Endobronchial Phenylephrine in Airway Bleeding During Bronchoscopy Does not Cause Hypertension: A Retrospective Observational Study.

BACKGROUND: Bleeding is a known complication during bronchoscopy, with increased incidence in patients undergoing a more invasive procedure. Phenylephrine is a potent vasoconstrictor that can control airway bleeding when applied topically and has been used as an alternative to epinephrine. The clinical effects of endobronchial phenylephrine on systemic vasoconstriction have not been clearly evaluated. Here, we compared the effects of endobronchial phenylephrine versus cold saline on systemic blood pressure. METHODS: In all, 160 patients who underwent bronchoscopy and received either endobronchial phenylephrine or cold saline from July 1, 2017 to June 30, 2022 were included in this retrospective observational study. Intra-procedural blood pressure absolute and percent changes were measured and compared between the 2 groups. RESULTS: There were no observed statistical differences in blood pressure changes between groups. The median absolute change between the median and the maximum intra-procedural systolic blood pressure in the cold saline group was 29 mm Hg (IQR 19 to 41) compared with 31.8 mm Hg (IQR 18 to 45.5) in the phenylephrine group. The corresponding median percent changes in SBP were 33.6 % (IQR 18.8 to 39.4) and 28% (IQR 16.8 to 43.5) for the cold saline and phenylephrine groups, respectively. Similarly, there were no statistically significant differences in diastolic and mean arterial blood pressure changes between both groups. CONCLUSIONS: We found no significant differences in median intra-procedural systemic blood pressure changes comparing patients who received endobronchial cold saline to those receiving phenylephrine. Overall, this argues for the vascular and systemic safety of phenylephrine for airway bleeding as a reasonable alternative to epinephrine.

Intraoperative Use of Phenylephrine versus Ephedrine and Postoperative Delirium: A Multicenter Retrospective Cohort Study.

BACKGROUND: The treatment of intraoperative hypotension with phenylephrine may impair cerebral perfusion through vasoconstriction, which has been linked to postoperative delirium. The hypothesis was that intraoperative administration of phenylephrine, compared to ephedrine, is associated with higher odds of postoperative delirium. METHODS: A total of 103,094 hospitalized adults undergoing general anesthesia for noncardiac, non-neurosurgical procedures between 2008 and 2020 at two tertiary academic healthcare networks in Massachusetts were included in this multicenter hospital registry study. The primary exposure was the administration of phenylephrine versus ephedrine during surgery, and the primary outcome was postoperative delirium within 7 days. Multivariable logistic regression analyses adjusted for a priori defined confounding variables including patient demographics, comorbidities, and procedural factors including magnitude of intraoperative hypotension were applied. RESULTS: Between the two healthcare networks, 78,982 (76.6%) patients received phenylephrine, and 24,112 (23.4%) patients received ephedrine during surgery; 770 patients (0.8%) developed delirium within 7 days. The median (interquartile range) total intraoperative dose of phenylephrine was 1.0 (0.2 to 3.3) mg and 10.0 (10.0 to 20.0) mg for ephedrine. In adjusted analyses, the administration of phenylephrine, compared to ephedrine, was associated with higher odds of developing postoperative delirium within 7 days (adjusted odds ratio, 1.35; 95% CI, 1.06 to 1.71; and adjusted absolute risk difference, 0.2%; 95% CI, 0.1 to 0.3%; P = 0.015). A keyword and manual chart review-based approach in a subset of 45,465 patients further validated these findings (delirium incidence, 3.2%; adjusted odds ratio, 1.88; 95% CI, 1.49 to 2.37; P < 0.001). Fractional polynomial regression analysis further indicated a dose-dependent effect of phenylephrine (adjusted coefficient, 0.08; 95% CI, 0.02 to 0.14; P = 0.013, per each µg/kg increase in the cumulative phenylephrine dose). CONCLUSIONS: The administration of phenylephrine compared to ephedrine during general anesthesia was associated with higher odds of developing postoperative delirium. Based on these data, clinical trials are warranted to determine whether favoring ephedrine over phenylephrine for treatment of intraoperative hypotension can reduce delirium after surgery.

