Vasodilator Drugs Research Articles

Haemodynamic Effects of Pimobendan during General Anaesthesia in Healthy Senior Dogs: A Prospective, Randomised, Triple-Blinded, Placebo-Controlled Clinical Study.

Pimobendan is an inotropic and vasodilator drug with no sympathomimetic effects. This study aimed to evaluate the haemodynamic effects of pimobendan during anaesthesia in healthy senior dogs. A prospective, randomised, triple-blinded, placebo-controlled clinical study was conducted. Thirty-three dogs (median [range]: 9 [7, 12] years) were anaesthetised for surgical procedures. The dogs were randomly allocated into two groups: eighteen dogs received intravenous pimobendan at a dose of 0.15 mg/kg (PIMOBENDAN), and fifteen dogs received intravenous saline solutions at a dose of 0.2 mL/kg (PLACEBO). Data were recorded before, 1 min, 10 min, and 20 min after injection. Velocity-time integral (VTI), peak-velocity (PV), and mean-acceleration (MA) were measured using an oesophageal Doppler monitor (ODM). Heart rate and mean arterial pressure were also registered. The data were analysed using a two-way ANOVA for trimmed means. Statistical differences were considered if p < 0.05. Twenty minutes after injection, the VTI (13.0 cm [10.4, 22.3]), PV (95.0 [83.0, 160] m/s), and MA (12.6 [9.40, 17.0] m/s2) were significantly higher in the PIMOBENDAN group compared to the PLACEBO group (VTI: 10.5 [6.50, 17.4] cm, PV: 80.0 [62.0, 103] m/s and MA: 10.2 [7.00, 16.0] ms2). No significant differences were observed in the rest of the variables. Using pimobendan during anaesthesia increases VTI, PV, and MA, as measured by an ODM.

Glyceryl Trinitrate, a Vasodilating Drug Acts as an Antibiofilm Agent in Serratia marcescens

Objectives: Serratia marcescens is a gram-negative pathogen of many species. The ability of S. marcescens to form biofilms and its potent innate resistance to antimicrobials and cleaning solutions are both essential for its pathogenicity and survival. The present study was conducted to investigate the effect of glyceryl trinitrate (GTN) on the biofilm of S. marcescens, as an alternative for antibiotic therapy.&#x0D; Methods: Different specimens, including ear swabs, burns, mid-stream urine, wound swabs, and sputum, were collected from patients who were brought to Al-Ramadi Hospital, Iraq. All samples were cultured, and the colonies that were obtained were detected using the VITEK® 2 compact. The ability of biofilms to develop was examined using the microtiter plate technique. The bactericidal effectiveness of GTN was estimated by the broth microdilution technique. The presence of fimA and fimC in S. marcescens isolates was detected using the polymerase chain reaction (PCR) method. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess the effect of GTN on fimA and fimC gene expression. &#x0D; Results: The results demonstrated that GTN has no effect on S. marcescens growth; while its biofilm was significantly (p&lt;0.05) influenced. Moreover, all S. marcescens isolates had fimA and fimC, and the presence of GTN reduced the expression of these genes.&#x0D; Conclusion: The findings of this study reveal that GTN can act as a promising antibiofilm agent in reference to S. marcescens.

Functional coronary angiography for the assessment of the epicardial vessels and the microcirculation.

Over the last decade, steady progress has been made in the ability to assess coronary stenosis relevance by merging computerised analyses of angiograms with fluid dynamic modelling. The new field of functional coronary angiography (FCA) has attracted the attention of both clinical and interventional cardiologists as it anticipates anew era of facilitated physiological assessment of coronary artery disease, without the need for intracoronary instrumentation or vasodilator drug administration, and an increased adoption of ischaemia-driven revascularisation. This state-of-the-art review performs adeep dive into the foundations and rationale behind FCA indices derived from either invasive or computed angiograms. We discuss the currently available FCA systems, the evidence supporting their use, and the specific clinical scenarios in which FCA might facilitate patient management. Finally, the rapidly growing application of FCA to the diagnosis of coronary microvascular dysfunction is discussed. Overall, we aim to provide astate-of-the-art review not only to digest the achievements made so far in FCA, but also to enable the reader to follow the many publications and developments in this field that will likely take place in years to come.

Repurposing of the Drug Tezosentan for Cancer Therapy.

