Effects Of Phenylephrine Research Articles

Basic pharmacological evaluation of modified phenyl carbamic acid derivatives on cardiovascular functions under in vitro conditions in rats.

The study aimed to evaluate the basic pharmacological effects of modified phenyl carbamic acid derivates with a basic part made of N-phenylpiperazine (compounds 6a, 6b, 6c, 6d) in Wistar rats. The compounds were evaluated for their ability to decrease the phenylephrine-induced contraction of the aortic strips of rats after repeated administration of the compounds and their ability to inhibit the positive chronotropic effect of isoproterenol on spontaneously beating rat atria. The ability to inhibit the vasoconstriction effect of phenylephrine was confirmed in all compounds in the range from 10.39 % to 13.65 %. The most significant vasoconstriction was achieved in compound 6d (86.35%, p < 0.001). None of the compounds reached the effect of carvedilol. All compounds proved an antagonistic ability to the positive chronotropic effect of isoproterenol. The highest value of the anti-isoproterenol effect was identified for the compound 6c (pA2 = 8.21 ± 0.56; p < 0.05). Only compound 6a decreased heart rate significantly (by 3.17%, p < 0.05), so we can indicate its potential negative chronotropic effect. The obtained results showed that the evaluated compounds confirmed the basic characteristics of beta-blockers with additional α-adrenolytic properties.

Assessment of the effects of two commonly used mydriatics on the macular and peripapillary microvascular systems of healthy children: An Optical Coherence Tomography Angiography Study.

To evaluate the effects of pupil dilation caused by topical applications of 2.5% phenylephrine and 0.5% tropicamide on retinal microvascularization using optical coherence tomography angiography (OCTA). Healthy children were included in this prospective observational study. Baseline OCTA measurements were taken for all children before dilatation. Then they were randomly divided into two groups, the tropicamide group given 0.5% tropicamide solution and the phenylephrine group given 2.5% phenylephrine solution. After dilation OCTA images were taken for the second time from all children. The effect of dilation using two different mydriatic agents caused a decrease in mean radial peripapillary capillary density (RPC-VD) and superior RPC-VD (p=0.008 and p=0.001). Remarkably, this reduction due to dilatation was also determined to be caused by the combined effect of both mydriatic agents (p=0.016 and p=0.013). Although phenylephrine showed a slightly greater decrease than tropicamide, the effects of the two mydriatic drugs were not superior to each other (p=0.166 and p=0.167). Dilation with 2.5% phenylephrine or 0.5% tropicamide significantly decreased mean RPC-VD and superior RPC-VD. Although there was no statistically significant difference between the two mydriatic agents, phenylephrine caused a greater reduction than tropicamide. This effect of dilation and phenylephrine on VD should be considered in studies using OCTA and focusing on peripapillary areas.

A Comparison of the Effect of Phenylephrine and Norepinephrine on Uteroplacental Vascular Resistance During the Treatment of Postspinal Hypotension in Preeclamptic Patients: A Randomized Controlled Study

(Eur J Anaesthesiol. 2024;41(2):150–152. doi: 10.1097/EJA.0000000000001924) Preeclampsia is often characterized by moderate to severe hypertension, and thus postspinal hypotension is less common; however, because of the physiology involved, the effects and hazards of postspinal hypotension in these patients are more severe. Recent research in this area has presented norepinephrine as an alternative to phenylephrine in patients with normal blood pressure and is as yet poorly understood as a treatment for patients with preeclampsia. This article is a letter to the editor describing the outcome of a randomized controlled trial whose aim was to provide evidence for norepinephrine in the context of preeclampsia.