Intracameral phenylephrine for surgical mydriasis and intraoperative floppy-iris syndrome: systemic adverse effects and optimal dose.

Phenylephrine, a potent sympathomimetic, induces mydriasis via iris dilator muscle contraction. Intracameral (IC) phenylephrine has been successfully used in cataract surgery for initial mydriasis, maintaining mydriasis, and management of intraoperative floppy-iris syndrome. Serious systemic adverse events (mainly cardiovascular) have been described with topical phenylephrine drops, but we found very little evidence of such adverse events associated with IC phenylephrine use. However, we suspect under-reporting of such adverse events, as they may instead be ascribed to anxiety, positioning, anesthesia, etc. Optimal dosage/concentrations for IC phenylephrine use in different purposes have not been fully studied. In the absence of robust evidence, we suggest that lower but effective IC phenylephrine concentrations are used: a lower concentration (0.31%), in conjunction with an anticholinergic and lidocaine, may be used for initial mydriasis. For management of intraoperative floppy-iris syndrome, 0.31% may be effective, though a higher concentration (1% to 1.25%) may be required.

Tripartite motif­containing 14 may aggravate cardiac hypertrophy via the AKT signalling pathway in neonatal rat cardiomyocytes and transgenic mice.

Tripartite motif­containing 14 (TRIM14) is an E3 ubiquitin ligase that primarily participates in the natural immune response and in tumour development via ubiquitination. However, the role of TRIM14 in cardiac hypertrophy is not currently clear. The present study examined the role of TRIM14 in cardiac hypertrophy and its potential molecular mechanism. TRIM14 was overexpressed in neonatal rat cardiomyocytes using adenovirus and cardiomyocyte hypertrophy was induced using phenylephrine (PE). Cardiomyocyte hypertrophy was assessed by measuring cardiomyocyte surface area and markers of hypertrophy. In addition, TRIM14­transgenic (TRIM14­TG) mice were created and cardiac hypertrophy was induced using transverse aortic constriction (TAC). Cardiac function, heart weight­to­body weight ratio (HW/BW), cardiomyocyte cross­sectional area, cardiac fibrosis and hypertrophic markers were further examined. The expression of AKT signalling pathway­related proteins was detected. TRIM14 overexpression in cardiomyocytes promoted PE­induced increases in cardiomyocyte surface area and hypertrophic markers. TRIM14­TG mice developed worse cardiac function, greater HW/BW, cross­sectional area and cardiac fibrosis, and higher levels of hypertrophic markers in response to TAC. TRIM14 overexpression also increased the phosphorylation levels of AKT, GSK­3ß, mTOR and p70S6K in vivo and in vitro. To the best our knowledge, the present study was the first to reveal that overexpression of TRIM14 aggravated cardiac hypertrophy in vivo and in vitro, which may be related to activation of the AKT signalling pathway.

Association of the exclusive use of intraoperative phenylephrine for treatment of hypotension with the risk of acute kidney injury after noncardiac surgery.

STUDY OBJECTIVE: The hypothesis that the exclusive use of the commonly used vasopressor phenylephrine during the intraoperative period in noncardiac surgery is associated with postoperative acute kidney injury (AKI) was tested. DESIGN: A retrospective cohort analysis of 16,306 adults undergoing major noncardiac surgery who either did or did not receive phenylephrine was conducted. The primary outcome was the association of the use of phenylephrine with the risk of postoperative AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Logistic regression models with all independently associated potential confounders, and an exploratory model considering only patients with no untreated minutes of hypotension (post-phenylephrine in the exposed cohort, or entire case in the unexposed cohort) were used in the analysis. SETTING: The study was conducted in a tertiary care university hospital where a total of 8,221 patients were exposed to phenylephrine, and 8,085 were not. RESULTS: In unadjusted analysis, phenylephrine exposure was associated with an increased risk of AKI (OR 1.615, 95% CI [1.522-1.725], p < 0.001). In an adjusted model including several variables associated with AKI, phenylephrine remained associated with AKI (OR 1.325 [1.153-1.524]), as did post-phenylephrine exposure lengths of hypotension. Exclusion of patients with >1 min of post-phenylephrine exposure hypotension, also demonstrated that phenylephrine use was associated with AKI (OR 1.478, [1.245-1.753]). CONCLUSIONS: The exclusive use of intraoperative phenylephrine is associated with an increased risk of postoperative renal injury. Anesthesiologists must consider a balanced approach to correct hypotension under anesthesia, including judicious choices for fluids, inotropic support when indicated, and an appropriate adjustment of the plane of anesthesia.

