Vasodilation In Patients Research Articles

Effects of inhaled nitric oxide on endothelial function in patients with ischemic stroke

BACKGROUND: A crucial pathogenetic link in the development of stroke is the deterioration of endothelial function, which is a pathological condition characterized by an imbalance between endothelium-dependent relaxing and constricting factors. An example of an endothelium-dependent relaxing factor is nitric oxide, a substance synthesized by the body’s cells that has a vasodilating, antithrombogenic, anti-inflammatory, and antiproliferative effect. Studies have shown the neuroprotective function of inhaled nitric oxide after ischemia; however, determining the minimum effective dose of inhaled nitric oxide in patients who have suffered an acute cerebrovascular accident remains challenging. AIM: To analyze the protective effect of exogenous nitric oxide using the TIANOX device on the vascular endothelium in patients who have had an ischemic stroke in the early and late recovery period during medical rehabilitation. MATERIALS AND METHODS: The study involved 21 patients (10 people in the main group, 56.9±8.9 years old, 11 people in the control group, 57.2±8.8 years old) in the early or late recovery period after an ischemic stroke. Patients in the main group underwent an individual medical rehabilitation program and a course of 8–10 inhalations of a gas mixture with nitric oxide at 20 ppm for 20 minutes. Those in the control group underwent an individual rehabilitation course without nitric oxide therapy. Flow-dependent vasodilation of the brachial artery was evaluated to assess endothelial function. RESULTS: In the main group, a statistically insignificant (p 0.05) increase was found in the diameter of the brachial artery (3.68±0.64 mm), whereas in the control group, this indicator at rest during repeated diagnostics was less than the initial one (3.09±0.87 mm). During repeated diagnostics, the average endothelial shear velocity in patients of the control group increased from 141.53±52.62 to 159.3±82 versus from 143.17±43.53 to 143.48±46.37 in the main group; however, the results were not statistically significant (p=0.753). CONCLUSION: The increase in the diameter of the brachial artery during flow-dependent vasodilation in patients in the main group may indicate a prosthetic effect of the exogenous form of nitric oxide when using the Tianox device on the vascular endothelium, owing to the possibility of depositing nitric oxide in the body. To confirm the obtained data, a larger sample size of patients is critical in order to further divide the groups of patients into early and late recovery periods after ischemic stroke.

Prostacyclin pathway vasodilators in patients with chronic thromboembolic pulmonary hypertension (CTEPH): A systemic review and meta-analysis of randomized controlled trials.

Although surgical and interventional therapy has emerged as the primary treatment for patients with chronic thromboembolic pulmonary hypertension (CTEPH), there remains a subset of patients who need medication therapy. This study aimed to evaluate the efficacy and safety outcomes of prostacyclin pathway vasodilators, providing further insight for clinical decision-making. A literature search was conducted in PubMed, Embase, and CENTRAL databases from inception to December 2023. Literature screening and quality assessment were carried out with the Cochrane Risk of Bias Tool. Data analysis was conducted using RevMan 5.4 software. We included 6 randomized controlled trials with 387 patients. Prostacyclin pathway vasodilators demonstrated a significant improvement in PVR (-125.26 dynes·sec·cm-5, 95%CI: -219.29 to -31.23, Z = 2.61, and p < 0.009), RAP (-0.78 mmHg, 95%CI: -1.52 to -0.04, Z = 2.06, and p = 0.04), cardiac index (0.62, 95%CI: 0.54 to 0.69, Z = 16.13, and p < 0.00001), and the number of patients showing improvement in WHO functional class (3.86, 95%CI: 1,92 to 7.77, Z = 3.79, and p = 0.0002) compared to controls, moreover, a trend towards improvement was observed in mPAP, 6MWD, and NT-proBNP. Regarding the safety endpoints, no significant difference was found in both groups in terms of serious adverse events and all-cause deaths. The prostacyclin pathway vasodilators present therapeutic potential for CTEPH patients with inoperable or persistent/recurrent PH after PEA/BPA primarily characterized by distal small-vessel and microvasculopathy. However, the current clinical evidence remains insufficient and controversial, necessitating further validation.