Adenosine 2A Receptors Link Astrocytic Alpha-1 Adrenergic Signaling to Wake-Promoting Dopamine Neurons

BACKGROUNDSleep and arousal disorders are common, but the underlying physiology of wakefulness is not fully understood. The locus coeruleus promotes arousal via alpha-1 adrenergic receptor (α1AR) driven recruitment of wake-promoting dopamine (DA) neurons in the ventral periaqueductal gray (vPAGDA neurons). α1AR expression is enriched on vPAG astrocytes, and chemogenetic activation of astrocytic Gq signaling promotes wakefulness. Astrocytes can release extracellular "gliotransmitters," such as ATP and adenosine, but the mechanism underlying how vPAG astrocytic α1ARs influence sleep/wake behavior and vPAGDA neuron physiology is unknown. METHODSIn this study, we utilized genetic manipulations with ex vivo calcium imaging in vPAGDA neurons and astrocytes, patch-clamp electrophysiology, and behavioral experiments in mice to probe our hypothesis that astrocytic α1ARs mediate noradrenergic modulation of wake-promoting vPAGDA neurons via adenosine signaling. RESULTSActivation of α1ARs with phenylephrine increased calcium transients in vPAGDA neurons and vPAG astrocytes, and increased vPAGDA neuron excitability ex vivo. Chemogenetic Gq-DREADD activation of vPAG astrocytes similarly increased vPAGDA neuron calcium activity and intrinsic excitability. Conversely, shRNA knockdown of vPAG astrocytic α1ARs reduced the excitatory effect of phenylephrine on vPAGDA neurons and blunted arousal during the wake phase. Pharmacological blockade of adenosine 2A (A2A) receptors precludes the α1AR-induced increase in vPAGDA calcium activity and excitability in brain slices, as well as the wake-promoting effects of vPAG α1AR activation in vivo. CONCLUSIONSWe have identified a crucial role for vPAG astrocytic α1AR receptors in sustaining arousal through heightened excitability and activity of vPAGDA neurons mediated by local A2A receptors.

Phenylephrine Enhances the Mitogenic Effect of S-Allyl-L-cysteine on Primary Cultured Hepatocytes through Protein Kinase C-Induced B-Raf Phosphorylation.

The co-mitogenic effects of the α1-adrenoceptor agonist phenylephrine on S-allyl-L-cysteine (SAC)-induced hepatocyte proliferation were examined in primary cultures of adult rat hepatocytes. The combination of phenylephrine (10-10-10-6 M) and SAC (10-6 M) exhibited a significant dose-dependent increase in the number of hepatocyte nuclei and viable cells compared to SAC alone. This combination also increased the progression of hepatocyte nuclei into the S-phase. The potentiating effect of phenylephrine on SAC-induced cell proliferation was counteracted by prazosin (an α1-adrenergic receptor antagonist) and GF109203X (selective protein kinase C (PKC) inhibitor). In addition, PMA (direct PKC activator) potentiated the proliferative effects of SAC similarly to phenylephrine. In essence, these findings suggest that PKC activity plays a crucial role in enhancing SAC-induced cell proliferation. Moreover, the effects of phenylephrine on SAC-induced Ras activity, Raf phosphorylation, and extracellular signal-regulated kinase 2 (ERK2) phosphorylation were investigated. Phenylephrine (or PMA) in combination with SAC did not augment Ras activity, but further increased ERK2 phosphorylation and its upstream B-Raf phosphorylation. These results indicate that PKC activation, triggered by stimulating adrenergic α1 receptors, further amplifies SAC-induced cell proliferation through enhanced ERK2 phosphorylation via increased B-Raf-specific phosphorylation in primary cultured hepatocytes.

A retrospective study of the effects of a vasopressor bolus on systolic slope (dP/dt) and dynamic arterial elastance (Eadyn)