Phenylephrine versus cafedrine/theodrenaline (Akrinor) for the treatment of spinal anaesthesia-induced maternal hypotension during caesarean section: a retrospective single-centre cohort study.

OBJECTIVE: The main objective of this study was to assess the impact of phenylephrine and cafedrine/theodrenaline on the mother and newborn after spinal anaesthesia for caesarean section. SETTING: University teaching hospital. DESIGN: A single-centre retrospective data cohort study. PATIENTS: All obstetric patients who were scheduled for caesarean section in a 2-year period. INTERVENTIONS: Administration of either intravenous phenylephrine prophylactically or cafedrine/theodrenaline (Akrinor) reactively to maintain blood pressure after spinal anaesthesia. MAIN OUTCOME MEASURE: Maternal hypotension, heart rate during caesarean section and after admission to IMC, fetal arterial cord pH and base excess levels, maternal volume resuscitation and the use of rescue medication. RESULTS: 852 data sets could be included: n=440 Akrinor, n=412 in the phenylephrine cohort. During caesarean section blood pressure was slightly higher in the phenylephrine group compared with the Akrinor group, while hypotension <100 mm Hg systolic blood pressure (SBP) occurred significantly more often during arrival at the IMC after surgery when phenylephrine was used. Heart rate was lower and rescue medication was significantly more frequently given in the phenylephrine cohort. Irrespective of the medication used, women with baseline levels of <120 mm Hg SBP had a high risk to develop hypotension <100 mm Hg after spinal anaesthesia for caesarean section. While there was no statistical difference in mean umbilical arterial pH levels, the incidence of acidosis, defined as pH <7.2, was significantly higher with phenylephrine. CONCLUSION: Phenylephrine was not superior to Akrinor to treat spinal anaesthesia-induced maternal hypotension during caesarean section. TRIAL REGISTRATION NUMBER: DRKS00025795.

Evaluation of efficacy of intracameral lidocaine and tropicamide injection in manual small-incision cataract surgery: A prospective clinical study.

Purpose: The study was conducted to evaluate efficacy of intracameral lidocaine hydrochloride 1% and tropicamide injection 0.02% for anaesthesia and mydriasis in manual small-incision cataract surgery (MSICS) and to report any adverse drug reaction. Methods: This was a randomized, prospective, observational study on 32 participants that took place from October 2021 to March 2022 (6 months). Patients between age group 40-75 year with nuclear sclerosis cataract and pupil diameter >6 mm in preoperative evaluation were included in the study. Patients with pseudoexfoliation, rigid pupil, senile miosis, history of uveitis, ocular trauma, recent ocular infections, with known allergy to tropicamide, all types of glaucoma were excluded from the study. Results: Thirty-two eyes with nuclear sclerosis cataract who underwent MSICS were studied. Fixed dose combination of 2 ml phenyl epinephrine (0.31%), tropicamide (0.02%), and lidocaine (1%) intracamerally was used for mydriasis and analgesia. More than 7 mm pupillary dilatation was achieved within 20 seconds of injection in 29 cases (90.6%). Mild pain and discomfort was noted in 12 cases (37.5%). Postoperative day 1 unaided visual acuity was in the range of 6/18-6/12 for all patients and grade 1 iritis was seen in 7 cases (21.8%) which was self-limiting. No adverse event like corneal decompensation or TASS were noted. Conclusion: Thus, Intracameral injection of mydriatic provides rapid and sustainable mydriasis and analgesia for manual SICS.

Physiopathology of the Priapism Secondary to Tamsulosin: Clinical Cases of Our Hospital and Literature Review.

