Primary Data on ATTR-Amyloidosis Prevalence Among Elderly Patients With Left Ventricular Hypertrophy in Russia.

AIM: To estimate the prevalence of amyloid cardiomyopathy (CM) caused by transthyretin amyloidosis (ATTR) and immunoglobulin light chain (AL) amyloidosis among patients aged >65 years with interventricular septal (IVS) hypertrophy of ≥14 mm. MATERIAL AND METHODS: From January through August 2023, 60 patients (mean age 7.2±7.3 years, 34 (56.67%) men) were enrolled. Patients meeting the inclusion criteria underwent an echocardiographic study with determining the myocardial longitudinal strain, myocardial scintigraphy with 99mTc-pyrfotech, myocardial single-photon emission computed tomography, measurement of N-terminal fragment of brain natriuretic peptide and troponin I, and the immunochemical study of serum and urine proteins with measurement of free light chains. In the presence of grades 2 and 3 radiopharmaceutical uptake according to scintigraphy, a molecular genetic study was performed for differential diagnosis of wild-type transthyretin amyloidosis (wtATTR) and hereditary/variant (hATTR) ATTR-CM. RESULTS: According to data of myocardial scintigraphy with 99mTc-pyrfotech, grade 3 uptake in the absence of monoclonal secretion was detected in 5 (8.3%) cases and grade 2 radiotracer uptake in the absence of monoclonal secretion was detected in 6 (10%) patients. Myeloma complicated by AL amyloidosis and primary AL amyloidosis were found in 5 (8.3%) patients. CONCLUSION: Among patients aged ≥65 years with IVS hypertrophy ≥14 mm, amyloid CM was detected in 20% of cases (12 patients), including 5 cases (8.3%) of AL amyloidosis and 7 cases (11.7%) of ATTR amyloidosis.

Hemodynamic Changes in Intrarenal Blood Flow are Associated With Poor Prognosis in Patients With Acute Decompensated Heart Failure.

AIM: To evaluate a potential role of different patterns of intrarenal blood flow using Doppler ultrasound as a part of determining the severity of venous congestion, predicting impairment of renal function and an unfavorable prognosis in patients with acute decompensated chronic heart failure (ADCHF). MATERIAL AND METHODS: This prospective observational single-site study included 75 patients admitted in the intensive care unit for ADCHF. Upon admission all patients underwent bedside renal venous Doppler ultrasound to determine the blood flow pattern (continuous, biphasic, monophasic). In one hour after the initiation of intravenous diuretic therapy, sodium concentration was measured in a urine sample. The primary endpoint was the development of acute kidney injury (AKI). The secondary endpoints were the development of diuretic resistance (a need to increase the furosemide daily dose by more than 2 times compared with the baseline), decreased natriuretic response (defined as urine sodium concentration less than 50-70 mmol/l), and in-hospital death. RESULTS: According to the data of Doppler ultrasound, normal renal blood flow was observed in 40 (53%) patients, biphasic in 21 (28%) patients, and monophasic in 14 (19%) patients. The monophasic pattern of intrarenal blood flow was associated with the highest incidence of AKI: among 14 patients in this group, AKI developed in 100% of cases (OR 3.8, 95% CI: 2.5-5.8, p<0.01), while among patients with normal and moderate impairment of renal blood flow, there was no significant increase in the risk of developing AKI. The odds of in-hospital death were increased 25.77 times in patients with monophasic renal blood flow (95% CI: 5.35-123.99, p<0.001). Patients with a monophasic intrarenal blood flow pattern were also more likely to develop diuretic resistance compared to patients with other blood flow patterns (p<0.001) and had a decreased sodium concentration to less than 50 mmol/l (p<0.001) in a spot urine test obtained one hour after the initiation of furosemide administration. CONCLUSION: Patients with monophasic intrarenal blood flow are at a higher risk of developing AKI, diuretic resistance with decreased natriuretic response, and in-hospital death.

Predictors of tachycardia-induced cardiomyopathy in patients with first-time decompensation of chro-nic heart failure with reduced left ventricular ejection fraction of nonischemic etiology and persistent atrial tachyarrhythmia.

