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1.
Medicine (Baltimore) ; 99(28): e20946, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664094

RESUMO

BACKGROUND: The beach chair position (BCP), used during shoulder surgery, is associated with hypotension, bradycardia, and risk of cerebral hypoperfusion. Phenylephrine is commonly used as a first treatment of choice of intraoperative hypotension during surgery. We evaluated the hemodynamic effects of 2 doses of intravenous phenylephrine infusion administered before being placed in BCP for arthroscopic shoulder surgery. The primary endpoint was the incidence of hypotension after positional change. METHODS: Sixty-six patients were randomized to receive either intravenous normal saline (group NS) or intravenous phenylephrine infusion (0.5 µg/kg/min, group LP or 1.0 µg/kg/min, group HP) for 5 minutes before being placed in the BCP. Mean arterial pressure(MAP), heart rate, stroke volume variation, and cardiac index were measured before and after positional change. RESULTS: The total incidence of hypotension after the BCP was 93.65%, but was not significantly different among the 3 groups. However, there was a significant difference in trends between the groups for MAP for 5 minutes after BCP (P = .028). Comparison of changes in MAP at 1 minute compared to post-induction MAP was significantly different between group HP and group NS (P = .014). CONCLUSION: Infusion of 0.5 and 1.0 µg/kg/min of phenylephrine for 5 minutes before the BCP has no preventive effect for incidence of hypotension. However, this study showed that 1.0 µg/kg/min of phenylephrine infusion for 5 minutes can attenuate the severity of hypotension.


Assuntos
Hipotensão/etiologia , Hipotensão/prevenção & controle , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/prevenção & controle , Posicionamento do Paciente/efeitos adversos , Fenilefrina/administração & dosagem , Idoso , Feminino , Humanos , Hipotensão/epidemiologia , Incidência , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego
2.
Pol Merkur Lekarski ; 48(285): 215-220, 2020 Jun 17.
Artigo em Polonês | MEDLINE | ID: mdl-32564050

RESUMO

Demographic data clearly show the progressive aging of societies. Problems and specificity of anaesthesia in the elderly becomes a particularly important issue in this context. Spinal anesthesia is a method often used to anesthetize elderly patients, and hypotension is one of its most common early complications. Untreated or improperly treated hypotension increases the risk of perioperative complications such as myocardial infarction, ischemic stroke or acute renal failure. The prevention of hypotension consists of intravenous fluid therapy and pre-emptive use of vasoconstrictor drugs. Among vasoconstrictors, ephedrine and phenylephrine are commonly used to treat hypotension due to spinal anaesthesia. Both drugs are available in Poland. Issues related to their use in the treatment of hypotension caused by spinal anaesthesia in the elderly, including the features of both drugs, their method of administration and dosage based on the literature and own experience are the subject of this study. It should be noted, however, that most studies in the use of ephedrine and phenylephrine as a targeted treatment for hypotension concern the obstetric patient population while the elderly population is underrepresented and the results are inconclusive.


Assuntos
Anestesia , Hipotensão , Idoso , Anestesia/efeitos adversos , Anestesia Obstétrica/efeitos adversos , Cesárea , Feminino , Humanos , Hipotensão/etiologia , Fenilefrina , Polônia , Gravidez
3.
Crit Care ; 24(1): 95, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188462