OBJECTIVE: To describe two cases of man with the diagnosis of ischemic priapism after the intake of tamsulosin and to revise the scientific literature. METHODS: We present two cases of men that developed an ischemic priapism after the intake of tamsulosin prescribed for STUI and were treated in our hospital. We described the two cases, from the diagnosis until the surgery that was performed. Also, we review the scientific literature about this topic. RESULTS: In one hand, a 67 years old man with the previous diagnosis of diabetes mellitus, hypertension and dyslipidemia that take a one single dosis of tamsulosin and developed a priapism of 9 hours of duration. He was diagnosticated of low-flow priapism that was reverted after the use of intracavernosal phenylephrine. On the other hand, a 61 years old man without any medical condition. He developed a priapism after the intake of also one single dosis of tamsulosin and came to the hospital after 48 hours of the beginning of the erection. In this case, the use of intracavernosal phenylephrine wasn´t effective so we decided to performed a distal shunt between cavernosal and spongy body according to the techniques of Winter, Ebbehoj and Al-Ghorab. All of them without results. At the end, we tried a proximal shunt according Quackles technique, also ineffective. The patient declined another surgery for implantation of a pennis prothesis and went home after four days of hospitalization with the disappearance of the pain. CONCLUSIONS: The tamsulosin is a drug well known by urologist that have a safety profile probed with the years. Nevertheless, it's association with a disease like the priapism forced us to explain to our patients this rare adverse effect.

The safety of intracameral phenylephrine - A systematic review.

Intracameral phenylephrine is commonly used in ophthalmic surgery as an alternative or supplement to mydriatic eye drops; hence, the importance of an evidence-based understanding of its risk-benefit profile is vital. We performed a comprehensive search in the PubMed, Google Scholar, and Cochrane databases for published studies and case reports relating to the use of intracameral phenylephrine. Articles from 1958 to 2021 with the following keywords were used: "intracameral phenylephrine," "intracameral mydriatics," "phenylephrine," "pupil dilation," "complications." Intracameral phenylephrine was first used in 2003 as an alternative to topical mydriatics. Since then, it is being increasingly used with a variety of benefits, including rapid onset of mydriasis, and cost-effectiveness. There are various case reports, however, of ocular and systemic complications associated with intracameral phenylephrine such as generation of free radicals, toxic anterior segment syndrome, inconsistent pupillary dilation during surgery, and ventricular fibrillation. Alternatives to intracameral phenylephrine such as iris hooks, a Malyugin ring, intracameral epinephrine, and intracameral tropicamide were compared with intracameral phenylephrine. Intracameral phenylephrine appears to have a good safety profile.

A randomized comparison of hemodynamic changes in response to a heart rate-dependent phenylephrine/ephedrine protocol versus ephedrine-only for spinal hypotension during elective cesarean section.

AIM: To compare incidences of abnormal heart rate (HR) between the phenylephrine/ephedrine protocol (P/E protocol) against the ephedrine-only (C) protocol, conventionally used for treating predelivery hypotension following spinal anesthesia for cesarean section. METHODS: Two hundred and sixty-eight parturients with pre-delivery hypotension after spinal anesthesia were equally randomized to (1) Group P/E (n = 134), phenylephrine 100 mcg in 10 mL intravenously if HR ≥ 60 beats/min (bpm), or ephedrine 6 mg intravenously if HR < 60 bpm, and 2) Group C (n = 134). The primary outcome was the incidence of the parturients with abnormal HR after vasopressor administration. The secondary outcome was the mean differences of HR and hypotensive periods during the pre-delivery period. RESULTS: There was no significant difference of between-group incidences of bradycardia (12.0% in Group P/E vs 6.7% in Group C, p = 0.136) and tachycardia (26.9% vs 35.8%, p = 0.114). Mean HR was 81.9 bpm (95% confidence interval [CI] 79.9, 84.3) in Group P/E, and 88.8 bpm (86.8, 90.6) in Group C (p < 0.001). The duration of hypotension in relation to the time interval from spinal anesthesia to delivery was 20.9% (95% CI 18.4-23.2) in Group P/E, and 26.5% (23.9-29.3) in Group C (p < 0.01). The calculated area under the curve (AUC) of abnormal HR in relation to time was significantly reduced only in Group P/E (p < 0.010). CONCLUSIONS: The incidences of out-of-range HR were comparable, but the P/E protocol resulted in a lower mean HR and better control of systolic blood pressure than the ephedrine-only protocol.

