Effects of aminophylline therapy on urine output and kidney function in children with acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication of children admitted to the paediatric intensive care unit. One key management modality of AKI is the use of diuretics to reduce fluid overload. Aminophylline, a drug that is well known for its use in the treatment of bronchial asthma, is also purported to have diuretic effects on the kidneys. This retrospective cohort study assesses the effect of aminophylline in critically ill children with AKI. METHODS: A retrospective chart review of children admitted to the paediatric intensive care unit of the Red Cross War Memorial Children's Hospital (RCWMCH) with AKI who received aminophylline (from 2012 to June 2018) was carried out. Data captured and analyzed included demographics, underlying disease conditions, medications, urine output, fluid balance, and kidney function. RESULTS: Data from thirty-four children were analyzed. Urine output increased from a median of 0.4 mls/kg/hr [IQR: 0.1, 1.1] at six hours prior to aminophylline administration to 0.6 mls/kg/hr [IQR: 0.2, 1.9] at six hours and 1.6 mls/kg/hr [IQR:0.2, 4.2] at twenty-four hours post aminophylline therapy. The median urine output significantly varied across the age groups over the 24-h time period post-aminophylline, with the most response in the neonates. There was no significant change in serum creatinine levels six hours post-aminophylline administration [109(IQR: 77, 227)-125.5(IQR: 82, 200) micromole/l] P-value = 0.135. However, there were significant age-related changes in creatinine levels at six hours post-aminophylline therapy. CONCLUSIONS: Aminophylline increases urine output in critically ill children with AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Effects of Intracerebral Aminophylline Dosing on Catalepsy and Gait in an Animal Model of Parkinson's Disease.

Parkinson's disease (PD) is a progressive disorder characterized by the apoptosis of dopaminergic neurons in the basal ganglia. This study explored the potential effects of aminophylline, a non-selective adenosine A1 and A2A receptor antagonist, on catalepsy and gait in a haloperidol-induced PD model. Sixty adult male Swiss mice were surgically implanted with guide cannulas that targeted the basal ganglia. After seven days, the mice received intraperitoneal injections of either haloperidol (experimental group, PD-induced model) or saline solution (control group, non-PD-induced model), followed by intracerebral infusions of aminophylline. The assessments included catalepsy testing on the bar and gait analysis using the Open Field Maze. A two-way repeated-measures analysis of variance (ANOVA), followed by Tukey's post hoc tests, was employed to evaluate the impact of groups (experimental × control), aminophylline (60 nM × 120 nM × saline/placebo), and interactions. Significance was set at 5%. The results revealed that the systemic administration of haloperidol in the experimental group increased catalepsy and dysfunction of gait that paralleled the observations in PD. Co-treatment with aminophylline at 60 nM and 120 nM reversed catalepsy in the experimental group but did not restore the normal gait pattern of the animals. In the non-PD induced group, which did not present any signs of catalepsy or motor dysfunctions, the intracerebral dose of aminophylline did not exert any interference on reaction time for catalepsy but increased walking distance in the Open Field Maze. Considering the results, this study highlights important adenosine interactions in the basal ganglia of animals with and without signs comparable to those of PD. These findings offer valuable insights into the neurobiology of PD and emphasize the importance of exploring novel therapeutic strategies to improve patient's catalepsy and gait.

Safety and efficacy of IV theophylline for regadenoson-associated side effect reversal.

BACKGROUND: Aminophylline injection has been on an intermittent nation-wide shortage due to manufacturing delays leaving a need for an alternative reversal agent for regadenoson-associated side effects. Intravenous theophylline should be a logical acceptable pharmacological alternative; however, data regarding its safety and efficacy as a reversal agent are lacking. METHODS: Utilizing electronic medical records at the University of Colorado hospital, we identified patients ≥ 18 years of age who had a pharmacologic stress test using regadenoson during periods of aminophylline shortage (3/1/2013 to 5/31/2013 and 4/1/2018 to 8/30/2018) in which theophylline was used as an alternative antidote for side effect reversal. Intravenous theophylline was prepared by the inpatient pharmacy to a concentration of 0.8 mg/mL in a total volume of 100 mL D5W. Specific side effects and side effect resolution were evaluated. RESULTS: Of the 122 patients evaluated, theophylline was administered in doses ranging from 40 to 75 mg with the majority receiving 40 mg. Complete resolution of regadenoson side effects occurred in 98 patients with 12 experiencing partial resolution and 1 without resolution. No adverse effects or events were reported. CONCLUSION: Due to limited availability of aminophylline, theophylline may be a safe and effective alternative to reverse regadenoson-associated side effects.