Pulmonary vasodilators in patients with advanced chronic kidney disease and pre‐capillary pulmonary hypertension—A case series

AbstractPulmonary hypertension (PH) is a prevalent complication among patients with chronic kidney disease (CKD). In these patients, pulmonary vasodilators may be useful but are underused. We describe a group of patients with precapillary PH and advanced CKD treated with pulmonary vasodilators. This was a case series of patients with CKD stage 4 and 5 and precapillary PH (isolated or combined) based on right heart catheterization (RHC) treated with pulmonary vasodilators from 2018 to 2023. Of 263 patients with isolated precapillary or combined PH and advanced CKD, only 17 (6%) were treated with pulmonary vasodilators; 53% (n = 9) with precapillary PH and 47% (n = 8) with combined PH. Most patients (94%, n = 16) received phosphodiesterase‐5 antagonists, while 12% (n = 2) received endothelin receptor antagonists. Adverse clinical outcomes were seen in 35% of patients within a year. The use of pulmonary vasodilator did not prevent adverse outcomes in patients with precapillary PH and advanced CKD.

Diabetes mellitus is associated with low exercise capacity and impaired peripheral vasodilation in patients with heart failure − a propensity score-matched study

AimsDiabetes mellitus (DM) and heart failure (HF) share vascular, skeletal and metabolic abnormalities that can reduce exercise capacity. We investigated whether exercise capacity differ in patients with type 2 DM compared to those without DM with HF of similar severity. Methods and resultsThe Studies Investigating Co-morbidities Aggravating HF (SICA-HF) prospectively enrolled 615 patients with chronic HF, 259 (42.1 %) of whom had DM. We assembled a propensity score-matched cohort of 231 pairs of patients with HF with or without DM who were balanced on age, sex and variables reflecting HF severity. Patients with DM had lower median peak VO2 (15.7 [13.0–19.1] vs. 17.3 [14.1–21.0] ml/min/kg; p = 0.005). Forearm blood flow reserve (per 1 ml/min/100 ml increase) was associated with lower exercise capacity (peak VO2 ≤ 16.6 ml/min/kg) in patients with DM (OR, 0.92; 95 % CI, (0.85–0.98; p = 0.014), but not in those without DM (OR, 0.98; 95 % CI, 0.93–1.02). A similar heterogeneity was also observed for HDL cholesterol. ConclusionsDiabetes is associated with a reduced exercise capacity in patients with HF. Most predictors of lower exercise capacity in HF are similar regardless of DM except impaired vascular function and lower HDL cholesterol which predict lower exercise capacity only in those with DM.

Vascular Reactivity during Cardiopulmonary Bypass in Patients at Punjab Institute of Cardiology and Shalamar Hospital Lahore, Pakistan

Background: The operative treatment of cardiac diseases remains associated with systemic inflammation and a suboptimal outcome in many patients. These inflammatory changes are manifested by systemic hypotension, myocardial failure, increased vascular permeability and consequent dysfunction of organs such as the lungs, gut and brain. In general terms, sympathetic innervations of the small arteries and arterioles allows vasoconstriction, thereby increasing resistance to blood flow, whereas innervations of the large arteries and veins decreases the volume in these vessels, resulting in the redistribution of blood volume. This study was conducted to determine the effect of vasodilator drugs on duration of vasodilatation in patients undergoing coronary artery bypass grafting (CABG) with Cardiopulmonary bypass (CPB).Methods: We evaluated prospectively the effect of vasodilator medications before CABG surgery on hemodynamic variables and use of vasoactive drugs. We studied 30 patients with good left ventricular function allocated randomly to continue vasodilator drugs before cardiac surgery. Arterial pressure, Cardiac output, systemic vascular resistance and use of vasoactive drugs were recorded during anaesthesia, perioperative and in the early postoperative period.Results: Patients who using vasodilator drugs before cardiac surgery had not significant relationship between vasodilator drugs and vessels reactivity (vasoconstriction &amp; vasodilatation). However, these patients required more vasodilator drugs to control hypertension after CPB and in the early postoperative period.Conclusion: There was no difference in hypotension at the onset of CPB or in the use of vasodilator drugs before cardiac surgery. We conclude that vasodilator drugs before cardiac surgery did not have sufficient effect to be recommended routinely.

