Regional Hemodynamics Research Articles

Структурно-функциональные изменения сосудов у женщин в ранней постменопаузе, возможности коррекции выявленных нарушений

To evaluate severity and pattern of structural and functional changes of vascular wall in early postmenopausal women receiving chronic treatment with a low-dose combination of 17β-estradiol (E2) 1 mg and drospirenone 2 mg (DRSP). Evaluation of structural and functional arterial remodeling might be important for assessment of cardiovascular risk in postmenopausal women. The study included 162 early postmenopausal women with postmenopausal syndrome. The women were divided into two groups. The main group consisted of 84 patients receiving the postmenopausal hormonal therapy (PMHT) with E2 1 mg / DRSP 2 mg (Angeliq, Bayer) and the control group included 78 women not receiving PMHT. The follow-up duration was 5.2 years. 24‑h blood pressure monitoring with evaluation of arterial stiffness (RWTT, AIx, ASI, AASI, (dP/dt) max) was performed. Endothelium-dependent dilation of the brachial artery was measured using the reactive hyperemia test. Aortic pulse wave velocity (aPWV) and common carotid intima-media thickness (ccIMT) were measured ultrasonically. At baseline, increased aPWV was observed in 15 (21.4 %) women of the main group and 19 (24.3 %) women of the control group (р=0.4). At the end of study, increased aPWV was observed in both groups but the increase was more pronounced in the control group. Increased pulse blood pressure (PBP) was observed in 27 (32.1 %) patients of the main group and 26 (33.3 %) patients of the control group (р=0.87). At the end of study, PBP decreased from 47.2±7.2 to 45.3±6.9 mm Hg (р.

The cerebral hemodynamic response to phonetic changes of speech in preterm and term infants: The impact of postmenstrual age.

Higher brain dysfunction, such as language delay, is a major concern among preterm infants. Cerebral substrates of cognitive development in preterm infants remain elusive, partly because of limited methods. The present study focuses on hemodynamic response patterns for brain function by using near-infrared spectroscopy. Specifically, the study investigates gestational differences in the hemodynamic response pattern evoked in response to phonetic changes of speech and cerebral hemispheric specialization of the auditory area in preterm infants (n = 60) and term infants (n = 20). Eighty neonates born between 26 and 41 weeks of gestational age (GA) were tested from 33 to 41 weeks of postmenstrual age (PMA). We analyzed the hemodynamic response pattern to phonemic and prosodic contrasts for multiple channels on temporal regions and the laterality index of the auditory area. Preterm infants younger than 39 weeks of PMA showed significantly atypical hemodynamic patterns, with an inverted response shape. Partial correlation analysis of the typicality score of hemodynamic response revealed a significant positive correlation with PMA. The laterality index of preterm infants from 39 weeks of PMA demonstrated a tendency rightward dominance for prosodic changes similar to term infants. We provide new evidence that alterations in hemodynamic regulation and the functional system for phonemic and prosodic processing in preterm infants catch up by their projected due dates.

Sex Characteristics of Hydrogen Sulfide Effect on Ischemia-Reperfusion in Rat Myocardium

The changes in cardiac hemodynamics against the background of ischemia-reperfusion in 40 male and female white rats and their relationship with the level of hydrogen sulfide (H2S) in the blood serum were studied. In a model of ischemia-reperfusion injury, we evaluated the parameters of cardiac hemodynamics (microcirculation rate, left ventricle oxygen saturation, right and left ventricular pressure) and hydrogen sulfide content in the blood serum. It has been found that in males background levels of microcirculation coefficient in the left ventricle and the content of H2S in the blood serum are significantly lower (by 9-18%) than those in females. Under experimental occlusion of the left coronary artery, H2S level decreases in the blood serum (in males by 64.5%, in females by 51.1%), which is accompanied by an inhibition of microcirculation and oxygen supply of the left ventricle cardiomyocytes (microcirculation coefficient and oxygen saturation are reduced), by weakening the contractive capacity and violation of intraventricular hemodynamics (pressure is reduced in left and right ventricles). These changes are more pronounced in males compared to females. Reperfusion of coronary vessels in animals of both sexes does not cause total recovery of H2S content in the serum and cardiac hemodynamics indicators to the background levels, indicating the formation of no-reflow coronary circulation syndrome. Infusion of NaHS not only prevents ischemia of the heart muscle, but also contributes to a more complete recanalization by improving effective perfusion in both males and females. Correlative analysis has shown that H2S level in the blood serum reveals direct links with microcirculation coefficient, left ventricle oxygen saturation, right and left ventricular pressure (in males, r = 0.54-0.62; in females, r = 0.60-0.70). These data suggest an important role of H2S system in the regulation of microcirculation and cardiac hemodynamics in male and female rats against the background of ischemia-reperfusion.

