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Annals of Anatomy = Anatomischer... Jun 2024A reliable estimation of time since death can be important for the law enforcement authorities. The compound method encompassing supravital reactions such as the...
BACKGROUND
A reliable estimation of time since death can be important for the law enforcement authorities. The compound method encompassing supravital reactions such as the chemical excitability of the iris can be used to further narrow intervals estimated by temperature-based methods. Postmortem iris excitability was mostly assessed by parasympatholytic or parasympathomimetic substances. Little is known regarding sympathomimetic agents. The present study aims to describe the postmortem iris excitability using the sympathomimetic drug phenylephrine.
METHODS
Cadavers were included after body donors gave written informed consent during lifetime. Exclusion criteria were known eye disease, or a postmortem interval exceeding 26 hours. A pupillometer with a minimum measurement range of 0.5 mm was used to determine the horizontal pupil diameter before and 20 minutes after the application of phenylephrine. Increase in pupil diameter was labeled as positive reaction, unchanged pupil diameter was labeled as negative reaction, and decrease in pupil diameter was labeled as paradox reaction.
RESULTS
30 eyes from 16 cadavers (median age = 80.0; 9 males, 7 females) were examined. Initial pupil size was in median 3.5 mm (interquartile range [IQR]: 3.0-4.5 mm) and progressed to 4.0 mm (IQR: 3.5-5.0 mm) 20 minutes after drug instillation. The achieved pupil diameter difference comprised in median 0.5 mm (IQR: 0.0-1.0 mm). A positive reaction was observed in 21 cases. Negative reactions were observed in 5 cases and paradox reactions in 4 cases. Overall, there was a statistically significant difference in diameter between the initial and the reactive pupil (P = 0.0002).
CONCLUSION
Although relatively rarely used, sympathomimetic drugs seem to be eligible for chemical postmortem iris excitability. Currently, assessment of postmortem iris excitability usually only involves parasympatholytic and parasympathomimetic agents. The findings of the present study give a hint that the application of a third agent with a sympathomimetic mechanism of action could provide additional information. Further studies assessing such a triple approach in the compound method in comparison with the current gold standard for estimation of time since death are mandatory to ensure reliable results.
Topics: Humans; Male; Female; Iris; Phenylephrine; Postmortem Changes; Pupil; Aged, 80 and over; Cadaver; Aged; Sympathomimetics
PubMed: 38460860
DOI: 10.1016/j.aanat.2024.152240 -
The American Journal of Emergency... Feb 2022There is limited evidence to support the efficacy and safety of push-dose vasopressor (PDP) use outside of the operating room (OR). Specifically, there are few... (Comparative Study)
Comparative Study
BACKGROUND
There is limited evidence to support the efficacy and safety of push-dose vasopressor (PDP) use outside of the operating room (OR). Specifically, there are few head-to-head comparisons of different PDP in these settings. The purpose of this study was to compare the efficacy and safety of push-dose phenylephrine (PDP-PE) and epinephrine (PDP-E) in the Emergency Department (ED).
METHODS
This retrospective, single-center study evaluated adults given PDP-PE or PDP-E in the ED from May 2017 to November 2020. The primary outcome was a change in heart rate (HR). Secondary outcomes included changes in blood pressure, adverse effects, dosing errors, fluid and vasopressor requirements, ICU and hospital lengths of stay (LOS), and in-hospital mortality.
RESULTS
Ninety-six patients were included in the PDP-PE group and 39 patients in the PDP-E group. Median changes in HR were 0 [-7, 6] and - 2 [-15, 5] beats per minute (BPM) for PDP-PE and PDP-E, respectively (p = 0.138). PDP-E patients had a greater median increase in systolic blood pressure (SBP) (33 [24, 53] vs. 26 [8, 51] mmHg; p = 0.049). Dosing errors occurred more frequently in patients that received PDP-E (5/39 [12.8%] vs. 2/96 [2.1%]; p = 0.021). PDP-E patients more frequently received continuous epinephrine infusions before and after receiving PDP-E. There were no differences in adverse effects, fluid requirements, LOS, or mortality.
CONCLUSION
PDP-E provided a greater increase in SBP compared to PDP-PE. However, dosing errors occurred more frequently in those receiving PDP-E. Larger head-to-head studies are necessary to further evaluate the efficacy and safety of PDP-E and PDP-PE.