Empagliflozin and Dapagliflozin Improve Endothelial Function in Mexican Patients with Type 2 Diabetes Mellitus: A Double-Blind Clinical Trial.

To assess the acute effect of empagliflozin versus dapagliflozin administration on flow-mediated vasodilation in patients with type 2 diabetes mellitus. A double-blind clinical trial, at the Experimental and Clinical Therapeutics Institute, University Health Sciences Center, at the Universidad de Guadalajara, in inpatients with T2D according to the 2023 ADA criteria. Thirty patients (15 males and 15 females), aged between 35 and 65 years, were included in this study, according to the 2023 ADA criteria. The eligible patients were randomly assigned to three groups: empagliflozin 25 mg once daily, dapagliflozin 10 mg once daily, or placebo once daily. Anthropometric parameters were taken using validated techniques. FMD was measured using a high-resolution semiautomatic ultrasound UNEX-EF 38G (UNEX Co., Ltd., Nagoya, Japan). Arterial tension was determined with the OMRON electronic digital sphygmomanometer (HEM 907 XL, Kyoto, Japan). The group of patients who received empagliflozin had a significantly lower baseline flow-mediated dilation (FMD) compared to the group receiving dapagliflozin (p = 0.017); at the end of this study, the empagliflozin group achieved a comparable FMD to the dapagliflozin group (p = 0.88). After the treatment period, the empagliflozin and dapagliflozin groups achieved similar FMD, suggesting a class effect.

Updates in the Pharmacotherapy of Pulmonary Hypertension in Patients with Heart Failure with Preserved Ejection Fraction.

Pulmonary hypertension (PH) associated with left heart disease (LHD) is a complex cardiopulmonary condition where a variable degree of pulmonary congestion, arterial vasoconstriction and vascular remodeling can lead to PH and right heart strain. Right heart dysfunction has a significant prognostic impact on these patients. Therefore, preserving right ventricular (RV) function is an important treatment goal. However, the treatment of PH in patients with left heart disease has produced conflicting evidence. The transition from pure LHD to LHD with PH is a continuum and clinically challenging. The heart failure with preserved ejection fraction (HFpEF) patient population is heterogeneous when it comes to PH and RV function. Appropriate clinical and hemodynamic phenotyping of patients with HFpEF and concomitant PH is paramount to making the appropriate treatment decision. This manuscript will summarize the current evidence for the use of pulmonary arterial vasodilators in patients with HFpEF.

Inhaled nitric oxide: well-known and new therapeutic indications

The use of nitric oxide is widespread in medical practice. Inhaled form of NO in patients with respiratory disease is especially interesting. As an inhalation therapy, nitric oxide reaches well-ventilated areas of the lungs, having a negligible systemic effect due to its rapid inactivation in the bloodstream. It has long been known that inhaled NO improves oxygenation in various pathological conditions. Low doses of inhaled nitric oxide are known as a vasodilator in patients with pulmonary hypertension, its use is possible even in newborns with hypoxemic respiratory failure and persistent pulmonary hypertension. In turn, high doses are used in the treatment of infectious lung diseases, besides, another surge of scientific interest in nitric oxide arose during the coronavirus pandemic. Although the antimicrobial potential of nitric oxide is widely known, it is little used in clinical practice. Endogenous antimicrobial activity is largely mediated by high local concentrations of NO. Numerous preclinical studies have demonstrated that NO has general static and bactericidal activity against viruses, bacteria, protozoa and fungi/yeast in vitro. Due to the dose-dependent positive and negative effects of NO, safety and efficacy tests of NO and its donors are needed to assess their role in the prevention and treatment of infections. This review provides information on the chemical structure, features of metabolism and delivery of inhaled NO, and also pays special attention to the antimicrobial effect in various diseases of the pulmonological profile.

