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Veterinary Ophthalmology May 2024To determine the mydriatic effect of topical 10% phenylephrine with 10 mg/mL rocuronium bromide and compare this protocol with and without pretreatment with proparacaine.
OBJECTIVE
To determine the mydriatic effect of topical 10% phenylephrine with 10 mg/mL rocuronium bromide and compare this protocol with and without pretreatment with proparacaine.
ANIMALS STUDIED
Ten client-owned pet adult eastern box turtles (Terrapene carolina carolina).
PROCEDURES
All turtles were sedated with 8 mg/kg alfaxalone intramuscularly. One group of four turtles received four 20 μL drops of 10% phenylephrine and four 20 μL drops of rocuronium bromide in the right eye. Another group of four turtles received one standard drop of proparacaine followed by four 20 μL drops of 10% phenylephrine and four 20 μL drops of rocuronium bromide in the right eye. Two control group turtles received four 20 μL drops of saline in the right eye. The left eye was untreated in all turtles. Drops of the same type were separated by 2 min while drops of different types were separated by 5 min. Pupil size was recorded at 0, 15, 30, 60, 90, 120, 180, 240, and 360 min after administration of the final drop.
RESULTS
Treatment with 10% phenylephrine and rocuronium bromide resulted in pupil diameter changes from baseline that were statistically significant from zero at 60, 90, and 120 min in the non-proparacaine group and 90 min in the proparacaine group. The time to peak effect was 90 min in the proparacaine group and 75 min in the non-proparacaine group. Saline-treated pupils in the control group decreased in diameter over the study period. Overall, the treated eyes of the proparacaine group and non-proparacaine group were not different from each other, but both dilated more than the control group.
CONCLUSIONS
Rocuronium bromide and 10% phenylephrine can produce effective and safe mydriasis in eastern box turtles, but there was wide interindividual variation in effectiveness. Proparacaine did not improve the mydriatic effect.
PubMed: 38760319
DOI: 10.1111/vop.13229 -
Medicine May 2024This study was aimed to analyze ocular biometric changes following cycloplegia in pediatric patients with strabismus and amblyopia. Cycloplegia is routinely used to... (Observational Study)
Observational Study
This study was aimed to analyze ocular biometric changes following cycloplegia in pediatric patients with strabismus and amblyopia. Cycloplegia is routinely used to measure refractive error accurately by paralyzing accommodation. However, effects on axial length (AL), anterior chamber depth (ACD), keratometry (Km), and white-to-white distance (WTW) are not well studied in this population. This retrospective study examined 797 patients (1566 eyes) undergoing cycloplegic refraction at a Samsung Kangbuk hospital pediatric ophthalmology clinic from 2010 to 2023. Ocular biometry was measured before and after instilling 1% cyclopentolate and 0.5% phenylephrine/0.5% tropicamide. Patients were categorized by strabismus diagnosis, age, refractive error and amblyopia status. Differences in AL, ACD, Km, WTW, and refractive error pre- and post-cycloplegia were analyzed using paired t tests. ACD (3.44 ± 0.33 vs 3.58 ± 0.29 mm, P < .05) and WTW (12.09 ± 0.42 vs 12.30 ± 0.60 mm, P < .05) increased significantly after cycloplegia in all groups except other strabismus subgroup (Cs) in both parameters and youngest subgroup (G1) in ACD. Refractive error demonstrated a hyperopic shift from -0.48 ± 3.00 D to -0.06 ± 3.32 D (P < .05) in overall and a myopic shift from -6.97 ± 4.27 to -8.10 ± 2.26 in high myopia (HM). Also, AL and Km did not change significantly. In conclusion, cycloplegia impacts ocular biometrics in children with strabismus and amblyopia, significantly increasing ACD and WTW. Refractive error shifts hyperopically in esotropia subgroup (ET) and myopically in high myopia subgroup (HM), eldest subgroup (G3) relating more to anterior segment changes than AL/Km. Understanding cycloplegic effects on biometry is important for optimizing refractive correction in these patients.