Systemic adverse events after screening of retinopathy of prematurity with mydriatic.

PURPOSE: To evaluate systemic adverse events after screening for retinopathy of prematurity (ROP) performed with mydriatic. METHODS: This was a retrospective case series study. Medical records of consecutive patients who underwent screening for ROP with 0.5% phenylephrine and 0.5% tropicamide eyedrops were retrospectively reviewed. The score of abdominal distention (0-5), volume of milk sucked and volume of stool, along with systemic details (pulse and respiration rates, blood pressure and number of periods of apnea) were collected at 1 week and 1 day before ROP examination, and at 1 day after examination. Results were compared between the days before and after examination. Correlation between body weight at the time of examination and the score of abdominal distention was examined. The numbers of infants with abdominal and/or systemic adverse events were compared between pre- and post-examination periods. RESULTS: Eighty-six infants met the inclusion criteria. The score of abdominal distention increased from 2.0 at 1 day before examination to 2.3 at 1 day after examination (p = 0.005), and the number of infants who had worsened abdominal distension increased after examination (p = 0.01). Infants with lower body weight had a higher score of abdominal distention (p < 0.0001, r = -0.57). The number of infants with reduced milk consumption increased after examination (p = 0.0001), as did the number of infants with decreased pulse rate (p = 0.0008). CONCLUSIONS: Screening for ROP with mydriatic may have adverse effects on systemic conditions. Infants should be carefully monitored after ROP screening with mydriatic.

Unilateral mydriasis following septoplasty with inferior turbinate reduction.

Nasal septoplasty and inferior turbinate reduction are common procedures performed in the treatment of nasal obstruction. These procedures are generally considered to be safe with minimal reported complications. Herein, we describe a case of a 43-year-old female who developed transient unilateral mydriasis following septoplasty with inferior turbinate reduction, likely due to the sympathomimetic agents used for vasoconstriction and mucosal decongestion.

Hemodynamic effects of norepinephrine versus phenylephrine infusion for prophylaxis against spinal anesthesia-induced hypotension in the elderly population undergoing hip fracture surgery: a randomized controlled trial.

BACKGROUND: Elderly population are at increased risk of spinal anesthesia-induced hypotension increasing their risk for postoperative morbidity and mortality. This study aimed to compare the hemodynamic effects of prophylactic infusion of norepinephrine (NE) versus phenylephrine (PE) in elderly patients undergoing hip fracture surgery under spinal anesthesia. METHODS: Elderly patients scheduled for hip fracture surgery were randomized to receive either NE infusion (8 µg/min) (NE group, n = 31) or PE infusion (100 µg/min) (PE group, n = 31) after spinal anesthesia. Outcomes included mean heart rate, mean blood pressure, cardiac output, incidence of spinal anesthesia-induced hypotension, incidence of bradycardia, and incidence of hypertension. RESULTS: Sixty-two patients with a mean age of 71 ± 6 years were included in the final analysis (31 patients in each group). The NE group showed a higher mean heart rate and cardiac output than the PE group. The NE group had a lower incidence of reactive bradycardia (10% vs. 36%, P = 0.031) and hypertension (3% vs. 36%, P = 0.003) than the PE group. No study participant developed hypotension, and the mean blood pressure was comparable between the two groups. CONCLUSIONS: Both NE and PE infusions effectively prevented spinal anesthesia-induced hypotension in elderly patients undergoing hip fracture surgery. However, NE provided more hemodynamic stability than PE; maintaining the heart rate, higher cardiac output, less reactive bradycardia, and hypertension.

QA project: Hemodynamic safety of endobronchial administration of phenylephrine for control of airway bleeding by bronchoscopy.

