Compensatory Vasodilation Research Articles

Middle Cerebral Artery Doppler before and after Fetal Spina Bifida Repair: An Indirect Sign of Hindbrain Compression and Decompression?

Reduced middle cerebral artery resistance indices (MCA-RI) in fetuses with spina bifida (fSB) are commonly observed. Compression of neuronal pathways in the brainstem due to hindbrain herniation (HH) and disturbed cerebrospinal fluid circulation likely cause an imbalance of the autonomic nervous system. This may increase systemic vasoconstriction and compensatory increase cerebral vasodilation (like brain sparing). The aim of this study was to systematically analyze all fetal MCA-RI before and after fSB repair and to compare their correlation with the presence and postsurgical resolution of HH. 173 patients were included. Standardized ultrasound examinations including MCA and umbilical artery (UA) Doppler as well as assessment of HH presence and regression were performed. Fetuses with MCA-RI <5th percentile (P) before fetal surgery were compared to the group with normal MCA-RI and correlated to the presence of HH before and its regression after fSB repair. 30% (49/161) fetuses showed RI's <5th P before fSB repair. All fetuses had normal UA-RI. 99.4% of fetuses (160/161) showed normal of MCA-RI before delivery. Normalization occurred within a mean of 1.3 ± 1.2 weeks. HH regression was observed in 97% in the group with normal MCA-RI and in 96% in the group with MCA-RI <5th P before surgery (p = 0.59). Time lapse to HH regression after fSB repair was 1.8 ± 1.7 and 1.9 ± 1.6 weeks, respectively. In fetuses with MCA-RIs <5 P before fSB repair, a parallel timely course of MCA-RI normalization and HH regression was noted. To suggest common pathogenic factor(s), more studies are needed. However, normalization of the fetal cerebral circulation could be a further benefit of fSB repair.

Unveiling the Link: Anemia as a Risk Factor for Cerebrovascular Accidents

Anemia, a prevalent hematological condition characterized by decreased red blood cell count or hemoglobin levels, has emerged as a significant risk factor for cerebrovascular accidents (CVAs) and commonly known as strokes. This review explores the intricate connection between anemia and the occurrence of CVAs, elucidating the underlying mechanisms and clinical implications. Anemia contributes to stroke risk through multiple pathways, including impaired oxygen delivery to the brain, alterations in cerebral hemodynamics, and disruption of neurovascular homeostasis. Furthermore, iron deficiency anemia’s predominant etiology-not only exacerbates hypoxia but also compromises neuronal integrity, predisposing individuals to ischemic and hemorrhagic stroke events. The hemodynamic consequences of anemia, including cerebral hypo-perfusion and increased thromboembolic risk, underscore its role as a silent culprit in stroke pathogenesis. Anemia-induced alterations in blood viscosity, endothelial dysfunction, and compensatory vasodilation contribute to the vulnerability of cerebral vasculature to ischemic insults. Moreover, iron deficiency exacerbates neurocognitive impairment and promotes neuro degeneration, exacerbating the risk of vascular cognitive decline and hemorrhagic stroke. Routine screening for anemia, particularly in highrisk populations, coupled with targeted interventions aimed at correcting underlying etiologies and optimizing hemoglobin levels, is essential for mitigating stroke risk and improving clinical outcomes.

Physiological Responses to Supramaximal Running Exercise with End-Expiratory Breath Holding up to the Breaking Point.

This study aimed to assess the physiological responses to repeated running exercise performed at supramaximal intensity and with end-expiratory breath holding (EEBH) up to the breaking point. Eight male runners participated in two running testing sessions on a motorized treadmill. In the first session, participants performed two sets of 8 repetitions at 125% of maximal aerobic velocity and with maximum EEBH. Each repetition started at the onset of EEBH and ended at its release. In the second session, participants replicated the same procedure, but with unrestricted breathing (URB). The change in cerebral and muscle oxygenation (Δ[Hbdiff]), total haemoglobin concentration (Δ[THb]) and muscle reoxygenation were continuously assessed. End-tidal oxygen (PETO2) and carbon dioxide pressure (PETCO2), arterial oxygen saturation (SpO2) and heart rate (HR) were also measured throughout exercise.On average, EEBH was maintained for 10.1 ± 1 s. At the breaking point of EEBH, PETO2 decreased to 54.1 ± 8 mmHg, whereas PETCO2 increased to 74.8 ± 3.1 mmHg. At the end of repetitions, SpO2 (nadir values 74.9 ± 5.0 vs. 95.7 ± 0.8%) and HR were lower with EEBH than with URB. Cerebral and muscle Δ[Hbdiff] were also lower with EEBH, whereas this condition induced higher cerebral and muscle Δ[THb] and greater muscle reoxygenation. This study showed that performing repeated bouts of supramaximal running exercises with EEBH up to the breaking point induced a fall in arterial, cerebral and muscle oxygenation compared with the URB condition. These phenomena were accompanied by increases in regional blood volume likely resulting from compensatory vasodilation to preserve oxygen delivery to the brain and muscles.

