-synthase (eNOS) activity, despite the observation that direct effects of low pH on eNOS enzymatic activity are inhibitory. This can be explained by the fact that acidosis increases the activity of signaling pathways that positively regulate eNOS activity. The role of NO in the regulation of vascular tone is greater in early postnatal ontogenesis compared to adulthood. Importantly, in early postnatal ontogenesis acidosis also augments functional eNOS activity and its contribution to the regulation of arterial contractility. Therefore, the effect of acidosis on total peripheral resistance in neonates may be stronger than in adults and can be one of the reasons for an undesirable decrease in blood pressure during neonatal asphyxia. The latter, however, should be proven in future studies

Russian and Foreign Experience of Placement for Orphans

Children are the main value of the country, they need care and special attention. The government is obliged to ensure the implementation of children's rights to upbringing, education and development. The family education of children is the priority form. However, there is a problem of orphanage and social orphanage, children left without parental care. There are various forms of placement for orphans. The family form of the placement, foster families, are priority in the world

Cognitive functions and patterns of brain activity in patients after simultaneous coronary and carotid artery revascularization

BackgroundOn-pump coronary artery bypass grafting (CABG) is associated with a high risk of neurological complications in patients with severe carotid stenosis. Moreover, early postoperative cognitive dysfunction (POCD) incidence remains high in patients undergoing simultaneous coronary and carotid surgery. Recent studies have shown that even moderate carotid stenosis (≥50%) is associated with postoperative cognitive decline after CABG. Data on brain health in the postoperative period of simultaneous coronary and carotid surgery are limited.ObjectivesThis study aimed to analyze early postoperative changes in the cognitive function and patterns of brain electrical activity in patients after simultaneous coronary and carotid artery revascularization.Materials and methodsBetween January 2017 and December 2020, consecutive patients were assigned to on-pump CABG with or without carotid endarterectomy (CEA) according to clinical indications. An extended neuropsychological and electroencephalographic (EEG) assessment was performed before surgery and at 7–10 days after CABG or CABG + CEA.ResultsA total of 100 patients were included [median age 59 (55; 65), 95% men, MMSE 27 (26; 28)], and among these, 46 underwent CEA. POCD was diagnosed in 29 (63.0%) patients with CABG + CEA and in 32 (59.0%) patients with isolated CABG. All patients presented with a postoperative theta power increase. However, patients with CABG + right-sided CEA demonstrated the most pronounced theta power increase compared to patients with isolated CABG.ConclusionThe findings of our study show that patients with CABG + CEA and isolated CABG have comparable POCD incidence; however, patients with CABG + right-sided CEA presented with lower brain activity

Влияние предоперационного когнитивного расстройства на изменения электрической активности головного мозга у пациентов, перенесших одномоментное вмешательство на каротидных и коронарных артериях

HighlightsThe presence of preoperative mild cognitive impairment (MCI) in patients undergoing combined carotid endarterectomy and coronary artery bypass grafting is associated with an increased theta activity at the frontal and parieto-occipital regions of both hemispheres after surgery. AbstractAim. To study the impact of preoperative cognitive impairment on changes in electrical activity of the brain in patients undergoing combined carotid endarterectomy and coronary artery bypass grafting.Methods. Sixty-three patients undergoing combined carotid endarterectomy (CAE) and coronary artery bypass grafting (CABG) were included in the study. The patients were divided into three groups, depending on the preoperative cognitive functions: without cognitive impairment (n = 17), with MCI (n = 29), and with severe cognitive impairment (n = 17). High-resolution electroencephalography (EEG) (62 channels, bandpass filtered between 0.1–50.0 Hz, sampling rate of 1000 Hz) was performed 3–5 days before and 7–10 days after surgery.Results. Patients with severe cognitive impairment at baseline presented with higher theta activity at the frontal region of the left hemisphere compared to patients without cognitive impairment and patients with MCI (p = 0.048). At the same time, patients with MCI showed the most pronounced theta activity increase after surgery compared to preoperative levels at the frontal and parieto-occipital cortical regions of both the left and right hemispheres (p≤0.05). Postoperative changes of theta activity in patients with severe cognitive impairment were minimal and statistically insignificant.Conclusion. Patients without severe preoperative cognitive impairment presented with higher grade brain dysfunction in the form of increased theta activity at the frontal and parieto-occipital regions after combined CAE and CABG. A smaller decrease in theta power after surgery in patients with severe preoperative cognitive impairment, on the one hand, can indicate compensation after cerebral ischemia and resistance to hypoperfusion during on-pump cardiac surgery, and on the other, can be a manifestation of the ceiling effect and insufficiency of brain functional reserves.Основные положенияНаличие предоперационного умеренного когнитивного расстройства у пациентов, перенесших одномоментное вмешательство на каротидных и коронарных артериях, ассоциировано с выраженным послеоперационным увеличением тета-активности во фронтальных и парието-окципитальных отделах обоих полушарий. РезюмеЦель. Изучено влияние предоперационного когнитивного расстройства на изменения электрической активности головного мозга у больных, перенесших одномоментное вмешательство на каротидных и коронарных артериях.Материалы и методы. В исследовании участвовали 63 пациента, перенесших одномоментно каротидную эндартерэктомию и коронарное шунтирование с применением искусственного кровообращения. В зависимости от предоперационного состояния когнитивных функций участники разделены на три группы: без когнитивного расстройства (n = 17), с умеренным (n = 29) и тяжелым (n = 17) когнитивным расстройством. Электроэнцефалография высокого разрешения (62 канала, полоса пропускания 0,1–50,0 Гц, частота дискретизации 1 000 Гц) проведена за 3–5 дней и на 7–10-е сутки после вмешательства.Результаты. Установлено, что до операции у пациентов с тяжелым когнитивным расстройством показатели тета-активности во фронтальных отделах левого полушария были выше, чем у лиц без когнитивного расстройства и с умеренным когнитивным нарушением (p = 0,048). При этом после вмешательства у пациентов с умеренным когнитивным расстройством наблюдалось максимально выраженное увеличение тета-активности по сравнению с предоперационным уровнем во фронтальных и парието-окципитальных отделах коры левого и правого полушарий (p≤0,05). Тогда как у лиц с тяжелым когнитивным расстройством послеоперационные изменения тета-ритма были минимальны и не достигали статистической значимости.Заключение. Пациенты без тяжелых форм предоперационного когнитивного дефицита после одномоментного вмешательства на каротидных и коронарных артериях демонстрируют большую выраженность мозговой дисфункции по показателям тета-активности фронтальных и парието-окципитальных областей коры мозга. При этом меньшая выраженность изменений тета-ритма после операции у больных с тяжелым предоперационным когнитивным расстройством, с одной стороны, может быть индикатором компенсации хронической ишемии головного мозга и устойчивости к гипоперфузии при искусственном кровообращении, с другой – проявлением потолочного эффекта и недостаточности функциональных резервов