scholarly journals Microcirculatory disturbances in the pathogenesis of local cold injuries

2019 ◽  
Vol 18 (2) ◽  
pp. 4-11
Author(s):  
M. I. Mikhailichenko ◽  
K. G. Shapovalov

The review is devoted to microcirculatory disorders in local cold injury and simultaneous endothelial dysfunction. The features of endocrine activity of endothelium, cytokine activity, expression of the main molecules of intercellular adhesion and the phenomenon of lymphocytic-platelet adhesion, metabolism of nitric oxide, the state of the microcirculatory bed of the victims in different periods of injury were described.

2019 ◽  
Vol 4 (5) ◽  
pp. 79-83 ◽  
Author(s):  
M. I. Mikhailichenko ◽  
K. G. Shapovalov ◽  
V. A. Mudrov ◽  
O. S. Gruzdeva

The relevance of cold injury is due to its high specific weight in the structure of injuries, complexities of complex therapy, and unsatisfactory results of treatment. It is known that in the pathogenesis of local cold injury, the leading role belongs to endothelial dysfunction, which secretes a huge amount of biologically active substances, including matrix metalloproteinases.Aim: to determine the dynamics of the content of matrix metalloproteinases of the second subfamily (MMP-2, MMP-9) in the serum of patients with local cold injury.Materials and methods. The study included 80 patients (60 men, 20 women) with frostbite of the III–IV degree of the foot to the level of the lower third of the leg in the late reactive period and the period of granulation and epithelization.Results. In the late reactive period in patients with cryopreservation, the level of MMP-2 was 3.4 times higher relative to the control (p = 0.011), on day 30 MMP-2 values did not differ from the control parameters (p = 0.103). The level of collagenase B (MMP-9) in patients with local cold injury on day 5 was 14.5 times higher than the control parameters (p = 0.002), on day 30 – 12.5 times higher compared to the control group (p = 0.000094).Conclusion. During the analysis of the data obtained, we can think about the dual nature of collagenases during the processes of inflammation. In a situation of distress, collagenases prevent endothelial dysfunction by eliminating the cellular structures of the endothelium to ensure adequate metabolism in tissues. Their importance as markers of failure of adequate flow of reparative processes is not excluded.


2015 ◽  
Vol 70 (5) ◽  
pp. 599-603 ◽  
Author(s):  
O. N. Sergeeva ◽  
N. P. Chesnokova ◽  
E. V. Ponukalina ◽  
I. E. Rogozhina ◽  
T. N. Glukhova

Until now, there is no systematic information on the role of endothelial dysfunction in the mechanisms of disorders of blood coagulation potential and microcirculation in different organs and tissues in preeclampsia.Objective: Our aim was to extend the existing principles of diagnosis of pre-eclampsia by establishing the role of endothelial dysfunction in the mechanisms of blood coagulation potential violations. Methods: A prospective comparative study was performed. Condition of coagulation processes studied by conventional techniques, parameters of a functional endothelium (nitric oxide metabolites, endothelin 1, thrombospondin, thrombomodulin and intercellular adhesion molecules in blood plasma) — by ELISA.Results: The study group included 55 patients with moderate preeclampsia and 49 pregnant women with severe pre-eclampsia, in the control group — 40 women with physiological pregnancy. In patients with pre-eclampsia moderate observed increase in plasma endothelin-1 (p 0.001), thrombospondin (p 0.001), intercellular adhesion molecules (p 0.001) while reducing the level of nitrogen oxide (p 0.001), increase in time of fibrinolysis (p 0.050) and decreased international normalized ratio (p 0.050) compared with the control group. With increasing severity of preeclampsia the researchers detected in blood plasma of patients a progressive increase in endothelin 1 (p1 0.020), thrombospondin (p1 0.001), intercellular adhesion molecules (p1 0.001) and decrease of nitric oxide metabolites (p1 0.001) and thrombomodulin (p1 0.001); the last combined with the activation of procoagulant hemostasis.Conclusion: There is a pathogenetic relationship between the development of endothelial dysfunction, impaired blood coagulation potential and the severity of clinical signs of preeclampsia. To widen the number of existing techniques to diagnose the severity of pre-eclampsia we recommende to mesure endothelin 1, thrombomodulin, thrombospondin, intercellular adhesion molecules and nitric oxide metabolites in the blood plasma, and use traditional indicators to assess the hemostatic system.


2020 ◽  
Vol 5 (3) ◽  
pp. 24-28
Author(s):  
M. I. Mikhailichenko ◽  
K. G. Shapovalov ◽  
V. A. Mudrov ◽  
O. S. Gruzdeva

Relevance. Cold injury is defined as a complex of pathophysiological and pathomorphological changes arising as a result of local or general cooling of the human body. Endothelial dysfunction provokes a powerful cascade of cellular interactions with expressed excretory activity, which ultimately leads to a pronounced remodeling of microcirculation and a protracted process of inflammation in the focus of alterations. Aim of the study. To establish the dynamics of the level of myeloperoxidase and calprotectin in the serum of patients with local cold injury. Materials and methods. The study included 80 patients with III–IV degree lesions in the late reactive period and the period of granulation and epithelialization. The average age of patients was 38 ± 8 years. The myeloperoxidase level was measured on the 5th and 30th days from the moment of cryopreservation using multiplex analysis of blood serum. Results. The level of myeloperoxidase and serum calprotectin increases. In late reactive period (day 5), MPO level in patients with frostbite is 7.25 times higher in comparison with control values, in the period of granulation and epithelialization (day 30), it remains elevated, but only 3.63 times higher than in the control group. In the late reactive period, the level of calprotectin in the blood serum of patients with local cold injury was 4.6 times higher in comparison with control values, and on the 30th day of cryopreservation, the value of calprotectin was 4.5 times higher than in the control group. Changes in the level of myeloperoxidase and serum calprotectin reflect the flow of destructive and reparative mechanisms in tissues during local cold trauma and can be used in predicting an unfavorable prolonged course of the wound process.