Phototherapy in complex treatment of wounds in patients with ischemic and neuroischemic form of diabetic syndrome

The aim of the study was to improve results of wound healing in patients with ischemic and neuroischemic forms of diabetic foot syndrome by using a combination of phototherapy, platelet-derived growth factor and modern cover materials The results of surgical treatment of 48 patients with ischemic and neuroischemic diabetic foot syndrome, which were divided into main group (24 patients) and comparison group (24 patients). All these patients who underwent treatment in the Department of acute vascular diseases in the Clinic of the SI “Institute of General and Urgent Surgery named after V.T. Zaitsev of the National Academy of Sciences of Ukraine” suffered from diabetes mellitus type II and had IV degree of foot ischemia according to Fontaine. The diagnostic was performed for all patients according to a standard algorithm. Analysis of the results of clinical, laboratory, non-invasive and invasive methods of examination in the preoperative period enabled to determine the degree of disorder in blood flow, the nature of collateral circulation and microcirculation. Patients of both groups underwent femoro-tibial and femoro-popliteal bypass, as well as hybrid reconstructions. The parameters of regional hemodynamics in patients of main group and the comparison group before and after revascularization were comparable. The patients of main group used the treatment technology developed by us. In cases of development of phlegmons of the foot after the opening of the abscess, vacuum therapy was performed for 7–14 days until the wound was completely cleaned. In the preoperative preparation complex, phototherapy was performed, according to local situation, wounds were irradiated with different wavelengths (405, 470 or 525 nm). After the wounds were cleaned, the wound defect was covered with PCL coating (Nanopharma, Czech Republic) with the application of a fibrin clot and platelet-rich plasma without fibrin, after which further local treatment was accompanied by irradiation of wounds with A. Korobov-V. Korobov photon matrices “Barva-Flex” (the wavelength of the maximum of the emission band of 660 nm). In two cases, the closure of bone defects with ILAYAOSTEOGEN® “A.A. PARTNERS” L.L.C. bone implants of medical company “ilaya” was used. Using these tactics, allow to achieve complete wound healing in 91.7% of patients and partial healing (more than 50%) in 8.3% of patients in main group. The terms of treatment of these patients did not exceed 2 months, high amputations were not required. In patients of comparison group against the background of traditional local treatment, the wounds healed within 2–4 months; in eight cases, repeated hospitalization was required to perform a plastic closure; in two cases amputation was performed below the knee. Thus, phototherapy and plastic closure of wounds of the lower extremities after revascularization in isch- emic diabetic foot syndrome is indicated in cases where the wounds have no tendency to spontaneous healing; introduction of the developed tactics of treatment of “problem” wounds of the lower extremities allowed to achieve complete healing in 91.7% of patients, partial (more than 50%) healing in 8.3% of patients and avoid high amputations; the use of a complex of treatment including phototherapy, wound closure with a synthetic coating with platelet growth factor, and the closure of bone defects with implants is an extremely effective stim- ulator of development in the wound of granulation tissue suitable for further autodermoplasty

