Dilatation Of Artery Research Articles

Heart involvement in multisystem inflammatory syndrome in children correlated with SARS-CoV-2 infection: a review by ANMCO/SICP

Acute clinical manifestations of COVID-19 are generally less severe in childhood, however a proportion of them can develop a severe systemic hyperinflammatory syndrome after SARS-CoV-2 infection, known as the multisystem inflammatory syndrome (multisystem inflammatory syndrome in children, MIS-C). Cardiovascular manifestations in MIS-C are frequent (34-82%), including myocardial dysfunction, coronary artery dilation or aneurysms, arrhythmias, conduction abnormalities, pericarditis and valvulitis. The most affected cases can develop cardiogenic shock needing intensive care unit admission, inotropic support and sometimes even mechanical circulatory support. The elevation of myocardial necrosis markers, the frequently transient left ventricular systolic dysfunction and the presence of changes on magnetic resonance imaging, support the hypothesis of an immune-mediated post-viral pathogenesis similar to myocarditis. Although MIS-C shows excellent short-term survival, further studies are needed to demonstrate complete reversibility of residual subclinical heart damage.

Emerging Insights Into the Pathophysiology of Multisystem Inflammatory Syndrome Associated With COVID-19 in Children.

Multisystem inflammatory syndrome in children (MIS-C) has emerged as a rare delayed hyperinflammatory response to SARS-CoV-2 infection and causes severe morbidity in the pediatric age group. Although MIS-C shares many clinical similarities to Kawasaki disease (KD), important differences in epidemiologic, clinical, immunologic, and potentially genetic factors exist and suggest potential differences in pathophysiology and points to be explored and explained. Epidemiologic features include male predominance, peak age of 6 to12 years, and specific racial or ethnicity predilections. MIS-C is characterized by fever, prominent gastrointestinal symptoms, mucocutaneous manifestations, respiratory symptoms, and neurologic complaints, and patients often present with shock. Cardiac complications are frequent and include ventricular dysfunction, valvular regurgitation, pericardial effusion, coronary artery dilation and aneurysms, conduction abnormalities, and arrhythmias. Emerging evidence regarding potential immunologic mechanisms suggest that an exaggerated T-cell response to a superantigen on the SARS-CoV-2 spike glycoprotein-as well as the formation of autoantibodies against cardiovascular, gastrointestinal, and endothelial antigens-are major contributors to the inflammatory milieu of MIS-C. Further studies are needed to determine both shared and distinct immunologic pathway(s) that underlie the pathogenesis of MIS-C vs both acute SARS-CoV-2 infection and KD. There is evidence to suggest that the rare risk of more benign mRNA vaccine-associated myopericarditis is outweighed by a reduced risk of more severe MIS-C. In the current review, we synthesize the published literature to describe associated factors and potential mechanisms regarding an increased risk of MIS-C and cardiac complications, provide insights into the underlying immunologic pathophysiology, and define similarities and differences with KD.

Clinical profile, cardiac involvement and outcome of children admitted with multisystem inflammatory syndrome in PICU at GB Pant children hospital Srinagar

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe hyper inflammatory post infectious complication of acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, which typically occurs 2-6 weeks after exposure to SARS-CoV-2. Aim was to determine the clinical profile, cardiac involvement and outcome of children admitted with multisystem inflammatory syndrome in pediatric intensive care unit. Methods: This prospective observational study was conducted in pediatric intensive care unit over period of two years. After informed consent from parents, all those patients meeting inclusion criteria were subjected to complete history, general and systemic physical examination. Routine baseline investigations included CBC, LFT, KFT, ABG, serum calcium and phosphorous, and other investigations like echocardiography, COVID-19 RAT and RTPCR and various inflammatory markers like serum ferritin, pro-calcitonin, CRP and ESR whenever required were done. Results: In our study out of 77 MIS-C patients 40 were males and 37 were females with a male female ratio of 1.1:1. The mean average age was 7.4 years. Out of them 47 (61%) patients had a history of COVID-19 infection/contact with positive COVID-19 cases 3 to 4 weeks before presentation. In our study gastrointestinal, respiratory, and cardiac systems were mostly involved. Rash and conjunctival congestion was seen in 81% of MIS-C patients. On echocardiography out of 77 MIS-C patients, 15 (19.5%) had pericardial effusion, 25 (32.5%) had coronary artery dilatations and 32 patients (41.5%) had left ventricular systolic dysfunction with LVEF <55%. Conclusions: Pediatric multisystem inflammatory syndrome is a serious and life-threatening illnesses having a significant impact on morbidity and mortality.

Arterial Stiffness as a Surrogate Marker of Cardiovascular Disease and Atherosclerosis in Patients with Arthritides and Connective Tissue Diseases: A Literature Review.