Tezosentan is a vasodilator drug that was originally developed to treat pulmonary arterial hypertension. It acts by inhibiting endothelin (ET) receptors, which are overexpressed in many types of cancer cells. Endothelin-1 (ET1) is a substance produced by the body that causes blood vessels to narrow. Tezosentan has affinity for both ETA and ETB receptors. By blocking the effects of ET1, tezosentan can help to dilate blood vessels, improve the blood flow, and reduce the workload on the heart. Tezosentan has been found to have anticancer properties due to its ability to target the ET receptors, which are involved in promoting cellular processes such as proliferation, survival, neovascularization, immune cell response, and drug resistance. This review intends to demonstrate the potential of this drug in the field of oncology. Drug repurposing can be an excellent way to improve the known profiles of first-line drugs and to solve several resistance problems of these same antineoplastic drugs.

Synthesis of pyrazolo[1,5-a][1,3,5]triazine and oxazolo[4,5-d]pyrimidine derivatives and study of their vasodilator activity

A number of pyrazolo[1,5-a][1,3,5]triazine and oxazolo[4,5-d]pyrimidine derivatives were synthesized and characterized. Pyrazolo[1,5-a][1,3,5]triazines with various substituents in the fourth position and a dichloromethyl group in the second position were obtained by the heterocyclization reaction of available N-(2,2-dichloro-1-cyanoethenyl)carboxamides and 5-aminopyrazoles. Oxazolo[4,5-d]pyrimidines were obtained by treating 2-phenyl-4-dichloromethylene-1,3-oxazol-5(4H)-one with the corresponding arylamidine hydrochloride in the presence of triethylamine. The resulting 4,5-dihydro-1H-imidazol-5(4)-ones undergo recyclization with subsequent cyclocondensation to the corresponding oxazolo[4,5-d]pyrimidin-7-ones when heated in pyridine. Oxazolo[4,5-d]pyrimidines with a labile chlorine atom in position 7, whose substitution with various amines leads to 7-aminoderivatives of oxazolo[4,5-d]pyrimidine, were obtained by heating the latter in phosphorus (V) oxychloride in the presence of N,N-dimethylaniline. The study of the effect of the synthesized compounds on vascular tone showed that some of the studied samples exhibited vasodilator activity of varying strength. It was established that 2-dichloromethyl-7-methyl-4-(furan-2-yl)pyrazolo[1,5-a][1,3,5]triazine and 2-dichloromethyl-7-methyl-4-(pyridin-3-yl)pyrazolo[1,5-a][1,3,5]triazine showed a pronounced dose-dependent vasodilator effect and therefore, subject to their further research, may be promising for the development of new vasodilator drugs. The study of the biological activity of oxazolo[4,5-d]pyrimidine derivatives did not reveal potential vasodilator agents among the presented compounds, as they demonstrated a low vasodilator effect or did not show vasoactivity.

Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension: Clinical Outcomes.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare major vessel pulmonary vascular disease that is characterised by fibrotic obstructions deriving from an organised clot. Recent advances in treatments for CTEPH have significantly improved outcomes. Apart from classical surgical pulmonary endarterectomy, balloon pulmonary angioplasty (BPA) and vasodilator drugs that were tested in randomised controlled trials of non-operable patients are now available. In Europe, CTEPH affects males and females equally. In the first European CTEPH Registry, women with CTEPH underwent pulmonary endarterectomy less frequently than men, especially at low-volume centres. In Japan, CTEPH is more common in females and is predominantly treated by BPA. More data on gender-specific outcomes are expected from the results of the International BPA Registry (NCT03245268).

Estimation of blood pressure In adult population in Baiji

Data was collected from 60 cases in age groups from 40-60 years ( 30 female and 30 male ).The cases included in this study was collected randomly in Baiji hospital from June to October 2006 .The data was obtained by using a questionnaire . It was found that the most common cases use Beta blockers as antihypertensive drugs , 12 cases use B-blocker plus Angiotensin converting enzymeinhibitors and 5 cases use B-blocker with diuretics.There are 8 cases use Angiotensin converting enzyme inhibitor only and 7 cases use vasodilator drugs .Regarding the measurement of bloodpressure and heart rate , in 36 cases complaining from increase blood pressure above the normal level there is increase in heart rate in 30 cases ( heart rate more than 100 beat / minute ) , andin24cases of normal blood pressure there is increase in heart rate in 5 cases only .The aim of this study is to investigate the prevalence of hypertension in age groups from 40-60 years in Baiji from June toOctober with some investigations