ОСОБЕННОСТИ ДИАГНОСТИКИ, ХИРУРГИЧЕСКОЙ ТАКТИКИ И ВОССТАНОВИТЕЛЬНЫХ ОПЕРАЦИЙ ПРИ НЕКРОТИЗИРУЮЩЕЙ ИНФЕКЦИИ МЯГКИХ ТКАНЕЙ

Objective: Improving diagnostic results and surgical treatment of necrotizing soft tissue infection. Methods: Analyzed the results of diagnostics and treatment of 68 patients with various forms of necrotizing infection for the period 2010-2017. There were 32 men (53.8%), women – 36 (46.2%) at the age of 30-84. In 27 (39.7%) patients the necrotic form of erysipelas occurred, in 41 (60.3%) necrotizing fasciitis and myonecrosis. In 60.3% of cases, the pathological process was localized in the region of the lower extremities. More than 90% of the patients had concomitant diseases, among them diabetes mellitus (78.2%), arterial hypertension (83.3%), coronary artery disease (75.6%) and anaemia of varying severity (74.3%). Results: The clinical picture of streptococcal necrotizing fasciitis (n=31) and myonecrosis (n=10) in the early stages was characterized by the absence of pathognomonic symptoms. The discrepancy between the severity of the general condition and local status in a number of cases led to the belated surgical intervention and, as a result, extensive postoperative wounds, requiring 16 cases of plastic closure. In 12 (75%) cases, full engraftment was noted, in 3 (18.7%) partial engraftment and in 1 (6.3%) observation – complete necrosis of the graft. Conditions of transplant engraftment were corrected carbohydrate metabolism, preserved regional hemodynamics and the presence of actively granulating wound surface. Conclusion: Necrotizing infection, which is a nonspecific inflammatory process of soft tissues, is characterized by progressive necrosis, rapid spreading, difficulty in diagnosing in the early stages of the disease, pronounced intoxication and high lethality. Keywords: Necrotizing infection , fasciitis , free skin grafting , surgical tactics.

Low Nasal NO in Congenital Heart Disease With Systemic Right Ventricle and Postcardiac Transplantation.

BackgroundNO bioavailability has not been systematically examined in congenital heart disease (CHD). To assess NO in patients with CHD, we measured nasal NO (nNO) generated by the nasal epithelia, given blood NO is difficult to measure (half‐life, <2 ms). Given NO's role in hemodynamic regulation and the association of NO bioavailability with heart failure risk, we hypothesized NO levels may differ with varying severity of CHD physiologic characteristics.Methods and ResultsSix‐hundred eighteen subjects, 483 with CHD and 135 controls, had nNO measured noninvasively via the nares using American Thoracic Society/European Respiratory Society guidelines. Subjects were dichotomized as having low or normal nNO based on age‐specific cutoff values. Prevalence of low nNO was examined by various CHD physiologic feature types. Low nNO was more prevalent with CHD than controls (odds ratio, 2.28; P=0.001). A logistic regression model showed overall significance (P=0.035) for single ventricle, systemic right ventricle, ventricular dysfunction, oxygen desaturation, and heterotaxy predicting low nNO, with systemic right ventricle independently having twice the odds of low nNO (odds ratio, 2.04; P=0.014). Patients with low nNO had a higher risk of experiencing heart transplant or death (hazard ratio, 2.75; P=0.048), and heart transplant recipients (N=16) exhibited 5 times the odds of low nNO (69% versus 30%; odds ratio, 5.1; P=0.001).ConclusionsPatients with CHD have increased prevalence of low nNO, with highest odds seen with systemic right ventricle and heart transplant. Further studies are needed to investigate heart failure risks in patients with CHD with left versus right systemic ventricle physiologic characteristics and utility of low nNO for predicting heart failure risk.

Zinc is a critical regulator of placental morphogenesis and maternal hemodynamics during pregnancy in mice

Zinc is an essential micronutrient in pregnancy and zinc deficiency impairs fetal growth. We used a mouse model of moderate zinc deficiency to investigate the physiological mechanisms by which zinc is important to placental morphogenesis and the maternal blood pressure changes during pregnancy. A 26% reduction in circulating zinc (P = 0.005) was exhibited in mice fed a moderately zinc-deficient diet. Zinc deficiency in pregnancy resulted in an 8% reduction in both near term fetal and placental weights (both P < 0.0001) indicative of disrupted placental development and function. Detailed morphological analysis confirmed changes to the placental labyrinth microstructure. Continuous monitoring of maternal mean arterial pressure (MAP) revealed a late gestation decrease in the zinc-deficient dams. Differential expression of a number of regulatory genes within maternal kidneys supported observations on MAP changes in gestation. Increased MAP late in gestation is required to maintain perfusion of multiple placentas within rodent pregnancies. Decreased MAP within the zinc-deficient dams implies reduced blood flow and nutrient delivery to the placenta. These findings show that adequate zinc status is required for correct placental morphogenesis and appropriate maternal blood pressure adaptations to pregnancy. We conclude that insufficient maternal zinc intake from before and during pregnancy is likely to impact in utero programming of offspring growth and development largely through effects to the placenta and maternal cardiovascular system.