The increased cardiovascular (CV) risk among patients with autoimmune rheumatic diseases, such as arthritides and connective tissue diseases, has been extensively documented. From a pathophysiological standpoint, systemic inflammation in the context of the disease can lead to endothelial dysfunction, accelerated atherosclerosis, and structural changes in vessel walls, which, in turn, are associated with exaggerated CV morbidity and mortality. In addition to these abnormalities, the increased prevalence of traditional CV risk factors, such as obesity, dyslipidemia, arterial hypertension, and impaired glucose metabolism, can further worsen the status of and overall prognosis for CV in rheumatic patients. However, data on appropriate CV screening methods for patients with systemic autoimmune diseases are scarce, and traditional algorithms may lead to an underestimation of the true CV risk. The reason for this is that these calculations were developed for the general population and thus do not take into account the effect of the inflammatory burden, as well as other chronic-disease-associated CV risk factors. In recent years, different research groups, including ours, have examined the value of different CV surrogate markers, including carotid sonography, carotid-femoral pulse wave velocity, and flow-mediated arterial dilation, in the assessment of CV risk in healthy and rheumatic populations. In particular, arterial stiffness has been thoroughly examined in a number of studies, showing high diagnostic and predictive value for the occurrence of CV events. To this end, the present narrative review showcases a series of studies examining aortic and peripheral arterial stiffness as surrogates of all-cause CV disease and atherosclerosis in patients with rheumatoid and psoriatic arthritis, as well as in systemic lupus erythematosus and systemic sclerosis. Moreover, we discuss the associations of arterial stiffness with clinical, laboratory, and disease-specific parameters.

The retinal neurovascular coupling is impaired in men with vasculogenic erectile dysfunction

The aim of this study was to study the retinal vessels in patients affected by vasculogenic erectile dysfunction (ED), using dynamic vessel analyzer (DVA). Patients with vasculogenic ED and control subjects were prospectively enrolled to undergo a complete urological and ophthalmologic evaluation, including DVA and structural optical coherence tomography (OCT). The main outcome measures were: (1) arterial dilation; (2) arterial constriction; (3) reaction amplitude (the difference between arterial dilation and constriction); and, (4) venous dilation. Thirty-five patients with ED and 30 male controls were included in the analysis. Mean ± SD age was 52.0 ± 10.8 years in the ED group and 48.1 ± 16.3 years in the control group (p = 0.317). In the dynamic analysis, the arterial dilation was lower in the ED group (1.88 ± 1.50%), as compared with the control group (3.70 ± 1.56%, p < 0.0001). Neither arterial constriction nor venous dilation differed between groups. The reaction amplitude was decreased in ED patients (2.40 ± 2.02%, p = 0.023), compared to controls (4.25 ± 2.20%). In the Pearson correlation analysis, the ED severity, was directly correlated with both reaction amplitude (R = .701, p = 0.004) and arterial dilation (R = .529, p = 0.042). In conclusion, subjects with vasculogenic ED are featured by a significant dysfunction of the retinal neurovascular coupling, which is inversely correlated with ED severity.

Endovascular treatment of a ruptured pure arterial malformation and associated dysplastic middle cerebral artery dissecting aneurysm: illustrative case.

Pure arterial malformations are characterized as unique cerebrovascular lesions with a dilated, coil-like appearance and tortuous arteries without early venous drainage. Historically, these lesions have been described as incidental findings with a benign natural history. However, pure arterial malformations can rarely demonstrate radiographic progression and develop associated focal aneurysms with an unclear risk of rupture. Whether radiographic progression of these lesions or the presence of an associated aneurysm warrants treatment remains controversial. A 58-year-old male presented with sudden-onset left hemiparesis. Computed tomography revealed a large, acute, right frontotemporoparietal intraparenchymal hemorrhage with underlying irregular curvilinear calcifications. Diagnostic cerebral angiography revealed a dysplastic right middle cerebral artery dissecting aneurysm along the M2 segment associated with a pure arterial malformation, which was treated with endovascular flow diversion in a delayed fashion. Pure arterial malformations with associated focal aneurysms may not exhibit a benign natural history as once thought. Intervention should be considered for ruptured pure arterial malformations to mitigate the risk of rerupture. Asymptomatic patients with a pure arterial malformation with an associated aneurysm should at least be followed closely with interval radiographic imaging to evaluate for malformation progression or changes in aneurysmal morphology.