BackgroundTo enhance the utility of functional hemodynamic monitoring, the variables systolic slope (dP/dt) and dynamic arterial elastance (Eadyn) are calculated by the Hypotension Prediction Index (HPI) Acumen® Software. This study was designed to characterize the effects of phenylephrine and ephedrine on dP/dt and Eadyn.MethodsThis was a retrospective, non-randomized analysis of data collected during two clinical studies. All patients required intra-operative controlled mechanical ventilation and had an indwelling radial artery catheter connected to an Acumen IQ sensor. Raw arterial pressure waveform data was downloaded from the patient monitor and all hemodynamic measurements were calculated off-line. The anesthetic record was reviewed for bolus administrations of either phenylephrine or ephedrine. Cardiovascular variables prior to drug administration were compared to those following vasopressor administrations. The primary outcome was the difference for dP/dt and Eadyn at baseline compared with the average after the bolus administration. All data sets demonstrated non-normal distributions so statistical analysis of paired and unpaired data followed the Wilcoxon matched pairs signed-rank test or Mann-Whitney U test, respectively.Results201 doses of phenylephrine and 100 doses of ephedrine were analyzed. All data sets are reported as median [95% CI]. Mean arterial pressure (MAP) increased from 62 [54,68] to 78 [76,80] mmHg following phenylephrine and from 59 [55,62] to 80 [77,83] mmHg following ephedrine. Stroke volume and cardiac output both increased. Stroke volume variation and pulse pressure variation decreased. Both drugs produced significant increases in dP/dt, from 571 [531, 645] to 767 [733, 811] mmHg/sec for phenylephrine and from 537 [509, 596] to 848 [779, 930] mmHg/sec for ephedrine. No significant changes in Eadyn were observed.ConclusionBolus administration of phenylephrine or ephedrine increases dP/dt but does not change Eadyn. dP/dt demonstrates potential for predicting the inotropic response to phenylephrine or ephedrine, providing guidance for the most efficacious vasopressor when treating hypotension.Trial registrationData was collected from two protocols. The first was deemed to not require written, informed consent by the Institutional Review Board (IRB). The second was IRB-approved (Effect of Diastolic Dysfunction on Dynamic Cardiac Monitors) and registered on ClinicalTrials.gov (NCT04177225).

Effect of phenylephrine versus ephedrine on the incidence of postoperative delirium in olderly adults undergoing knee arthroplasty under general anesthesia: a single-center trial

In addition to stabilizing blood pressure (BP), ephedrine and phenylephrine have distinct effects on regional cerebral oxygen saturation (rSO2). However, whether its effect on rSO2 affects the occurrence of postoperative delirium (POD) remains unclear. Therefore, the aim of this study is to compare the effects of ephedrine and phenylephrine for BP maintenance on the incidence of POD in olderly adults who underwent knee arthroplasty under general anesthesia. One hundred twenty patients who were between 60 and 90 years old and underwent knee arthroplasty were included in this study. The patients were randomly divided into two groups: the ephedrine group and the phenylephrine group. After anesthesia induction, ephedrine and phenylephrine were continuously infused to maintain the intraoperative mean arterial pressure within the normal range (baseline mean arterial pressure ± 20%). The primary outcome measures included the incidence of POD within 1–3 days after surgery. The incidence of POD on the first day after surgery was lower in the ephedrine group than in the phenylephrine group (33% vs. 7%, P < 0.001). However, there was no significant difference in the incidence of POD between the two groups on the second and third postoperative days. Compared with the phenylephrine group, the ephedrine group experienced significantly greater cardiac output (CO) and rSO2 (P < 0.05).Clinical Trials Registry: ChiCTR2200064849, principal investigator: Changjian Zheng.

Comparison of the effects of norepinephrine and phenylephrine on shivering and hypothermia in patients undergoing caesarean section under spinal anaesthesia at a tertiary hospital in China：a randomised, double-blind, controlled trial protocol

IntroductionPeripheral vasodilation causes a redistribution of body temperature from the core to the periphery, resulting in shivering and hypothermia. These are normal pathological and physiological processes during spinal anaesthesia. Two...

Comparative Study of Prophylactic Vs Conventional Phenylephrine Administration in Preventing Spinal Anaesthesia-Induced Hypotension in Elective caesarean Section Patients: A Quasi Experimental Trial

Objective: To determine the prophylactic effect of phenylephrine in patients undergoing spinal anaesthesia in comparison to the conventional group. Study design: Quasi experimental trial. Place and duration of study: HIT Hospital Taxila in the period of 6 months. Materials and methods: This quasi-experimental trial was conducted in HIT Hospital. Total 68 females were divided into two groups: Control group and Experimental group. Each group consisted of 34 patients aged between 20 to 40 years. The patients were scheduled for elective cesarean section deliveries under spinal anaesthesia. All patients of the experimental group were given prophylactic dose of phenylephrine 100mcg diluted in normal saline after undergoing spinal anaesthesia before the start of procedure. Control group patients were only given normal saline as a placebo after undergoing spinal anaesthesia before the start of procedure. Control group patients were given phenylephrine as conventional treatment only if they experienced hypotension during the procedure. Results: Among the patients in the experimental group none experienced hypotension. Their blood pressure remained fairly constant in the normal range. In the control group, 4 out of 34 patients (11.7%) had their blood pressure dropped below the cutoff point of 90/60 mmHg. Conclusions: Our results show that a prophylactic dosage regimen i.e., 100mcg of phenylephrine is effective in controlling spinal -anaesthesia -induced hypotension in patients undergoing Caesarean-section. In comparison with conventional group where hypotension occurs only in few patients.