Effects of lung protective mechanical ventilation associated with permissive respiratory acidosis on regional extra-pulmonary blood flow in experimental ARDS

BackgroundLung protective mechanical ventilation with limited peak inspiratory pressure has been shown to affect cardiac output in patients with ARDS. However, little is known about the impact of lung protective mechanical ventilation on regional perfusion, especially when associated with moderate permissive respiratory acidosis. We hypothesized that lung protective mechanical ventilation with limited peak inspiratory pressure and moderate respiratory acidosis results in an increased cardiac output but unequal distribution of blood flow to the different organs of pigs with oleic-acid induced ARDS.MethodsTwelve pigs were enrolled, 3 died during instrumentation and induction of lung injury. Thus, 9 animals received pressure controlled mechanical ventilation with a PEEP of 5 cmH2O and limited peak inspiratory pressure (17 ± 4 cmH2O) versus increased peak inspiratory pressure (23 ± 6 cmH2O) in a crossover-randomized design and were analyzed. The sequence of limited versus increased peak inspiratory pressure was randomized using sealed envelopes. Systemic and regional hemodynamics were determined by double indicator dilution technique and colored microspheres, respectively. The paired student t–test and the Wilcoxon test were used to compare normally and not normally distributed data, respectively.ResultsMechanical ventilation with limited inspiratory pressure resulted in moderate hypercapnia and respiratory acidosis (PaCO2 71 ± 12 vs. 46 ± 9 mmHg, and pH 7.27 ± 0.05 vs. 7.38 ± 0.04, p < 0.001, respectively), increased cardiac output (140 ± 32 vs. 110 ± 22 ml/min/kg, p<0.05) and regional blood flow in the myocardium, brain and spinal cord, adrenal and thyroid glands, the mucosal layers of the esophagus and jejunum, the muscularis layers of the esophagus and duodenum, and the gall and urinary bladders. Perfusion of kidneys, pancreas, spleen, hepatic arterial bed, and the mucosal and muscularis blood flow to the other evaluated intestinal regions remained unchanged.ConclusionsIn this porcine model of ARDS mechanical ventilation with limited peak inspiratory pressure resulting in moderate respiratory acidosis was associated with an increase in cardiac output. However, the better systemic blood flow was not uniformly directed to the different organs. This observation may be of clinical interest in patients, e.g. with cardiac, renal and cerebral pathologies.

Phrase Mining and Machine Learning in Textual Data to Uncover Distinct Protein Patterns in Cardiovascular Disease

Background: Decades of successful biomedical research have led to the rapid accumulation of large-volume text data (unstructured data). Defining relationships and structuring connections of these fragmented data from the many published can uncover valuable information hidden in this treasure trove. However, the quantity of text data is overwhelming and manual extraction is a forbitten task. This situation demands the development of automated tools to effectively and accurately processing the giant volume of available textual data (e.g., ~27M on PubMed, ~160M on Google Scholar). Objectives: To address this challenge, we developed a text-mining and machine learning algorithm to dissect textual data on CVD and identify protein patterns in datasets to uncover valuable information. Methods: We applied a novel phrase mining workflow, Context-aware Semantic Online Analytical Processing (CaseOLAP), to recognize patterns from six CVD datasets based on their MeSH-terms: cerebrovascular accidents (CVA), cardiomyopathies (CM), ischemic heart diseases (IHD), arrhythmias (ARR), valvular heart disease (VHD) and Congenital Heart Disease (CHD). We analyzed the patterns of 8,325 cardiac proteins in 1.1 million publications (1995-2016). Results: Over 8,325 proteins only a subset exhibited high CaseOLAP scores indicating high relevance in CVD, mainly displayed in IHD, CM and CVA. We identified six high scoring protein clusters unique to one CVD group. A principle component analysis indicated that IHD, CVA and CM showed distinct protein scoring patterns while CHD, VHD and ARR were clustered. We identified 10 protein clusters shared between two or more CVD groups with biological functions in inflammation, contractility, blood coagulation, hemodynamic regulation, cytoskeletal organization and neurotransmission. Inflammatory proteins appeared to be relevant in all CVDs, while proteins in neurotransmission and memory processing were relevant in CVA, ARR, VHD, and CHD. Conclusions: Using CaseOLAP on textual data across six CVDs we gained novel insights into patterns and relationships of their proteins. This text-mining algorithm offers promising biomedical applications to facilitate patient studies in clinical trials, case reports and electronic health records.