(352) Erection Hardness Score (EHS) Correlates With Resistive Index but Not Cavernosal Artery Dilation During Penile Doppler for Erectile Dysfunction and Peyronie's Disease

Abstract Introduction Penile Doppler Ultrasound (PDU) is a non-invasive diagnostic test used to assess organic erectile dysfunction (ED) and Peyronie’s disease and characterize functional changes in penile blood flow. Quantitative measurements taken during penile Doppler testing include changes in cavernosal artery diameter, the velocity of blood flow in the cavernosal artery in systolic and diastolic phases, and a calculated resistive index. It remains poorly understood which of these parameters best predict response to intracavernosal injection therapy and how they are influenced by comorbidities such as age, diabetes, smoking, hypertension, and obesity. Objective The objective of this study is to assess which parameters best predict response to intracavernosal trimix injection and determine the utility of measuring cavernosal artery diameter during penile Doppler testing. Methods This study is a single institutional retrospective cross-sectional review of men undergoing workup for organic ED and/or Peyronie's disease who elected to undergo penile Doppler testing. Only patients who received a standardized 30-1-10 trimix injection were included. Dosing was determined based on age and risk factors using a nomogram, and redosing was performed if the erection quality was below subjective optimal erection quality at home. Baseline cavernosal artery and plaque imaging were performed, and repeat measurements were obtained at 10 minutes following trimix injection. Results 93 men were included in the study with a median age of 59 (IQR 51-67). 47% carried a diagnosis of Peyronie's, 41% had hypertension, 29% were obese, and 30% were smokers. 40% met the criteria for venous leak (RI &amp;lt;0.8). Erectile hardness scale (EHS) scores of 1-4 were documented in 5, 21, 61, and 5 patients, respectively. Linear regression demonstrated no significant relationship between the change in cavernosal artery diameter and trimix dose, resistive index, comorbidities or other Doppler parameters measured. There was no direct relationship between the EHS scores and cavernosal artery dilation. However, there was a statistically significant relationship between EHS and age (p=0.004), trimix dose (p=0.008), and resistive index (p=0.001) on univariate regression. A multivariable model containing age, comorbidities, and these parameters correctly explained 31% of the variance demonstrated (p=0.001). Conclusions Provider-determined EHS scores were directly proportional to patient age, trimix dose, and resistive indices but not to changes in cavernosal artery diameter. Our findings suggest that this measurement may be safely omitted during the evaluation of organic ED and Peyronie’s Disease without changes in diagnostic or management pathways. Disclosure No

Cardiovascular involvement in Epstein-Barr virus infection.

Cardiovascular involvement is an uncommon but severe complication of Epstein-Barr virus (EBV) infection caused by direct damage and immune injury. Recently, it has drawn increasing attention due to its dismal prognosis. It can manifest in various ways, including coronary artery dilation (CAD), coronary artery aneurysm (CAA), myocarditis, arrhythmias, and heart failure, among others. If not treated promptly, cardiovascular damage can progress over time and even lead to death, which poses a challenge to clinicians. Early diagnosis and treatment can improve the prognosis and reduce mortality. However, there is a lack of reliable large-scale data and evidence-based guidance for the management of cardiovascular damage. Consequently, in this review, we attempt to synthesize the present knowledge of cardiovascular damage associated with EBV and to provide an overview of the pathogenesis, classification, treatment, and prognosis, which may enhance the recognition of cardiovascular complications related to EBV and may be valuable to their clinical management.

Characteristics and outcomes of multisystem inflammatory syndrome in children: A multicenter, retrospective, observational cohort study in Mexico.

Multisystem inflammatory syndrome in children associated with coronavirus disease 2019 (MIS-C), a novel hyperinflammatory condition secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with severe outcomes such as coronary artery aneurysm and death. This multicenter, retrospective, observational cohort study including eight centers in Mexico, aimed to describe the clinical characteristics and outcomes of patients with MIS-C. Patient data were evaluated using latent class analysis (LCA) to categorize patients into three phenotypes: toxic shock syndrome-like (TSSL)-MIS-C, Kawasaki disease-like (KDL)-MIS-C, and nonspecific MIS-C (NS-MIS-C). Risk factors for adverse outcomes were estimated using multilevel mixed-effects logistic regression. The study included 239 patients with MIS-C, including 61 (26%), 70 (29%), and 108 (45%) patients in the TSSL-MIS-C, KDL-MIS-C, and NS-MIS-C groups, respectively. Fifty-four percent of the patients were admitted to the intensive care unit, and 42%, 78%, and 41% received intravenous immunoglobulin, systemic glucocorticoids, and anticoagulants, respectively. Coronary artery dilatation and aneurysms were found in 5.7% and 13.2% of the patients in whom coronary artery diameter was measured, respectively. Any cause in-hospital mortality was 5.4%. Hospitalization after ten days of symptoms was associated with coronary artery abnormalities (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.2-2.0). Age ≥10 years (OR: 5.6, 95% CI: 1.4-2.04), severe underlying condition (OR: 9.3, 95% CI: 2.8-31.0), platelet count <150,000 /mm3 (OR: 4.2, 95% CI: 1.2-14.7), international normalized ratio >1.2 (OR: 3.8, 95% CI: 1.05-13.9), and serum ferritin concentration >1,500 mg/dl at admission (OR: 52, 95% CI: 5.9-463) were risk factors for death. Mortality in patients with MIS-C was higher than reported in other series, probably because of a high rate of cases with serious underlying diseases.