Topics: Aged; Blood Pressure; Emergency Service, Hospital; Epinephrine; Female; Heart Rate; Humans; Male; Middle Aged; Phenylephrine; Retrospective Studies; Vasoconstrictor Agents
PubMed: 34864289
DOI: 10.1016/j.ajem.2021.11.033 -
Cardiovascular Research Mar 2023The carotid bodies (CBs) of spontaneously hypertensive (SH) rats exhibit hypertonicity and hyperreflexia contributing to heightened peripheral sympathetic outflow. We...
AIMS
The carotid bodies (CBs) of spontaneously hypertensive (SH) rats exhibit hypertonicity and hyperreflexia contributing to heightened peripheral sympathetic outflow. We hypothesized that CB hyperexcitability is driven by its own sympathetic innervation.
METHODS AND RESULTS
To test this, the chemoreflex was activated (NaCN 50-100 µL, 0.4 µg/µL) in SH and Wistar rats in situ before and after: (i) electrical stimulation (ES; 30 Hz, 2 ms, 10 V) of the superior cervical ganglion (SCG), which innervates the CB; (ii) unilateral resection of the SCG (SCGx); (iii) CB injections of an α1-adrenergic receptor agonist (phenylephrine, 50 µL, 1 mmol/L), and (iv) α1-adrenergic receptor antagonist prazosin (40 µL, 1 mmol/L) or tamsulosin (50 µL, 1 mmol/L). ES of the SCG enhanced CB-evoked sympathoexcitation by 40-50% (P < 0.05) with no difference between rat strains. Unilateral SCGx attenuated the CB-evoked sympathoexcitation in SH (62%; P < 0.01) but was without effect in Wistar rats; it also abolished the ongoing firing of chemoreceptive petrosal neurones of SH rats, which became hyperpolarized. In Wistar rats, CB injections of phenylephrine enhanced CB-evoked sympathoexcitation (33%; P < 0.05), which was prevented by prazosin (26%; P < 0.05) in SH rats. Tamsulosin alone reproduced the effects of prazosin in SH rats and prevented the sensitizing effect of the SCG following ES. Within the CB, α1A- and α1B-adrenoreceptors were co-localized on both glomus cells and blood vessels. In conscious SH rats instrumented for recording blood pressure (BP), the CB-evoked pressor response was attenuated after SCGx, and systolic BP fell by 16 ± 4.85 mmHg.
CONCLUSIONS
The sympathetic innervation of the CB is tonically activated and sensitizes the CB of SH but not Wistar rats. Furthermore, sensitization of CB-evoked reflex sympathoexcitation appears to be mediated by α1-adrenoceptors located either on the vasculature and/or glomus cells. The SCG is novel target for controlling CB pathophysiology in hypertension.
Topics: Rats; Animals; Carotid Body; Rats, Wistar; Tamsulosin; Hypertension; Sympathetic Nervous System; Blood Pressure; Rats, Inbred SHR; Phenylephrine; Prazosin
PubMed: 35048948
DOI: 10.1093/cvr/cvac008 -
Acta Anaesthesiologica Scandinavica Jan 2023Oxygen supply to the brain is of special importance during intracranial surgery because it may be compromised by intracranial pathology. A high arterial blood pressure...
BACKGROUND
Oxygen supply to the brain is of special importance during intracranial surgery because it may be compromised by intracranial pathology. A high arterial blood pressure (mean arterial pressure above 80 mmHg) and a high arterial oxygen tension (PaO above 12 kPa) is therefore often targeted in these patients, when for example intracranial pressure is increased or when a mass effect on brain tissue from a tumour is present, and it is pursued by administering vasopressors such as phenylephrine and by increasing inspiratory oxygen fraction (FiO ). However, whether these interventions increase cerebral oxygenation remains uncertain. We aimed to investigate the effect of hyperoxia and phenylephrine on brain tissue oxygen tension (PbtO ) in patients undergoing craniotomy.
METHODS
In this experimental study, we included 17 adult patients scheduled for elective craniotomy. After securing a stable baseline of the oxygen probe, PbtO was measured in white matter peripherally in the surgical field during general anaesthesia. Primary comparisons were PbtO before versus after an increase in FiO from 0.30 to 0.80 as well as before versus after a bolus dose of phenylephrine (0.1-0.2 mg depending on patient haemodynamics). Data were analysed with the Wilcoxon signed rank test.