THE LONGITUDINAL STUDY RESULTS OF THE PHYSIOLOGICAL STATUS OF MALE NORTHERNERS - PARTICIPANTS OF THE PROJECT “MARS-500”

We studied physiological status and somatic health of 23 male volunteers (age 24-50 yrs) recruited as a "northern" control group for the experiment "Mars-500". The study was performed using standardized methods, established by the Institute of Medical and Biological Problems of the RAS, using hardware and software complex "Ecosan-2007". Repetitive experiments were carried out in 6 years. Collected data were processed using Biostat and Statistica statistical software. In the course of the study we found certain features in the physiological status and the somatic health of the participants related to their inhabitation in the North. We discovered that our volunteers had decreased somatic health levels according to the Apanasenko scale. Analyzing the heart rate variability in our subjects we observed tension in regulatory systems and a domination of the central regulation circuit over the autonomous circuit. Additionally our subjects showed a deterioration of the hemodynamics regulation under a physical load. After 6 years we observed statistically significant increases in the body mass, the heart rate after physical load, biological age, and significant decrease of the physical health, which indicate the accelerated ageing in the group of surveyed. A number of persons with premorbid status have increased, indicating the increased tension of the regulatory systems and the decrease in the adaptability potential.

Compromised Cerebrovascular Regulation and Cerebral Oxygenation in Pulmonary Arterial Hypertension.

BackgroundFunctional cerebrovascular regulatory mechanisms are important for maintaining constant cerebral blood flow and oxygen supply in heathy individuals and are altered in heart failure. We aim to examine whether pulmonary arterial hypertension (PAH) is associated with abnormal cerebrovascular regulation and lower cerebral oxygenation and their physiological and clinical consequences.Methods and ResultsResting mean flow velocity in the middle cerebral artery mean flow velocity in the middle cerebral artery (MCAvmean); transcranial Doppler), cerebral pressure‐flow relationship (assessed at rest and during squat‐stand maneuvers; analyzed using transfer function analysis), cerebrovascular reactivity to CO 2, and central chemoreflex were assessed in 11 patients with PAH and 11 matched healthy controls. Both groups also completed an incremental ramp exercise protocol until exhaustion, during which MCAvmean, mean arterial pressure, cardiac output (photoplethysmography), end‐tidal partial pressure of CO 2, and cerebral oxygenation (near‐infrared spectroscopy) were measured. Patients were characterized by a significant decrease in resting MCAvmean (P<0.01) and higher transfer function gain at rest and during squat‐stand maneuvers (both P<0.05). Cerebrovascular reactivity to CO 2 was reduced (P=0.03), whereas central chemoreceptor sensitivity was increased in PAH (P<0.01), the latter correlating with increased resting ventilation (R 2=0.47; P<0.05) and the exercise ventilation/CO2 production slope (V˙E/V˙CO2 slope; R 2=0.62; P<0.05) during exercise for patients. Exercise‐induced increases in MCAvmean were limited in PAH (P<0.05). Reduced MCAvmean contributed to impaired cerebral oxygen delivery and oxygenation (both P<0.05), the latter correlating with exercise capacity in patients with PAH (R 2=0.52; P=0.01).ConclusionsThese findings provide comprehensive evidence for physiologically and clinically relevant impairments in cerebral hemodynamic regulation and oxygenation in PAH.

Impact of mitochondrial nitrite reductase on hemodynamics and myocardial contractility

Inorganic nitrite (NO2−) can be reduced back to nitric oxide (NO) by several heme proteins called nitrite reductases (NR) which affect both the vascular tonus and hemodynamics. The objective of this study was to clarify the impact of several NRs on the regulation of hemodynamics, for which hemodynamic parameters such as heart rate, blood pressure, arterial stiffness, peripheral resistance and myocardial contractility were characterized by pulse wave analysis. We have demonstrated that NO2− reduced to NO in RBCs predominantly influences the heart rate, while myoglobin (Mb) and mitochondria-derived NO regulates arterial stiffness, peripheral resistance and myocardial contractility. Using ex vivo on-line NO-detection, we showed that Mb is the strongest NR occurring in heart, which operates sufficiently only at very low oxygen levels. In contrast, mitochondrial NR operates under both hypoxia and normoxia. Additional experiments with cardiomyocytes suggested that only mitochondria-derived generation of NO regulates cGMP levels mediating the contractility of cardiomyocytes. Our data suggest that a network of NRs is involved in NO2− mediated regulation of hemodynamics. Oxygen tension and hematocrit define the activity of specific NRs.