Aim    To identify possible predictors of tachycardia-induced cardiomyopathy (TICMP) in patients with newly developed decompensated chronic heart failure (CHF) of nonischemic origin with reduced left ventricular ejection fraction (LV EF) and with persistent atrial tachyarrhythmias. Material and methods    This study included 88 patients with newly developed decompensated CHF of nonischemic origin with reduced LV EF and persistent atrial tachyarrhythmias. Resting 12-lead electrocardiography (EGC) and transthoracic echocardiography (EchoCG) were performed upon admission and following the electrical impulse therapy for all patients. Also, 24-h ECG monitoring was performed to confirm sinus rhythm stability. After recovery of sinus rhythm, outpatient monitoring was performed for three months, including repeated EchoCG to evaluate the dynamics of heart chamber dimensions and LV EF. Results    The patients were divided into two groups based on the increase in LV EF: 68 responders (TICMP patients with a LV EF increase by >10%) and 20 non-responders (patients with an increase in LV EF by <10% during 3 months following the sinus rhythm recovery). According to results of the baseline EchoCG, LV EF did not significantly differ in the two subgroups (TICMP, 40±8.3 %, 18-50 % and non-responders, 38.55±7.9 %, 24-50 %); moreover, the incidence of cases with LV EF <30% did not differ either (9 patients TICMP and 2 non-responders, р=1.0). TICMP patients compared to non-responders, had significantly smaller left atrial dimensions (4.53±1.14 (2-7) cm and 5.68±1.41 (4-8) cm, р=0.034; 80.8±28.9 (27-215) ml and 117.8±41.3 (46-230) ml, р=0.03, respectively) and left ventricular end-systolic volume (ESV) (67.7±33.1 (29-140) ml and 104.5±44.7 (26-172) ml, р=0.02, respectively). The effect of major EchoCG parameters on the probability of TICMP development was assessed by one-factor and multifactor regression analyses with adjustments for age and sex. The probability of TICMP increased with the following baseline EchoCG parameters: end-diastolic volume (EDV) <174 ml [odd ratio (OR), 0.115, 95 % confidence interval (CI): 0.035-0.371], ESV <127 ml [OR, 0.034, 95 % CI: 0.007-0.181], left atrial volume <96 ml [OR, 0.08 , 95 % CI: 0.023-0.274], right ventricular dimension <4 cm [OR, 0.042 , 95 % CI: 0.005-0.389].Conclusion    Among patients with newly developed decompensation of CHF with reduced LV EF of non-ischemic origin and persistent atrial arrhythmias, TICMP was detected in 72 % of patients. The probability of TICMP did not depend on baseline EF and duration of arrhythmias, but increased with the following baseline EchoCG parameters: EDV< 174 ml, ESV< 127 ml, left atrial volume <96 ml, right ventricular dimension <4 cm. The multifactorial analysis showed that a right atrial volume <96 ml is an independent predictor for the development of TICMP.

[Guillain-Barre syndrome associated with COVID-19]. / Sindrom Giiena­Barre, assotsiirovannyi s COVID-19.

This paper reports two cases of Guillain-Barre syndrome associated with coronavirus infection COVID-19. The clinical symptoms and neurological status of patients, the data of the additional examination and the features of the prescribed therapy are described in detail. The issue of the tropicity of the SARS-CoV-2 virus to human nervous tissue and its possible ways of affecting the peripheral nervous system is discussed.

Atherosclerosis of the carotid and coronary arteries in elderly patients with acute coronary syndrome.