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?

Flow diversion jet: A dangerous mechanism in the flow diversion treatment of giant intracranial aneurysms.

Cerebral hyperperfusion syndrome (CHS) occurs after the restoration of blood flow to a previously low-flow, low-pressure region of the cerebral vasculature, which subsequently responds with chronic compensatory vasodilation, leading to a dysregulated state. Sudden restoration of normal blood flow can overwhelm the vasculature leading to intracranial hemorrhage (ICH). Separately, the Windkessel phenomenon describes the capacity for elastic vessels to expand with systolic pressure and decompress with diastole, thereby suppressing distal pulse pressure. We encountered a case involving giant basilar aneurysms in which we believe the Windkessel phenomenon precipitated a catastrophic manifestation of CHS at treatment. We present a 60-year-old female found to have marked dolichoectasia of the right cervical internal carotid, vertebral, and basilar arteries concurrent with two large vertebrobasilar dissecting-type fusiform aneurysms. Managed conservatively for ten years before developing gait ataxia, new imaging revealed dramatic interval growth of the larger aneurysm. Flow diversion with partial coiling of the aneurysms was pursued. The patient suffered intra-procedural catastrophic thalamic and midbrain hemorrhage with intraventricular extension. A meticulous review of the case data was undertaken. Our findings suggest that giant aneurysms can act as a Windkessel reservoir, depressing the distal pulse pressure. Flow diversion bypasses the reservoir, increasing the distal pulse pressure beyond the autoregulatory capacity, resulting in ICH analogous to CHS. CHS and Windkessel phenomenon can contribute to catastrophic sequelae in the treatment of giant intracranial aneurysms with flow diversion. Awareness of this mechanism can protect future patients from harm.

Comparison of Antera 3D® and TcPO2 for Evaluation of Blood Flow in Skin.

There is a need for quick skin blood flow tests that can be performed in the wound healing field. Antera 3D® is a compact scanner using multispectral imaging. It can perform quick assessment of skin conditions. The purpose of the present study was to investigate the ability of the Antera 3D® to assess skin blood flow in comparison with transcutaneous partial pressure of oxygen (TcPO2) measurements. This study was conducted on 13 patients with a history of lower extremity ulcers. Measurements of hemoglobin average level (hereafter, Hb score) measured by Antera 3D® and TcPO2 measured by a transcutaneous blood gas monitor were obtained at the same sites on the dorsal foot and lower leg. Differences in Hb score and TcPO2 were analyzed by t-test for each measurement site and for the presence of peripheral arterial disease (PAD). The correlation between TcPO2 and Hb score was analyzed by Pearson's correlation coefficient. Twenty-four limbs were tested. Hb score was higher (P < 0.001) and TcPO2 was lower (P = 0.056) in the dorsal foot compared to the lower leg. In the dorsal foot, Hb score was higher (P = 0.023) and TcPO2 was lower (P = 0.046) in patients with PAD compared to those without PAD. A significant negative correlation (r = -0.68; 95% confidence interval -0.85 to -0.38, P < 0.001) between TcPO2 and Hb score was observed in the dorsal foot. The negative correlation between TcPO2 and Hb score may reflect compensatory peripheral vasodilation due to occlusion or stenosis of central arteries. This study showed that Hb score measured by Antera 3D® may be related to skin blood flow.