The diuretic effect of adding aminophylline or theophylline to furosemide in pediatric populations: a systematic review.

The diuretic effect of the combined furosemide and aminophylline/theophylline among pediatric patients remains unclear. The primary aim of this systematic review was to examine the clinical diuretic effects (urine output and fluid balance) of co-administration of furosemide and aminophylline/theophylline as compared to furosemide alone in pediatric population. Ovid MEDLINE, CENTRAL, and EMBASE were searched from its inception until March 2022 for observational studies and randomized controlled trials (RCTs) comparing the administration of furosemide versus furosemide and aminophylline/theophylline in pediatric population. Case reports, case series, commentaries, letters to editors, systematic reviews, and meta-analyses were excluded. Five articles with a total sample population of 187 patients were included in this systematic review. As compared to the furosemide alone, our pooled data demonstrated that co-administration of furosemide and aminophylline/theophylline was associated with higher urine output (mean difference: 2.91 [90% CI 1.54 to 4.27], p < 0.0001, I2 = 90%) and a more negative fluid balance (mean difference - 28.27 [95% CI: - 46.21 to - 10.33], p = 0.002, I2 = 56%) than those who received furosemide alone. CONCLUSION: This is the first paper summarizing the evidence of combined use of furosemide with aminophylline/theophylline in pediatric population. Our systematic review demonstrated that the co-administration of furosemide and aminophylline/theophylline could potentially yield better diuretic effects of urine output and negative fluid balance than furosemide alone in pediatric patients with fluid overload. Given the substantial degree of heterogeneity and low level of evidence, future adequately powered trials are warranted to provide evidence regarding the combined use of aminophylline/theophylline and furosemide as diuretic in the pediatric population. WHAT IS KNOWN: • Fluid overload is associated with poor prognosis for children in the intensive care unit. • The ineffective result of furosemide alone, even at high dose, as diuretic agent for children with diuretic resistant fluid overload in the intensive care unit. WHAT IS NEW: • This is the first systematic review that compares furosemide alone and co-administration of furosemide and aminophylline/theophylline. • This paper showed potential benefit of co-administration of furosemide and aminophylline/theophylline promoting urine output and negative fluid balance compared to furosemide alone.

Doxapram for the prevention and treatment of apnea in preterm infants.