RESUMO

BACKGROUND: Concomitant vasoactive drugs are often required to maintain adequate perfusion pressure in patients with acute myocardial infarction (AMI) and cardiogenic shock (CS) receiving hemodynamic support with an axial flow pump (Impella CP). OBJECTIVE: To compare the effect of equipotent dosages of epinephrine, dopamine, norepinephrine, and phenylephrine on cardiac work and end-organ perfusion in a porcine model of profound ischemic CS supported with an Impella CP. METHODS: CS was induced in 10 pigs by stepwise intracoronary injection of polyvinyl microspheres. Hemodynamic support with Impella CP was initiated followed by blinded crossover to vasoactive treatment with norepinephrine (0.10 µg/kg/min), epinephrine (0.10 µg/kg/min), or dopamine (10 µg/kg/min) for 30 min each. At the end of the study, phenylephrine (10 µg/kg/min) was administered for 20 min. The primary outcome was cardiac workload, a product of pressure-volume area (PVA) and heart rate (HR), measured using the conductance catheter technique. End-organ perfusion was assessed by measuring venous oxygen saturation from the pulmonary artery (SvO2), jugular bulb, and renal vein. Treatment effects were evaluated using multilevel mixed-effects linear regression. RESULTS: All catecholamines significantly increased LV stroke work and cardiac work, dopamine to the greatest extend by 341.8 × 103 (mmHg × mL)/min [95% CI (174.1, 509.5), p < 0.0001], and SvO2 significantly improved during all catecholamines. Phenylephrine, a vasoconstrictor, caused a significant increase in cardiac work by 437.8 × 103 (mmHg × mL)/min [95% CI (297.9, 577.6), p < 0.0001] due to increase in potential energy (p = 0.001), but no significant change in LV stroke work. Also, phenylephrine tended to decrease SvO2 (p = 0.063) and increased arterial lactate levels (p = 0.002). CONCLUSION: Catecholamines increased end-organ perfusion at the expense of increased cardiac work, most by dopamine. However, phenylephrine increased cardiac work with no increase in end-organ perfusion.


Assuntos
Débito Cardíaco/efeitos dos fármacos , Coração Auxiliar , Hemodinâmica/efeitos dos fármacos , Choque Cardiogênico/terapia , Animais , Catecolaminas/uso terapêutico , Modelos Animais de Doenças , Dopamina , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Norepinefrina , Fenilefrina , Choque Cardiogênico/fisiopatologia , Suínos
4.
PLoS One ; 15(3): e0227316, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126062

RESUMO

Alpha adrenergic stimulation is known to produce vasoconstriction. We have earlier shown that, in spiral strips of small arteries Phenylephrine (PE) caused vasorelaxation under high nitric oxide (NO) environment. However, on further experimentation it was realized that the PE-induced vasorelaxant response occurred only with longitudinal strips of small arteries even under normal NO environment while circular strips showed contraction with PE even under high NO environment. Such PE-induced vasorelaxation of longitudinal strips was blocked by Phentolamine, an alpha-adrenergic receptor blocker. On delineation of specific receptor subtype, PE-induced relaxation was found to be mediated through alpha 1D receptor. However, this phenomenon is specific to small artery, as longitudinal smooth muscle of aorta showed only contractile response to adrenergic stimulation. There is no prior report of longitudinal smooth muscle in small artery up to our knowledge. The results of this study and histological examination of vessel sections suggest the presence of longitudinal smooth muscle in small artery and their relaxant response to alpha adrenergic stimulation is a novel phenomenon.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 1/farmacologia , Artérias/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Fenilefrina/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Artérias/fisiologia , Cabras , Extremidade Inferior/irrigação sanguínea , Músculo Liso Vascular/fisiologia
6.
Am J Physiol Heart Circ Physiol ; 318(4): H937-H946, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32142360