Inhaled Nitric Oxide and Higher Necrotizing Enterocolitis Rates in Congenital Heart Disease Patients

IntroductionCertain congenital cardiac lesions are at increased risk for the development of necrotizing enterocolitis (NEC). These patients are often reliant on pulmonary and systemic vasomodulators to maintain adequate perfusion and oxygenation. This study sought to determine whether pulmonary or systemic vasodilator treatment is protective against the development of NEC in this population. MethodsWe utilized International Classification of Diseases (ICD) codes to identify high risk congenital cardiac disease patients ≤6 mo of age, cared for at a tertiary children's hospital between January 2011 and January 2021. Cardiac anomalies were stratified into ductal dependent (pulmonary DD-P or systemic DD-S) or independent lesions. The rate of NEC development in those who received vasodilators (inhaled nitric oxide [iNO], pulmonary vasodilators, systemic vasodilators) was compared to controls in a multivariate analysis. ResultsOf the 352 patients, who met inclusion criteria, 77.6% had ductal dependent lesions (DD-S 41.9%, DD-P 35.7%), 19.5% received iNO, and 37.5% received other vasodilatory drugs. The overall NEC rate was 15.1%. On univariate analysis, DD-S, iNO use, and systemic vasodilators was associated with a significantly higher risk of NEC, while DD-P was associated with lower NEC risk. On multivariate analysis, only iNO (odds ratio 2.725, confidence interval [1.36-5.44]) and DD-S (odds ratio 2.279, confidence interval [1.02-5.11]) were independent risk factors for NEC. ConclusionsIn patients with at-risk congenital cardiac disease lesions, a ductus dependent systemic circulation or iNO treatment is associated with an increased risk of developing NEC. The presence of iNO or DD-S should be utilized as markers of increased risk both in the prevention and workup of suspected NEC.

Phosphodiesterase-5 (PDE5) Inhibitors in the Treatment of Erectile Dysfunction: A Review

A phosphodiesterase type 5 inhibitor (PDE5 inhibitor) is a vasodilating drug which works by blocking the degradative action of cGMP-specific phosphodiesterase type 5 (PDE5) on cyclic GMP in the smooth muscle cells lining the blood vessels supplying various tissues. These drugs dilate the corpora cavernosa of the penis, facilitating erection with sexual stimulation, and are used in the treatment of erectile dysfunction (ED). Sildenafil was the first effective oral treatment available for ED. Because PDE5 is also present in the smooth muscle of the walls of the arterioles within the lungs, two PDE5 inhibitors, sildenafil and tadalafil, are FDA-approved for the treatment of pulmonary hypertension. As of 2019, the wider cardiovascular benefits of PDE5 inhibitors are being appreciated.

PGRMC1 Ablation Protects from Energy-Starved Heart Failure by Promoting Fatty Acid/Pyruvate Oxidation.

Heart failure (HF) is an emerging epidemic with a high mortality rate. Apart from conventional treatment methods, such as surgery or use of vasodilation drugs, metabolic therapy has been suggested as a new therapeutic strategy. The heart relies on fatty acid oxidation and glucose (pyruvate) oxidation for ATP-mediated contractility; the former meets most of the energy requirement, but the latter is more efficient. Inhibition of fatty acid oxidation leads to the induction of pyruvate oxidation and provides cardioprotection to failing energy-starved hearts. One of the non-canonical types of sex hormone receptors, progesterone receptor membrane component 1 (Pgrmc1), is a non-genomic progesterone receptor associated with reproduction and fertility. Recent studies revealed that Pgrmc1 regulates glucose and fatty acid synthesis. Notably, Pgrmc1 has also been associated with diabetic cardiomyopathy, as it reduces lipid-mediated toxicity and delays cardiac injury. However, the mechanism by which Pgrmc1 influences the energy-starved failing heart remains unknown. In this study, we found that loss of Pgrmc1 inhibited glycolysis and increased fatty acid/pyruvate oxidation, which is directly associated with ATP production, in starved hearts. Loss of Pgrmc1 during starvation activated the phosphorylation of AMP-activated protein kinase, which induced cardiac ATP production. Pgrmc1 loss increased the cellular respiration of cardiomyocytes under low-glucose conditions. In isoproterenol-induced cardiac injury, Pgrmc1 knockout resulted in less fibrosis and low heart failure marker expression. In summary, our results revealed that Pgrmc1 ablation in energy-deficit conditions increases fatty acid/pyruvate oxidation to protect against cardiac damage via energy starvation. Moreover, Pgrmc1 may be a regulator of cardiac metabolism that switches the dominance of glucose-fatty acid usage according to nutritional status and nutrient availability in the heart.