BACKGROUND: Apnea of prematurity is a common problem in preterm infants that may have significant consequences on their development. Methylxanthines (aminophylline, theophylline, and caffeine) are effective in the treatment of apnea of prematurity. Doxapram is used as a respiratory stimulant in cases refractory to the methylxanthine treatment. OBJECTIVES: To evaluate the benefits and harms of doxapram administration on the incidence of apnea and other short-term and longer-term clinical outcomes in preterm infants. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was March 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) assessing the role of doxapram in prevention and treatment of apnea of prematurity and prevention of reintubation in preterm infants (less than 37 weeks' gestation). We included studies comparing doxapram with either placebo or methylxanthines as a control group, or when doxapram was used as an adjunct to methylxanthines and compared to methylxanthines alone as a control group. We included studies of doxapram at any dose and route. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were clinical apnea, need for positive pressure ventilation after initiation of treatment, failed apnea reduction after two to seven days, and failed extubation (defined as unable to wean from invasive intermittent positive pressure ventilation [IPPV] and extubate or reintubation for IPPV within one week). We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included eight RCTs enrolling 248 infants. Seven studies (214 participants) provided data for meta-analysis. Five studied doxapram for treatment of apnea in preterm infants. Three studied doxapram to prevent reintubation in preterm infants. None studied doxapram in preventing apnea in preterm infants. All studies administered doxapram intravenously as continuous infusions. Two studies used doxapram as an adjunct to aminophylline compared to aminophylline alone and one study as an adjunct to caffeine compared to caffeine alone. When used to treat apnea, compared to no treatment, doxapram may result in a slight reduction in failed apnea reduction (risk ratio [RR] 0.45, 95% confidence interval [CI] 0.20 to 1.05; 1 study, 21 participants; low-certainty evidence). The evidence is very uncertain about the effect of doxapram on need for positive pressure ventilation after initiation of treatment (RR 0.31, 95% CI 0.01 to 6.74; 1 study, 21 participants; very low-certainty evidence). Doxapram may result in little to no difference in side effects causing cessation of therapy (0 events in both groups; risk difference [RD] 0.00, 95% CI -0.17 to 0.17; 1 study, 21 participants; low-certainty evidence). Compared to alternative treatment, the evidence is very uncertain about the effect of doxapram on failed apnea reduction (RR 1.35, 95% CI 0.53 to 3.45; 4 studies, 84 participants; very low-certainty evidence). The evidence is very uncertain about the effect of doxapram on need for positive pressure ventilation after initiation of treatment (RR 2.40, 95% CI 0.11 to 51.32; 2 studies, 37 participants; very-low certainty evidence; note 1 study recorded 0 events in both groups. Thus, the RR and CIs were calculated from 1 study rather than 2). Doxapram may result in little to no difference in side effects causing cessation of therapy (0 events in all groups; RD 0.00, 95% CI -0.15 to 0.15; 37 participants; 2 studies; low-certainty evidence). As adjunct therapy to methylxanthine, the evidence is very uncertain about the effect of doxapram on failed apnea reduction after two to seven days (RR 0.08, 95% CI 0.01 to 1.17; 1 study, 10 participants; very low-certainty evidence). No studies reported on clinical apnea, chronic lung disease at 36 weeks' postmenstrual age (PMA), death at any time during initial hospitalization, long-term neurodevelopmental outcomes in the three comparisons, and need for positive pressure ventilation and side effects when used as adjunct therapy to methylxanthine. In studies to prevent reintubation, when compared to alternative treatment, the evidence is very uncertain about the effect of doxapram on failed extubation (RR 0.43, 95% CI 0.10 to 1.83; 1 study, 25 participants; very low-certainty evidence). As adjunct therapy to methylxanthine, doxapram may result in a slight reduction in 'clinical apnea' after initiation of treatment (RR 0.36, 95% CI 0.13 to 0.98; 1 study, 56 participants; low-certainty evidence). Doxapram may result in little to no difference in failed extubation (RR 0.92, 95% CI 0.52 to 1.62; 1 study, 56 participants; low-certainty evidence). The evidence is very uncertain about the effect of doxapram on side effects causing cessation of therapy (RR 6.42, 95% CI 0.80 to 51.26; 2 studies, 85 participants; very low-certainty evidence). No studies reported need for positive pressure ventilation, chronic lung disease at 36 weeks' PMA, long-term neurodevelopmental outcomes in the three comparisons; failed extubation when compared to no treatment; and clinical apnea, death at any time during initial hospitalization, and side effects when compared to no treatment or alternative treatment. We identified two ongoing studies, one conducted in Germany and one in multiple centers in the Netherlands and Belgium. AUTHORS' CONCLUSIONS: In treating apnea of prematurity, doxapram may slightly reduce failure in apnea reduction when compared to no treatment and there may be little to no difference in side effects against both no treatment and alternative treatment. The evidence is very uncertain about the need for positive pressure ventilation when compared to no treatment or alternative treatment and about failed apnea reduction when used as alternative or adjunct therapy to methylxanthine. For use to prevent reintubation, doxapram may reduce apnea episodes when administered in adjunct to methylxanthine, but with little to no difference in failed extubation. The evidence is very uncertain about doxapram's effect on death when used as adjunct therapy to methylxanthine and about failed extubation when used as alternative or adjunct therapy to methylxanthine. There is a knowledge gap about the use of doxapram as a therapy to prevent apnea. More studies are needed to clarify the role of doxapram in the treatment of apnea of prematurity, addressing concerns about long-term outcomes. The ongoing studies may provide useful data.

Caffeine versus other methylxanthines for the prevention and treatment of apnea in preterm infants.