RESUMO

The arterial baroreflex has dominant control over multiunit muscle sympathetic nerve activity (MSNA) burst occurrence, but whether this extends to all single units or is influenced by resting blood pressure status is unclear. In 22 men (32 ± 8 yr), we assessed 68 MSNA single units during sequential bolus injections of nitroprusside and phenylephrine (modified Oxford). Sympathetic baroreflex sensitivity (sBRS) was quantified as the weighted negative linear regression slope between diastolic blood pressure (DBP) and single-unit spike firing probability and multiple spike firing. Strong negative linear relationships (r ≥ -0.50) between DBP and spike firing probability were observed in 63/68 (93%) single units (-2.27 ± 1.27%·cardiac cycle-1·mmHg-1 [operating range, 18 ± 8 mmHg]). In contrast, only 45/68 (66%) single units had strong DBP-multiple spike firing relationships (-0.13 ± 0.18 spikes·cardiac cycle-1·mmHg-1 [operating range, 14 ± 7 mmHg]). Participants with higher resting DBP (65 ± 3 vs. 77 ± 3 mmHg, P < 0.001) had similar spike firing probability sBRS (low vs. high, -2.08 ± 1.08 vs. -2.46 ± 1.42%·cardiac cycle-1·mmHg-1, P = 0.33), but a smaller sBRS operating range (20 ± 6 vs. 16 ± 9 mmHg, P = 0.01; 86 ± 24 vs. 52 ± 25% of total range, P < 0.001) and a higher proportion of single units without arterial baroreflex control outside this range [6/31 (19%) vs. 21/32 (66%), P < 0.001]. Participants with higher resting DBP also had fewer single units with arterial baroreflex control of multiple spike firing (79 vs. 53%, P = 0.04). The majority of MSNA single units demonstrate strong arterial baroreflex control over spike firing probability during pharmacological manipulation of blood pressure. Changes in single-unit sBRS operating range and control of multiple spike firing may represent altered sympathetic recruitment patterns associated with the early development of hypertension.NEW & NOTEWORTHY Muscle sympathetic single units can be differentially controlled during stress. In contrast, we demonstrate that 93% of single units maintain strong arterial baroreflex control during pharmacological manipulation of blood pressure. Interestingly, the operating range and proportion of single units that lose arterial baroreflex control outside of this range are influenced by resting blood pressure levels. Altered single unit, but not multiunit, arterial baroreflex control may represent changes in sympathetic recruitment patterns in early stage development of hypertension.


Assuntos
Artérias/fisiologia , Barorreflexo , Pressão Sanguínea , Músculo Liso Vascular/fisiologia , Sistema Nervoso Simpático/fisiologia , Adulto , Artérias/efeitos dos fármacos , Humanos , Masculino , Condução Nervosa , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Vasodilatadores/farmacologia
7.
Am J Physiol Heart Circ Physiol ; 318(5): H1041-H1048, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32196361

RESUMO

Discrete calcium signals within the vascular endothelium decrease with age and contribute to impaired endothelial-dependent vasodilation. Calreticulin (Calr), a multifunctional calcium binding protein and endoplasmic reticulum (ER) chaperone, can mediate calcium signals and vascular function within the endothelial cells (ECs) of small resistance arteries. We found Calr protein expression significantly decreases with age in mesenteric arteries and examined the functional role of EC Calr in vasodilation and calcium mobilization in the context of aging. Third-order mesenteric arteries from mice with or without EC Calr knockdown were examined for calcium signals and constriction to phenylephrine (PE) or vasodilation to carbachol (CCh) after 75 wk of age. PE constriction in aged mice with or without EC Calr was unchanged. However, calcium signals and vasodilation to endothelial-dependent agonist carbachol were significantly impaired in aged EC Calr knockdown mice. Ex vivo incubation of arteries with the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) significantly improved vasodilation in mice lacking EC Calr. Our data suggests diminished vascular Calr expression with age can contribute to the detrimental effects of aging on endothelial calcium regulation and vasodilation.NEW & NOTEWORTHY Calreticulin (Calr) is responsible for key physiological processes in endoplasmic reticulum, especially in aging tissue. In particular, endothelial Calr is crucial to vascular function. In this study, we deleted Calr from the endothelium and aged the mice up to 75 wk to examine changes in vascular function. We found two key differences: 1) calcium events in endothelium were severely diminished after muscarinic stimulation, which 2) corresponded with a dramatic decrease in muscarinic vasodilation. Remarkably, we were able to rescue the effect of Calr deletion on endothelial-dependent vasodilatory function using tauroursodeoxycholic acid (TUDCA), an inhibitor of endoplasmic reticulum stress that is currently in clinical trials.