P394 PULMONARY HYPERTENSION IN SEARCH OF GROUP

Abstract Episode of haemoptysis in a 25–year–old woman with the following medical history: surgical closure of Botallo‘s duct at the age of 5 months, coeliac disease, growth retardation, polycystic ovary, visus alterations. In the emergency room CT angiography of the chest showed the presence of subpleural parenchymal consolidation in the right lower lobe, with associated ground–glass opacities, cardiomegaly, severe pulmonary artery dilatation and hepatomegaly with intrathoracic involvement by a hernia of Morgagni on the right side. A porto–systemic shunt with an intrahepatic course was also noted in the duct at the VIII segment with an autonomic outlet in the right atrium. The patient was transferred to the Internal Medicine ward. Objective examination revealed an elf facies with hypertelorism, short stature, bradypsychism. On interview she reported dyspnoea on light exertion and frequent lipohymic episodes. Haematochemical examinations showed increased of bilirubinemia mainly indirect, Transaminases and of NTproBNP and normal ammonium levels. Blood gas analysis showed a tendency to respiratory alkalosis with oxyaemia at lower limits. Because of the suspicion of a syndromic picture, a genetic examination was performed. Cardiological evaluation showed a high ultrasound probability of pulmonary hypertension (PH). Transferred to cardiology, catheterisation confirmed pulmonary arterial hypertension (mPAP 64mmHg) precapillary (wedge 4mmHg) with high PVR (11 Wood Units) not responsive to nitric oxide. In addition, there was a superior vena cava protruding into the coronary sinus and an extrahepatic shunt with an isolated outlet in the RA without gradient. The hepatobiliary surgery consultation concluded for Abernethy syndrome, which is a rare congenital syndrome characterised by an extrahepatic portosystemic shunt in which the blood from the splanchnic and lienal circulation bypasses the portal vein and the liver, draining into the systemic circulation via an abnormal conduit. PH is a rare complication of this syndrome, maintained by hyperafflux, vasoactive mediators and the formation of microthrombi and intimal fibrosis in the pulmonary circulation. An HR–CT excluded venulo–capillary plexiform disease. Macitentan 10 mg/day was introduced, then continued at home for the benefit shown and follow–up at the Pulmonary Work Group was initiated. This PH, due to its association with an extremely rare pathology, required the collaboration of a diverse group of specialists.

P141 ACUTE MYOCARDIAL INFARCTION OR SOMETHING MORE? CASE REPORT AND CHALLENGES ASSESSMENT OF GIANT CORONARY ANEURYSM MANAGEMENT

Abstract Background Coronary Artery Aneurysms (CAA) are defined as localized coronary artery dilations more than 1.5 times the diameter of the adjacent segments. Giant CAA (GCAAs) are rare coronary diseases and the presence of multiple CAAs, located in more than one coronary artery, is even more uncommon. The pathophysiology is unknown but the majority are due to atherosclerosis. There is currently no consensus concerning the management. Case presentation: We report the case of a 72–year–old man, referred to our emergency department due to chest pain. The patient’s electrocardiogram was consistent with myocardial infarction with inferior leads ST–segment elevation. Two-dimensional echocardiography showed hypertrophic Left Ventricle (LV) with akinesia of the infero–postero-lateral LV wall and hypokinesia of the remaining LV segments (LVEF = 40%). Coronary angiography and computed tomography revealed multiple CAAs, some of them giant, associated with significant coronary artery disease: two CAAs on the right coronary artery, including a giant one (Dmax 11 mm and Dmax 32 mm); one large aneurism on the circumflex artery (D max 20.5 mm) and one on the left main descendent artery (D max 8 mm). The patient had a previous history of hypertension, dyslipidemia and abdominal aortic aneurysm. He had no history of percutaneous coronary intervention or cardiac surgical procedures. Serological studies for vasculitis or connective tissue disease were all negative. The patient underwent surgical exclusion of the giant right CAA with ligation of the proximal and distal ends of the aneurysm and double bypass surgery to the obtuse marginal and right posterior descending coronary arteries. Conclusions CAAs’ treatment options include medical treatment, interventional or surgical management. No clear evidence about the better option exists, but it seems that surgical option should be favored in cases of bigger, more tortuous and more calcified CAAs. Based on these evidences and the anatomic lesions of our patient, we opted for surgery and he successfully underwent CAAs resection with coronary bypasses. We reported our experience and we examined the current knowledge on CAA/GCAA. Overall, management is hampered by lack of evidence. We need prospective studies and registries to further our knowledge in the management of this disorder and prognosis. From our attitude, surgical treatment should be performed for multiple GCAA to prevent fatal complications.