MIRACULUS OUTCOME OF NON-OCCLUSIVE MESENTRIC ISCHAEMIA (NOMI) IN CARDIOGENIC SHOCK- A CASE REPORT

Introduction: Non-occlusive mesenteric ischemia (NOMI) is an acute mesenteric circulatory disorder which includes all types of mesenteric ischemia without any blockage of blood vessels. It is usually seen in elderly age group with risk factors of previous myocardial infarction, congestive cardiac failure and post-cardiac surgery, renal disease, vasopressor use, aortic insufciency. NOMI is an infrequent cause of acute mesenteric ischemia with atypical symptoms &amp; constitutes 20-30% cases of acute mesenteric ischemia (AMI). The mortality rate is generally high, at least 50%, being the deadliest type of acute mesenteric ischemia (AMI). A high index of suspicion is required. Treatment is based on correction of the underlying cause, supportive therapy, vasodilation and surgery. Presenting a challenging case of an elderly patient with Diabetes Mellitus for 15 years in cardiogenic shock with NOMI. Colonoscopy was diagnostic of ischemic colitis. Patient was managed conservatively with successful outcome NOMI is a rare disease with a difcult d Conclusion: iagnosis because of the unspecic symptomatology. Early recognition with high suspicion of index is necessary. Case highlights the challenges in the diagnosis and the multiple difculties during management. Treatment with supportive therapy, vasodilator drugs and surgery if needed can signicantly improve prognosis &amp; lower mortality

Synthesis of 1-nicotinoylo-3-(meta-nitrophenyl)- thiourea derivatives with anti-inflammatory activity

Thiourea derivatives are used in many industries: medicine, agriculture, engineering, rubber industry, organic synthesis. On their basis, various preparations for the needs of the national economy were obtained. The latest studies of thiourea derivatives, carried out at the present time, are prompted not only by theoretical, but also by practical needs. From this point of view, thiourea derivatives are of undoubted interest in substances with different biological activities. They are widely used in agriculture and have been used as herbicides, fungicides, insecticides, bactericides, dyes, growth stimulants, etc. Of particular interest is the use of these compounds in medicine as antitumor, antiviral, anti-inflammatory, antiarrhythmic, vasodilator and other drugs. Today, most of the derivatives of thiourea, urea, the search for new highly effective low-toxic biologically active compounds based on them is constantly ongoing, as can be judged by the large number of publications in the world scientific and patent literature. This article proposes a simple and convenient method for the preparation of 1-nicotinoyl-3-(m-nitrophenyl)-thioureas based on heterocyclic thioisocyanate with nitroaniline in a dimethylformamide medium, in rather high yields. And also studied the anti-inflammatory activity of the synthesized drug.

Pulmonale Endarteriektomie und Behandlung der chronisch thromboembolischen pulmonalen Hypertonie

Pulmonary Endarterectomy and Treatment for Chronic Thromboembolic Pulmonary Hypertension Abstract. Chronic thromboembolic pulmonary hypertension is a relatively rare disease which mostly evolves as a complication of acute pulmonary embolism resulting from the fibrotic organization of residual thrombotic material despite adequate anticoagulation leading to precapillary pulmonary hypertension and persistence of its symptoms. The elevated pulmonary vascular resistance leads to right ventricular heart failure, its symptoms and reduced prognosis. The therapy of choice is the pulmonary endarterectomy, which leads to a reduction of symptoms, optimization of the hemodynamics and improved prognosis. Misdiagnosis and delayed referral often lead to disease progression along with poor surgical outcome. In case of more distal, surgically non-accessible disease, treatment consists of balloon pulmonary angioplasty and pulmonary vasodilator drugs.