Resuscitation with epinephrine worsens cerebral capillary no-reflow after experimental pediatric cardiac arrest: An in vivo multiphoton microscopy evaluation

Epinephrine is the principal resuscitation therapy for pediatric cardiac arrest (CA). Clinical data suggest that although epinephrine increases the rate of resuscitation, it fails to improve neurological outcome, possibly secondary to reductions in microvascular flow. We characterized the effect of epinephrine vs. placebo administered at resuscitation from pediatric asphyxial CA on microvascular and macrovascular cortical perfusion assessed using in vivo multiphoton microscopy and laser speckle flowmetry, respectively, and on brain tissue oxygenation (PbO2), behavioral outcomes, and neuropathology in 16–18-day-old rats. Epinephrine-treated rats had a more rapid return of spontaneous circulation and brisk immediate cortical reperfusion during 1–3 min post-CA vs. placebo. However, at the microvascular level, epinephrine-treated rats had penetrating arteriole constriction and increases in both capillary stalling (no-reflow) and cortical capillary transit time 30–60 min post-CA vs. placebo. Placebo-treated rats had increased capillary diameters post-CA. The cortex was hypoxic post-CA in both groups. Epinephrine treatment worsened reference memory performance vs. shams. Hippocampal neuron counts did not differ between groups. Resuscitation with epinephrine enhanced immediate reperfusion but produced microvascular alterations during the first hour post-resuscitation, characterized by vasoconstriction, capillary stasis, prolonged cortical transit time, and absence of compensatory cortical vasodilation. Targeted therapies mitigating the deleterious microvascular effects of epinephrine are needed.

Postdural puncture headache in obstetrics : Pathogenesis, diagnostics and treatment

Postdural puncture headache (PDPH) is one of the most important complications of peripartum neuraxial analgesia. Loss of cerebrospinal fluid volume and pressure as well as compensatory intracranial vasodilation are assumed to be responsible. Potentially severe long-term sequelae necessitate the correct diagnosis of PDPH, exclusion of relevant differential diagnoses (with atypical symptoms and when indicated via imaging techniques) and rapid initiation of effective treatment. Nonopioid analgesics, caffeine and occasionally theophylline, gabapentin and hydrocortisone are the cornerstones of pharmacological treatment, while the timely placement of an autologous epidural blood patch (EBP) represents the gold standard procedure when symptoms persist despite the use of analgesics. Procedures using neural treatment are promising alternatives, especially when an EBP is not desired by the patient or is contraindicated. Interdisciplinary and interprofessional consensus standard procedures can contribute to optimization of the clinical management of this relevant complication.

Editors' Note: Teaching NeuroImages: Pseudopathologic Brain Parenchymal Enhancement due to Vascular Compression in Parotid Tumor

In “Teaching NeuroImages: Pseudopathologic Brain Parenchymal Enhancement due to Vascular Compression in Parotid Tumor,” Teixeira et al. present a CT angiogram (CTA) obtained through right antecubital vein injection that shows intracranial vascular reflux in the cortical veins and pseudopathologic enhancement of the right brain parenchyma in a patient with a right-sided parotid gland tumor who had transient left hemiparesis but had a normal digital subtraction angiogram (DSA) and a normal repeat CTA obtained through left-sided vein injection. The authors initially described the enhancement as being in the distribution of the right middle cerebral artery territory, but they subsequently agreed with Chen et al. that the involvement of the occipital lobe suggests the enhancement pattern is more consistent with the drainage territory of the right superficial cerebral veins. Chen et al. note the mechanism for this finding is unclear and question (1) whether the DSA showed any anomalies in the venous sinuses; and (2) whether the pseudopathologic enhancement could have been related to the fact that the initial injection was performed through a right-sided vein, suggesting there could be severe stenosis of the right brachiocephalic vein. On further review, Teixeira et al. reported the DSA showed a hypoplastic right anterior cerebral artery, occlusion of the right internal jugular vein, and critical stenosis of the right vertebral artery origin. They suspect the patient's symptoms were the result of compression of the right internal carotid artery by the tumor in the setting of right vertebral artery stenosis, which led directly to either compensatory vasodilation or precipitated blood-brain barrier disruption. Although there was also occlusion of the right internal jugular vein, the patent right external jugular vein may have led to rapid spread of contrast into the right hemisphere and retrograde flow into the dilated capillary bed. They postulated that the CTA obtained through left-sided injection was normal because either the patent left internal jugular vein reduced the contrast velocity or vascular autoregulation was reestablished. In “Teaching NeuroImages: Pseudopathologic Brain Parenchymal Enhancement due to Vascular Compression in Parotid Tumor,” Teixeira et al. present a CT angiogram (CTA) obtained through right antecubital vein injection that shows intracranial vascular reflux in the cortical veins and pseudopathologic enhancement of the right brain parenchyma in a patient with a right-sided parotid gland tumor who had transient left hemiparesis but had a normal digital subtraction angiogram (DSA) and a normal repeat CTA obtained through left-sided vein injection. The authors initially described the enhancement as being in the distribution of the right middle cerebral artery territory, but they subsequently agreed with Chen et al. that the involvement of the occipital lobe suggests the enhancement pattern is more consistent with the drainage territory of the right superficial cerebral veins. Chen et al. note the mechanism for this finding is unclear and question (1) whether the DSA showed any anomalies in the venous sinuses; and (2) whether the pseudopathologic enhancement could have been related to the fact that the initial injection was performed through a right-sided vein, suggesting there could be severe stenosis of the right brachiocephalic vein. On further review, Teixeira et al. reported the DSA showed a hypoplastic right anterior cerebral artery, occlusion of the right internal jugular vein, and critical stenosis of the right vertebral artery origin. They suspect the patient's symptoms were the result of compression of the right internal carotid artery by the tumor in the setting of right vertebral artery stenosis, which led directly to either compensatory vasodilation or precipitated blood-brain barrier disruption. Although there was also occlusion of the right internal jugular vein, the patent right external jugular vein may have led to rapid spread of contrast into the right hemisphere and retrograde flow into the dilated capillary bed. They postulated that the CTA obtained through left-sided injection was normal because either the patent left internal jugular vein reduced the contrast velocity or vascular autoregulation was reestablished.