BACKGROUND: Methylxanthines, including caffeine, theophylline, and aminophylline, work as stimulants of the respiratory drive, and decrease apnea of prematurity, a developmental disorder common in preterm infants. In particular, caffeine has been reported to improve important clinical outcomes, including bronchopulmonary dysplasia (BPD) and neurodevelopmental disability. However, there is uncertainty regarding the efficacy of caffeine compared to other methylxanthines. OBJECTIVES: To assess the effects of caffeine compared to aminophylline or theophylline in preterm infants at risk of apnea, with apnea, or in the peri-extubation phase. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Epistemonikos, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and clinicaltrials.gov in February 2023. We also checked the reference lists of relevant articles to identify additional studies. SELECTION CRITERIA: Studies: randomized controlled trials (RCTs) and quasi-RCTs Participants: infants born before 34 weeks of gestation for prevention and extubation trials, and infants born before 37 weeks of gestation for treatment trials Intervention and comparison: caffeine versus theophylline or caffeine versus aminophylline. We included all doses and duration of treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We evaluated treatment effects using a fixed-effect model with risk ratio (RR), risk difference (RD), and 95% confidence intervals (CI) for categorical data, and mean, standard deviation, and mean difference for continuous data. We used the GRADE approach to evaluate the certainty of evidence. MAIN RESULTS: We included 22 trials enrolling 1776 preterm infants. The indication for treatment was prevention of apnea in three studies, treatment of apnea in 13 studies, and extubation management in three studies. In three studies, there were multiple indications for treatment, and in one study, the indication for treatment was unclear. In 19 included studies, the infants had a mean gestational age between 28 and 32 weeks and a mean birth weight between 1000 g and 1500 g. One study's participants had a mean gestational age of more than 32 weeks, and two studies had participants with a mean birth weight of 1500 g or more. Caffeine administrated for any indication may result in little to no difference in all-cause mortality prior to hospital discharge compared to other methylxanthines (RR 1.12, 95% CI 0.68 to 1.84; RD 0.02, 95% CI -0.05 to 0.08; 2 studies, 396 infants; low-certainty evidence). Only one study enrolling 79 infants reported components of the outcome moderate to severe neurodevelopmental disability at 18 to 26 months. The evidence is very uncertain about the effect of caffeine on cognitive developmental delay compared to other methylxanthines (RR 0.17, 95% CI 0.02 to 1.37; RD -0.12, 95% CI -0.24 to 0.01; 1 study, 79 infants; very low-certainty evidence). The evidence is very uncertain about the effect of caffeine on language developmental delay compared to other methylxanthines (RR 0.76, 95% CI 0.37 to 1.58; RD -0.07, 95% CI -0.27 to 0.12; 1 study, 79 infants; very low-certainty evidence). The evidence is very uncertain about the effect of caffeine on motor developmental delay compared to other methylxanthines (RR 0.50, 95% CI 0.13 to 1.96; RD -0.07, 95% CI -0.21 to 0.07; 1 study, 79 infants; very low-certainty evidence). The evidence is very uncertain about the effect of caffeine on visual and hearing impairment compared to other methylxanthines. At 24 months of age, visual impairment was seen in 8 out of 11 infants and 10 out of 11 infants in the caffeine and other methylxanthines groups, respectively. Hearing impairment was seen in 2 out of 5 infants and 1 out of 1 infant in the caffeine and other methylxanthines groups, respectively. No studies reported the outcomes cerebral palsy, gross motor disability, and mental development. Compared to other methylxanthines, caffeine may result in little to no difference in BPD/chronic lung disease, defined as 28 days of oxygen exposure at 36 weeks' postmenstrual age (RR 1.40, 95% CI 0.92 to 2.11; RD 0.04, 95% CI -0.01 to 0.09; 3 studies, 481 infants; low-certainty evidence). The evidence is very uncertain about the effect of caffeine on side effects (tachycardia, agitation, or feed intolerance) leading to a reduction in dose or withholding of methylxanthines compared to other methylxanthines (RR 0.17, 95% CI 0.02 to 1.32; RD -0.29, 95% CI -0.57 to -0.02; 1 study, 30 infants; very low-certainty evidence). Caffeine may result in little to no difference in duration of hospital stay compared to other methylxanthines (median (interquartile range): caffeine 43 days (27.5 to 61.5); other methylxanthines 39 days (28 to 55)). No studies reported the outcome seizures. AUTHORS' CONCLUSIONS: Although caffeine has been shown to improve important clinical outcomes, in the few studies that compared caffeine to other methylxanthines, there might be little to no difference in mortality, bronchopulmonary dysplasia, and duration of hospital stay. The evidence is very uncertain about the effect of caffeine compared to other methylxanthines on long-term development and side effects. Although caffeine or other methylxanthines are widely used in preterm infants, there is little direct evidence to support the choice of which methylxanthine to use. More research is needed, especially on extremely preterm infants born before 28 weeks of gestation. Data from four ongoing studies might provide more evidence on the effects of caffeine or other methylxanthines.