Differential Functional Contribution of BK Channel Subunits to Aldosterone-Induced Channel Activation in Vascular Smooth Muscle and Eventual Cerebral Artery Dilation.

Calcium/voltage-activated potassium channels (BK) control smooth muscle (SM) tone and cerebral artery diameter. They include channel-forming α and regulatory β1 subunits, the latter being highly expressed in SM. Both subunits participate in steroid-induced modification of BK activity: β1 provides recognition for estradiol and cholanes, resulting in BK potentiation, whereas α suffices for BK inhibition by cholesterol or pregnenolone. Aldosterone can modify cerebral artery function independently of its effects outside the brain, yet BK involvement in aldosterone's cerebrovascular action and identification of channel subunits, possibly involved in steroid action, remains uninvestigated. Using microscale thermophoresis, we demonstrated that each subunit type presents two recognition sites for aldosterone: at 0.3 and ≥10 µM for α and at 0.3-1 µM and ≥100 µM for β1. Next, we probed aldosterone on SM BK activity and diameter of middle cerebral artery (MCA) isolated from β1-/- vs. wt mice. Data showed that β1 leftward-shifted aldosterone-induced BK activation, rendering EC50~3 μM and ECMAX ≥ 10 μM, at which BK activity increased by 20%. At similar concentrations, aldosterone mildly yet significantly dilated MCA independently of circulating and endothelial factors. Lastly, aldosterone-induced MCA dilation was lost in β1-/- mice. Therefore, β1 enables BK activation and MCA dilation by low µM aldosterone.

Basal NAD(H) redox state permits hydrogen peroxide-induced mesenteric artery dilatation.

Smooth muscle voltage-gated K+ (Kv) channels in resistance arteries control vascular tone and contribute to the coupling of blood flow with local metabolic activity. Members of the Kv1 family are expressed in vascular smooth muscle and are modulated upon physiological elevation of local metabolites, including the glycolytic end-product l-lactate and superoxide-derived hydrogen peroxide (H2 O2 ). Here, we show that l-lactate elicits vasodilatation of small-diameter mesenteric arteries in a mechanism that requires lactate dehydrogenase (LDH). Using the inside-out configuration of the patch clamp technique, we show that increases in NADH that reflect LDH-mediated conversion of l-lactate to pyruvate directly stimulate the activity of single Kv1 channels and significantly enhance the sensitivity of Kv1 activity to H2 O2 . Consistent with these findings, H2 O2 -evoked vasodilatation was significantly greater in the presence of 10mM l-lactate relative to lactate-free conditions, yet was abolished in the presence of 10mM pyruvate, which shifts the LDH reaction towards the generation of NAD+ . Moreover, the enhancement of H2 O2 -induced vasodilatation was abolished in arteries from double transgenic mice with selective overexpression of the intracellular Kvβ1.1subunit in smooth muscle cells. Together, our results indicate that the Kvβ complex of native vascular Kv1 channels serves as a nodal effector for multiple redox signals to precisely control channel activity and vascular tone in the face of dynamic tissue-derived metabolic cues. KEY POINTS: Vasodilatation of mesenteric arteries by elevated external l-lactate requires its conversion by lactate dehydrogenase. Application of either NADH or H2 O2 potentiates single Kv channel currents in excised membrane patches from mesenteric artery smooth muscle cells. The binding of NADH enhances the stimulatory effects of H2 O2 on single Kv channel activity. The vasodilatory response to H2 O2 is differentially modified upon elevation of external l-lactate or pyruvate. The presence of l-lactate enhances the vasodilatory response to H2 O2 via the Kvβ subunit complex in smooth muscle.

Effect of Jiawei Tongqiao Huoxue decoction in basilar artery dolichoectasia mice through yes-associated protein/transcriptional co-activator with PDZ-binding motif pathway