INFLUENCE OF MESENCHYMAL STEM CELLS ON EFFICIENCY OF ANGIOGENESIS, STATE OF VASCULAR TONE, INTENSITY OF LIPID PEROXIDATION AND METABOLIC ACTIVITY OF CARDIOMYOCYTES IN EXPERIMENTAL MYOCARDIAL INFARCTION

In contrast to medical and surgical methods of treatment of coronary heart disease and its complications, cellular cardiomyoplasty is aimed at creating new cells and stable lineages of normally functioning heart tissue. Autologous mesenchymal bone marrow stem cells are a promising source for such cardiomyoplasty. To study the effect of stem cell myocardial transplantation on the processes of its post−infarction state, acute myocardial infarction in laboratory rats was experimentally modeled with subsequent transplantation of autologous mesenchymal stem cells of bone marrow and comparative study in blood serum of cardiovyocytes metabolic activity markers, neoangiogenesis, vessel tonus as well as myocardial lipid peroxidation. The cells were intravenously injected into the necrotized myocardium and left ventricle. The study found that regardless of the method of administration, stem cell transplantation contributes to a significant increase in angiogenic factors, i.e. nitrogen oxide and endothelial growth factor, a significant decrease in vasoconstrictor endothelin−1, the level of TBA−active products and haptoglobin, enzyme activity, namely cardiac ischemia markers, increase in ceruloplasmin. All this indicates positive effects: leveling ischemia by improving myocardial perfusion due to compensatory vasodilation, limiting the rate of lipid peroxidation and stimulating antioxidant factors, improving the energy balance of the myocardium by increasing the level of energy substrates and activation of their aerobic pathways. Thus, cellular cardiomyoplasty improves metabolism and prevents the process of post−ischemic myocardial remodeling. Key words: cardiomyoplasty, mesenchymal stem cells, myocardial infarction, myocardial metabolism.

IMMUNE MECHANISMS FOR THE DEVELOPMENT OF HEPATORENAL SYNDROME IN LIVER CIRRHOSIS

Hepatorenal syndrome is a life-threatening complication of liver cirrhosis. 90% of patients with liver cirrhosis die within 2 months since the onset of hepatorenal syndrome development. For many years the hypothesis of the hemodynamic mechanism of hepatorenal syndrome development was accepted as the only true one, according to this hypothesis compensatory systemic vasodilation in response to portal hypertension causes renal ischemia and the development of functional specific acute kidney damage, the so-called “hepatorenal syndrome – acute kidney damage”. In recent years some works were published that substantiate the role of a systemic inflammatory reaction in the development of hepatorenal syndrome; this inflammatory reaction being associated with activation of innate immunity cells in response to a bacterial infection, including that to the microflora of the intestine which is adjacent to the liver. Data has been obtained which indicated that Toll-like receptors (TLRs), in particular TLR4 and TLR9 are involved in the development of hepatorenal syndrome.