RESULTS
We obtained complete data sets in 11 patients undergoing the FiO increase and six patients receiving the phenylephrine bolus. PbtO was 22 (median; 5%-95% range, 4.6-54) mmHg during 30% oxygen, 68 (8.4-99) mmHg during 80% oxygen (p = .004 compared to 30% oxygen), 21 (4.5-81) mmHg before phenylephrine, and 19 (4.2-56) mmHg after phenylephrine (p = .56 compared to before phenylephrine).
CONCLUSION
In patients undergoing craniotomy under general anaesthesia, brain tissue oxygen tension increased with a high inspiratory oxygen fraction but remained unchanged after a bolus dose of phenylephrine.
Topics: Adult; Humans; Hyperoxia; Phenylephrine; Brain; Oxygen; Brain Injuries; Hypertension
PubMed: 36112064
DOI: 10.1111/aas.14149 -
Anatomical Record (Hoboken, N.J. : 2007) Nov 2022The assumption that the coronary capillary blood flow is exclusively regulated by precapillary vessels is not supported by recent data. Rather, the complex coronary... (Review)
Review
The assumption that the coronary capillary blood flow is exclusively regulated by precapillary vessels is not supported by recent data. Rather, the complex coronary capillary bed has unique structural and geometric characteristics that invalidate many assumptions regarding red blood cell (RBC) transport, for example, data based on a single capillary or that increases in flow are the result of capillary recruitment. It is now recognized that all coronary capillaries are open and that their variations in flow are due to structural differences, local O demand and delivery, and variations in hematocrit. Recent data reveal that local mechanisms within the capillary bed regulate flow via signaling mechanisms involving RBC signaling and endothelial-associated pericytes that contract and relax in response to humoral and neural signaling. The discovery that pericytes respond to vasoactive signals (e.g., nitric oxide, phenylephrine, and adenosine) underscores the role of these cells in regulating capillary diameter and consequently RBC flux and oxygen delivery. RBCs also affect blood flow by sensing and releasing nitric oxide to facilitate relaxation of pericytes and a consequential capillary dilation. New data indicate that these signaling mechanisms allow control of blood flow in specific coronary capillaries according to their oxygen requirements. In conclusion, mechanisms in the coronary capillary bed facilitate RBC density and transit time, hematocrit, blood flow and O delivery, factors that decrease capillary heterogeneity. These findings have important clinical implications for myocardial ischemia and infarction, as well as other vascular diseases.
Topics: Adenosine; Capillaries; Erythrocytes; Nitric Oxide; Oxygen; Phenylephrine
PubMed: 35521832
DOI: 10.1002/ar.24951 -
BMC Pulmonary Medicine Jun 2021Different from current cognition, our study demonstrated that adrenergic receptors agonist phenylephrine significantly relaxed isolated pulmonary artery but constricted...
BACKGROUND
Different from current cognition, our study demonstrated that adrenergic receptors agonist phenylephrine significantly relaxed isolated pulmonary artery but constricted pulmonary veins. Through comparing differences in the effects of commonly used vasoactive drugs on pulmonary artery and veins, the study aimed to improve efficiency and accuracy of isolated pulmonary vascular experiments, and to provide experimental basis for clinical drug use.
METHODS
The contractile responses of pulmonary arteries and veins from twelve-week-old Male Sprague-Dawley rats to phenylephrine, arginine vasopressin (AVP), U46619, endothelin-1, and potassium chloride (KCl) were recorded, as well as the relaxation in response to phenylephrine, AVP, acetylcholine. To further explore the mechanism, some vessels was also pre-incubated with adrenergic receptors antagonists propranolol, prazosin and nitric oxide synthesis inhibitor N[gamma]-nitro-L-arginine methyl ester (L-NAME) before addition of the experimental drugs.
RESULTS
Phenylephrine constricted pulmonary veins directly, but constricted pulmonary artery only after incubation with propranolol or/and L-NAME. The pulmonary artery exhibited significant relaxation to AVP with or without L-NAME incubation. AVP more clearly constricted the veins after incubation with L-NAME. Changes in vascular tension also varied from pulmonary artery to veins for KCl stimulation. Different from phenomena presented in veins, acetylcholine did not relax pulmonary artery preconstricted by KCl, U46619, and endothelin-1.