Topics: Humans; Amblyopia; Strabismus; Retrospective Studies; Male; Female; Child; Biometry; Mydriatics; Child, Preschool; Refraction, Ocular; Cyclopentolate; Refractive Errors; Adolescent; Anterior Chamber; Axial Length, Eye
PubMed: 38758890
DOI: 10.1097/MD.0000000000038143 -
American Journal of Physiology. Heart... Jul 2024One of the initiating events in preeclampsia (PE) is placental ischemia. Rodent models of placental ischemia do not present with vascular endothelial dysfunction, a...
One of the initiating events in preeclampsia (PE) is placental ischemia. Rodent models of placental ischemia do not present with vascular endothelial dysfunction, a hallmark of PE. We previously demonstrated a role for leptin in endothelial dysfunction in pregnancy in the absence of placental ischemia. We hypothesized that placental ischemia requires hyperleptinemia and endothelial mineralocorticoid receptor (ECMR) expression to induce PE-associated endothelial dysfunction in pregnant mice. We induced placental ischemia via the reduced uterine perfusion pressure (RUPP) procedure in pregnant ECMR-intact () and ECMR deletion () mice at (GD) . RUPP pregnant mice also received concurrent leptin infusion via miniosmotic pump (0.9 mg/kg/day). RUPP increased blood pressure via radiotelemetry and decreased fetal growth in pregnant mice. Both increases in blood pressure and reduced fetal growth were abolished in RUPP mice. Placental ischemia did not decrease endothelial-dependent relaxation to acetylcholine (ACh) but increased phenylephrine (Phe) contraction in mesenteric arteries of pregnant mice, which was ablated by ECMR deletion. Addition of leptin to RUPP mice significantly reduced ACh relaxation in pregnant mice, accompanied by an increase in soluble FMS-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PLGF) ratio. In conclusion, our data indicate that high leptin levels drive endothelial dysfunction in PE and that ECMR is required for clinical characteristics of hypertension and fetal growth restriction in placental ischemia PE. Collectively, we show that both ECMR and leptin play a role to mediate PE. Leptin is a key feature of preeclampsia that initiates vascular endothelial dysfunction in preeclampsia characterized by placental ischemia. Endothelial mineralocorticoid receptor (ECMR) deletion in placental ischemia protects pregnant mice from elevations in blood pressure and fetal growth restriction in pregnancy. Increases in leptin production mediate the key pathological feature of endothelial dysfunction in preeclampsia in rodents. ECMR activation contributes to the increase in blood pressure and fetal growth restriction in preeclampsia.
Topics: Animals; Pregnancy; Female; Leptin; Placenta; Ischemia; Receptors, Mineralocorticoid; Pre-Eclampsia; Mice, Knockout; Blood Pressure; Mice, Inbred C57BL; Mice; Disease Models, Animal; Fetal Growth Retardation; Endothelium, Vascular; Vasodilation
PubMed: 38758130
DOI: 10.1152/ajpheart.00188.2024 -
Bioscience Reports Jun 2024Surgeries that require general anesthesia occur in 1.5-2% of gestations. Isoflurane is frequently used because of its lower possibility of affecting fetal growth....
Surgeries that require general anesthesia occur in 1.5-2% of gestations. Isoflurane is frequently used because of its lower possibility of affecting fetal growth. Therefore, we examined the isoflurane anesthesia-induced effects on maternal hemodynamic and vascular changes. We hypothesized that isoflurane would enhance endothelium-dependent vasodilation as a consequence of increased nitric oxide and decreased metalloproteinases (MMPs). Female rats (n=28) were randomized into 4 groups (7 rats/group): conscious (non-anesthetized) non-pregnant group, non-pregnant anesthetized group, conscious pregnant group, and pregnant anesthetized group. Anesthesia was performed on the 20th pregnancy day, and hemodynamic parameters were monitored. Nitric oxide metabolites, gelatinolytic activity of MMP-2 and MMP-9, and the vascular function were assessed. Isoflurane caused no significant hemodynamic changes in pregnant compared with non-pregnant anesthetized group. Impaired acetylcholine-induced relaxations were observed only in conscious non-pregnant group (by approximately 62%) versus 81% for other groups. Phenylephrine-induced contractions were greater in endothelium-removed aorta segments of both pregnant groups (with or without isoflurane) compared with non-pregnant groups. Higher nitric oxide metabolites were observed in anesthetized pregnant in comparison with the other groups. Reductions in the 75 kDa activity and concomitant increases in 64 kDa MMP-2 isoforms were observed in aortas of pregnant anesthetized (or not) groups compared with conscious non-pregnant group. Isoflurane anesthesia shows stable effects on hemodynamic parameters and normal MMP-2 activation in pregnancy. Furthermore, there were increases in nitric oxide bioavailability, suggesting that isoflurane provides protective actions to the endothelium in pregnancy.