REV-ERBα ameliorates heart failure through transcription repression.

A cure for heart failure remains a major unmet clinical need, and current therapies targeting neurohomonal and hemodynamic regulation have limited efficacy. The pathological remodeling of the myocardium has been associated with a stereotypical gene expression program, which had long been viewed as the consequence and not the driver of the disease until very recently. Despite the advance, there is no therapy available to reverse the already committed gene program. Here, we demonstrate that transcriptional repressor REV-ERB binds near driver transcription factors across the genome. Pharmacological activation of REV-ERB selectively suppresses aberrant pathologic gene expression and prevents cardiomyocyte hypertrophy. In vivo, REV-ERBα activation prevents development of cardiac hypertrophy, reduces fibrosis, and halts progression of advanced heart failure in mouse models. Thus, to our knowledge, modulation of gene networks by targeting REV-ERBα represents a novel approach to heart failure therapy.

Abstract 162: MicroRNAs Mediate the Hemodynamic Regulation of Endothelium-to-Smooth Muscle Signaling

Vascular endothelial cells (ECs) at arterial branches and curvatures experience disturbed blood flow and induce a quiescent-to-activated phenotypic transition of the adjacent smooth muscle cells (SMCs) and a subsequent smooth muscle hyperplasia. However, the mechanism underlying the flow pattern-specific initiation of EC-to-SMC signaling remains elusive. Our previous study has demonstrated that endothelial microRNA-126-3p (miR-126-3p) acts as a key intercellular molecule to increase turnover of the recipient SMCs, and that its release is reduced by atheroprotective laminar shear (LS) to ECs. In the current study we found that atherogenic oscillatory shear (OS), but not atheroprotective pulsatile shear (PS), promotes the regulated exocytosis, particularly the secretion of non-membrane-bound miR-126-3p and other microRNAs (miRNAs) via the activation of soluble N-ethyl-maleimide-sensitive fusion protein attachment protein receptors (SNAREs), VAMP3 and SNAP23. Quantitative PCR arrays identify 15 EC-secreted miRNAs whose levels in the vesicle-poor supernatant of flow perfusate are differentially regulated (P&lt;0.05) by OS versus PS. The fold changes of 11 miRNAs are either greater than 2.0 or less than 0.5. Knockdown of VAMP3 and SNAP23 reduces the secretion of miR-126-3p and miR-200a-3p, as well as the proliferation, migration, and suppression of contractile markers in SMCs caused by EC-coculture. Pharmacological intervention of mTORC1 in ECs blocks endothelial secretion and EC-to-SMC transfer of miR-126-3p through transcriptional inhibition of VAMP3 and SNAP23. Systemic inhibition of VAMP3 and SNAP23 by rapamycin or periadventitial application of the endocytosis inhibitor dynasore ameliorates the disturbed flow-induced neointimal formation, whereas intraluminal overexpression of SNAP23 aggravates it. Our findings demonstrate the flow-pattern-specificity of SNAREs activation and its contribution to the miRNA-mediated EC-SMC communication, uncovering potential targets for future diagnosis and therapeutic interventions for proliferative vascular diseases.

Role of the Primary Cilia on the Macula Densa and Thick Ascending Limbs in Regulation of Sodium Excretion and Hemodynamics.

We investigated the significance of the primary cilia on the macula densa and thick ascending limb (TAL) in regulation of renal hemodynamics, sodium excretion, and blood pressure in this study. A tissue-specific primary cilia knock-out (KO) mouse line was generated by crossing NKCC2-Cre mice with IFT88-Δ/flox mice (NKCC2CRE; IFT88Δ/flox), in which the primary cilia were deleted from the macula densa and TAL. NO generation was measured with a fluorescent dye (4,5-diaminofluorescein diacetate) in isolated perfused juxtaglomerular apparatus. Deletion of the cilia reduced NO production by 56% and 42% in the macula densa and TAL, respectively. NO generation by the macula densa was inhibited by both a nonselective and a selective nitric oxide synthesis inhibitors, whereas TAL-produced NO was inhibited by a nonselective and not by a selective NO synthesis 1 inhibitor. The tubuloglomerular feedback response was enhanced in the KO mice both in vitro measured with isolated perfused juxtaglomerular apparatuses and in vivo measured with micropuncture. In response to an acute volume expansion, the KO mice exhibited limited glomerular filtration rate elevation and impaired sodium excretion compared with the wild-type mice. The mean arterial pressure measured with telemetry was the same for wild-type and KO mice fed a normal salt diet. After a high salt diet, the mean arterial pressure increased by 17.4±1.6 mm Hg in the KO mice. On the basis of these findings, we concluded that the primary cilia on the macula densa and TAL play an essential role in the control of sodium excretion and blood pressure.