Применение селективного ингибитора фосфодиэстеразы–5 силденафила при беременности с учетом его возможного влияния на плод

Objective of the Review: To evaluate the possibilities and effectiveness of the use of sildenafil in obstetric practice, its effect on both the fetus and the mother's body. Key points. Sildenafil is a potent vasodilator drug used to treat pulmonary hypertension in adults and children. In addition to the vasodilating effect, sildenafil has a proliferative effect on the vascular network, reduces the muscle mass of the vascular wall. The vasodilating effect of sildenafil also appears on the uterus and myometrial vessels, which leads to increased uterine circulation and thickening of the endometrium. Its use during pregnancy is mainly limited to a few specific indications. In particular, high pulmonary hypertension – is sufficient reason to prescribe this drug off–label even at the stage of pregnancy planning. To date, antenatal therapy with sildenafil for conditions such as preeclampsia, preterm labor, oligohydramnios, congenital diaphragmatic hernia, intranatal fetal distress, and intrauterine growth restriction are being actively studied in many countries. More than 130 in vivo and ex vivo animal studies, pharmacological and toxicokinetic studies have demonstrated the safety of sildenafil. It has been proven that there is no teratogenic effect, as well as an increase in the frequency of congenital anomalies in the fetus. Conclusion. The use of sildenafil during pregnancy is of interest to researchers around the world. Based on preliminary data, it can be assumed that serious side effects in pregnant women, negative effects on the fetus, an increase in the frequency of stillbirths, neonatal deaths and congenital anomalies associated with taking sildenafil were not observed. However, additional fundamental studies are needed, including using experimental animal models, in order to finally evaluate the ability of sildenafil to overcome the transplacental barrier, as well as the possibility and effectiveness of its use in various groups of patients. Keywords: sildenafil, transplacental transfer, safety during pregnancy, pharmacology, hemodynamics.

Prediction of new onset atrial fibrillation recurrence or persistence with artificial intelligence: first insights of the PRAFAI study

Abstract Introduction Atrial fibrillation (AF) is the most prevalent arrhythmia in the world and it is associated with a high rate of cardiovascular morbidity and mortality. A higher burden of atrial fibrillation is related to more adverse cardiovascular events and the rhythm control strategy (maintenance or recovery of sinus rhythm) is particularly indicated in patients with paroxysmal symptomatic atrial fibrillation. All things considered, in order to select the optimal therapeutic strategy, it might be useful to accurately predict the probability of recurrence or permanence of AF after its onset. The predictive models implemented so far, show a limited predictive power or were built on samples of patients undergoing specific therapies. Thus, developing an specific model based on features derived from electronic health records (EHR) of patients with a first AF episode seems essential. Purpose To develop an artificial intelligence powered predictive model based on EHR variables in order to predict the AF recurrence after its onset. Methods The methodological design of the research is based on the analysis of secondary data from a retrospective cohort obtained from the EHR of a tertiary hospital. All new onset AF from 2015 to 2018 were identified by ICD codes, and a 2 years EHR driven follow-up was made to determine the AF recurrence or permanence of the arrhythmia in those patients. A systematic review was pursued to determine which features exhibited a greater predictive power for AF recurrence, and they were inquired to the system for the mentioned participants. After the standardization of the variables and a feature selection process, several missing value imputation methods and around 12 different Machine Learning algorithms were tested to predict the AF recurrence in a subset of patients who developed AF in the first semester of 2015, in order to select the algorithms with the highest prediction accuracy for further tests. Results 523 patients had an AF onset in the first semester of 2015. Among them, 310 (59.3%) had AF recurrence in a 2 years period. A support vector machine (SVM) algorithm with a median imputation method to handle missing values performed the best and had an 0.77 AUC in the training set and 0.71 in the test set. Hyperthyroidism, vasodilator drug use and obstructive sleep apnea were notoriously related to AF recurrence, while Ic antiarrhythmic drugs, AF ablation, cognitive impairment and anxiety were the most influential variables for the absence of recurrence. Classical AF recurrence factors such as age or left atrium diameter ratify their role in this setting. Conclusion A SVM Machine Learning algorithm discloses an accurate AF recurrence probability based on EHR features. Pharmacologic and epidemiological variables, added to classically assessed ones, seem to be specially related to this arrhythmic recurrence. Further research including the whole cohort features will probably improve the accuracy of this selected SVM algorithm. Funding Acknowledgement Type of funding sources: None.