Topics: Animals; Female; Pregnancy; Rats; Anesthetics, Inhalation; Endothelium, Vascular; Hemodynamics; Isoflurane; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Nitric Oxide; Vasodilation; Rats, Wistar
PubMed: 38757914
DOI: 10.1042/BSR20240192 -
Bratislavske Lekarske Listy 2024In the present study, two structurally similar alkaloids from trees of Cinchona genus, chloroquine and cinchonine, were examined for their vasorelaxant effects in...
BACKGROUND
In the present study, two structurally similar alkaloids from trees of Cinchona genus, chloroquine and cinchonine, were examined for their vasorelaxant effects in a model of phenylephrine-induced smooth muscle contractions.
METHODS
Potential mechanisms of action associated with endothelial vasorelaxant compounds, voltage-gated Ca2+ channels (LTCCs), and inositol triphosphate receptors were examined in isolated rat aortic rings. Also, an in silico approach was used to predict the activity of the two test compounds.
RESULTS
Experimental results revealed that both chloroquine and cinchonine significantly decrease phenylephrine-induced smooth muscle contractions, although to a different extent. Evaluated mechanisms of action indicate that endothelium is not involved in the vasorelaxant action of the two tested alkaloids. On the other hand, voltage-gated Ca2+ channels were found to be the dominant way of action associated with the vasorelaxant action of chloroquine and cinchonine. Finally, IP3R is found to have only a small impact on the observed activity of the tested compounds.
CONCLUSION
Molecular docking studies predicted that chloroquine possesses a significant activity toward a suitable model of LTCCs, while cinchonine does not. The results of the present study point to the fact that great caution should be paid while administering chloroquine to vulnerable patients, especially those with cardiovascular disorders (Tab. 3, Fig. 3, Ref. 28).
Topics: Animals; Chloroquine; Rats; Muscle, Smooth, Vascular; Molecular Docking Simulation; Calcium Channels; Vasodilator Agents; Muscle Tonus; Male; Rats, Wistar; Computer Simulation; Phenylephrine
PubMed: 38757591
DOI: 10.4149/BLL_2024_53 -
MedRxiv : the Preprint Server For... May 2024Individuals with spinal cord injury (SCI) commonly have autonomic dysreflexia (AD) with increased sympathetic activity. After SCI, individuals have decreased baroreflex...
Why do different people with Spinal Cord Injury have differing severity of symptoms with Autonomic Dysreflexia? Exploring relationships of vascular alpha-1 adrenoreceptor and baroreflex sensitivity after SCI.
INTRODUCTION
Individuals with spinal cord injury (SCI) commonly have autonomic dysreflexia (AD) with increased sympathetic activity. After SCI, individuals have decreased baroreflex sensitivity and increased vascular responsiveness.
OBJECTIVE
To evalate relationship between baroreflex and blood vessel sensitivity with autonomic dysreflexia symptoms.
DESIGN
Case control.
SETTING
Tertiary academic center.
PATIENTS
14 individuals with SCI, 17 matched uninjured controls.