CONCLUSIONS
According to the results, phenylephrine, KCl, AVP, and acetylcholine could be used to distinguish pulmonary arteries and pulmonary veins in vitro. This also suggested that the pulmonary arteries and pulmonary veins have great differences in physiology and drug reactivity.
Topics: Acetylcholine; Animals; Arginine Vasopressin; Male; Phenylephrine; Potassium Chloride; Pulmonary Artery; Pulmonary Veins; Rats; Rats, Sprague-Dawley; Vasoconstrictor Agents
PubMed: 34090386
DOI: 10.1186/s12890-021-01558-8 -
Microcirculation (New York, N.Y. : 1994) Aug 2018Changes in microvascular perfusion have been reported in many diseases, yet the functional significance of altered perfusion is often difficult to determine. This is...
OBJECTIVE
Changes in microvascular perfusion have been reported in many diseases, yet the functional significance of altered perfusion is often difficult to determine. This is partly because commonly used techniques for perfusion measurement often rely on either indirect or by-hand approaches.
METHODS
We developed and validated a fully automated software technique to measure microvascular perfusion in videos acquired by fluorescence microscopy in the mouse gastrocnemius. Acute perfusion responses were recorded following intravenous injections with phenylephrine, SNP, or saline.
RESULTS
Software-measured capillary flow velocity closely correlated with by-hand measured flow velocity (R = 0.91, P < 0.0001). Software estimates of capillary hematocrit also generally agreed with by-hand measurements (R = 0.64, P < 0.0001). Detection limits range from 0 to 2000 μm/s, as compared to an average flow velocity of 326 ± 102 μm/s (mean ± SD) at rest. SNP injection transiently increased capillary flow velocity and hematocrit and made capillary perfusion more steady and homogenous. Phenylephrine injection had the opposite effect in all metrics. Saline injection transiently decreased capillary flow velocity and hematocrit without influencing flow distribution or stability. All perfusion metrics were temporally stable without intervention.
CONCLUSIONS
These results demonstrate a novel and sensitive technique for reproducible, user-independent quantification of microvascular perfusion.
Topics: Animals; Automation; Blood Flow Velocity; Hematocrit; Mice; Microcirculation; Microscopy, Fluorescence; Microscopy, Video; Microvessels; Perfusion; Phenylephrine; Reproducibility of Results; Saline Solution; Software
PubMed: 29908041
DOI: 10.1111/micc.12482 -
Journal of Cataract and Refractive... May 2017To evaluate the study drug OMS302 (Omidria [phenylephrine and ketorolac injection 1.0%/0.3%]) compared with a balanced salt solution (vehicle), ketorolac, and... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the study drug OMS302 (Omidria [phenylephrine and ketorolac injection 1.0%/0.3%]) compared with a balanced salt solution (vehicle), ketorolac, and phenylephrine on pupil diameter during cataract surgery and early postoperative ocular pain.
SETTING
Twenty-three centers in the United States.
DESIGN
Randomized clinical trial.
METHODS
Patients were randomized (1:1:1:1) to receive vehicle, phenylephrine, ketorolac, or the study drug containing phenylephrine and ketorolac administered intracamerally during surgery. Intraoperative pupil diameter was determined each minute by video capture. Postoperative ocular pain was evaluated for up to 12 hours.
RESULTS
The study evaluated 223 patients. The study drug was significantly better than the vehicle and ketorolac in maintaining mydriasis (least-squares mean differences 0.9 ± 0.1 [SEM] and 0.7 ± 0.1 for the study drug versus vehicle and ketorolac, respectively; P < .0001 each). Ocular pain assessed using the Visual Analog Scale was significantly reduced for the study drug compared with the vehicle or phenylephrine (least-squares mean difference -4.6 ± 2.2 and P = .042 and 5.9 ± 2.2 and P = .009, respectively). Significantly fewer patients treated with the study drug (3 [6.1%]) had an intraoperative pupil diameter smaller than 6.0 mm compared with those treated with the vehicle (25 [47.2%]; P < .0001), ketorolac (18 [34.6%]; P = .0004), or phenylephrine (11 [22.4%]; P = .0216).