BACKGROUND: Phenylephrine has been administered endobronchially for airway bleeding during bronchoscopy as an alternative to epinephrine. Topical phenylephrine, often used in nasal surgery as a vasoconstrictor agent has been linked to cardiovascular morbidity. OBJECTIVE: To evaluate the safety of bronchoscopic instillation of phenylephrine during bronchoscopy. METHODS: We retrospectively reviewed patients who received endobronchial phenylephrine in our endoscopy suite. We compared the changes in blood pressure and heart rate before and after endobronchial phenylephrine administration. The safety of endobronchial phenylephrine was assessed with regards to the changes in hemodynamics and acute cardiovascular event, and 30-day mortality. Acute cardiovascular complications included acute coronary syndrome, aortic dissection, tachyarrhythmias, pulmonary edema and stroke. RESULTS: We identified 30 patients who received endobronchial phenylephrine 100mcg/ml with a mean total volume of 6.5 ± 10.6 ml. They were given mainly for balloon dilation and cryobiopsy procedure (96.7%). On excluding patients who received concurrent IV pressor, there was a statistically significant increase of mean arterial pressure (MAP) by 12 ± 21 mmHg, p = 0.01 within 30 min of endobronchial phenylephrine compared to procedure day MAP baseline. There was 27% of patients with more than 20% increase in their MAP but none of the patients had MAP more than 140 nor the occurrence of acute cardiovascular event. There was no significant change in the patients' heart rate following endobronchial phenylephrine. CONCLUSION: In our review, endobronchial phenylephrine with dose comparable to IV administration can cause significant raise in MAP but their absolute levels did not go beyond 180/120 mmHg nor resulted in acute cardiovascular complications.

Mydrane intracameral injection site can be an alternative to mydriatic drops instillation in cataract surgery.

The aim of this study is to compare Mydrane (combination of tropicamide 0.02%, phenylephrine 0.31% and lidocaine 1%) and mydriatic drops (tropicamide 1% and phenylephrine 10%) used for cataract surgery in terms of efficacy in pupil dilation and impact on corneal endothelial cell density (CD) and central corneal thickness (CCT). Prospective study including 64 eyes of 64 patients that underwent phacoemulsification with intraocular lens implantation. Patients were randomized into two groups: Mydrane group received: tropicamide and phenylephrine one day preoperatively and Mydrane during the surgery. Reference group received: tropicamide and phenylephrine preoperatively. Pupil size was measured only in Mydrane group, in the same eye of the same patient one day preoperatively after mydriatic drops were given and during the surgery, after intracameral Mydrane injection. CD and CCT were evaluated one day preoperatively and one month postoperatively in all patients and compared between Mydrane and reference groups. The results show CCT and CD significantly decreased after surgery in both groups. There is no difference in this decrease between groups. In Mydrane group there was no difference in dilated pupil diameter between Mydrane and mydriatic drops. Gender, diabetes mellitus, POAG, alpha-1 blocker treatment failed to affect pupil dilation obtained with Mydrane. Cataract surgery affects CCT and CD regardless of which mydriatic protocol had been used. Pupil diameter was similar after drops instillation and after Mydrane injection in all patients from the Mydrane group.

Vasopressor selection during critical care management of brain dead organ donors and the effects on kidney graft function.

BACKGROUND: Delayed graft function (DGF), the need for dialysis in the first week following kidney transplant, affects approximately one quarter of deceased-donor kidney transplant recipients. Donor demographics, donor serum creatinine, and graft cold ischemia time are associated with DGF. However, there is no consensus on the optimal management of hemodynamic instability in organ donors after brain death (DBDs). Our objective was to determine the relationship between vasopressor selection during donor management and the development of DGF. METHODS: Prospective observational data, including demographic and critical care parameters, were collected for all DBDs managed by 17 organ procurement organizations from nine Organ Procurement and Transplantation Network Regions between 2012 and 2018. Recipient outcome data were linked with donor data through donor identification numbers. Donor critical care parameters, including type of vasopressor and doses, were recorded at three standardized time points during donor management. The analysis included only donors who received at least one vasopressor at all three time points. Vasopressor doses were converted to norepinephrine equivalent doses and analyzed as continuous variables. Univariate analyses were conducted to determine the association between donor variables and DGF. Results were adjusted for known predictors of DGF using binary logistic regression. RESULTS: Complete data were available for 5,554 kidney transplant recipients and 2,985 DBDs. On univariate analysis, donor serum creatinine, donor age, donor subtype, kidney donor profile index, graft cold ischemia time, phenylephrine dose, and dopamine dose were associated with DGF. After multivariable analysis, increased donor serum creatinine, donor age, kidney donor profile index, graft cold ischemia time, and phenylephrine dose remained independent predictors of DGF. CONCLUSION: Higher doses of phenylephrine were an independent predictor of DGF. With the exception of phenylephrine, the selection and dose of vasopressor during donor management did not predict the development of DGF. LEVEL OF EVIDENCE: Prognostic study, Level III.