INTERVENTIONS
All participants quantified AD symptoms using the Autonomic Dysfunction Following SCI (ADFSCI)-AD survey. Participants received three intravenous phenylephrine boluses, reproducibly increasing systolic blood pressure (SBP) 15-40 mmHg. Continuous heart rate (R-R interval, ECG), beat-to-beat blood pressures (finapres), and popliteal artery flow velocity were recorded. Vascular responsiveness (α1 adrenoreceptor sensitivity) and heart rate responsiveness to increased SBP (baroreflex sensitivity) were calculated.
MAIN OUTCOME MEASURES
Baroreflex sensitivity after increased SBP; Vascular responsiveness through quantified mean arterial pressure (MAP) 2-minute area under the curve and change in vascular resistance.
RESULTS
SCI and control cohorts were well-matched with mean age 31.9 and 29.6 years (p=0.41), 21.4% and 17.6% female respectively. Baseline MAP (p=0.83) and R-R interval (p=0.39) were similar. ADFSCI-AD scores were higher following SCI (27.9+/-22.9 vs 4.2+/-2.9 in controls, p=0.002).To quantify SBP response, MAP area under the curve was normalized to dose/bodyweight. Individuals with SCI had significantly larger responses (0.26+/-0.19 mmHg*s/kg*ug) than controls (0.06+/-0.06 mmHg*s/kg*ug, p=0.002). Similarly, leg vascular resistance increased after SCI (24% vs 6% to a normalized dose, p=0.007). Baroreflex sensitivity was significantly lower after SCI (15.0+/-8.3 vs 23.7+/-9.3 ms/mmHg, p=0.01). ADFSCI-AD subscore had no meaningful correlation with vascular responsiveness (R=0.008) or baroreflex sensitivity (R=0.092) after SCI.
CONCLUSIONS
While this confirms smaller previous studies suggesting increased α1 adrenoreceptor sensitivity and lower baroreflex sensitivity in individuals with SCI, these differences lacked correlation to increased symptoms of AD. Further research into physiologic mechanisms to explain why some individuals with SCI develop symptoms is needed.
PubMed: 38746296
DOI: 10.1101/2024.05.02.24306772 -
Journal of Bronchology & Interventional... Jul 2024Bleeding is a known complication during bronchoscopy, with increased incidence in patients undergoing a more invasive procedure. Phenylephrine is a potent... (Observational Study)
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.
Topics: Humans; Phenylephrine; Retrospective Studies; Bronchoscopy; Male; Female; Middle Aged; Aged; Vasoconstrictor Agents; Hypertension; Blood Pressure
PubMed: 38745445
DOI: 10.1097/LBR.0000000000000968 -
Frontiers of Medicine Jun 2024lncRNA ZNF593 antisense (ZNF593-AS) transcripts have been implicated in heart failure through the regulation of myocardial contractility. The decreased transcriptional...
lncRNA ZNF593 antisense (ZNF593-AS) transcripts have been implicated in heart failure through the regulation of myocardial contractility. The decreased transcriptional activity of ZNF593-AS has also been detected in cardiac hypertrophy. However, the function of ZNF593-AS in cardiac hypertrophy remains unclear. Herein, we report that the expression of ZNF593-AS reduced in a mouse model of left ventricular hypertrophy and cardiomyocytes in response to treatment with the hypertrophic agonist phenylephrine (PE). In vivo, ZNF593-AS aggravated pressure overload-induced cardiac hypertrophy in knockout mice. By contrast, cardiomyocyte-specific transgenic mice (ZNF593-AS MHC-Tg) exhibited attenuated TAC-induced cardiac hypertrophy. In vitro, vector-based overexpression using murine or human ZNF593-AS alleviated PE-induced myocyte hypertrophy, whereas GapmeR-induced inhibition aggravated hypertrophic phenotypes. By using RNA-seq and gene set enrichment analyses, we identified a link between ZNF593-AS and oxidative phosphorylation and found that mitofusin 2 (Mfn2) is a direct target of ZNF593-AS. ZNF593-AS exerts an antihypertrophic effect by upregulating Mfn2 expression and improving mitochondrial function. Therefore, it represents a promising therapeutic target for combating pathological cardiac remodeling.