Ethnopharmacological relevanceThe Jiawei Tongqiao Huoxue decoction (JTHD), composed of Acorus calamus var. angustatus Besser, Paeonia lactiflora Pall., Conioselinum anthriscoides ‘Chuanxiong’, Prunus persica (L.) Batsch, Ziziphus jujuba Mill., Carthamus tinctorius L., Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep, Zingiber officinale Roscoe, Leiurus quinquestriatus, and Moschus berezovskii Flerov, was developed based on Tongqiao Huoxue decoction in Wang Qingren's “Yilin Gaicuo” in the Qing Dynasty. It has the effect of improving not only the blood flow velocity of vertebral and basilar arteries but also the blood flow parameters and wall shear stress. Especially in recent years, the potential efficacy of traditional Chinese medicine (TCM) for the treatment of basilar artery dolichoectasia (BAD) has attracted great attention as there are still no specific remedies for this disease. However, its molecular mechanism has not been elucidated. To identify the potential mechanisms of JTHD will help to intervene BAD and provide a reference for its clinical application. Aim of the studyThis study aims to establish a mouse model of BAD and explore the mechanism of JTHD regulating yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) pathway for attenuating BAD mice development. Materials and methodsSixty post-modeling C57/BL6 female mice were randomly divided into sham-operated, model, atorvastatin calcium tablet, low-dose JTHD, and high-dose JTHD groups. After 14 days of modeling, the pharmacological intervention was given for 2 months. Then, JTHD was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). ELISA was utilized to detect the changes in vascular endothelial growth factor (VEGF) and lipoprotein a (Lp-a) in serum. EVG staining was conducted to observe the pathological changes of blood vessels. TUNEL method was employed to detect the apoptosis rate of vascular smooth muscle cells (VSMCs). Micro-CT and ImagePro Plus software were used to observe and calculate the tortuosity index, lengthening index, percentage increase in vessel diameter, and tortuosity of the basilar artery vessels in mice. Western blot analysis was performed to detect the expression levels of YAP and TAZ proteins in the vascular tissues of mice. ResultsMany effective compounds such as choline, tryptophan, and leucine with anti-inflammation and vascular remodeling were identified in the Chinese medicine formula by LC-MS analysis. The serum levels of VEGF in the model mice decreased significantly while the levels of Lp-a increased obviously compared with those in the sham-operated group. The intima-media of the basilar artery wall showed severe disruption of the internal elastic layer, atrophy of the muscular layer, and hyaline changes of the connective tissue. Apoptosis of VSMCs added. Dilatation, elongation, and tortuosity of the basilar artery became notable, and tortuosity index, lengthening index, percentage increase in vessel diameter, and bending angle remarkably improved. The expression levels of YAP and TAZ protein in blood vessels elevated conspicuously (P < 0.05, P < 0.01). JTHD group markedly reduced the lengthening, bending angle, percentage increase in vessel diameter, and tortuosity index of basilar artery compared with the model group after 2 months of pharmacological intervention. The group also decreased the secretion of Lp-a and increased the content of VEGF. It inhibited the destruction of the internal elastic layer, muscular atrophy, and hyaline degeneration of connective tissue in basilar artery wall. The apoptosis of VSMCs was decreased, and the expression levels of YAP and TAZ proteins were abated (P < 0.05, P < 0.01). ConclusionsThe mechanism of inhibition of basilar artery elongation, dilation, and tortuosity by JTHD, which has various anti-BAD effective compound components, may be related to the reduction in VSMCs apoptosis and downregulation of YAP/TAZ pathway expression.

Clinical Course and Outcome of Cardiovascular Manifestations in Children With Multisystem Inflammatory Syndrome Associated With SARS-CoV-2 Infection in Georgia.

A SARS-CoV-2 infection is usually characterized by a very mild clinical course in the pediatric population. However, children can be severely affected, and clinical manifestations may differ from adults, mainly in terms of post-COVID-19 infection complications already known as multisystem inflammatory syndrome in children (MIS-C). As the name suggests, this condition involves many systems, including the cardiovascular system, clinical manifestations of which include myocarditis, coronary artery aneurysms, conduction abnormalities, and arrhythmias. This research aims to define the cardiac manifestations caused by multi-inflammatory processes occurring after acute SARS-CoV-2 infection, possibly find a correlation between a certain cardiac abnormality and inflammatory markers, and evaluate the dynamics of cardiovascular complications and how treatment affects it. From February 2020 to March 2022, 103 patients with MIS-C were hospitalized and treated at M.Iashvili Children's Central Hospital, Tbilisi, Georgia. Based on our results, 55% of them had cardiovascular involvement with various manifestations involving coronary artery dilation, valvular insufficiencies, heart rate abnormalities, and pericardial effusion. Our study revealed that only one statistically significant correlation was observedbetween D-dimer levels and heart rate abnormalities, but there was no correlation between these two values. All of the MIS-C patients reported in our study have received standardized treatment courses with steroids, intravenous immune globulin (IVIG), or IVIG combined with steroids; each patient's illness has resolved without any sequelae, and cardiac manifestations have returned to baseline. Nevertheless, systematic longer-term follow-up is needed to provide clarity on the evolution of medium- and long-term cardiac outcomes in MIS-C.