Abstract 13824: Salsalate Does Not Improve Endothelial Function and Insulin-Stimulated Vasodilation in Patients With Metabolic Syndrome

Background: Insulin resistance accelerates systemic inflammation and vascular dysfunction. Salsalate suppresses inflammation and may improve insulin sensitivity and insulin-mediated, endothelium-dependent vasodilation. Hypothesis: We hypothesized that salsalate treatment would improve insulin-stimulated forearm blood flow (FBF) in volunteers with metabolic syndrome compared to placebo. Methods: We conducted a randomized, double-blind, placebo-controlled crossover trial (NCT00760019) evaluating 4-weeks of salsalate 1.5 grams TID on insulin-stimulated FBF during an insulin clamp in patients with and without metabolic syndrome. Results: Nineteen patients received salsalate (13 metabolic syndrome and 6 healthy controls). Patients with metabolic syndrome were older (36.3 vs 57.1 years old, p=0.002) with higher BMIs (33.9 vs 25.5 kg/m 2 , p=0.001) and higher insulin levels (10.8 vs 4.3 μU/mL, p=0.01). Those with metabolic syndrome had impaired insulin sensitivity by Homeostatic Model Assessment for Insulin Resistance (HOMA IR, 2.66 vs 0.87, p=0.005) and Matsuda Index (MI, 5.81 vs 3.32, p=0.001). After salsalate treatment, insulin sensitivity was unchanged (Panel A &amp; B) and there was no significant reduction in insulin levels (Panel C) or inflammation by C-reactive protein (Panel D). Insulin stimulation increased FBF in patients treated with placebo (p=0.012) and salsalate (p=0.003), but salsalate blunted the FBF response in those with metabolic syndrome (p=0.022, Panel E). In multivariable linear regression, metabolic syndrome, HOMA IR, and MI associated with insulin-stimulated FBF independent of salsalate treatment. Conclusion: Salsalate improved neither insulin sensitivity nor systemic inflammation, and it blunted insulin-stimulated vasodilation in patients with metabolic syndrome. Salsalate does not modulate systemic inflammation and worsens arteriolar endothelial dysfunction in patients with metabolic syndrome.

Targeted treatment strategy for patients with severe pulmonary hypertension secondary to connective tissue diseases

AbstractBackgroundPulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTD) (CTD‐PAH) remains a difficult challenge in clinical practice. We aimed to evaluate the effects of targeted vasodilators in patients with severe CTD‐PAH.MethodsThe data of 53 patients with severe CTD‐PAH hospitalized at the Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, were retrospectively reviewed. Patients were followed up for an average of 2 years to track their outcomes. The efficacy of treatment and the survival rate of patients with severe CTD‐PAH were determined.ResultsAmong the causes of severe CTD‐PAH, systemic lupus erythematosus (SLE) was the most common (39.6%), and the age at onset in patients with SLE‐PAH was younger than that of patients with other CTD. Bosentan was more effective than sildenafil in reducing pulmonary artery pressure, improving cardiac function, and increasing survival time. Combination therapy with targeted vasodilators significantly improved the prognosis of patients with severe CTD‐PAH compared with monotherapy.ConclusionsPatients with severe CTD‐PAH should be treated early with targeted vasodilators. In this study, bosentan was superior to sildenafil. Combined treatment might be an option for severe CTD‐PAH.

Partial vasopressin 1a receptor agonism reduces portal hypertension and hyperaldosteronism and induces a powerful diuretic and natriuretic effect in rats with cirrhosis and ascites

The vasopressin system has emerged as a therapeutic focus for lowering portal hypertension and reducing splanchnic vasodilation in patients with refractory ascites. Clinically available vasopressin agonists are limited by preferential selectivity for V1 receptors that also have steep concentration–response curves with potential risks of excess vasoconstriction and/or complete antidiuretic effects. OCE-205 is a novel, selective, partial V1a receptor agonist with mixed agonist/antagonist activity and no V2 receptor activation at therapeutic doses. We carried out two studies assessing the in vivo effects of OCE-205 in different rat models of cirrhosis and ascites. In a carbon tetrachloride rat cirrhosis model, OCE-205 administration produced a marked reduction in portal hypertension and hyperaldosteronism, along with robust diuretic and natriuretic effects. These effects were accompanied by marked decreases in ascites volume, with three of five animals experiencing total mobilization of ascites. There was no evidence of fluid overload or sodium or water retention, confirming OCE-205′s lack of V2 receptor activity. In a second, corroborative study using a bile duct ligation rat model of ascites, OCE-205 produced significant decreases in ascites volume and body weight and a significant increase in urine volume versus vehicle. Urine sodium excretion increased significantly after the first administration of OCE-205 relative to vehicle; however, repeat administration over 5 days did not lead to hyponatremia. Thus, in separate in vivo models, the mixed agonist/antagonist OCE-205 demonstrated relevant and expected endpoint findings consistent with its known mechanism of action and in vitro pharmacology without apparent unwanted effects or nonspecific toxicities.