Clinical features, complications, and outcomes of exogenous and endogenous catecholamine-triggered Takotsubo syndrome: A systematic review and meta-analysis of 156 published cases.

Innumerable physical stress factors including externally administered catecholamines, and pheochromocytomas and paragangliomas (PPGLs) have been reported to trigger Takotsubo syndrome (TS). A systematic search of PubMed/MEDLINE identified 156 patients with catecholamine-induced TS up to December 2017. Data were compared within the catecholamine-induced TS cohort, but some comparisons were also done to a previously published large all-TS cohort (n = 1750). The mean age was 46.4 ± 16.4 years (72.3% women). The clinical presentation was dramatic with high complication rates in (68.2%, n = 103; multiple complications 34.6%, n = 54). The most common TS ballooning pattern was apical or mid-apical (45.2%, n = 69), followed by basal pattern (28.8%, n = 45), global pattern (16.0%, n = 25), mid-ventricular (8.3%, n = 13), focal (0.6%, n = 1), and unidentified pattern (1.9%, n = 3). There was an increase in the prevalence of apical sparing ballooning pattern compared to all-TS population (37.7% vs 18.3%, P < .00001). Higher complication rates were observed in TS with global ballooning pattern compared to apical ballooning pattern (23/25, 92% vs 38/65, 58.5%; P = .0022). Higher complication rates were observed in patients with age < 50 years than patients >50 years (73/92, 79.3% vs 29/56, 51.8%, P = 0.0009). Recurrence occurred exclusively in patients with PPGL-induced TS (18/107 patients, 16.8%). PPGL-induced TS was characterized by more global ballooning's pattern (22/104, 21.2% vs 3/49, 6.1%, P = 0.02), and lower left ventricular ejection fraction (25.54 ± 11.3 vs 31.82 ± 9.93, P = 0.0072) compared to exogenous catecholamine-induced TS. In conclusion, catecholamine-induced TS was characterized by a dramatic clinical presentation with extensive left ventricular dysfunction, and high complication rate.

Maf1 ameliorates cardiac hypertrophy by inhibiting RNA polymerase III through ERK1/2.

Rationale: An imbalance between protein synthesis and degradation is one of the mechanisms of cardiac hypertrophy. Increased transcription in cardiomyocytes can lead to excessive protein synthesis and cardiac hypertrophy. Maf1 is an RNA polymerase III (RNA pol III) inhibitor that plays a pivotal role in regulating transcription. However, whether Maf1 regulates of cardiac hypertrophy remains unclear. Methods: Cardiac hypertrophy was induced in vivo by thoracic aortic banding (AB) surgery. Both the in vivo and in vitro gain- and loss-of-function experiments by Maf1 knockout (KO) mice and adenoviral transfection were used to verify the role of Maf1 in cardiac hypertrophy. RNA pol III and ERK1/2 inhibitor were utilized to identify the effects of RNA pol III and ERK1/2. The possible interaction between Maf1 and ERK1/2 was clarified by immunoprecipitation (IP) analysis. Results: Four weeks after surgery, Maf1 KO mice exhibited significantly exacerbated AB-induced cardiac hypertrophy characterized by increased heart size, cardiomyocyte surface area, and atrial natriuretic peptide (ANP) expression and by exacerbated pulmonary edema. Also, the deficiency of Maf1 causes more severe cardiac dilation and dysfunction than wild type (WT) mice after pressure overload. In contrast, compared with adenoviral-GFP injected mice, mice injected with adenoviral-Maf1 showed significantly ameliorated AB-induced cardiac hypertrophy. In vitro study has demonstrated that Maf1 could significantly block phenylephrine (PE)-induced cardiomyocyte hypertrophy by inhibiting RNA pol III transcription. However, application of an RNA pol III inhibitor markedly improved Maf1 knockdown-promoted cardiac hypertrophy. Moreover, ERK1/2 was identified as a regulator of RNA pol III, and ERK1/2 inhibition by U0126 significantly repressed Maf1 knockdown-promoted cardiac hypertrophy accompanied by suppressed RNA pol III transcription. Additionally, IP analysis demonstrated that Maf1 could directly bind ERK1/2, suggesting Maf1 could interact with ERK1/2 and then inhibit RNA pol III transcription so as to attenuate the development of cardiac hypertrophy. Conclusions: Maf1 ameliorates PE- and AB-induced cardiac hypertrophy by inhibiting RNA pol III transcription via ERK1/2 signaling suppression.