The vasodilator naftidrofuryl attenuates short-term brain glucose hypometabolism in the lithium-pilocarpine rat model of status epilepticus without providing neuroprotection

Status epilepticus (SE) triggered by lithium-pilocarpine is a model of epileptogenesis widely used in rats, reproducing many of the pathological features of human temporal lobe epilepsy (TLE). After the SE, a silent period takes place that precedes the occurrence of recurrent spontaneous seizures. This latent stage is characterized by brain glucose hypometabolism and intense neuronal damage, especially at the hippocampus. Importantly, interictal hypometabolism in humans is a predictive marker of epileptogenesis, being correlated to the extent and severity of neuronal damage. Among the potential mechanisms underpinning glucose metabolism impairment and the subsequent brain damage, a reduction of cerebral blood flow has been proposed.Accordingly, our goal was to evaluate the potential beneficial effects of naftidrofuryl (25 mg/kg i.p., twice after the insult), a vasodilator drug currently used for circulatory insufficiency-related pathologies. Thus, we measured the effects of naftidrofuryl on the short-term brain hypometabolism and hippocampal damage induced by SE in rats. 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) neuroimaging along with various neurohistochemical assays aimed to assess brain damage were performed.SE led to both severe glucose hypometabolism in key epilepsy-related areas and hippocampal neuronal damage. Although naftidrofuryl showed no anticonvulsant properties, it ameliorated the short-term brain hypometabolism induced by pilocarpine. Strikingly, the latter was neither accompanied by neuroprotective nor by anti-inflammatory effects. We suggest that naftidrofuryl, by acutely enhancing brain blood flow around the time of SE improves the brain metabolic state but this effect is not enough to protect from the damage induced by SE.

Freestanding hydrogel lumens for modeling blood vessels and vasodilation.

Lumen structures exist throughout the human body, and the vessels of the circulatory system are essential for carrying nutrients and oxygen and regulating inflammation. Vasodilation, the widening of the blood vessel lumen, is important to the immune response as it increases blood flow to a site of inflammation, raises local temperature, and enables optimal immune system function. A common method for studying vasodilation uses excised vessels from animals; major drawbacks include heterogeneity in vessel shape and size, time-consuming procedures, sacrificing animals, and differences between animal and human biology. We have developed a simple, user-friendly in vitro method to form freestanding cell-laden hydrogel rings from collagen and quantitatively measure the effects of vasodilators on ring size. The hydrogel rings are composed of collagen I and can be laden with human vascular smooth muscle cells, a major cellular and structural component of blood vessels, or lined with endothelial cells in the lumen. The methods presented include a 3D printed device (which is amenable to future fabrication by injection molding) and commercially available components (e.g., Teflon tubing or a syringe) to form hydrogel rings between 2.6-4.6mm outer diameter and 0.79-1.0mm inner diameter. Here we demonstrate a significant difference in ring area in the presence of a known vasodilator, fasudil (p<0.0001). Our method is easy to implement and provides a foundation for a medium-throughput solution to generating vessel model structures for future investigations of the fundamental mechanisms of vasodilation (e.g., studying uncharacterized endogenous molecules that may have vasoactivity) and testing vasoactive drugs.

Carbohydrate-Derived Polytriazole Nanoparticles Enhance the Anti-Inflammatory Activity of Cilostazol.

Poly(amide-triazole) and poly(ester-triazole) synthesized from d-galactose as a renewable resource were applied for the synthesis of nanoparticles (NPs) by the emulsification/solvent evaporation method. The NPs were characterized as stable, spherical particles, and none of their components, including the stabilizer poly(vinyl alcohol), were cytotoxic for normal rat kidney cells. These NPs proved to be useful for the efficient encapsulation of cilostazol (CLZ), an antiplatelet and vasodilator drug currently used for the treatment of intermittent claudication, which is associated with undesired side-effects. In this context, the nanoencapsulation of CLZ was expected to improve its therapeutic administration. The carbohydrate-derived polymeric NPs were designed taking into account that the triazole rings of the polymer backbone could have attractive interactions with the tetrazole ring of CLZ. The activity of the nanoencapsulated CLZ was measured using a matrix metalloproteinase model in a lipopolysaccharide-induced inflammation system. Interestingly, the encapsulated drug exhibited enhanced anti-inflammatory activity in comparison with the free drug. The results are very promising since the stable, noncytotoxic NP systems efficiently reduced the inflammation response at low CLZ doses. In summary, the NPs were obtained through an innovative methodology that combines a carbohydrate-derived synthetic polymer, designed to interact with the drug, ease of preparation, adequate biological performance, and environmentally friendly production.