Effect of type 2 diabetes, surgical incision, and volatile anesthesia on hemodynamics in the rat.

Diabetic patients have increased cardiac complications during surgery, possibly due to impaired autonomic regulation. Anesthesia lowers blood pressure and heart rate (HR), whereas surgical intervention has opposing effects. The interaction of anesthesia and surgical intervention on hemodynamics in diabetes is unknown, despite being a potential perioperative risk factor. We aimed to determine the effect of diabetes on the integrative interaction between hemodynamics, anesthesia, and surgical incision. Zucker type 2 diabetic rats (DM) and their nondiabetic littermates (ND) were implanted with an intravenous port for drug delivery, and a radiotelemeter to measure mean arterial blood pressure (MAP) and derive HR (total n = 50). Hemodynamic pharmacological responses were assessed under conscious, isoflurane anesthesia (~2–2.5%), and anesthesia–surgical conditions; the latter performed as a laparotomy. MAP was not different between groups under conscious conditions (ND 120 ± 6 vs. DM 131 ± 4 mmHg, P > 0.05). Anesthesia reduced MAP, but not differently in DM (ND −30 ± 6 vs. DM −38 ± 4 ΔmmHg, P > 0.05). Despite adequate anesthesia, surgical incision increased MAP, which tended to be less in DM (ND +21 ± 4 vs. DM +13 ± 2 ΔmmHg, P = 0.052). Anesthesia disrupted central baroreflex HR responses to sympathetic activation (sodium nitroprusside 10 μg·kg−1, ND conscious 83 ± 13 vs. anesthetized 16 ± 5 Δbpm; P < 0.05) or to sympathetic withdrawal (phenylephrine 10 μg·kg−1, ND conscious −168 ± 37 vs. anesthetized −20 ± 6 Δbpm; P < 0.05) with no additional changes observed after surgical incision or during diabetes. During perioperative conditions, type 2 diabetes did not impact on short‐term hemodynamic regulation. Anesthesia had the largest hemodynamic impact, whereas surgical effects were limited to modulation of baseline blood pressure.

Retinal vein occlusion after intake of sildenafil citrate

This article describes the case of a possible rare complication of sildenafil citrate use - central retinal vein occlusion. Sildenafil citrate influences on regional and systemic hemodynamics. The role of predisposing factors (arterial hypertension, hyperhomocysteinemia) and provoking factors (physical exercise, visiting sauna and a double dose of the potency regulator) is discussed. Combination of provoking factors including use of sildenafil citrate has resulted in acute decrease in regional perfusion pressure with the development of central retinal vein occlusion.

Diagnostic value OF oct-angiography AND regional hemodynamic assesSment in patients with retinal vein occlusion

Introduction. Ischemic maculopathy is the main cause of irreversible vision loss due to retinal vein occlusion (RVO). Fluorescein angiography (FA), which is the gold standard for evaluating retinal capillary plexuses, does not allow for the visualization of separate intraretinal capillary networks. Optical coherence tomography angiography (OCT-angiography) enables the possible visualization of four capillary plexi and allows for the quantitative analysis of microcirculation to quantitatively estimate capillary network density and non-perfusion areas.&#x0D; Aim. To investigate microcirculation changes using OCT-angiography data and to compare the changes with opthalmoplethysmography indices in patients with RVO.&#x0D; Material and methods. The study included 12 patients with RVO. In all patients, a routine ophthalmic examination was performed, and ocular blood flow was estimated using FA, OCT-angiography, and ophthalmoplethysmography.&#x0D; Results. Ischemia in the macular area was detected in four patients (25%) according to FA results, and in eight (67%) accor ding to OCT-angiography data. Compared with the unaffected eye, significant decrease in the density of both superficial and deep capillary plexuses as well as a decrease in flow area and enlargement of foveal avascular zone were observed. A significant close direct correlation was established between capillary density in the superficial capillary plexus (r 0.8) and the deep capillary plexus (r 0.7), choroidal thickness, and opthalmoplethysmography indices (r 0.6).&#x0D; Conclusion. Compared with FA, OCT-angiography is a more sensitive method to detect macular capillary perfusion. In cases with RVO, the combination of the above mentioned methods with ophthalmoplethysmography allows for the comprehensive evaluation of regional hemodynamics.