Aim    To study the relationship between severities of the carotid artery injury and the atherosclerotic process in coronary arteries of elderly patients with acute coronary syndrome (ACS).Material and methods    The study included 110 patients aged >75 years. Based on the degree of maximal carotid stenosis according to data of duplex scanning (DS), all patients were divided into group I, (>50% stenosis) and group II (<50% stenosis).Results    According to coronary angiographic data, multivessel disease was observed in 63.6 % of patients. Patients of group I more frequently had three-vessel coronary artery disease than patients of group II (35.8 and 5.3 %, р<0.001). Coronary angiography and DS showed that 82.7 % patients (in group II, not all carotid stenoses were hemodynamically significant) had a combined damage of coronary and carotid arteries; carotid artery stenoses of >50% were associated with three-vessel coronary artery disease. A correlation between atherosclerosis of carotid and coronary arteries was found. Considering this correlation, a scale was introduced that suggested the severity of coronary atherosclerosis based on DS of carotid arteries. The score was assigned by assessing the degree of maximal stenoses in carotid arteries. A ROC analysis has determined a threshold score suggestive of the severity of coronary atherosclerosis: score <6, absence of >70% coronary stenosis; score >6, likely presence of >70% coronary stenosis (sensitivity, 70 %; specificity, 89 %).Conclusion    Combined coronary and carotid artery disease was detected in 82.7% of elderly patients with ACS. A correlation between the severity of atherosclerosis in carotid and coronary arteries was found. DS of carotid arteries can be extensively used in evaluation of elderly patients with ACS, which will allow additional stratification of patients at high risk of cerebrovascular and recurrent cardiovascular diseases.

RNA Sequencing and Cell Models of Virus-Associated Cancer (Review).

The review summarizes findings from the studies based on the application of technologies for transcriptome analysis to modern cellular model systems of human papillomavirus-associated cancer (HPV) (cervical cancer, head and neck tumors). A diversity of three-dimensional cancer models, such as spheroids, organoids (organotypic cultures), explants, mouse xenografts, are addressed. Particular attention is paid to the use of patient-derived biomaterial for establishing short-term cultures of primary tumor cells, as well as generating multicomponent (heterocellular) systems that comprise, together with the tumor component, other elements of its microenvironment. A number of unique biological properties of HPV-induced neoplasia are discussed, which make generating cell models a unique task. The novel findings in the field of molecular mechanisms of the onset and progression of HPV-associated cancer achieved by using RNA sequencing are presented for each variant of the model systems. These findings are considered in regard to applied aspects of their use, in terms of the opportunities for preclinical testing of new drugs, personalized diagnostics and selection of individual, most effective treatment regimens. The issues of drug resistance development, molecular-cellular heterogeneity, epigenetic reprogramming, and the role of the stromal microenvironment are reviewed. The paper accentuates the problems related to the limitations of the applicability of a particular model system. The areas with a significant lagging behind in omics research of virus-associated cancer in comparison with other types of oncological pathology and possible causes of this lag are noted. The future prospects for the development of model systems of HPV-associated tumors in the field of high-tech tissue engineering, in particular, the use of bioprinting and microfluidic biochips, are also outlined. The combination of these techniques with the methods of whole genome profiling will significantly increase the translational potential of the described model cell systems.

[Tachicardia-induced cardiomyopathy. Case report].

The tachycardia-induced cardiomyopathy is a rare case of reversible heart failure and left ventricle disfunction. The diagnostic approach and treatment strategy are described in this article. Also the clinical case of heart failure compensation in the patient with left ventricle dilatation and atrial flutter after the reverse to sinus rhythm is after catheter ablation presented.

[Characteristics of the Renin-Angiotensin-Aldosterone System in Carriers of Polymorphic Variants of the VDR Gene With Arterial Hypertension and Obesity].

AIM: to study the renin-angiotensin-aldosterone-system (RAAS) in patients with polymorphic variants of the vitamin D receptor gene (VDR), arterial hypertension (AH) and obesity. MATERIALS AND METHODS: We included in this study 98 patients with stage II-III AH and obesity (33 men, 65 women, mean age 61.1±9.9 years and BMI 43.3±5.0 kg/m2). The VDR gene study included genotypes TaqI, BsmI, FokI. After identification of TaqI, BsmI, FokI VDR gene sites we carried out measurements of levels of RAAS markers. RESULTS: We revealed an associative relationship between the presence of allele G of the BsmI site, C/C homozygosity of FokI site of VDR gene and presence of AH in patients with obesity. An increase of renin level was noted only in the homozygous T/T genotype of FokI, no differences in the concentration of aldosterone and angiotensin were detected between any of the studied genotypes. CONCLUSION: Polymorphic alleles and genotypes of the VDR gene can be used as predictors of AH development in obese patients with subsequent characterization of the state of the RAAS system.