#2887 ASSESSMENT OF EXTRA-BONE CALCIFICATION IN PATIENTS UNDERGOING PROGRAMMED HEMODIALYSIS

Abstract Background and Aims Chronic kidney disease is associated with the accumulation of so-called medium molecules in the blood, in particular parathyroid hormone, and the formation of secondary hyperparathyroidism with a tendency to extra-bone calcification. The most vulnerable organ in relation to calcification is the vascular wall. The ail of the study to study the features of vascular wall remodeling in patients with chronic kidney disease who are being treated with programmed hemodialysis. Method The study included 86 patients with CKD C5 (mean age 47.44±5.04 years) who had been on programmed hemodialysis for at least 6 months. All patients underwent examination, including multislice spiral computed tomography (MSCT) with an assessment of the calcium content in the coronary arteries (Agatston index), ultrasound examination of the carotid arteries with determination of the thickness of the intima-media complex, the degree of endothelium-dependent vasodilation in a sample with 5-minute compression of the brachial artery and determination of changes in the diameter of the brachial artery. The data obtained (presented in the form of an arithmetic mean and its standard error) were compared with normal values typical for a healthy population. Results There was an accumulation of calcium in the coronary vessels with an average Agatstone index of 146.83 ± 13.26 units. Also, during MSCT, calcifications were found in the aortic wall in 86 out of 57 patients. The intima-media complex in patients with CKD was significantly increased and averaged 1.21±0.06mm. The degree of endothelium-dependent vasodilation in patients with CKD was reduced and amounted to 5.48± 0.03% of the initial diameter of the brachial artery. Correlation analysis revealed significant positive associations of average strength between the value of the Agatson index, the thickness of the intima-media complex of the carotid arteries and the concentration of parathyroid hormone in peripheral blood (g = +0.58,P&amp;lt;0.05 with the Agatson index and P = 0.42, P&amp;lt;0.05 with the thickness of the intima-media complex), as well as a significant negative relationship between the product of the concentration of calcium and phosphorus in peripheral blood and the degree of endothelium-dependent vasodilation (g = -0.49, P&amp;lt;0.05). Conclusion In patients with CKD, against the background of programmed hemodialysis, there is a remodeling of the heart with an increase in the size of the heart cavities and LV myocardial mass, a violation of regional and general LV contractile function, LV diastolic dysfunction and an increase in pressure in the pulmonary artery system. The introduction of sevelamer hydrochloride into the therapy regimen is associated with the prevention of the progression of cardiac remodeling. Calcification of the aortic valve progresses, regardless of the therapy used. Vascular remodeling in patients with CKD on the background of programmed hemodialysis is manifested by an increase in the thickness of the intima-media complex of the carotid arteries and a violation of endothelium-dependent vasodilation in favor of paradoxical vasoconstriction. Against the background of calcium carbonate therapy, structural disorders of the vascular wall progress. The introduction of sevelamer phosphate binder into the therapy regimen allows to prevent the progression and improve the functional state of endothelial function.