[Same-eye comparison of pupillary dilation with an intraoperative standardized intracameral combination of mydriatics (Mydrane®) versus a preoperative ophthalmic (Mydriasert®) in standard cataract surgery in non-diabetic patients (French translation of the article)]. / Comparaison intra-individuelle de la dilatation pupillaire par une solution intracamérulaire standardisée combinée de mydriatiques (Mydrane®) en peropératoire versus un insert ophtalmique (Mydriasert®) en préopératoire dans la chirurgie de la cataracte standard de patients non diabétiques.

INTRODUCTION: Cataract surgery is the most commonly performed surgery in the world, and its success depends in part on the quality of mydriasis. PURPOSE: To compare, for the same eye, the pupillary dilation obtained with Mydrane® (standardized intracameral solution of 0.02% tropicamide, combined with 0.31% phenylephrine and 1% lidocaine) intraoperatively versus Mydriasert® (0.28mg tropicamide insert and 5.4mg phenylephrine) with a contact time between 45 and 60 minutes in the preoperative period. METHODS: Single center prospective study from November 2016 to January 2018 at the Laveran Army Instructional Hospital in Marseille. Patients referred for surgery were dilated at the preoperative consultation with Mydriasert®. The pupillary diameter after 45-60 minutes of contact with the insert was manually measured, by two different examiners, through the "iris image" tab of the Pentacam® elevation topography. Patients were dilated on the day of their cataract surgery with 0.2cc of Mydrane® injected in the anterior chamber through a paracentesis. Thirty seconds later, prior to injection of viscoelastic, an eye photograph was taken by screen capture. The pupillary diameter was evaluated by two different examiners with to the Piximeter 5.9 metrology software. The difference in pupil dilation between Mydriasert® and Mydrane® was tested with the paired series Student t-test. RESULTS: In total, 111 eyes of 82 patients were included. Mydriasert® achieved a mean pupillary dilation of 7.21±0.79mm. The mydriasis obtained with Mydrane® averaged 6.35±0.8mm. This difference of 0.86mm was statistically significant (P<0.001) with a confidence interval of 95% [-0.97; -0.74]. CONCLUSION: On average, Mydrane® dilates the pupil less than Mydriasert®. However, the mydriasis obtained with Mydrane® remains comfortable for the performance of the capsulorhexis. It helps save preoperative time and affords additional anesthetic to the cataract surgery. Nevertheless, the use of Mydriasert® is beneficial when extra mydriasis is required.

Lycopene protects against pressure overload-induced cardiac hypertrophy by attenuating oxidative stress.

Oxidative stress is considered an important pathogenic process of cardiac hypertrophy. Lycopene is a kind of carotenoid antioxidant that protects the cardiovascular system, so we hypothesized that lycopene might inhibit cardiac hypertrophy by attenuating oxidative stress. Phenylephrine and pressure overload were used to set up the hypertrophic models in vitro and in vivo respectively. Our data revealed that treatment with lycopene can significantly block pressure overload-induced cardiac hypertrophy in in vitro and in vivo studies. Further studies demonstrated that lycopene can reverse the increase in reactive oxygen species (ROS) generation during the process of hypertrophy and can retard the activation of ROS-dependent pro-hypertrophic MAPK and Akt signaling pathways. In addition, protective effects of lycopene on the permeability transition pore opening in neonatal cardiomyocytes were observed. Moreover, we demonstrated that lycopene restored impaired antioxidant response element (ARE) activity and activated ARE-driven expression of antioxidant genes. Consequently, our findings indicated that lycopene inhibited cardiac hypertrophy by suppressing ROS-dependent mechanisms.