Comparison of intravenous bolus phenylephrine, ephedrine and mephentermine for maintenance of arterial blood pressure during spinal anaesthesia in caesarean section

Background: Subarachnoid block, although being highly efficient, often has limitation such as hypotension which can result in adverse maternal and fetal outcome, continues to be a matter of concern to the Anesthesiologist. The study was to compare the effect of phenylephrine, ephedrine and mephentermine, for maintenance of arterial pressure during spinal anaesthesia for caesarean section. Methodology: A prospective randomized double blinded study involving 90 patients with hypotension after subarachnoid block under spinal anesthesia was conducted, dividing them into three groups: P (Phenylephrine) 100 mcg, E (Ephedrine) 6 mg, and M (Mephentermine) 6 mg. Patients were compared based on age, weight, height, hemodynamic parameters, complications, and neonatal APGAR scores. Results: On inter-group comparison rise in systolic, diastolic and mean arterial blood pressure at 1,2,4 and 6min after drug administration were significantly high in phenylephrine group (p &lt;0.01) compared to ephedrine and mephentermine group. Thereafter the differences narrowed off. Heart rate was raised during episodes of hypotension. The mean heart rate was decreased significantly (p&lt;0.05) in phenylephrine group compared to other two groups. The neonatal APGAR score were &gt;/= 7 in the three groups at the 1st and 5th min. Conclusion: The study found that phenylephrine, ephedrine, and mephentermine effectively maintained arterial blood pressure in intravenous bolus form during subarachnoid block for caesarean section. Phenylephrine, a fast-acting, short-lived normotensive drug, significantly reduced heart rate compared to ephedrine and mephentermine, but did not cause significant adverse effects on mother and fetus. Keywords: hypotension; ephedrine; mephentermine; phenylephrine; subarachnoid block

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

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. 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. 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 29mmHg (IQR 19 to 41) compared with 31.8mmHg (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. 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.

Norepinephrine or phenylephrine for the prevention of post-spinal hypotension after caesarean section: A double-blinded, randomized, controlled study of fetal heart rate and fetal cardiac output

Study objectiveSpinal anesthesia often causes hypotension, with consequent risk to the fetus. The use of vasopressor agents has been highly recommended for the prevention of spinal anesthesia-induced hypotension during caesarean delivery. Many studies have shown that norepinephrine can provide more stable maternal hemodynamics than phenylephrine. We therefore tested the hypothesis that norepinephrine preserves fetal circulation better than phenylephrine when used to treat maternal hypotension consequent to spinal anesthesia. DesignProspective, randomized, double-blinded study. SettingOperating room. PatientsWe recruited 223 parturients with uncomplicated singleton pregnancies who were scheduled for elective caesarean section under combined spinal-epidural anesthesia. InterventionsThe patients received prophylactic intravenous infusion of either 0.08 μg/kg/min norepinephrine or 0.5 μg/kg/min phenylephrine for prevention of spinal anesthesia-induced hypotension. MeasurementsChanges in fetal heart rate and fetal cardiac output before and after spinal anesthesia were measured using noninvasive Doppler ultrasound. Main results90 subjects who received norepinephrine infusion and 93 subjects who received phenylephrine infusion were ultimately analyzed in the present study. The effects of norepinephrine and phenylephrine on the change of fetal heart rate and fetal cardiac output at 3 and 6 min after spinal block were similar. Although there was a statistically significant decrease in fetal cardiac output at 6 min after subarachnoid block initiation in both the norepinephrine group (mean difference 0.02 L/min; 95% CI, 0–0.04 L/min; P = 0.03) and the phenylephrine group (mean difference 0.02 L/min; 95% CI, 0–0.04 L/min; P = 0.02), it remained within the normal range. ConclusionsProphylactic infusion of comparable doses of phenylephrine or norepinephrine has similar effects on fetal heart rate and cardiac output changes after spinal anesthesia. Neither phenylephrine nor norepinephrine has meaningful detrimental effects on fetal circulation or neonatal outcomes.