#6650 SGLT2-INHIBITION IMPROVES VASCULAR FUNCTION IN TYPE 2 DIABETES: A DOUBLE BLIND, RANDOMIZED, PLACEBO CONTROLLED CROSSOVER TRIAL

Abstract Background and Aims Sodium glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular events and protects kidney function in type 2 diabetes (DM2) patients. These benefits may partly be related to improvement of vascular function. In this study we examined the effects of SGLT2i treatment on vasodilatory capacity in patients with DM2. Method Using a double-blind, randomized, placebo-controlled cross-over study design, we included 15 patients with DM2 and preserved kidney function (eGFR &amp;gt; 60 ml/min/1.73 m2). Each participant received four weeks of SGLT2i treatment (empagliflozin 10 mg once daily) or matching placebo. After a two-week wash-out period, each participant was crossed over to four weeks of the opposite treatment. At the end of each treatment period, vascular function was evaluated by venous occlusion plethysmography. Forearm blood flow (FBF) was measured during intra-arterial infusion of increasing concentrations of acetylcholine (ACh) and sodium nitroprusside (SNP), assessing endothelium-dependent and independent vasodilation, respectively. Repeated measures two-way ANOVA was performed to compare absolute FBF between groups. Results 11/15 (73%) of participants were male. Mean age was 68±9 (SD) years (range 49-82), eGFR was 81±10 ml/min/1.73 m2 and duration of diabetes was 15.8±9 years. 11/15 (73%) had hypertension and 9/15 (60%) received treatment with an ACE-inhibitor or Angiotensin-II blocker. 4/15 (27%) had cardiovascular disease. The median albumin-to-creatinine ratio was 29 mg/g (range: 4-1293). Both ACh and SNP dose-dependently increased FBF (Figure 1 and 2). FBF during SNP infusion was significantly higher during empagliflozin treatment as compared to placebo (p = 0.004), whereas there was no difference between empagliflozin and placebo in FBF during ACh infusion (P = 0.399). Conclusion Empagliflozin improves endothelium-independent vasodilatation in patients with DM2, whereas no changes could be observed in endothelium-dependent vasodilation. These results suggest that SGLT2i positively affects vascular function and that the effect is not related to nitric oxide from the endothelium.

Impaired β 2 -adrenergic endothelium-dependent vasodilation in patients previously hospitalized with coronavirus disease 2019.

The pulse wave response to salbutamol (PWRS) - change in augmentation index (AIx) - provides a means to assess endothelial vasodilator function in vivo . Endothelial dysfunction plays a relevant role in the pathogenesis of hypertension and cardiovascular disease and appears to underlie many of the complications of coronavirus disease 2019 (COVID-19). However, to what degree this persists after recovery is unknown. Individuals previously hospitalized with COVID-19, those recovered from mild symptoms and seronegative controls with well known risk factors for endothelial dysfunction were studied. To assess the involvement of nitric oxide-cyclic guanosine monophosphate pathway (NO-cGMP) on PWRS, sildenafil was also administrated in a subsample. One hundred and one participants (60 men) aged 47.8 ± 14.1 (mean ± SD) years of whom 33 were previously hospitalized with COVID-19 were recruited. Salbutamol had minimal effect on haemodynamics including blood pressure and heart rate. It reduced AIx in controls ( n = 34) and those recovered from mild symptoms of COVID-19 ( n = 34) but produced an increase in AIx in those previously hospitalized: mean change [95% confidence interval] -2.85 [-5.52, -0.188] %, -2.32 [-5.17,0.54] %, and 3.03 [0.06, 6.00] % for controls, those recovered from mild symptoms and those previously hospitalized, respectively ( P = 0.001). In a sub-sample ( n = 22), sildenafil enhanced PWRS (change in AIx 0.05 [-2.15,2.24] vs. -3.96 [-7.01. -2.18], P = 0.006) with no significant difference between hospitalized ( n = 12) and nonhospitalized participants ( n = 10). In patients previously hospitalized with COVID-19, there is long-lasting impairment of endothelial function as measured by the salbutamol-induced stimulation of the NO-cGMP pathway that may contribute to cardiovascular complications.

Selective Use of Pulmonary Vasodilators in Patients with Fontan Physiology.