Abstract 228: The Establishment of a Novel Atherosclerosis Regression Model in Mice

Background: Inhibition of plaque progression by various anti-atherosclerotic drugs is a canonical aspect underlying their therapeutic efficacy. Although existed animal models of plaque regression are available for drug evaluation, they are either highly invasive or time-consuming. We therefore aimed to establish a practical method to study the mechanism of atherosclerosis regression based on hemodynamic regulation of atherosclerosis. Methods: A carotid plaque regression model in mice was developed based on the previously described model. Briefly, a single slipknot was applied to all three branches of the left carotid artery (LCA) in ApoE -/- mice. After 2 weeks on HFD, the blood flow in LCA was reconstructed by slipknot release. Mice were housed for additional 4 weeks. Carotid ultrasonography was used to verify successful induction of disturbed flow and the reconstruction of the blood flow. Atherosclerotic plaques were stained with Sudan IV. The infiltration of smooth muscle cells and macrophages were determined by immunofluorescence staining. Results: Histology studies demonstrated similar cellular components and lipid deposition between the d-flow induced plaques in the LCA in WT mice and atherosclerotic plaques in aorta of ApoE -/- mice on HFD. However, a significantly higher proportion of SMC (n=5, p&lt;0.0001) and lower macrophage infiltration (n=6, p=0.0056) were observed in the induced carotid plaques compared to the aortic plaques. After the release of the knots, an abrupt increase in flow velocity indicated a successful restoration of blood flow from the LCA to its branches. At this point, the restored flow in ligated LCA was still lower compared to the untied right carotid artery (RCA). After the procedure, mice were given chew diet for additional 4 weeks and blood flow was re-accessed using carotid ultrasonography. Results showed no significant difference of blood flow between LCA and RCA, indicating nearly complete regression of carotid atherosclerosis. Conclusion: We have established a highly reproducible atherosclerosis regression model with less invasiveness and genetic independence that supplies a practical tool for evaluation of anti-atherosclerotic drugs and for the pathophysiology of atherosclerosis regression.

Physiopathological implications of P2X1 and P2X7 receptors in regulation of glomerular hemodynamics in angiotensin II-induced hypertension.

Deleterious effects of purinergic P2X1 and P2X7 receptors (P2XRs) in ANG II-dependent hypertension include increased renal vascular resistance, and impaired autoregulation and pressure natriuresis. However, their specific effects on the determinants of glomerular hemodynamics remain incompletely delineated. To investigate the P2XR contributions to altered glomerular hemodynamics in hypertension, the effects of acute blockade of P2X1R, P2X7R, and P2X4R with NF449, A438079, and PSB12054, respectively, were evaluated in ANG II-infused rats (435 ng·kg-1·min-1). P2X1R or P2X7R blockade reduced afferent (6.85 ± 1.05 vs. 2.37 ± 0.20 dyn·s-1·cm-5) and efferent (2.85 ± 0.38 vs. 0.99 ± 0.07 dyn·s-1·cm-5) arteriolar resistances, leading to increases in glomerular plasma flow (75.82 ± 5.58 vs. 206.7 ± 16.38 nl/min), ultrafiltration coefficient (0.0198 ± 0.0024 vs. 0.0512 ± 0.0046 nl·min-1·mmHg-1), and single-nephron glomerular filtration rate (22.73 ± 2.02 vs. 51.56 ± 3.87 nl/min) to near normal values. Blockade of P2X4R did not elicit effects in hypertensive rats. In normotensive sham-operated rats, only the P2X1R antagonist caused an increase plasma flow and single-nephron glomerular filtration rate, whereas the P2X4R antagonist induced glomerular vasoconstriction that was consistent with evidence that P2X4R stimulation increases release of nitric oxide from endothelial cells. Mean arterial pressure remained unchanged in both hypertensive and normotensive groups. Western blot analysis showed overexpression of P2X1R, P2X7R, and P2X4R proteins in hypertensive rats. Whereas it has been generally assumed that the altered glomerular vascular resistances in ANG II hypertension are due to AT1 receptor-mediated vasoconstriction, these data indicate a predominant P2X1R and P2X7R control of glomerular hemodynamics in ANG II hypertension.