Prevalence, clinical characteristics and factors predicting major cardiovascular events in patients with coronary artery ectasia

Abstract Funding Acknowledgements Type of funding sources: None. Background Coronary artery ectasia (CAE) is an uncommon angiographic finding associated with the occurrence of severe cardiovascular outcomes during the long term. However, the factors that predict major adverse cardiovascular events after the diagnosis of CAE are not well understood. Purpose To define the prevalence, clinical characteristics and factors predicting major cardiovascular events in a large series of patients with coronary artery ectasia. Methods Retrospective, observational, cohort study of patients who underwent coronary angiography between April 2018 and April 2021 at a national cardiovascular center in Latin America. CAE was defined as segmental dilation of a coronary artery with caliber discrepancy 1.5 greater compared to an adjacent segment. Baseline clinical variables were assessed during index hospital stay. The primary outcome of the study was the composite of cardiovascular death, acute myocardial infarction and angina. Results Among 4,435 patients undergoing coronary angiography during the study period, 298 (6.73%) were diagnosed with CAE and constituted the final analytic sample. The main reason for performing coronary angiography was ACS (78%). Patients were mostly male (87.1%), and the prevalence of cardiovascular risk factors was high. During a median follow up of 17 months (1-151), 31 (12.0%) patients developed at least one component of the primary endpoint (Figure 1.) Bivariate analysis identified chronic kidney disease (CKD) (p=0.006) and initial presentation in the form of ACS (p&amp;lt;0.001) as predictors of MACE during follow up. Conclusions In our study, we found a high prevalence of CAE. Cardiovascular risk factors during baseline evaluation were frequent; CKD and initial presentation in the form of ACS were identified as predictors for the occurrence of long term events.

Effect of cognitive processing therapy on markers of cardiovascular risk in posttraumatic stress disorder patients: A randomized clinical trial

ObjectivePosttraumatic stress disorder (PTSD) is associated with elevated risk of coronary heart disease (CHD); however, the effects of PTSD treatment on CHD biomarkers is unknown. This study examined whether cognitive processing therapy (CPT) improves 24-hourheart rate variability (HRV), a predictor of CHD mortality. MethodsIndividuals between the ages of 40 and 65 years with PTSD (n = 112) were randomized to receive 12 sessions of CPT or a Waiting List (WL) intervention comprised of 6 weekly telephone checks of emotional status. The primary outcome variable was 24-hour HRV estimated from the standard deviation of all normal R-R intervals (SDNN); secondary outcomes were the root mean square of successive differences between heart beats (RMSSD), low-frequency HRV (LF-HRV) and high-frequency HRV (HF-HRV). Secondary outcomes also included 24-hour urinary catecholamine excretion, plasma C-reactive protein (CRP), and flow-mediated dilation (FMD) of the brachial artery. For outcomes, linear mixed longitudinal models were used to estimate mean differences (Mdiff). ResultsParticipants randomized to the CPT group did not show improved SDNN (Mdiff = 9.8; 95%CI, −2.7 to 22.3; p = 0.12), the primary outcome variable, but showed improved RMSSD (Mdiff = 3.8; 95% CI, 0.5 to 7.1; p = 0.02), LF- HRV (Mdiff =0.3; 95% CI, 0.1 to 0.5; p = 0.01), and HF-HRV (Mdiff = 0.3; 95% CI, 0.0 to 0.6; p = 0.03) compared to WL. There were no differences between groups in catecholamine excretion, FMD, or inflammatory markers. ConclusionTreating PTSD may not only improve quality of life but may also help ameliorate heightened CHD risk characteristics of PTSD.

Endothelial-endothelial signaling as a mechanism for neurovascular coupling

The brain is an energetically expensive organ, consuming 20% of the body’s cardiac output at rest while only accounting for 2% of its mass. Unable to store long-term energy reserves, the brain rapidly redistributes blood flow to active regions in order to meet moment-to-moment changes in metabolic demand. This dynamic process, known as neurovascular coupling, is the basis of most non-invasive human imaging and plays a crucial role in maintaining brain health. However, despite its broad-ranging importance, the cellular mechanisms that underlie neurovascular coupling remain elusive. During neurovascular coupling, activity-evoked signals drive smooth muscle relaxation, resulting in arterial dilation and a robust increase in downstream capillary blood flow. These dilation events occur quickly – on the order of milliseconds – and spread rapidly through the arterial network to effectively recruit perfusion. Electrical signals propagated along the cerebrovascular endothelium are increasingly speculated to underpin this phenomenon, but this idea remains fundamentally untested. Here, we leverage a combination of mouse genetics, molecular biology techniques, and in vivo imaging in awake mice to evaluate the role of propagated electrical signals in the neurovascular coupling response. Our preliminary results indicate that brain endothelial cells are capable of electrical communication and establish a foundation to test the physiological significance of the signals they relay. R01 HL153261/HL/NHLBI NIH HHS/United States; HHMI/Howard Hughes Medical Institute/United States This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Recovery of the Functional Activity of K&lt;sub&gt;ATP&lt;/sub&gt;-Channels of Pial Arteries after Ischemia/Reperfusion Using Cell Therapy