Comparison of the effect of intravenous phenylephrine and norepinephrine boluses for post-spinal hypotension on neonatal outcome in elective caesarean section: A randomised controlled trial.

There is limited data on the effects of norepinephrine on neonatal outcomes and maternal complications relative to other vasopressors. The study aimed to compare neonatal outcomes and maternal complications after bolus intravenous doses of phenylephrine and norepinephrine for post-spinal hypotension in elective caesarean section women. This randomised study was done on 100 elective caesarean section women under spinal anaesthesia. Block randomisation divided women into two groups to receive intravenous phenylephrine 50 μg bolus (Group A) or norepinephrine 5 μg bolus (Group B) following post-spinal hypotension. Groups were evaluated and compared for umbilical arterial blood gas analysis, birth weight, APGAR (appearance, pulse, grimace, activity, and respiration) score, maternal haemodynamics, and complications. Kolmogorov-Smirnov and Shapiro-Wilk tests were used to verify data normality. Independent samples t-test or Mann-Whitney U test was employed to compare continuous variables based on data normality, and the Chi-square test was used to determine categorical variable associations. Demographic characteristics of women were found to be comparable between groups. Umbilical arterial potential of hydrogen, partial pressure of oxygen, partial pressure of carbon dioxide, base excess, bicarbonate, birth weight, and APGAR scores were comparable across groups, showing no significant differences (P > 0.05). Groups had similar maternal haemodynamic characteristics and episodes of nausea, vomiting, and chest pain across groups without statistical significance (P > 0.05). No notable distinction was found between neonatal outcomes and maternal complications between phenylephrine and norepinephrine bolus regimens. Norepinephrine can be used as an alternative to phenylephrine post-spinal hypotension in women undergoing elective caesarean section.

Prediction of preload dependency using phenylephrine-induced peripheral perfusion index during general anaesthesia: a prospective observational study

BackgroundTracking preload dependency non-invasively to maintain adequate tissue perfusion in the perioperative period can be challenging.The effect of phenylephrine on stroke volume is dependent upon preload. Changes in stroke volume induced by phenylephrine administration can be used to predict preload dependency. The change in the peripheral perfusion index derived from photoplethysmography signals reportedly corresponds with changes in stroke volume in situations such as body position changes in the operating room. Thus, the peripheral perfusion index can be used as a non-invasive potential alternative to stroke volume to predict preload dependency. Herein, we aimed to determine whether changes in perfusion index induced by the administration of phenylephrine could be used to predict preload dependency.MethodsWe conducted a prospective single-centre observational study. The haemodynamic parameters and perfusion index were recorded before and 1 and 2 min after administering 0.1 mg of phenylephrine during post-induction hypotension in patients scheduled to undergo surgery. Preload dependency was defined as a stroke volume variation of ≥ 12% before phenylephrine administration at a mean arterial pressure of < 65 mmHg. Patients were divided into four groups according to total peripheral resistance and preload dependency.ResultsForty-two patients were included in this study. The stroke volume in patients with preload dependency (n = 23) increased after phenylephrine administration. However, phenylephrine administration did not impact the stroke volume in patients without preload dependency (n = 19). The perfusion index decreased regardless of preload dependency. The changes in the perfusion index after phenylephrine administration exhibited low accuracy for predicting preload dependency. Based on subgroup analysis, patients with high total peripheral resistance tended to exhibit increased stroke volume following phenylephrine administration, which was particularly prominent in patients with high total peripheral resistance and preload dependency.ConclusionThe findings of the current study revealed that changes in the perfusion index induced by administering 0.1 mg of phenylephrine could not predict preload dependency. This may be attributed to the different phenylephrine-induced stroke volume patterns observed in patients according to the degree of total peripheral resistance and preload dependency.Trial registrationUniversity Hospital Medical Information Network (UMIN000049994 on 9/01/2023).