Fontan-associated liver disease is a well-known sequela following the Fontan procedure for patients living with single-ventricle heart disease. Pulmonary vasodilators, such as phosphodiesterase type 5 inhibitors, have emerged as a potential therapeutic option for lowering central venous pressures by reducing pulmonary vascular resistance. We performed a single-center retrospective review of Fontan patients who were placed on pulmonary vasodilator therapy with prehemodynamic and posthemodynamic, MR elastography, and histologic assessments. A total of 125 patients with Fontan circulation underwent surveillance with cardiac catheterization during the review period. Fifty-three (42%) patients who did not have increased end-diastolic pressures at the time of cardiac catheterization were started on phosphodiesterase type 5 inhibitor therapy. Nine patients (17%) underwent posttherapy follow-up catheterization. The mean Fontan pressure decreased from 15.4 ± 3.3 mmHg to 13.3 ± 2.5 mmHg (p=0.026), after initiation of pulmonary vasodilatory therapy. There was no change in end-diastolic pressure, transpulmonary gradient, wedge pressure, pulmonary vascular resistance, cardiac index, or saturation. Eleven patients (21%) underwent pretherapy MR elastography testing with posttherapy follow-up MR elastography. We found no improvement in liver stiffness score following the application of pulmonary vasodilators. Three patients underwent pretherapy and posttherapy liver biopsies, with variable histological changes observed within the hepatic parenchyma. These data demonstrate indeterminate results for the selective use of pulmonary vasodilators but highlight the need for large prospective randomized control trials of pulmonary vasodilator therapies to fully assess the benefit of such therapies in Fontan-associated liver disease.

Vasodilation in patients with calcium channel blocker poisoning treated with high-dose insulin: a comparison of amlodipine versus non-dihydropyridines

Background: High dose insulin (HDI), an inotrope and vasodilator, is a standard therapy for calcium channel blocker (CCB) poisoning. HDI causes vasodilation by stimulating endothelial nitric oxide synthase (eNOS). Most literature supporting HDI for CCB poisoning involves verapamil toxicity; however, amlodipine now causes more CCB poisonings. Unlike other CCBs, amlodipine stimulates eNOS and may cause synergistic vasodilation with HDI. The purpose of this study was to determine if amlodipine-poisoned patients treated with HDI had more evidence of vasodilation than similarly treated patients with non-dihydropyridine (non-DHP) poisoning. Methods: This was a retrospective study from a single poison center. Cases were identified via the generic code “Calcium Antagonists” in which the therapy “High Dose Insulin/Glucose” was “performed, whether or not recommended” from 2019–2021. Evidence of vasodilation was assessed via maximum number of vasopressor infusions per case, vasopressor doses, and use of rescue methylene blue to treat refractory vasoplegia. Results: Thirty-three patients were enrolled: 18 poisoned with amlodipine, 15 with non-DHPs (verapamil n = 10, diltiazem n = 5). The median number of maximum concomitant vasopressors in the amlodipine group was 3 (IQR: 2–5; range 0–6) and 2 in the non-DHP group (IQR: 1–3; range 0–5; p = 0.04); median difference in maximum concomitant vasopressors between groups was 1 (95% confidence interval: 0–2). Median maximum epinephrine dosing was higher in the amlodipine group (0.31 mcg/kg/min) compared to non-DHPs (0.09 mcg/kg/min; p = 0.03). Use of rescue methylene blue was more common in the amlodipine group (7/18 [39%]) than in the non-DHP group (0; p = 0.009). Conclusions: Amlodipine poisoned patients treated with HDI required more vasopressors, higher doses of epinephrine, and more often received rescue methylene blue than similarly treated patients with verapamil or diltiazem poisoning. These differences suggest amlodipine-poisoned patients had more evidence of vasodilation. Further study is warranted to determine if synergistic vasodilation occurs when HDI is used to treat amlodipine poisoning.

Predicting the response to pulmonary vasodilator therapy in systemic sclerosis with pulmonary hypertension by using quantitative chest CT.

Systemic sclerosis (SSc) is associated with pulmonary vascular disease and interstitial lung disease, making it difficult to differentiate pulmonary arterial hypertension and pulmonary hypertension (PH) due to lung diseases and/or hypoxia and to decide treatments. We aimed to predict the response to pulmonary vasodilators in patients with SSc and PH. Eighty-four SSc patients were included with 47 having PH. Chest computed tomography was evaluated using software to calculate the abnormal lung volume (ALV). To define the response to vasodilators, Δ mean pulmonary artery pressure (mPAP)/basal mPAP was used (cut-off value: 10%). The predictive value was evaluated by using the receiver operating characteristic curve. The mean (±standard deviation) value of ALV was 26.8 (±32.2) %. A weak correlation was observed between ALV and forced vital capacity (FVC) (R = -0.46). The predictive value of ALV [area under curve (AUC) = 0.74] was superior to that of FVC (AUC = 0.62) for the response to vasodilators. No hemodynamic parameters differed between patients with high and low ALV, whereas survival was worse in high ALV. Quantitative chest computed tomography well predicted the response to vasodilators in patients with SSc and PH. Our results suggest its utility in differentiating the dominance of pulmonary vascular disease or interstitial lung disease.