This study aims to examine the efficiency of intravenous transplantation of human mesenchymal stem cells (hMSCs) performed 7 days after cerebral ischemia/reperfusion (I/R) for recovery of the functional activity of KATP-channels of cerebral arteries. Using a device for intravital visualization of pial vessels, the reaction of arteries to the KATP-channel blocker glibenclamide (GB), the activator of the same channels of pinacidil (PI), acetylcholine (ACh), and ACh against a background of GB action (ACh/GB) 14 and 21 days after I/R and intravenous hMSC transplantation performed 7 days after ischemic exposure. On exposure to GB 14 days after I/R, 1.5–1.8 times fewer arteries narrowed than in the sham–operated (SO) rats. By day 21 after I/R, the constriction reaction was completely restored, except for arteries with a diameter more 40 μm. In the cell–therapy group, the constrictor response to GB was completely recovered to the level of SO animals in arteries with a diameter less than 40 μm by 14 day after I/R exposure; in arteries with a diameter of more than 40 μm, the constriction reaction did not recover until 21 days. The number of dilations per ACh/GB compared to a clear ACh in SO rats was reduced in 1.6–1.8 times on 14 day after I/R and in 1.6–6.6 after 21 days. In I/R animals on 14 day, the number of dilatations per ACh/GB compared to clear ACh was significantly increased in arteries with a diameter of more than 20 μm by 1.5–1.7 times, and after 21 days in arteries with a diameter of more than 40 μm by 1.2 times. After the introduction of hMSC, GB blocked ACh–mediated dilation in arteries less than 40 μm in diameter both on days 14 and 21 after I/R. In arteries with a diameter of more than 40 μm the functional activity of KATP-channels did not recover until 21 days. Conclusion. I/R of the rat cerebral cortex reduces the contribution of KATP-channels to maintaining the basal tone of the pial arteries and almost completely excludes these channels from the formation of ACh–mediated dilation during 21 days of the postischemic period. Practically did not participate in the dilatory response. Intravenous transplantation of hMSC, performed 7 days after I/R, results in restoration of participation of SMC KATP-channels in maintaining the basal tone and ACh–mediated dilatation of pial arteries with a diameter less than 40 μm already 14 days after I/R.

Abstract 424: Arachidonic Acid Synergizes With Aspirin In Cardioprotection Following Acute Myocardial Infarction

Introduction: Membrane-released arachidonic acid (AA) is metabolized via cyclooxygenase pathway to form prostanoids, including thromboxane, prostacyclin and prostaglandin E2. Aspirin suppresses platelet synthesis of thromboxane, rendering its first-line use for anti-thrombosis in patients with acute myocardial ischemia. We report that endogenous PGE2 protects against myocardial ischemia-reperfusion (MI/R) injury (Nat Commun. 2019;10(1):1888). The impact of AA administration while suppressing thromboxane on MI/R injury is unknown. Methods and Results: C57BL/6J mice were treated intravenously with vehicle, AA, aspirin, or their combination and then subjected to 30min coronary artery ligation and 24hr reperfusion. Cardiac function was assessed by ultrasonography and infraction size quantified by TTC staining. Cardiac microcirculation was assessed by laser doppler flow and vasomotor reactivity determined with isolated coronary arteries. Single treatment with AA at an optimized dose of 0.1mg/Kg, or combined with aspirin at a dose of 10mg/Kg that allowed sufficient suppressing of platelet activation over 24hr, decreased infarct size and improved heart function. Impressively, combination of AA with aspirin provided additional cardioprotection compared with either single treatment. While aspirin, not AA, ameliorated microvascular obstruction following MI/R injury, co-administration of AA and aspirin further increased coronary microcirculatory blood perfusion with improved vascular permeability compared with aspirin alone. MI/R impaired endothelium-dependent dilatation of coronary arteries, and the dual treatment, not AA or ASA alone, increased coronary artery relaxation. Cardiac infiltrated neutrophils and platelet-neutrophil aggregates were also reduced by the combination treatment, consistent with a suppressed leukocyte-ECs adhesion as assessed in vitro. Conclusions: AA and aspirin synergistically protect against MI/R injury and this is attributable to suppressed neutrophil inflammation and improved microvascular obstruction. AA might be used as an adjunct therapy to aspirin in patients with acute myocardial infarction.