Regulation of nerve-evoked contractions of the murine vas deferens

Stimulation of sympathetic nerves in the vas deferens yields biphasic contractions consisting of a rapid transient component resulting from activation of P2X1 receptors by ATP and a secondary sustained component mediated by activation of α1-adrenoceptors by noradrenaline. Noradrenaline can also potentiate the ATP-dependent contractions of the vas deferens, but the mechanisms underlying this effect are unclear. The purpose of the present study was to investigate the mechanisms underlying potentiation of transient contractions of the vas deferens induced by activation of α1-adrenoceptors. Contractions of the mouse vas deferens were induced by electric field stimulation (EFS). Delivery of brief (1s duration) pulses (4 Hz) yielded transient contractions that were inhibited tetrodotoxin (100 nM) and guanethidine (10 µM). α,β-meATP (10 µM), a P2X1R desensitising agent, reduced the amplitude of these responses by 65% and prazosin (100 nM), an α1-adrenoceptor antagonist, decreased mean contraction amplitude by 69%. Stimulation of α1-adrenoceptors with phenylephrine (3 µM) enhanced EFS and ATP-induced contractions and these effects were mimicked by the phorbol ester PDBu (1 µM), which activates PKC. The PKC inhibitor GF109203X (1 µM) prevented the stimulatory effects of PDBu on ATP-induced contractions of the vas deferens but only reduced the stimulatory effects of phenylephrine by 40%. PDBu increased the amplitude of ATP-induced currents recorded from freshly isolated vas deferens myocytes and HEK-293 cells expressing human P2X1Rs by 93%. This study indicates that: (1) potentiation of ATP-evoked contractions of the mouse vas deferens by α1-adrenoceptor activation were not fully blocked by the PKC inhibitor GF109203X and (2) that the stimulatory effect of PKC on ATP-induced contractions of the vas deferens is associated with enhanced P2X1R currents in vas deferens myocytes.

A comparative study of the local effect of tranexamic acid and phenylephrine on the amount of bleeding in rhinoplasty: A randomized clinical trial.

Bleeding during nose surgery is very important, because it can cause a problem in the surgeon's field of view and lead to an increase in the probability of surgical complications. The aim of this study was to compare the local effects of tranexamic acid and phenylephrine on bleeding in rhinoplasty. The present study is a double-blind clinical trial in which 98 patients who were candidates for rhinoplasty Shiraz were randomly divided into 49 groups of phenylephrine and tranexamic acid. In the first group, 1 cc of phenylephrine and in the second group, 1 cc of tranexamic acid was used locally and then the variables in the two groups were compared. The current study was approved by the Iranian Clinical Trial Registration Center with code IRCT20201205049602N1. The average blood pressure and heart rate in the phenylephrine group first increased and then decreased, but in the tranexamic acid group decreased from the beginning to 30 minutes. Based on the results of the test, there was a difference between the two groups in terms of the amount of bleeding, and a statistically significant relationship was observed. The average bleeding volume was lower in the phenylephrine group (p<0.0001). Results of this study showed that the amount of bleeding in the phenylephrine group was lower than that of tranexamic acid. It is recommended to use phenylephrine in rhinoplasty surgery to reduce bleeding and improve the surgeon's vision.

Comparison of effects of norepinephrine and phenylephrine on maternal haemodynamics and foetal well-being after subarachnoid block for elective caesarean sections: A randomised double-blind controlled trial

Comparison of effects of norepinephrine and phenylephrine on maternal haemodynamics and foetal well-being after subarachnoid block for elective caesarean sections: A randomised double-blind controlled trial

Morphofunctional traits and reactivity of the portal vein

Background: Portal vein is the most enigmatic vessel of our body because it regulates own contractile performances using a special pace-maker mechanism represented by cells of Cajal. The contribution of various metabolic mediators and natural vasotropic agents in the control of the portal blood circuit is much less studied compared to the arterial system in general and the hepatic system in particular. The studies designed on the structure, function, and reactivity of the portal vein in different preconditioning have brought some common but also distinct evidence of the arterial system. Nitric oxide production is higher partly due to reduced arginase expression, but muscular media is thinner. Periodic spontaneous contractions directed towards the liver gate are characteristic for portal vein (PV), and the longitudinal muscle fibers are considered to be responsible for this phenomenon. Spontaneous rhythmic oscillations of the cells of Cajal are triggered by increasing calcium ion concentration leading to their depolarization. PV constrictor effect of phenylephrine is dependent on the activity of receptors to ET-1. For PV is characterized the acetylcholine induced contraction either in vivo or in vitro, and this effect is thought to be dependent on ET-1. Conclusions: The establishment of main particularities of portal vein reactivity of action of different paracrine, endocrine, and hemodynamical stimuli represents an important tool for prediction of contractile disorders leading plausible to portal hypertension. Likewise, a well proven interplay between cholinergic and adrenergic stimulations and on the other hand between Ang II and ET-1 actions must be a support for pharmacological modulating of portal vein reactivity disorders.