Abstract 14666: Coronary Arterial Calcification Influences Fractional Flow Reserve: Comparison of Guide Wire Type FFR With Vasodilator and FFRangio Without Vasodilator

Introduction: Fractional flow reserve (FFR) measures percutaneous coronary intervention (PCI) performance. FFR was determined by guide wire (GW)-type FFR. It is now evaluated by computed tomography (CT; FFRCT) or invasive coronary angiography (FFRangio; CathWorks, USA), whereby coronary arteries are traced on a conventional angiogram from three different angles to form three-dimensional images; the calculated FFR is FFRangio. In contrast to GW-type FFR, FFRangio does not need a vasodilator drug (e.g. nicorandil) load or GW. Hypothesis: Coronary calcification may influence the effect of vasodilator drugs, causing a difference between FFRangio and GW-type FFR depending on coronary calcium score (CCS). Methods: FFRangio and GW-type FFR (SJN, Zeon, ACIST) were simultaneously evaluated at catheter examinations in 11 coronary arteries from 9 patients before PCI (six males, mean age 72±11 years). Nicorandil (2 mg) was directly injected when measuring GW-type FFR. Cardiac CT was performed to measure CCS. Results: The correlation coefficients between FFR magnitude (=mean of FFRangio and GW-type FFR) and CCS in all vessels, and a vessel with FFR measurement, were -0.845 and -0.843, respectively. The correlation coefficients between difference in FFRangio minus GW-type FFR and CCS in all vessels, and a vessel with FFR measurement, were 0.627 and 0.752, respectively. The greater the CCS of both all vessels and a vessel in FFR measurements, the smaller the FFR. The greater the CCS of both all vessels and a vessel with FFR measurement, the greater the difference in FFRangio minus GW-type FFR (Figures). This may indicate the greater the CCS, the smaller the vasodilation effect of a direct nicorandil injection. Conclusions: Of GW-type FFR, FFRangio, and FFR CT, only GW-type FFR requires a vasodilator injection. Coronary arteries, known to cause blooming artifacts and impair the accuracy of FFRCT, also influence vasodilator effects, especially with borderline FFR (0.75-0.80).

Inhaled Nitric Oxide Treatment Is Associated with Higher Rates of Necrotizing Enterocolitis in At-risk Congenital Cardiac Disease Patients

INTRODUCTION: Certain congenital cardiac lesions are at increased risk for the development of necrotizing enterocolitis (NEC). These patients with these lesions are often reliant on pulmonary and systemic vasomodulators to maintain adequate perfusion and oxygenation. This study sought to determine whether pulmonary or systemic vasodilator treatment is protective against the development of NEC in this population. METHODS: We used ICD codes to identify high-risk congenital cardiac disease patients ≤6 months of age, cared for at a tertiary children’s hospital between January 2011 and January 2021. Cardiac anomalies were stratified into ductal-dependent (pulmonary DD-P or systemic DD-S) or independent lesions. The rate of NEC development in those who received vasodilators (inhaled nitric oxide [iNO], pulmonary vasodilators, systemic vasodilators) was compared with controls in a multivariate analysis. RESULTS: Of the 353 patients who met inclusion criteria, 77.6% had ductal-dependent lesions (DD-S 41.9%, DD-P 35.7%), 19.5% received iNO, and 51.8% received other vasodilatory drugs. The overall NEC rate was 15.3%. On univariate analysis, DD-S, iNO use, and systemic vasodilators had a significantly higher risk of NEC, and DD-P was associated with lower NEC risk (Figure). On multivariate analysis, only iNO (odds ratio 2.725 [CI 1.36 to 5.44]) and DD-S (odds ratio 2.279 [CI 1.02 to 5.11]) were independent risk factors for NEC.FigureCONCLUSION: In patients with at-risk congenital cardiac disease lesions, a ductus-dependent systemic circulation and/or iNO treatment increases the risk of developing NEC. The presence of iNO or DD-S should be used as a marker of increased risk both in the prevention and workup of suspected NEC.