A mix of aminophylline and heparin plus nitroglycerin can reduce bradycardia during rotational atherectomy on the right coronary artery and dominant circumflex artery.

BACKGROUND: Rotational atherectomy (RA) may cause bradyarrhythmias and transitory atrioventricular block when performed in the right coronary artery (RCA) or a dominant circumflex (CX) coronary artery. However, there are no studies of a solution that can prevent coronary flow deterioration and bradycardia complications that may occur during RA. We aimed to create an alternative rota-flush solution to minimize the risk of bradycardia and complete atrioventricular block (AVB) that can occur during RA. MATERIALS AND METHODS: The study comprised 60 patients who were randomly divided into two groups: 30 received rotaphylline (= 240 mg aminophylline, 10,000 U unfractionated heparin, and 2000 mcg nitroglycerin to 1000 mL saline), and 30 received the traditional rota-flush (= 10,000 U unfractionated heparin, 2000 mcg nitroglycerin, and 1000 mL saline). The incidence of bradycardia or high-grade AVB (HAVB) during RA, coronary slow-flow phenomenon or no-reflow phenomenon, and coronary spasm were the primary endpoints of the study. Procedure success and RA-related procedural complications were secondary endpoints. RESULTS: The use of rotaphylline was an independent predictor of bradycardia and HAVB after accounting for all other factors (OR: 0.47, 95% CI: 0.24-0.79, p < 0.001). Lesion length (OR: 2.17, 95% CI: 1.24-3.04, p < 0.001), burr-to-artery ratio (OR: 0.59, 95% CI: 0.39-1.68, p < 0.001), and total run duration (OR: 0.79, 95% CI: 0.35-1.43, p < 0.001) were additional independent predictors. CONCLUSION: Bradycardia and the development of HAVB may be avoided by rotaphylline intracoronary infusion during RA applied to the RCA and dominant CX lesions. Multicenter studies including sizable patient populations should be conducted to validate the present findings.

Alterations in the gut microbiome and metabolome profiles of septic rats treated with aminophylline.

The treatment of sepsis remains a major challenge worldwide. Aminophylline has been shown to have anti-inflammatory effects; however, the role of aminophylline in sepsis, a disease characterized by immune dysregulation, is unknown. In this study, we combined microbiome sequencing and metabolomic assays to investigate the effect of aminophylline administration on the intestinal flora and metabolites in septic rats. Sixty SD rats were randomly divided into three groups: a sham-operated (SC) group, a sepsis model (CLP) group and a CLP + aminophylline treatment (Amino) group. The intestinal flora and metabolic profile of rats in the CLP group were significantly different than those of the SC group, while aminophylline administration resulted in a return to a state similar to healthy rats. Differential abundance analysis showed that aminophylline significantly back-regulated the abundance of Firmicutes, unidentified_Bacteria, Proteobacteria, Lactobacillus, Escherichia-Shigella and other dominant bacteria (P < 0.05) and altered chenodeoxycholic acid, isolithocholic acid and a total of 26 metabolites (variable importance in the projection (VIP) > 1, P < 0.05). In addition, we found that there were significant correlations between differential metabolites and bacterial genera of the Amino and CLP groups. For example, Escherichia-Shigella was associated with 12 metabolites, and Lactobacillus was associated with two metabolites (P < 0.05), suggesting that differences in the metabolic profiles caused by aminophylline were partly dependent on its influence on the gutmicrobiome. In conclusion, this study identified a novel protective mechanism whereby aminophylline could regulate disordered intestinal flora and metabolites in septic rats.

Plasma Concentration Detection of Aminophylline with Multi-Walled Carbon Nanotube-Modified Electrodes in the Treatment of Ticagrelor-Related Dyspnea.

It was aimed at the plasma concentration detection of aminophylline under multi-walled carbon nanotube (MWNT) modified electrodes and the curative effect of aminophylline for ticagrelor-related dyspnea (TRD). 120 patients with TRD and coronary atherosclerotic heart disease (CAHD) in Wuhan Sixth Hospital Hospital were randomly divided into an intervention group and a control group, with 60 cases in each. The novel chitosan/gold nanoparticles-MWNTs (CTS/Au NPs-MWNTs) composite was prepared for studying the electrochemical behaviors of aminophylline on the electrodes. The clinical curative effect of aminophylline, as well as the levels of peripheral blood T lymphocyte subsets and inflammatory cytokines, was observed in the treatment of TRD. The actual plasma molar concentration of aminophylline was 23.6-47.8 µmol/L. After treatment, the total effective rate in the intervention group was higher than that in the control group significantly (95% VS 65%) (P<0.05). The forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) of the intervention group were better than those of the control group remarkably (P<0.05). The intervention group showed lower levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 as well as the higher IL-10 significantly in serum compared with the control group (P<0.05). After follow-up, there was no cardiovascular death in either group. The CTS/Au NPs-MWNTs could be used for detecting the plasma concentration of aminophylline in blood samples. Aminophylline could notably relieve the clinical symptoms, reduce the inflammatory response, and regulate the immunity of patients with good safety.