[IMMUNE RESPONSE IN CHRONIC BRONCHIOLITIS OBLITERANS IN CHILDREN].

The qaim of the research was to evaluate a condition of cellular and humoral immunity in 139 children with bronchiolitis obliterans in age from 2 years to 14 years of life. There was a minor immunosuppression during exacerbation followed by normalization in remission. There was a slight decrease in the level of IgA, an increased concentration of IgM and high value of the circulating immune complexes during the exacerbation with normalization as acute inflammation subsided. An analysis of interleukin dynamics revealed a significant increase in the concentration of pro- and anti-inflammatory cytokines in the acute stage of the disease with a tendency to normalization in remission. Thus, there is no place marked immunosuppression. Analyzed changes are adequate and are a response to viral and bacterial infection.

Maternal serum soluble fms-like tyrosine kinase-1 at 22 and 32 weeks in the prediction of pre-eclampsia.

OBJECTIVE: To investigate the potential value of repeat measurements of maternal serum concentration of soluble fms-like tyrosine kinase-1 (sFlt-1) at 22 and 32 weeks' gestation in the prediction of pre-eclampsia (PE) in women delivering after 32 weeks. METHODS: The data were derived from prospective screening for adverse obstetric outcomes in women attending their routine hospital visit at 19-24 and/or 30-34 weeks' gestation in one of two maternity hospitals in England. Serum sFlt-1 was measured in 7565 and 8264 singleton pregnancies at 19-24 and 30-34 weeks, respectively. Bayes' theorem was used to combine the a-priori risk from maternal factors with sFlt-1 multiples of the median (MoM) values. The performance of screening for PE developing after the 30-34-week visit by sFlt-1, measured at 19-24, 30-34 and at both 19-24 and 30-34 weeks was examined. RESULTS: In pregnancies with PE, sFlt-1 in both the second and third trimesters was increased and the deviation from normal was inversely related to the gestational age at which delivery became necessary for maternal or fetal indications. Serum sFlt-1 at 19-24 weeks was not useful in predicting PE beyond the 30-34-week visit, but the addition of sFlt-1 at 19-24 weeks improved the prediction of PE provided by sFlt-1 at 30-34 weeks. Screening by maternal factors and sFlt-1 at 30-34 weeks predicted 94% of preterm PE and 54% of term PE, at a false-positive rate of 10%; this was improved to 99% and 64%, respectively, by the additional measurement of sFlt-1 at 19-24 weeks. CONCLUSIONS: Measurement of sFlt-1 in the second trimester improves the prediction of PE provided by screening in the early third-trimester. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

[TREATMENT OF SEVERE INTRAPATUM ASPHYXIA.]

THE AIM: Estimate of efficiency of newborns with severe birth asphyxia treatment using systemic therapeutic hypothermia. MATERIALS AND METHODS: a retrospective open-controlled clinical research with a resolution of the Ethics;Committee performed in 33 neonates born in asphyxia and treated at the NICU All newborns due to the presence of indications, overall controlled hypothermia was conducted according to the approved protocol, using the apparatus Allon 2001". RESULTS: The neurological status at admission: Sarnat II was detected in 60.6% (20) children; Sarnat III was detected in 39.4% (13) children. The correlation ofApgar scores with the most severe hypoxic ischemic encephalopathy. Pupillary reflexes admission absent in 48.5% (16) newborns. Convulsions within first hours of lfe were observed in 57.6% (19) newborns. Convulsions within I day of life were observed in 81.8 % (27) newborns. The correlation of the amniotic infection (AI) and meconium aspiration syndrome (MAS) treatment using high-frequency mechanical ventilation (p<0,05) and prolongation of mechanical ventilation for more than 5 days (p<0,01). At the beginning of systemic hypothermia fraction of inspired oxygen (FiO2), mean airway pressure (MAP), respiratory rate (RR) were down to the 12th hour of life and reaches a minimum at the end of the third day. These trends have been observed in children with MAS. The correlation of the use of high-frequency mechanical ventilation using high doses ofcardiotonics and the transition to the infusion of epinephrine or norepinephrine (p <0.01).There were no deaths in the studying group. CONCLUSIONS: 1. Reliable predictor of the clinical outcomes severity of hypoxic-ischemic encephalopathy (HIE) by the end of the first month lf is the presence of convulsions within the first hour of lf (p<0. 03). 2. When comparing the evaluation on Apgar scale with the data of acid-base balance and severity of HIE a significant correlation between the estimation at the first minute is I point and at the fifth minute 3 point and more severe pH shift, base deficiency, hyperlactatacidosis and severe HIE. 3. MAS and AI are the most frequent accompanying diseases that complicates the severity of newborn status causing prolonged artificial ventilation and the infusion ofcardiotonics. 4. There is a decrease in all parameters of artficial lung ventilation to the twelfth hour life in early systemic hypothermia and reached minimum by the end of the third day.