Topics: Animals; Humans; Male; Mice; Cardiomegaly; Disease Models, Animal; GTP Phosphohydrolases; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Myocytes, Cardiac; RNA, Long Noncoding; Up-Regulation; Ventricular Remodeling
PubMed: 38743133
DOI: 10.1007/s11684-023-1036-4 -
Intensive Care Medicine Experimental May 2024Catecholamines are commonly used as therapeutic drugs in intensive care medicine to maintain sufficient organ perfusion during shock. However, excessive or sustained...
BACKGROUND
Catecholamines are commonly used as therapeutic drugs in intensive care medicine to maintain sufficient organ perfusion during shock. However, excessive or sustained adrenergic activation drives detrimental cardiac remodeling and may lead to heart failure. Whether catecholamine treatment in absence of heart failure causes persistent cardiac injury, is uncertain. In this experimental study, we assessed the course of cardiac remodeling and recovery during and after prolonged catecholamine treatment and investigated the molecular mechanisms involved.
RESULTS
C57BL/6N wild-type mice were assigned to 14 days catecholamine treatment with isoprenaline and phenylephrine (IsoPE), treatment with IsoPE and subsequent recovery, or healthy control groups. IsoPE improved left ventricular contractility but caused substantial cardiac fibrosis and hypertrophy. However, after discontinuation of catecholamine treatment, these alterations were largely reversible. To uncover the molecular mechanisms involved, we performed RNA sequencing from isolated cardiomyocyte nuclei. IsoPE treatment resulted in a transient upregulation of genes related to extracellular matrix formation and transforming growth factor signaling. While components of adrenergic receptor signaling were downregulated during catecholamine treatment, we observed an upregulation of endothelin-1 and its receptors in cardiomyocytes, indicating crosstalk between both signaling pathways. To follow this finding, we treated mice with endothelin-1. Compared to IsoPE, treatment with endothelin-1 induced minor but longer lasting changes in cardiomyocyte gene expression. DNA methylation-guided analysis of enhancer regions identified immediate early transcription factors such as AP-1 family members Jun and Fos as key drivers of pathological gene expression following catecholamine treatment.
CONCLUSIONS
The results from this study show that prolonged catecholamine exposure induces adverse cardiac remodeling and gene expression before the onset of left ventricular dysfunction which has implications for clinical practice. The observed changes depend on the type of stimulus and are largely reversible after discontinuation of catecholamine treatment. Crosstalk with endothelin signaling and the downstream transcription factors identified in this study provide new opportunities for more targeted therapeutic approaches that may help to separate desired from undesired effects of catecholamine treatment.
PubMed: 38733526
DOI: 10.1186/s40635-024-00632-9 -
Anesthesia and Pain Medicine Apr 2024Cesarean sections are commonly performed under spinal anesthesia, which can lead to hypotension, adversely affecting maternal and fetal outcomes. Hypotension following... (Review)
Review
Cesarean sections are commonly performed under spinal anesthesia, which can lead to hypotension, adversely affecting maternal and fetal outcomes. Hypotension following spinal anesthesia is generally defined as a blood pressure of 80-90% below the baseline value. Various strategies have been implemented to reduce the incidence of spinal anesthesia-induced hypotension. The administration of vasopressors is a crucial method for preventing and treating hypotension. In the past decade, phenylephrine, a primarily alpha-adrenergic agonist, has been the preferred vasopressor for cesarean sections. Recently, norepinephrine, a potent alpha-agonist with modest beta-agonist activity, has gained popularity owing to its advantages over phenylephrine. Vasopressors can be administered via a bolus or continuous infusion. Although administering boluses alone is simpler in a clinical setting, continuous prophylactic infusion initiated immediately after spinal anesthesia is more effective in reducing the incidence of hypotension. Tailoring the infusion dose based on the patient's body weight and adjusting the rate in response to blood pressure changes, in addition to using a prophylactic or rescue bolus, helps reduce blood pressure variability during cesarean sections under spinal anesthesia until neonatal delivery.
PubMed: 38725163
DOI: 10.17085/apm.24037