Aminophylline in combination with caffeine citrate in neurodevelopmental treatment and follow-up of high-risk preterm infants using GMs assessment.

To explore the application effect of aminophylline combined with caffeine citrate and GMs in the evaluation of neurodevelopmental treatment and follow-up in high-risk preterm infants. A retrospective analysis of 66 high-risk preterm infants admitted to Hengshui People's Hospital from January 2020 to June 2021 was conducted. The children who received only conventional treatment were set as the control group, while those who received aminophylline and caffeine citrate on the basis of conventional treatment were set as the experimental group, 33 cases each group; GMs were used to evaluate the neurodevelopmental function of the children, and the treatment effect was analyzed. The normal proportion of GMs assessment results in the twisting phase and restless movement phase of the experimental group was superior to the control group (P<0.05); The proportion of children with normal neurodevelopment in the experimental group was significantly higher than that in the control group (P<0.05). Aminophylline in combination with caffeine citrate can help promote the neurodevelopment of children and improve their physical health using GMs assessment in the treatment and follow-up of high-risk preterm infants.

Immunological outcomes in infants with ROP after dexamethasone and aminophylline.

This research aims to improve anaesthesia services given to preterm infants by the use of dexamethasone and aminophylline administrated under sevoflurane, and to analyze its effect on the cell-mediated immunity (CD4+CD25+Foxp3+(T-reg) and CD4+CD25highFoxp3+CD127low). We have examined 74 premature babies with retinopathy of prematurity (ROP) at the 3-5 stages during the 25-32 week gestation period (1-6 months after birth). Both immunomodulators had no significant effect on clinical parameters after one dose (P > .05). Aminophylline (2.4% solution, 0.1 mL/kg or 0.132 mL per infant on average) and dexamethasone (0.4% solution, 0.1 mg/kg or 0.132 mL per infant on average) were intravenously injected 15 minutes before the end of the surgery. Required anaesthesia depth was maintained with inhalation anaesthetic (1.5-2.0 IAC), and the minimum fresh gas flow was not less than 2 L. Blood samples were taken from the vein (anaesthesia induction stage) into the tubes containing EDTA (the anticoagulant), stored at 20-25°C, and then, processed and stained within 24 hours after sampling. Both immunomodulators had no significant effect on clinical parameters after one dose (P > .05). Short-term shift in regulatory T-cell level affected by dexamethasone has a negative effect combined with further withdrawal effect that this hormonal drug has. Aminophylline has such clinical effects as improving pulmonary ventilation, decrease in apnoea frequency, and improving blood gas indices. Aminophylline has less expressed but more prolonged positive effect during the day when used for several days. It may lead to a persistent positive effect with progressive treatment outcomes.

Aminophylline shortage and current recommendations for reversal of vasodilator stress: An ASNC information statement endorsed by SCMR.

Pharmacologic reversal of serious or intolerable side effects (SISEs) from vasodilator stress is an important safety and comfort measure for patients experiencing such effects. While typically performed using intravenous aminophylline, recurrent shortages of this agent have led to a greater need to limit its use and consider alternative agents. This information statement provides background and recommendations addressing indications for vasodilator reversal, timing of a reversal agent, incidence of observed SISE with vasodilator stress, clinical and logistical considerations for aminophylline-based reversal, and alternative non-aminophylline based reversal protocols.

Theophylline and Caffeine as Alternatives During an Aminophylline Shortage.

The latest aminophylline shortage has prompted a need for alternative reversal agents for pharmacological stress testing. Cardiac stress testing is common for diagnosis and prognosis in patients with coronary heart disease. Options for pharmacological stress test agents include adenosine, regadenoson, dipyridamole, and dobutamine, whereas aminophylline is the recommended reversal agent. Adenosine and dobutamine can be used as alternatives to regadenoson and dipyridamole to decrease or eliminate the use of aminophylline. Alternatives to aminophylline include theophylline and caffeine. It is important to efficiently identify alternatives during a drug shortage to maintain optimal patient outcomes.