Assuntos
Envelhecimento/metabolismo , Calreticulina/metabolismo , Endotélio Vascular/metabolismo , Envelhecimento/fisiologia , Animais , Sinalização do Cálcio , Calreticulina/genética , Carbacol/farmacologia , Endotélio Vascular/fisiologia , Deleção de Genes , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Fenilefrina/farmacologia , Ácido Tauroquenodesoxicólico/farmacologia , Vasoconstritores/farmacologia , Vasodilatação
8.
Am J Physiol Regul Integr Comp Physiol ; 318(4): R730-R742, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32022595

RESUMO

The two kidney-one clip (2K1C) renovascular hypertension depends on the renin-angiotensin system and sympathetic overactivity. The maintenance of 2K1C hypertension also depends on inputs from the carotid bodies (CB), which when activated stimulate the respiratory activity. In the present study, we investigated the importance of CB afferent activity for the ventilatory responses in 2K1C hypertensive rats and for phrenic and hypoglossal activities in in situ preparations of normotensive rats treated with angiotensin II. Silver clips were implanted around the left renal artery of male Holtzman rats (150 g) to induce renovascular hypertension. Six weeks after clipping, hypertensive 2K1C rats showed, in conscious state, elevated resting tidal volume and minute ventilation compared with the normotensive group. 2K1C rats also presented arterial alkalosis, urinary acidification, and amplified hypoxic ventilatory response. Carotid body removal (CBR), 2 wk before the experiments (4th week after clipping), significantly reduced arterial pressure and pulmonary ventilation in 2K1C rats but not in normotensive rats. Intra-arterial administration of angiotensin II in the in situ preparation of normotensive rats increased phrenic and hypoglossal activities, responses that were also reduced after CBR. Results show that renovascular hypertensive rats exhibit increased resting ventilation that depends on CB inputs. Similarly, angiotensin II increases phrenic and hypoglossal activities in in situ preparations of normotensive rats, responses that also depend on CB inputs. Results suggest that mechanisms that depend on CB inputs in renovascular hypertensive rats or during angiotensin II administration in normotensive animals increase respiratory drive.


Assuntos
Corpo Carotídeo/fisiologia , Hipertensão Renovascular/fisiopatologia , Ratos Sprague-Dawley , Angiotensina II/administração & dosagem , Angiotensina II/farmacologia , Animais , Nervo Hipoglosso/fisiologia , Masculino , Fenilefrina/administração & dosagem , Fenilefrina/farmacologia , Nervo Frênico/fisiologia , Ratos , Sistema Nervoso Simpático , Simpatomiméticos/farmacologia
9.
Anaesthesia ; 75(6): 800-808, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32012226

RESUMO

Phenylephrine is recommended for the management of hypotension after spinal anaesthesia in women undergoing caesarean section. Noradrenaline, an adrenergic agonist with weak ß-adrenergic activity, has been reported to have a more favourable haemodynamic profile than phenylephrine. However, there are concerns that noradrenaline may be associated with a higher risk of fetal acidosis, defined as an umbilical artery pH < 7.20. We performed a systematic review of trials comparing noradrenaline with phenylephrine, concentrating on primary outcomes of fetal acidosis and maternal hypotension. We identified 13 randomised controlled trials including 2002 patients. Heterogeneity among the studies was high, and there were too few data to calculate a pooled effect estimate. Fetal acidosis was assessed in four studies that had a low risk of bias and a low risk of confounding, that is, studies which used a prophylactic vasopressor and where women received the allocated vasopressor only. There were no significant differences between these studies. No significant differences were observed for hypotension. Two trials found a significantly lower incidence of bradycardia when using noradrenaline. Cardiac output was significantly higher after noradrenaline in two of three studies. For other secondary outcomes including nausea, vomiting and Apgar scores at 1 and 5 min, no studies found significant differences. The evidence so far is too limited to support an advantage of noradrenaline over phenylephrine. Concerns of a deleterious effect of noradrenaline on fetal blood gas status cannot currently be assuaged by the available data from randomised controlled studies.