A Near Infrared Spectroscopy System for Assessing Rehabilitation on Peripheral Arterial Occlusion Patients

PurposeA near-infrared spectroscopy system was developed to evaluate peripheral arterial occlusive disease (PAOD). The wireless device can take measurements when patients are doing rehabilitation exercise.MethodsTwo LED modules with wavelengths of 740 nm, 808 nm and 850 nm were placed over 32 mm away from the photodiode to detect the deep backscattering from muscle tissue. The absorbance difference from the extent of tissue oxygenation was extracted using a modified Beer’s law. Measurements taken on different muscle groups were applied to determine which branch of artery is occluded.ResultsThe changes in oxygenation of gastrocnemius and tibialis anterior muscle were recorded when PAOD patients were riding a stationary bicycle. The drop in oxygenation with exercise generally should recover within 15 min of continuing exercise. Otherwise, the artery is not capable to provide enough blood supply to the exercising muscles. Since gastrocnemius is the primary muscle used in biking exercise, the compensatory vasodilation in gastrocnemius leads to hypoperfusion in tibialis anterior muscle.ConclusionThis NIRS system is helpful for detecting the changes in tissue oxygenation during exercise. Muscle hypoxia was more obvious during exercise when the artery had some degree of occlusion.

Essential Role of Hemoglobin βCys93 in Cardiovascular Physiology.

The supply of oxygen to tissues is controlled by microcirculatory blood flow. One of the more surprising discoveries in cardiovascular physiology is the critical dependence of microcirculatory blood flow on a single conserved cysteine within the β-subunit (βCys93) of hemoglobin (Hb). βCys93 is the primary site of Hb S-nitrosylation [i.e., S-nitrosothiol (SNO) formation to produce S-nitrosohemoglobin (SNO-Hb)]. Notably, S-nitrosylation of βCys93 by NO is favored in the oxygenated conformation of Hb, and deoxygenated Hb releases SNO from βCys93. Since SNOs are vasodilatory, this mechanism provides a physiological basis for how tissue hypoxia increases microcirculatory blood flow (hypoxic autoregulation of blood flow). Mice expressing βCys93A mutant Hb (C93A) have been applied to understand the role of βCys93, and RBCs more generally, in cardiovascular physiology. Notably, C93A mice are unable to effect hypoxic autoregulation of blood flow and exhibit widespread tissue hypoxia. Moreover, reactive hyperemia (augmentation of blood flow following transient ischemia) is markedly impaired. C93A mice display multiple compensations to preserve RBC vasodilation and overcome tissue hypoxia, including shifting SNOs to other thiols on adult and fetal Hbs and elsewhere in RBCs, and growing new blood vessels. However, compensatory vasodilation in C93A mice is uncoupled from hypoxic control, both peripherally (e.g., predisposing to ischemic injury) and centrally (e.g., impairing hypoxic drive to breathe). Altogether, physiological studies utilizing C93A mice are confirming the allosterically controlled role of SNO-Hb in microvascular blood flow, uncovering essential roles for RBC-mediated vasodilation in cardiovascular physiology and revealing new roles for RBCs in cardiovascular disease.

Hypoxic Training Is Beneficial in Elite Athletes.

There is no doubt that many hypoxic conditions or prolonged exposures to altitude result in “biological costs of hypoxic adaptations that outweigh their benefits” (1), particularly in endurance athletes exposed to a) exercise-induced arterial hypoxemia leading to a larger decrease in VO2max and aerobic endurance; b) increased sympathetic activity and decreased baroreflex sensitivity; and c) increased pulmonary arterial pressure. There is also no doubt that sleeping in moderate altitude (2000-3000 m) as performed by the athletes using either live high-train high (LHTH) or live high-train low (LHTL) methods leads to periodic breathing, intermittent hypoxia (IH) and increase in desaturation periods; e.g. 3% oxygen desaturation index, but to a larger extent in hypobaric hypoxia (HH, real altitude) than in normobaric hypoxia (NH, simulated altitude), as shown at 2250 m (2). The three main questions debated in the present contrasting perspective are however different: 1. Are there any evidences showing if the “counteracting maladaptation” (reported above) outweigh the benefits of the different hypoxic methods at short- or long-term in elite athletes? ; 2. Are there any robust data supporting that hypoxic training is beneficial in elite athletes? ; 3. Contradictory, are there robust data showing that hypoxic training is not beneficial in elite athletes?