Effects of aminophylline on airway epithelial-mesenchymal transition in brown Norway rats after repeated allergen challenge.

Purpose: Chronic asthma is characterized by airway inflammation and remodeling. The aim of this study is to evaluate the effects of aminophylline on airway epithelial-mesenchymal transition (EMT). Materials and methods: Two experimental groups of brown Norway rats that were repeatedly challenged with aerosolized ovalbumin (OA) were given oral aminophylline (OA-aminophylline group) or saline only (OA-saline group). A third group was challenged by saline as a control. The rats were anesthetized and pulmonary function were performed. Immuno-histochemical staining of epithelial markers (zonula occludens-1 (ZO-1)) and mesenchymal markers (vimentin) in the airway were performed. The protein expressions of ZO-1, E-cadherin, vimentin, fibronectine, TGF-ß1, SMAD 2/3, JNK, and p38 MAPK were examined by western blot. Results: Aminophylline had beneficial effects on airway inflammation, and airway remodeling in the OA-aminophylline group compared to the OA-saline group. The OA-saline group had decreased ZO-1 but increased vimentin according to immuno-histochemical staining. The protein expression indicated decreases in ZO-1 and E-cadherin but increases in vimentin, fibronectine, TGF-ß1, SMAD 2/3, JNK, and p38 MAPK in comparison to the other two groups. The OA-aminophylline group had higher ZO-1 but lower vimentin in immuno-histochemical staining compared to the OA-saline group. The protein expression showed higher ZO-1 and E-cadherin but lower vimentin, fibronectine, TGF-ß1, SMAD 2/3, JNK, and p38 MAPK when compared to the OA-saline group. Conclusions: Ovalbumin increases airway remodeling and airway EMT. Aminophylline is effective in preventing airway remodeling and airway EMT in Brown Norway rats after repeated allergen challenge.

Acute hemodynamic effects of methylxanthine therapy in preterm neonates: Effect of variations in subgroups.

BACKGROUND: Methylxanthines have cardiac stimulant effects. The current study aimed to compare acute hemodynamic changes between caffeine and aminophylline in ≤34 weeks' preterm neonates. METHODS: The study was performed using information on echocardiography measurements from preterm neonates recruited for apnea of prematurity (75 of 240) and preventing extubation failure (113 of 156) studies. The neonates were randomized either to the caffeine or aminophylline groups. Neonates with no maintenance followed by loading doses with both the methylxanthines (caffeine and aminophylline) and incomplete echocardiography examination were excluded. RESULTS: Cardiac parameters were found to be similar between groups. The heart rate was higher among the aminophylline-treated neonates (p < 0.001) than among the caffeine-treated ones. End-systolic volume was higher among both caffeine- (p < 0.001) and aminophylline-treated neonates (p = 0.001) when compared with pretreatment values. End-diastolic volume was statistically higher in both groups' neonates (p = 0.01). The odds of increase in cardiac output was higher; however, increase in ejection fraction was less in caffeine-treated small-for-gestation-age neonates. CONCLUSION: Caffeine has similar effects on cardiac parameters as aminophylline; however, caffeine-treated small-for-gestation stratification gave rise to significant cardiac variations.

TRPC3 overexpression and intervention in airway smooth muscle of ovalbumin-induced hyperresponsiveness and remodeling.

Transient receptor potential canonical channel 3 (TRPC3) proteins function as non-voltage-gated Ca2+ -permeable channels and play divergent roles in many processes of pathophysiology. The purpose of this study was to determine the relationship between TRPC3 expression and airway hyperresponsiveness and remodeling in ovalbumin-induced asthmatic Kunming mice. Mice were sensitized and challenged by ovalbumin to establish asthmatic model. Hematoxylin-eosin staining, hydroxyproline assay, and isometric tracheal ring force measurement were used to evaluate airway remodeling and hyperresponsiveness in asthmatic mice. Western blot was performed to detect the expression of TRPC3 proteins. MTT assay was used to measure the proliferation of airway smooth muscle cells. TRPC3 protein expression increased in airway smooth muscle of asthmatic mice. GdCl3 , a nonspecific TRPC blocker, attenuated the contractile force of airway smooth muscle. Fetal bovine serum stimulated airway smooth muscle cells proliferation and augmented TRPC3 protein expression. Both TRPC3 blockade by GdCl3 or specific TRPC3 antibodies and gene silencing by siRNA inhibited the proliferation of airway smooth muscle cells. In contrast, the current drugs treatment for asthma such as Dexamethasone and Aminophylline had no effects on TRPC3 protein overexpression. Therefore, TRPC3 protein overexpression may be involved in airway smooth muscle hyperresponsiveness and remodeling in asthmatic mice, providing evidence for a new direction of asthma pathogenesis research and a new target for drug intervention.