[Septic Shock: Innate Molecular Genetic Mechanisms of the Development of Generalized Inflammation].

The capacity for immune surveilance and protection against genetically alien agents is a basic property of multicellular organisms, and increasing significance in realizing this, capacity is assigned to mechanisms of innate immunity. The data accumulated to date show that many components of these mechanisms have a very wide spectrum of biological functions and play essential roles at different stages of ontogeny. An illustrative example is the signal system activated by tumor necrosis factor alpha (TNFα), which is responsible for the inflammation process. Analysis of its structural organization has shown that signaling mechanisms initiating inflammation largely overlap with mechanisms of programmed cell death. This is why hypersecretion of TNFα may lead to systemic inflammatory reation, or septic shok, and, hence, have a fatal outcome. Although studies on the TNFα-dependent mechanism have long history, many aspects of its regulation remain obscure. In particular, this concerns the nature of interspecific differences in the sensitivity of mammals to TNFα action and the ability of TNFα to activate oppositely directed cell programs depending on cell type or ambient conditions. The numerous data obtained in studies on different experimental systems need generalization and critical analysis. This review is an attempt at such an analysis. Its scope is concentrated on modern views on the divergence of TNFα-induced signal at the level of intracellular receptor-associated proteins. A description is given to potential "molecular triggers" responsible for switching between the main TNFα-dependent signaling pathways: inflammation, apoptosis, and necroptosis. The contribution of necroptosis (genetically programmed necrotic cell death) to the development of systemic inflammation and the lethal effect of TNFα are described. Consideration is also given to various lines of mice possessing natural resistance or sensitivity to TNFα, which hold much promise as models for deciphering the molecular genetic bases of the regulation of innate immune reactions and other TNFα-dependent processes.

[Low calorie diet influence optimization on body composition at obese patients with secondary diastolic heart failure].

In open prospective monocentric study in 3 parallel groups we studied the effectiveness of correction of body composition using low calorie diet therapy with inclusion of specialized food products (SFP)--sources of polyphenols and iridoids made on the basis of the juice of Morinda citrifolia L. fruits. We studied 90 patients aged from 30 to 50 years old with grade III obesity and clinically expressed secondary diastolic heart failure. The duration of diet therapy was 42 days. It was shown that low-calorie diet has non-optimal effect on the body composition in morbidly obese patients with secondary diastolic heart failure, namely leading to the expressed loss of body fatless (7.2%, p=0.00008) and muscle mass (by 16.6%, p=0.00004); at the same time the reduction of total body weight is noted only by 2.3% (p=0.053), reduction of waist measurement by 1.3% (p=0.028) and reduction of hips measurement by 1.3% (p=0.09), accompanied by the reduction of body fat by 8.5% (p=0.000017) and of liquid by 7.3% (p=0.0018). The introduction of the SFP into the diet optimizes the effect of low calorie diet therapy on the anthropometric parameters and body composition. The most important effect of the SFP is the ability to prevent the excess loss of muscle mass in patients, and this effect is being dose-dependent. The loss of muscle mass in two groups of patients was 3.1-4.1% after 6 weeks of diet therapy, while in the control group it was 8.5% (p=0.0051). We have concluded that the inclusion of the SFP, manufactured on the basis Morinda citrifolia L. (noni) juice to the low calorie diet allows to initiate mainly the loss of the body fat with the simultaneous protection of active cellular mass, which is without doubt can be considered as the advantage compared to the standard low calorie diet.

[The comparative characteristic of coefficients of endogenic intoxication under severe acute pancreatitis].