Assuntos
Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Cesárea , Hipotensão/prevenção & controle , Norepinefrina/uso terapêutico , Fenilefrina/uso terapêutico , Adulto , Feminino , Humanos , Hipotensão/induzido quimicamente , Gravidez , Vasoconstritores/uso terapêutico
10.
Phytomedicine ; 68: 153171, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32018211

RESUMO

BACKGROUND: Cardiac hypertrophy is a prominent feature of heart remodeling, which may eventually lead to heart failure. Tongmaiyangxin (TMYX) pills are a clinically used botanical drug for treating multiple cardiovascular diseases including chronic heart failure. The aim of the current study was to identify the bioactive compounds in Tongmaiyangxin pills that attenuate cardiomyocytes hypertrophy, and to investigate the underlying mechanism of action. METHODS AND RESULTS: The anti-hypertrophy effect of TMYX was validated in isoproterenol-induced cardiac hypertrophy model in C57BL/6 mice. After TMYX treatment for 2 weeks, the heart ejection fraction and fractional shortening of the mice model was increased by approximately 20% and 15%, respectively, (p < 0.05). Besides, TMYX dose-dependently reduced the cross section area of cardiomyocytes in the angiotensin-II induced hypertrophy H9c2 model (p < 0.01). Combining high content screening and liquid chromatography mass spectrometry, four compounds with anti-cardiac hypertrophy effects were identified from TMYX, which includes emodin, licoisoflavone A, licoricone and glyasperin A. Licoisoflavone A is one of the compounds with most significant protective effect and we continued to investigate the mechanism. Primary cultures of neonatal rat cardiomyocytes were treated with a hypertrophic agonist phenylephrine (PE) in the presence or absence of licoisoflavone A. After 48 h of treatment, cells were harvested and mitochondrial acetylation was analyzed by western blotting and Image analysis. Interestingly, the results suggested that the anti-hypertrophic effects of licoisoflavone A depend on the activation of the deacetylase Sirt3 (p < 0.01). Finally, we showed that licoisoflavone A-treatment was able to decrease relative ANF and BNP levels in the hypertrophic cardiac cells (p < 0.01), but not in cells co-treated with Sirt3 inhibitors (3-TYP) (p > 0.05). CONCLUSION: TMYX exerts its anti-hypertrophy effect possibly through upregulating Sirt3 expression. Four compounds were identified from TMYX which may be responsible for the anti-hypertrophy effect. Among these compounds, licoisoflavone A was demonstrated to block the hypertrophic response of cardiomyocytes, which required its positive regulation on the expression of Sirt3. These results suggested that licoisoflavone A is a potential Sirt3 activator with therapeutic effect on cardiac hypertrophy.


Assuntos
Cardiomegalia/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Isoflavonas/farmacologia , Sirtuína 3/metabolismo , Acetilação , Angiotensina II/efeitos adversos , Animais , Cardiomegalia/induzido quimicamente , Células Cultivadas , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Isoproterenol/efeitos adversos , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fenilefrina/efeitos adversos , Ratos
11.
Am J Physiol Renal Physiol ; 318(2): F496-F505, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31904286

RESUMO

Urethral smooth muscle (USM) generates tone to prevent urine leakage from the bladder during filling. USM tone has been thought to be a voltage-dependent process, relying on Ca2+ influx via voltage-dependent Ca2+ channels in USM cells, modulated by the activation of Ca2+-activated Cl- channels encoded by Ano1. However, recent findings in the mouse have suggested that USM tone is voltage independent, relying on Ca2+ influx through Orai channels via store-operated Ca2+ entry (SOCE). We explored if this pathway also occurred in the pig using isometric tension recordings of USM tone. Pig USM strips generated myogenic tone, which was nearly abolished by the Cav1.2 channel antagonist nifedipine and the ATP-dependent K+ channel agonist pinacidil. Pig USM tone was reduced by the Orai channel blocker GSK-7975A. Electrical field stimulation (EFS) led to phentolamine-sensitive contractions of USM strips. Contractions of pig USM were also induced by phenylephrine. Phenylephrine-evoked and EFS-evoked contractions of pig USM were reduced by ~50-75% by nifedipine and ~30% by GSK-7975A. Inhibition of Ano1 channels had no effect on tone or EFS-evoked contractions of pig USM. In conclusion, unlike the mouse, pig USM exhibited voltage-dependent tone and agonist/EFS-evoked contractions. Whereas SOCE plays a role in generating tone and agonist/neural-evoked contractions in both species, this dominates in the mouse. Tone and agonist/EFS-evoked contractions of pig USM are the result of Ca2+ influx primarily through Cav1.2 channels, and no evidence was found supporting a role of Ano1 channels in modulating these mechanisms.