Medical Management of Chronic Thromboembolic Pulmonary Hypertension

Medical therapy in chronic thromboembolic pulmonary hypertension (CTEPH) has two primary goals- to prevent recurrent thromboembolic events and to reduce right ventricular afterload with targeted medications (vasodilators) for pulmonary hypertension. These medical strategies are used in conjunction with mechanical treatments for CTEPH (pulmonary thromboendarterectomy (PTE) or balloon angioplasty). In the context of this review, we discuss anticoagulation strategies, patient selection for vasodilator therapy with particular focus on hemodynamic and clinically meaningful definitions of residual pulmonary hypertension after PTE and inoperable disease and then summarize the current randomized clinical trials (RCT) which have studied effectiveness of vasodilators in patients with CTEPH.

Relationship of Daily Coffee Intake with Vascular Function in Patients with Hypertension.

We evaluated the relationship of daily coffee intake with endothelial function assessed by flow-mediated vasodilation and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation in patients with hypertension. A total of 462 patients with hypertension were enrolled in this cross-sectional study. First, we divided the subjects into two groups based on information on daily coffee intake: no coffee group and coffee group. The median coffee intake was two cups per day in the coffee group. There were significant differences in both flow-mediated vasodilation (2.6 ± 2.8% in the no coffee group vs. 3.3 ± 2.9% in the coffee group, p = 0.04) and nitroglycerine-induced vasodilation (9.6 ± 5.5% in the no coffee group vs. 11.3 ± 5.4% in the coffee group, p = 0.02) between the two groups. After adjustment for confounding factors, the odds ratio for endothelial dysfunction (OR: 0.55, 95% CI: 0.32–0.95) and the odds ratio for vascular smooth muscle dysfunction (OR: 0.50, 95% CI: 0.28–0.89) were significantly lower in the coffee group than in the no coffee group. Next, we assessed the relationship of the amount of daily coffee intake with vascular function. Cubic spline curves revealed that patients with hypertension who drank half a cup to 2.5 cups of coffee per day had lower odds ratios for endothelial dysfunction assessed by flow-mediated vasodilation and vascular smooth muscle dysfunction assessed by nitroglycerine-induced vasodilation. Appropriate daily coffee intake might have beneficial effects on endothelial function and vascular smooth muscle function in patients with hypertension.

Cardioprotection with Nitroglycerin in Cardiovascular Anesthesia

Introduction: For the anesthesiologist, it is very important to consider cardiovascular protection at the time of each procedure. Especially if the patient represents a high risk for presenting coronary or vascular involvement, although the surgical approach is not more complex, since the fact of using anesthesia in a patient already leads to being under perioperative risks to which they must be subjected. Nitroglycerin is a widely used vasodilator in patients with coronary disease. However, the study of its concomitant use in anesthetized patients who will undergo surgery is not very clear. Materials and methods: A narrative review was carried out, in which different databases were used such as Scielo, PubMed, ScienceDirect, academic google, among others. The selection of articles was made through indexed journals in English and Spanish languages from 2010 to 2021. Results: Myocardial ischemia is one of the most frequent causes of perioperative morbidity and mortality. Nitroglycerin is a vasoactive agent that has been used in patients under anesthesia with highly variable results. However, it has had a beneficial effect in patients with significant hemodynamic or cardiovascular compromise. Conclusion: The use of nitroglycerin in the patient under anesthesia could have a cardioprotective effect if it is used safely, and not prolonged. In addition, the adverse effects that this can generate in the patient must be considered and each case should be evaluated individually, interposing the benefit, but not as a routine use, especially in patients with great hemodynamic compromise.