The sample included 43 patients with severe acute pancreatitis. Two coefficients of endogenic intoxication were applied: Kei1 = (AMP/ECA)x 100, AMP -average molecular peptides, ECA--effective concentration of albumin and Kei2 = (Kplp/aos/ECA) x 100, PLP--products of lipid peroxidation, AOS--indicators of antioxidant system. ECA--effective concentration of albumin. The comparative characteristic of both coefficients is given. It is established that Kei2 provides more informative indicators of endogenic intoxication in patients died at third day after operation. The study proved that both Kei can be applied for evaluation of endogenic intoxication and prognosis of generalized pancreonecrosis depending on resources of laboratory service.

Recombinant Semliki Forest virus vectors encoding hepatitis B virus small surface and pre-S1 antigens induce broadly reactive neutralizing antibodies.

Most hepatitis B virus (HBV) vaccines consist of viral small surface (S) protein subtype adw2 expressed in yeast cells. In spite of good efficacy, HBV-genotype and subtype differences, escape mutants and insufficient Th1 activation remain potential problems. To address these problems, we generated recombinant Semliki Forest virus (rSFV) vectors encoding S protein, subtype adw2 or ayw2, or a fragment of the large surface protein, amino acids 1-48 of the pre-S1 domain, fused to S (pre-S1.1-48/S). The antigen loop in S protein and the selected pre-S1 sequences are known targets of neutralizing antibodies. BALB/c mice were immunized intravenously with 10(7) rSFV particles and 10(8) rSFV particles 3 weeks later. Antibodies induced by rSFV encoding S proteins reacted preferentially with subtype determinants of yeast-derived S antigen but equally well with patient-derived S antigen. Immunization with rSFV encoding pre-S1.1-48/S resulted in formation of pre-S1- and S-specific immunoglobulin G (IgG), while immunization with the isogenic mutant without S start codon induced pre-S1 antibodies only. Neutralizing antibodies were determined by mixing with plasma-derived HBV/ayw2 and subsequent inoculation of susceptible primary hepatocyte cultures from Tupaia belangeri. S/adw2 antisera neutralized HBV/ayw2 as effectively as antisera raised with S/ayw2. The pre-S1 antibodies also completely neutralized HBV infectivity. The IgG1/IgG2a ratios ranged from 0.28 to 0.88 in the four immunized groups and were lowest for the pre-S1.1-48/S vector, indicating the strongest Th1 response. This vector type may induce subtype-independent and S-escape-resistant neutralizing antibodies against HBV.

Activation of N-methyl D-aspartate (NMDA) receptors has no influence on rheological properties of erythrocytes.

PURPOSE: Red blood cells (RBCs) express N-methyl D-aspartate (NMDA) receptors on their surface. We tested if NMDA receptor activation or inhibition had an influence on RBC deformability and aggregability. METHODS: Heparinized blood was drawn from healthy volunteers and centrifuged. RBCs were washed twice and resuspended with a hematocrit of 30% in a same buffer solution containing 3% dextran 70. Aliquots were prepared: a) control; b) containing 100 µM homocysteic acid (NMDA receptor agonist); c) 100 µM memantine (NMDA receptor inhibitor) and 100 µM homocysteic acid. RBC suspension viscometry (Contraves LS-30) was done at 37 °C with shear rates of 37.6 s(-1) and 0.1 s(-1). RBC aggregability was assessed with a Myrenne aggrometer and sedimentation rate. RESULTS: Neither NMDA receptor activation nor inhibition had an influence on biophysical properties of RBCs. RBC suspension viscosity at a shear rate of 37.6 s(-1) was 3.62 ± 0.16, 3.61 ± 0.13, and 3.62 ± 0.16 mPa.s for control, homocysteic acid, and memantine + homocysteic acid, respectively, indicating an unchanged RBC deformability. The RBC aggregability parameters (low shear viscosity, Myrenne aggregometry at stasis (M) and 3 s(-1) (M1), and the sedimentation rate) showed no influence of either memantine and/or homocysteic acid. A large interindividual variability in RBC aggregability was observed. A good correlation was found between M, M1 and sedimentation values, but not with low shear viscosity values. CONCLUSIONS: An activation or inhibition of NMDA receptors on RBCs has no influence on their deformability and aggregability. RBC aggregability varies largely among individuals, which was consistently detected by the sedimentation rate and the Myrenne aggregometer, but not by low shear viscosity, which should not be used for this purpose.