Assuntos
Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Ativados pela Liberação de Cálcio/metabolismo , Sinalização do Cálcio , Contração Isométrica , Músculo Liso/metabolismo , Uretra/metabolismo , Animais , Benzamidas/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo L/efeitos dos fármacos , Canais de Cálcio Ativados pela Liberação de Cálcio/antagonistas & inibidores , Sinalização do Cálcio/efeitos dos fármacos , Estimulação Elétrica , Feminino , Técnicas In Vitro , Contração Isométrica/efeitos dos fármacos , Masculino , Músculo Liso/efeitos dos fármacos , Nifedipino/farmacologia , Fenilefrina/farmacologia , Pirazóis/farmacologia , Sus scrofa , Uretra/efeitos dos fármacos
12.
Sci Rep ; 10(1): 1257, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31988341

RESUMO

End-expiratory occlusion test (EEOT) has been proposed as a preload responsiveness test that overcomes several limitations of pulse pressure (PPV) and stroke volume (SVV) variations. We compared the ability of EEOT versus SVV and PPV to predict fluid responsiveness during the increase of the vasomotor tone in a rabbit model of hemorrhage. Ten rabbits were anesthetized, paralyzed, and mechanically ventilated during basal load (BL), after progressive blood withdrawal (BW), and after volume replacement. Other two sets of data were obtained during vasomotor increase by phenylephrine (PHE) infusion in BL and BW. We estimated the change of stroke volume (∆SVEEOT) and aortic flow (∆AoFEEOT) during the EEOT. PPV and SVV were obtained by the variation of beat-to-beat PP and SV, respectively. Baseline PPV, SVV, ∆SVEEOT, and ∆AoFEEOT increased significantly after BW, with a decrease of aortic flow (P < 0.05). PHE induced a significant decrease of PPV and SVV, but without affecting ∆SVEEOT, and ∆AoFEEOT. We conclude that ∆SV and ∆AoF during EEOT kept the ability to predict fluid responsiveness during PHE infusion in a rabbit hemorrhage model. This result may suggest the advantage of EEOT with respect to SVV and PPV in predicting fluid responsiveness during vasomotor tone increase.


Assuntos
Hemorragia/fisiopatologia , Respiração com Pressão Positiva/métodos , Animais , Pressão Sanguínea/fisiologia , Modelos Animais de Doenças , Feminino , Hidratação/métodos , Hemodinâmica , Monitorização Fisiológica/métodos , Fenilefrina/farmacologia , Coelhos , Volume Sistólico/fisiologia , Sistema Vasomotor
13.
Urology ; 135: 66-70, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31541647

RESUMO

OBJECTIVE: To define age-specific normal Color Doppler Duplex Ultrasound (CDDU) parameters based on a large institutional database of men referred for vascular erectile testing, but found to have normal and sustained rigidity following penile injection of alprostadil. METHODS: A retrospective review of patients who underwent CDDU from January 1, 2005 to December 31, 2014 was conducted. The indications for CDDU assessments included complaint of erectile dysfunction refractory to PDE-5 inhibitors, new-onset penile curvature, or secondary consultation for erectile dysfunction. Pearson correlation test was used to evaluate the association between ordinal age groups with peak systolic velocity (PSV) and resistive index (RI) measurements to determine the effect of age on erectile response. RESULTS: A total of 2043 patients underwent CDDU from January 1, 2005 to December 31, 2014. 259 patients (12.7%) with a mean age 53.7 and a mean BMI of 27.2 were noted to have normal erectile rigidity and normal Doppler parameters (PSV >35 cm/s, RI >0.90). Prolonged erection, defined by need to inject phenylephrine reversal agent at 1-2 hours, occurred in 93% of patients. When age was categorized by decade, a negative correlation coefficient was obtained for previsual sexual stimulation PSV (-0.09, P = .164) and postvisual sexual stimulation PSV (-0.23, P = .005). CONCLUSION: In men with normal vascular erections there appears to be a significant, age-related decline in postvisual sexual stimulation PSV without compromise to cavernous venous occlusion as measured by RI. We have used Doppler parameters in patients without vascular ED to define age-specific normalcy.