Abstract 070: The Prostaglandin Ep4 Receptor in Endothelium Modulates eNos Expression and Aortic Integrity

Prostaglandin EP4 receptor (EP4R) plays pivotal role in mediating PGE2-induced vasodilation and blood pressure homeostasis. Our previous work demonstrated that absence of EP4R in all tissues was associated with salt sensitivity and exaggerated Ang II-dependent hypertension. While cell-specific elimination of EP4R from vascular smooth muscle cells (VSMCs) attenuated EP4-dependent vasodilation, but the severity of Ang II-dependent hypertension was not affected. These findings indicate the effects of EP4R to resist hypertension are not attributable to the compensatory vasodilation mediated by EP4R in VSMCs and must be mediated by other cell lineages. Within the vasculature, endothelial cells (ECs) also express high levels of EP4R. To assess the role of EP4R in ECs, we generated conditional EC-specific EP4R knockout mice mice using Tie2-CreERT2 and EP4 flox/flox mouse lines (ECKO). After pre-treatment with tamoxifen, we measured the blood pressure in conscious mice using radiotelemetry. At baseline, there were no significant differences in blood pressure between ECKO and controls 107.9±1.7 VS 109.3±1 mmHg). The response of ECKOs to Ang II infusion was variable. In one cohort, MAP during Ang II infusion was significantly lower than controls (142.8±3.1 vs 133.2±1.9 mmHg, p=0.02) whereas in a second cohort there was no difference in MAP with Ang II infusion between groups (131.7±2.3 vs 135.6±2.1 mmHg). Interestingly, the incidence of aortic aneurysm was significantly higher in ECKOs (12/27) compared to controls (2/25; p=0.01 by Fisher exact test). As urine sodium excretion during Ang II infusion was increased in ECKOs, we considered the possibility that aneurysm formation may have impacted the blood pressure. We also found the ECs isolated from ECKOs have significantly higher eNOS mRNA expression compared to control (fold change: 1.35±0.13; p=0.046). To determine whether this difference in eNOS expression have a functional impact, we compared blood pressure responses to L-NAME following Ang II infusion. ECKOs showed exaggerated response to L-NAME compared to controls (MAP increases +5.2±1.4 mmHg in ECKO vs. +0.5±1.5 mmHg in control; p=0.03). Thus, EP4R in ECs play important role in regulating EC function, impacting blood pressure and aortic integrity.

Noninvasive optical assessment of resting-state cerebral blood flow in children with sickle cell disease

Sickle cell disease (SCD) is a genetic blood disorder that has profound effects on the brain. Chronic anemia combined with both macro- and microvascular perfusion abnormalities that arise from stenosis or occlusion of blood vessels increased blood viscosity, adherence of red blood cells to the vascular endothelium, and impaired autoregulatory mechanisms in SCD patients all culminate in susceptibility to cerebral infarction. Indeed, the risk of stroke is 250 times higher in children with SCD than in the general population. Unfortunately, while transcranial Doppler ultrasound (TCD) has been widely clinically adopted to longitudinally monitor macrovascular perfusion in these patients, routine clinical screening of microvascular perfusion abnormalities is challenging with current modalities (e.g., positron emission tomography and magnetic resonance imaging) given their high-cost, requirement for sedation in children year, and need for trained personnel. We assess the feasibility of a low-cost, noninvasive optical technique known as diffuse correlation spectroscopy (DCS) to quantify an index of resting-state cortical cerebral blood flow (BFI) in 11 children with SCD along with 11 sex- and age-matched healthy controls. As expected, BFI was significantly higher in SCD subjects compared to healthy controls ( ). Within SCD subjects, BFI was inversely proportional to resting-state arterial hemoglobin levels ( ), consistent with expected anemia-induced compensatory vasodilation that aims to maintain adequate oxygen delivery to the tissue. Further, in a subset of patients measured with TCD ( ), DCS-measured blood flow was correlated with TCD-measured blood flow velocity in middle cerebral artery ( ), although the trend was not statistically significant ( ). These results are consistent with those of several previous studies using traditional neuroimaging techniques, suggesting that DCS may be a promising low-cost tool for assessment of tissue-level CBF in pediatric SCD.