1951 ◽  
Author(s):  
Josef Pichotka ◽  
R. B. Lewis ◽  
Ella Freytag

2020 ◽  
Vol 26 (30) ◽  
pp. 3633-3651 ◽  
Author(s):  
Javier Blanco-Rivero ◽  
Fabiano E. Xavier

Cardiovascular diseases (CVD) are considered a major health problem worldwide, being the main cause of mortality in developing and developed countries. Endothelial dysfunction, characterized by a decline in nitric oxide production and/or bioavailability, increased oxidative stress, decreased prostacyclin levels, and a reduction of endothelium-derived hyperpolarizing factor is considered an important prognostic indicator of various CVD. Changes in cyclic nucleotides production and/ or signalling, such as guanosine 3', 5'-monophosphate (cGMP) and adenosine 3', 5'-monophosphate (cAMP), also accompany many vascular disorders that course with altered endothelial function. Phosphodiesterases (PDE) are metallophosphohydrolases that catalyse cAMP and cGMP hydrolysis, thereby terminating the cyclic nucleotide-dependent signalling. The development of drugs that selectively block the activity of specific PDE families remains of great interest to the research, clinical and pharmaceutical industries. In the present review, we will discuss the effects of PDE inhibitors on CVD related to altered endothelial function, such as atherosclerosis, diabetes mellitus, arterial hypertension, stroke, aging and cirrhosis. Multiple evidences suggest that PDEs inhibition represents an attractive medical approach for the treatment of endothelial dysfunction-related diseases. Selective PDE inhibitors, especially PDE3 and PDE5 inhibitors are proposed to increase vascular NO levels by increasing antioxidant status or endothelial nitric oxide synthase expression and activation and to improve the morphological architecture of the endothelial surface. Thereby, selective PDE inhibitors can improve the endothelial function in various CVD, increasing the evidence that these drugs are potential treatment strategies for vascular dysfunction and reinforcing their potential role as an adjuvant in the pharmacotherapy of CVD.


2021 ◽  
Vol 22 (10) ◽  
pp. 5332
Author(s):  
Raquel G. Bardallo ◽  
Rui Teixeira da Silva ◽  
Teresa Carbonell ◽  
Emma Folch-Puy ◽  
Carlos Palmeira ◽  
...  

The total damage inflicted on the liver before transplantation is associated with several surgical manipulations, such as organ recovery, washout of the graft, cold conservation in organ preservation solutions (UW, Celsior, HTK, IGL-1), and rinsing of the organ before implantation. Polyethylene glycol 35 (PEG35) is the oncotic agent present in the IGL-1 solution, which is an alternative to UW and Celsior solutions in liver clinical transplantation. In a model of cold preservation in rats (4 °C; 24 h), we evaluated the effects induced by PEG35 on detoxifying enzymes and nitric oxide, comparing IGL-1 to IGL-0 (which is the same as IGL-1 without PEG). The benefits were also assessed in a new IGL-2 solution characterized by increased concentrations of PEG35 (from 1 g/L to 5 g/L) and glutathione (from 3 mmol/L to 9 mmol/L) compared to IGL-1. We demonstrated that PEG35 promoted the mitochondrial enzyme ALDH2, and in combination with glutathione, prevented the formation of toxic aldehyde adducts (measured as 4-hydroxynonenal) and oxidized proteins (AOPP). In addition, PEG35 promoted the vasodilator factor nitric oxide, which may improve the microcirculatory disturbances in steatotic grafts during preservation and revascularization. All of these results lead to a reduction in damage inflicted on the fatty liver graft during the cold storage preservation. In this communication, we report on the benefits of IGL-2 in hypothermic static preservation, which has already been proved to confer benefits in hypothermic oxygenated dynamic preservation. Hence, the data reported here reinforce the fact that IGL-2 is a suitable alternative to be used as a unique solution/perfusate when hypothermic static and preservation strategies are used, either separately or combined, easing the logistics and avoiding the mixture of different solutions/perfusates, especially when fatty liver grafts are used. Further research regarding new therapeutic and pharmacological insights is needed to explore the underlying mitochondrial mechanisms exerted by PEG35 in static and dynamic graft preservation strategies for clinical liver transplantation purposes.


Physiology ◽  
1993 ◽  
Vol 8 (4) ◽  
pp. 145-148 ◽  
Author(s):  
AGB Kovach ◽  
AM Lefer

Circulatory shock results in dysfunction of the endothelium in various vascular beds. This dysfunction is characterized by marked impairment in the vasculature's ability to relax to endothelium-dependent vasodilators. This loss of endothelium-derived relaxing factor, or nitric oxide, leads to profound tissue injury.


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