Detrimental effects of nitroglycerin use during regadenoson vasodilator stress testing: A cautionary tale.

Vasodilator agents such as adenosine and regadenoson are commonly used pharmacologic stressors to assess for ischemia in patients undergoing myocardial perfusion studies. The recommended reversal agent for this mode of stress is aminophylline, although nitroglycerin is commonly administered as an attempt to reverse the symptoms or electrocardiographic (EKG) changes during the stress test. We demonstrate through two cases that incorrect administration of nitroglycerin can induce hypotension and worsen coronary steal, whereas appropriate administration of aminophylline can reverse the effects of pharmacologic vasodilators. While nitroglycerin is often used in patients with organic angina, it has the potential to worsen ischemia in the setting of pharmacologic vasodilator administration. These cases underscore the importance of administering the correct reversal agent for pharmacologic stress tests.

Regadenoson use in chronic kidney disease and end-stage renal disease: A focused review.

Regadenoson is a selective A2A adenosine receptor agonist that has been approved as a vasodilator stress agent with single-photon emission-computed tomography (SPECT) myocardial perfusion imaging (MPI). Since its approval by the Food and Drug Administration (FDA) in 2008, it has become the most commonly used pharmacologic stress agent with SPECT-MPI. Given that it is predominantly renally excreted, its use in patients with chronic kidney disease has been the subject of active post-marketing clinical research. Until recently, prescribing information regarding the use of regadenoson in patients with end-stage renal disease (ESRD) was not defined in the package insert. Based on accumulating data since its initial approval, the FDA has recently outlined the use of regadenoson in patients with ESRD in a label update on January 17, 2017. In this review, we discuss the evidence leading to the recent label update, focusing on the pharmacokinetics of regadenoson in patients with impaired kidney function, the safety and tolerability of regadenoson in patients with chronic kidney disease and ESRD, and the prognostic value of regadenoson stress MPI in this patient population.

An interquartile relationship between polyherbal extract based lozenges linkus a phase IV comparative randomised control trial.

The aim of the study is to determine the efficacy of polyherbal linkus with the other pharmaceutical marketed syrup having Acefyllin Piperazine, Diphenhydramine group and Aminophylline Diphenhydramine group on the basis of interquartile ranges on children. It was open label multi centric randomize control trial. The study was conducted on different private schools of East and West Malir, Karachi Pakistan with the special approval from the school's honors .informed consent and assents were taking before the enrollment of the study subjects .The study enrolled participants were 147 who evaluate on cough. Participants were divided into 3 interventional group according to the treatment regimen .One group of participant received Linkus Syrup however the 2nd group received Acefyllin Piperazine and 3rd group received Aminophylline Diphenhydramine group. The frequency of the cough on linkus syrup was considered to be achieved on the basis of interquartile relationship and impact has been observed on child and parent sleep and found significant (p <0.01).Poly herbal Linkus Syrup has the significant impact on cough frequency and associated problem on children and parent's sleep with minimum side effects (p<0.01) however the pharmacological treatments are considered to be more unwanted effects on human subjects.

Prevention of Contrast-Induced Acute Kidney Injury: an Update.

Contrast-induced acute kidney injury (CI-AKI) is a common complication of intravascular administration of contrast media used in coronary angiography, percutaneous coronary intervention and other diagnostic and interventional procedures. This review article aims at summarizing the published literature regarding the prevention of CI-AKI, by focusing on available high-quality meta-analyses addressing this matter. Apart from adequate hydration, a number of pharmacologic agents have been proposed as potential candidates to be included in the routine preparation, prior to the patient's arrival in the cardiac catheterization laboratory. Among them, statins and N-acetylcysteine appear to be the most extensively studied ones. Throughout this article we present the available data on CI-AKI prevention and provide a critical clinical appraisal, as well as a summary of currently available guidelines.