Angiotensin II Type 1 Receptor Antagonist Azilsartan Restores Vascular Reactivity Through a Perivascular Adipose Tissue-Independent Mechanism in Rats with Metabolic Syndrome.

Perivascular adipose tissues (PVAT) are involved in the regulation of vascular tone. In mesenteric arteries, the compensatory vasodilatory effects of PVAT appear when vascular relaxation is impaired and disappear at around 23weeks of age in SHRSP.Z-Leprfa/IzmDmcr (SHRSP.ZF) rats with metabolic syndrome (MetS). The renin-angiotensin system is involved in the development of endothelium and vascular dysfunction. Therefore, we investigated whether azilsartan, a potent angiotensin II type 1 (AT1) receptor antagonist, can protect against the deterioration of the PVAT compensatory vasodilator function that occurs with aging in MetS. Two age groups of SHRSP.ZF rats (13 and 20weeks of age) were administered azilsartan or vehicle through oral gavage once daily for 10weeks. The vasodilation response of the isolated superior-mesenteric arteries upon addition of endothelium-dependent and -independent agonists was determined in the presence or absence of PVAT using organ bath methods. In vivo treatment with azilsartan improved the acetylcholine-induced vasodilation in mesenteric arteries with and without PVAT at both time-points. The mRNA levels of AT1 receptor and AT1 receptor-associated protein were unchanged in PVAT upon azilsartan treatment. Furthermore, in vitro treatment with azilsartan (0.1 and 0.3μM for 30min) did not affect the compensatory effect of PVAT on vasodilation in response to acetylcholine in SHRSP.ZF rat mesenteric arteries. Our results provide evidence supporting the use of azilsartan for the long-term protection against vascular dysfunctions in MetS. Azilsartan did not improve the dysfunction of PVAT-mediated modulation of vascular tone during MetS. The protective effect of azilsartan is mediated by restoring the endothelium- and vascular smooth muscle-mediated mechanisms.

Repeated sprint training in hypoxia – an innovative method

The year 2018 marked the 50th anniversary of the Mexico Olympic games, which represents the starting point of scientific research on hypoxic training. Since the original “Live High – Train High”, many altitude/hypoxic training methods have been developed. The aim of the present review is to present the most recent method called “Repeated Sprint training in Hypoxia” (RSH). RSH is of unprecedented interest in the altitude training area with 25 studies published in the 5-year period following the pioneer article in 2013, and with only two studies that did not report any beneficial effects. Potential mechanisms include transcriptional factors involved in oxygen-signaling and oxygen-carrying capacity and mitochondrial metabolism enzymes, improved behavior of fasttwitch fibers notably via compensatory vasodilatation, improved vascular relaxation and greater microvascular oxygen delivery as well as faster rate of phosphocreatine resynthesis. In general, RSH leads to superior repeated-sprint ability (i.e., faster mean sprint times or higher power outputs associated with a better resistance to fatigue during a repeated-sprint test) in normoxic conditions. RSH where hypoxia is induced by voluntary hypoventilation at low lung volume (named VHL) may also improve repeated-sprint performance more than in normoxia. Practically, RSH benefits have been demonstrated for a large range of team- (rugby, football, LaCrosse, Australian Football, field hockey), endurance (cycling, track and field, cross-country ski), racket (tennis) or combat (Jiu-Jitsu) sports.

Post-dural puncture headache: Epidemiology, onset mechanisms, clinical symptoms, diagnosis and therapy