Role of CB1 Cannabinoid Receptors in Vascular Responses and Vascular Remodeling of the Aorta in Female Mice.

Both the endocannabinoid system (ECS) and estrogens have significant roles in cardiovascular control processes. Cannabinoid type 1 receptors (CB1Rs) mediate acute vasodilator and hypotensive effects, although their role in cardiovascular pathological conditions is still controversial. Estrogens exert cardiovascular protection in females. We aimed to study the impact of ECS on vascular functions. Experiments were performed on CB1R knockout (CB1R KO) and wild-type (WT) female mice. Plasma estrogen metabolite levels were determined. Abdominal aortas were isolated for myography and histology. Vascular effects of phenylephrine (Phe), angiotensin II, acetylcholine (Ach) and estradiol (E2) were obtained and repeated with inhibitors of nitric oxide synthase (NOS, Nω-nitro-L-arginine) and of cyclooxygenase (COX, indomethacin). Histological stainings (hematoxylin-eosin, resorcin-fuchsin) and immunostainings for endothelial NOS (eNOS), COX-2, estrogen receptors (ER-α, ER-β) were performed. Conjugated E2 levels were higher in CB1R KO compared to WT mice. Vasorelaxation responses to Ach and E2 were increased in CB1R KO mice, attenuated by NOS-inhibition. COX-inhibition decreased Phe-contractions, while it increased Ach-relaxation in the WT group but not in the CB1R KO. Effects of indomethacin on E2-relaxation in CB1R KO became opposite to that observed in WT. Histology revealed lower intima/media thickness and COX-2 density, higher eNOS and lower ER-β density in CB1R KO than in WT mice. CB1R KO female mice are characterized by increased vasorelaxation associated with increased utilization of endothelial NO and a decreased impact of constrictor prostanoids. Our results indicate that the absence or inhibition of CB1Rs may have beneficial vascular effects.

Effects of phenylephrine on systemic and cerebral circulations in humans: a systematic review with mechanistic explanations.

We conducted a systematic review of the literature reporting phenylephrine-induced changes in blood pressure, cardiac output, cerebral blood flow and cerebral tissue oxygen saturation as measured by near-infrared spectroscopy in humans. We used the proportion change of the group mean values reported by the original studies in our analysis. Phenylephrine elevates blood pressure whilst concurrently inducing a reduction in cardiac output. Furthermore, despite increasing cerebral blood flow, it decreases cerebral tissue oxygen saturation. The extent of phenylephrine's influence on cardiac output (r = -0.54 and p = 0.09 in awake humans; r = -0.55 and p = 0.007 in anaesthetised humans), cerebral blood flow (r = 0.65 and p = 0.002 in awake humans; r = 0.80 and p = 0.003 in anaesthetised humans) and cerebral tissue oxygen saturation (r = -0.72 and p = 0.03 in awake humans; r = -0.24 and p = 0.48 in anaesthetised humans) appears closely linked to the magnitude of phenylephrine-induced blood pressure changes. When comparing the effects of phenylephrine in awake and anaesthetised humans, we found no evidence of a significant difference in cardiac output, cerebral blood flow or cerebral tissue oxygen saturation. There was also no evidence of a significant difference in effect on systemic and cerebral circulations whether phenylephrine was given by bolus or infusion. We explore the underlying mechanisms driving the phenylephrine-induced cardiac output reduction, cerebral blood flow increase and cerebral tissue oxygen saturation decrease. Individualised treatment approaches, close monitoring and consideration of potential risks and benefits remain vital to the safe and effective use of phenylephrine in acute care.