CONCLUSIONS
The study drug was safe and efficacious in maintaining mydriasis and reducing postoperative ocular pain. Both ketorolac and phenylephrine contributed to the therapeutic effects, with the combination showing superiority to either agent alone in maintaining an intraoperative pupil diameter of 6.0 mm or larger.
Topics: Cataract Extraction; Eye Pain; Humans; Ketorolac; Mydriasis; Mydriatics; Pain, Postoperative; Phenylephrine; Pupil
PubMed: 28602319
DOI: 10.1016/j.jcrs.2017.02.030 -
The Journal of Surgical Research Oct 2022The study aims to investigate the effect of parabiosis method on endothelial dysfunction in naturally aging mice and determine the time projections for predicted...
INTRODUCTION
The study aims to investigate the effect of parabiosis method on endothelial dysfunction in naturally aging mice and determine the time projections for predicted improvement in the mentioned target group.
METHODS
The balb/c mice were separated into six groups, these being; isochronic old, heterochronic old (HP-O), isochronic young, heterochronic young, young control, and old control. After parabiosis protocol, animals were sacrificed at the third, fifth, seventh, and ninth weeks, and their thoracic aortas were isolated. The vasodilatation and vasoconstriction responses of the vessels were detected using potassium chloride and phenylephrine, acetylcholine (ACh), and sodium nitroprusside.
RESULTS
Aging had a significant decreasing effect on maximum ACh relaxation responses (P < 0.01). However, in the HP-O group, the maximum ACh relaxation response in the third week was significantly lower (P < 0.05), but this effect disappeared in the ninth week. Maximum phenylephrine contraction responses were lower in the heterochronic parabiosis group (P < 0.05).
CONCLUSIONS
ACh responses increased at the end of the ninth week in the HP-O group, therefore, the parabiosis model may have an improving effect on endothelial dysfunction seen in aging.
Topics: Acetylcholine; Animals; Endothelium, Vascular; Female; Mice; Nitroprusside; Parabiosis; Phenylephrine; Vasoconstriction; Vasodilation
PubMed: 35598495
DOI: 10.1016/j.jss.2022.04.054 -
European Journal of Clinical... Aug 2015Increased bioavailability of phenylephrine is reported when combined with paracetamol in over-the-counter formulations for the symptomatic treatment of the common cold... (Review)
Review
BACKGROUND
Increased bioavailability of phenylephrine is reported when combined with paracetamol in over-the-counter formulations for the symptomatic treatment of the common cold and influenza. Such formulations could increase phenylephrine-related cardiovascular adverse events particularly in susceptible individuals. Quantification of the effect of phenylephrine concentration on blood pressure allows simulation of potential adverse combination therapy effects.
METHODS
MEDLINE and EMBASE databases were searched for papers discussing or describing any adverse effect, hypersensitivity or safety concerns related to phenylephrine alone or in combination with other drugs. The pharmacodynamic relationship between plasma phenylephrine concentration and mean arterial blood pressure was characterized using published observations of blood pressure changes after ophthalmic eye drops. The resulting pharmacokinetic and pharmacodynamic parameters were then used to predict mean arterial blood pressure (MAP) changes in that population if given an oral combination of phenylephrine and paracetamol.
RESULTS
There were 1172 papers identified for examination. Forty-seven reports fulfilled the inclusion criteria. Increases in blood pressure and decreases in heart rate have been reported with doses over 15 mg. It has been estimated that a 20-mmHg increase in systolic blood pressure would occur with an oral dose of 45 mg phenylephrine in normotensive healthy people. Those taking monoamine oxidase inhibitors report increased systolic blood pressure of greater than 60 mmHg. Blood pressure and heart rate changes are potentiated in patients with underlying hypertension. Simulation showed a modest increase in MAP when phenylephrine 10 mg was co-administered with paracetamol 1 g (4.2 vs 12.3 mmHg).
CONCLUSIONS
Combination paracetamol phenylephrine oral therapy has potential to increase blood pressure more than phenylephrine alone in those with cardiovascular compromise.
Topics: Acetaminophen; Adrenergic alpha-1 Receptor Agonists; Analgesics, Non-Narcotic; Arterial Pressure; Drug Interactions; Drug Therapy, Combination; Heart Rate; Humans; Phenylephrine
PubMed: 26022219
DOI: 10.1007/s00228-015-1876-1