Introduction. Post-dural puncture headache is classified as a secondary headache attributable to non-vascular intracranial disorders and belongs to the group of headaches caused by low cerebrospinal fluid pressure. Etiopathogenesis. The pathogenesis is not completely clear, but it is thought to be caused by the cerebrospinal fluid leak through the duct opening. Cerebrospinal fluid efflux leads to a decrease in intracranial pressure and stretching of the pain sensitive intracranial structures. A drop in intracranial pressure can cause compensatory cerebrovascular vasodilation, contributing to the onset of a headache. Diagnosis and Therapy. Post-dural puncture headache clinically presents as an orthostatic headache. In most cases, the diagnosis is made based on a typical clinical picture and it can be confirmed by magnetic resonance imaging and measurement of cerebrospinal fluid pressure. The condition is usually benign, most often with spontaneous recovery. The therapy involves conservative treatment, medications, as well as some invasive methods: epidural blood patches, blockage of the greater occipital nerve, and in most severe cases, epidural injection of fibrin sealant or surgical dural repair. Conclusion. Post-dural puncture headache is a common complaint in the clinical practice of neurologists and anesthesiologists. The prognosis is usually favourable, while the therapy may include conservative or invasive treatment procedures.

Mechanisms of Age‐related Compensatory Vasodilation: Insight from Passive Leg Movement

Passive leg movement (PLM) provides a potentially clinically relevant assessment of nitric oxide (NO)‐mediated vascular function. In young individuals pharmacological inhibition of NO synthase (NOS) with L‐NG‐monomethyl arginine (L‐NMMA) decreases the hyperemic and vasodilatory response to PLM by ~ 80%. Aging is associated with a reduced PLM response that is not further attenuated by NOS inhibition, implying that the age‐related reduction is primarily NO‐mediated. Although the PLM response is reduced with age, older individuals exhibit a significant and transient increase in hyperemia during PLM. Currently, it is not clear what factors contribute to this remaining hyperemic response and if compensatory endothelial derived factors are responsible for the remaining, albeit, diminished response. Therefore, this study sought to determine the contribution of prostaglandins (PG) and epoxyeicosatrienoic acids (EETs) to the PLM‐induced hyperemic response. The hyperemic response to continuous PLM was determined under control (saline infusion), NOS inhibition by L‐NMMA, and combined inhibition of NOS by L‐NMMA, cyclooxygenase by Ketorolac (KET), and cytochrome p450 by Fluconazole (FLUC) (L‐NMMA+KET+FLUC) in 7 young (26±2 yrs.) and 7 old (69±2 yrs.) healthy men. Leg blood flow (LBF) was measured by Doppler ultrasound and changes in peak LBF and the overall LBF response, as measured by the area under the LBF response curve (i.e., AUC), were determined. Aging was associated with an attenuated LBF Peak (Young; 1490±184 ml/min, Old; 788±96 ml/min, p &lt; 0.01) and LBF AUC (Young; 455±76 ml, Old; 217±44 ml, p &lt; 0.02) response to PLM. In young men, LBF Peak (−431±147 ml/min, p = 0.03) and LBF AUC (−315±118 ml, p = 0.04) were significantly attenuated by L‐NMMA. The combination of LNMMA+KET+FLUC did not evoke a greater reduction beyond that induced by L‐NMMA for LBF Peak (−355±89 ml/min, p = 0.6) or LBF AUC (−302±40 ml, p = 0.9). In contrast, L‐NMMA failed to significantly alter the LBF Peak (−41±83 ml/min, p = 0.6) and LBF AUC (−56±38 ml, p = 0.2) response in the old, while the combined inhibition by LNMMA+KET+FLUC resulted in a significant, 50% reduction, in LBF AUC (−109±36 ml, p = 0.03) and tended to decrease LBF Peak (−92±44 ml/min, p = 0.08). Taken together, these findings indicate the vasodilatory response to PLM is predominantly NO‐mediated in the young, whereas with advancing age PGs and EETs appear to be the major dilating mechanisms. Importantly, the hyperemic and vasodilatory response to PLM is reduced with age indicating that these compensatory vasodilatory mechanisms are not able to fully correct for the age‐related reduction in endothelial function. Finally, despite pharmacological inhibition of three endothelial‐dependent vasodilatory pathways, a substantial hyperemic response remains in both the young and the old suggesting that a currently unidentified mechanism, likely acting directly on the smooth muscle, contributes to the remaining PLM‐induced response.Support or Funding InformationThis study was supported by Veteran Affairs Rehabilitation Research and Development Grant IK2RX001215 CDA2 (to J. D. Trinity) and Merit Grants E1697R and E6910R (to R. S. Richardson); American Heart Association Grant 14SDG1850039 (to J. D. Trinity); and National Heart, Lung, Blood Institute Grant PO1‐HL‐091830 (to R. S. Richardson)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.