First aid kit for hypoxic survival: sensors and strategies.

Survival success under conditions of acute oxygen deprivation depends on efficiency of the central and peripheral chemoreception, optimization of oxygen extraction from the hypoxic environment and its delivery to the periphery, and adjustments of energy production and consumption. This article uses a comparative approach to assess the efficiency of adaptive strategies used by anoxia-tolerant and hypoxia-sensitive species to support survival during the first minutes to 1 h of oxygen deprivation. An aquatic environment is much more demanding in terms of diurnal and seasonal variations of the ambient oxygen availability from anoxia to hyperoxia than is an air environment. Therefore, fishes and aquatic turtles have developed a number of adaptive responses, which are lacking in most of the terrestrial mammals, to cope with these extreme conditions. These include efficient central and peripheral chemoreception, acute changes in respiratory rate and amplitude, and acute increase of the gas-exchange interface. A special set of adaptive mechanisms are engaged in reduction of the energy expenditure of the major oxygen-consuming organs: the brain and the heart. Both reduction of ATP consumption and a switch to alterative energy sources contribute to the maintenance of ATP and ion balance in hypoxia-tolerant animals. Hypoxia and hyperoxia are conditions favoring development of oxidative stress. Efficient protection from oxidation in anoxia-tolerant species includes reduction in the glutamate levels in the brain, stabilization of the mitochondrial function, and maintenance of nitric oxide production under conditions of oxygen deprivation. We give an overview of the current state of knowledge on some selected molecular and cellular acute adaptive mechanisms. These include the mechanisms of chemoreception in adult and neonatal mammals and in fishes, acute metabolic adaptive responses in the brain, and the role of nitrite in the preservation of heart function under hypoxic conditions.

Oxygen-dependent ion transport in erythrocytes.

The present contribution reviews current knowledge of apparently oxygen-dependent ion transport in erythrocytes and presents modern hypotheses on their regulatory mechanisms and physiological roles. In addition to molecular oxygen as such, reactive oxygen species, nitric oxide, carbon monoxide, regional variations of cellular ATP and hydrogen sulphide may play a role in the regulation of transport, provided that they are affected by oxygen tension. It appears that the transporter molecules themselves do not have direct oxygen sensors. Thus, the oxygen level must be sensed elsewhere, and the effect transduced to the transporter. The possible pathways involved in the regulation of transport, including haemoglobin as a sensor, and phosphorylation/dephosphorylation reactions both in the transporter and its upstream effectors, are discussed.

Amiodarone inhibits arterial thrombus formation and tissue factor translation.

BACKGROUND: In patients with coronary artery disease and reduced ejection fraction, amiodarone reduces mortality by decreasing sudden death. Because the latter may be triggered by coronary artery thrombosis as much as ventricular arrhythmias, amiodarone might interfere with tissue factor (TF) expression and thrombus formation. METHODS AND RESULTS: Clinically relevant plasma concentrations of amiodarone reduced TF activity and impaired carotid artery thrombus formation in a mouse photochemical injury model in vivo. PTT, aPTT, and tail bleeding time were not affected; platelet number was slightly decreased. In human endothelial and vascular smooth muscle cells, amiodarone inhibited tumor necrosis factor (TNF)-alpha and thrombin-induced TF expression as well as surface activity. Amiodarone lacking iodine and the main metabolite of amiodarone, N-monodesethylamiodarone, inhibited TF expression. Amiodarone did not affect mitogen-activated protein kinase activation, TF mRNA expression, and TF protein degradation. Metabolic labeling confirmed that amiodarone inhibited TF protein translation. CONCLUSIONS: Amiodarone impairs thrombus formation in vivo; in line with this, it inhibits TF protein expression and surface activity in human vascular cells. These pleiotropic actions occur within the range of amiodarone concentrations measured in patients, and thus may account at least in part for its beneficial effects in patients with coronary artery disease.