Assuntos
Envelhecimento/fisiologia , Disfunção Erétil/diagnóstico , Ereção Peniana/fisiologia , Pênis/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana/efeitos dos fármacos , Pênis/irrigação sanguínea , Pênis/fisiologia , Fenilefrina/administração & dosagem , Fenilefrina/antagonistas & inibidores , Inibidores da Fosfodiesterase 5/farmacologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Estudos Retrospectivos , Falha de Tratamento , Agentes Urológicos/uso terapêutico , Adulto Jovem
14.
Anaesthesia ; 75(4): 487-492, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31811659

RESUMO

Spinal hypotension is a common and clinically important problem during caesarean section. Current consensus recommendations for resource-rich settings suggest the use of a titrated phenylephrine infusion, in combination with fluid coloading, for prevention of maternal hypotension. In resource-limited settings, where syringe drivers are unavailable, these recommendations advise the addition of 500 µg phenylephrine to the first 1 l of intravenous fluid given after initiation of spinal anaesthesia, with additional vasopressor boluses as required. This prospective, alternating intervention study compared the use of a conventional phenylephrine rescue bolus strategy for prevention of hypotension, defined as systolic arterial pressure < 90 mmHg, with a phenylephrine infusion given according to the consensus recommendation. We studied 300 women having elective caesarean section. There were 77 (51%) women who developed hypotension in the bolus group vs. 55 (37%) in the phenylephrine infusion group (p = 0.011). This represented a 29% reduction in hypotension, with a number needed to treat of 6.8. The six highest systolic arterial pressure readings occurred in the phenylephrine infusion group (range 166-188 mmHg), and there were four instances of bradycardia (heart rate < 50 beats.min-1 ) with preserved systolic arterial pressure in each group. There were no adverse clinical sequelae, and no differences in neonatal Apgar scores in either group. The consensus recommendation for phenylephrine and fluid co-administration in resource-limited settings appears effective in preventing maternal hypotension, but at the cost of sporadic systolic hypertension.


Assuntos
Cesárea , Hidratação/métodos , Hipotensão/prevenção & controle , Fenilefrina/uso terapêutico , Vasoconstritores/uso terapêutico , Adulto , Terapia Combinada/métodos , Países em Desenvolvimento , Procedimentos Cirúrgicos Eletivos , Feminino , Recursos em Saúde , Humanos , Infusões Intravenosas , Fenilefrina/administração & dosagem , Estudos Prospectivos , África do Sul , Resultado do Tratamento , Vasoconstritores/administração & dosagem
15.
Br J Anaesth ; 124(3): e95-e107, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31810562

RESUMO

BACKGROUND: The optimal choice of vasopressor drugs for managing hypotension during neuraxial anaesthesia for Caesarean delivery is unclear. Although phenylephrine was recently recommended as a consensus choice, direct comparison of phenylephrine with vasopressors used in other healthcare settings is largely lacking. Therefore, we assessed this indirectly by collating data from relevant studies in this comprehensive network meta-analysis. Here, we provide the possible rank orders for these vasopressor agents in relation to clinically important fetal and maternal outcomes. METHODS: RCTs were independently searched in MEDLINE, Web of Science, Embase, The Cochrane Central Register of Controlled Trials, and clinicaltrials.gov (updated January 31, 2019). The primary outcome assessed was umbilical arterial base excess. Secondary fetal outcomes were umbilical arterial pH and Pco2. Maternal outcomes were incidences of nausea, vomiting, and bradycardia. RESULTS: We included 52 RCTs with a total of 4126 patients. Our Bayesian network meta-analysis showed the likelihood that norepinephrine, metaraminol, and mephentermine had the lowest probability of adversely affecting the fetal acid-base status as assessed by their effect on umbilical arterial base excess (probability rank order: norepinephrine > mephentermine > metaraminol > phenylephrine > ephedrine). This rank order largely held true for umbilical arterial pH and Pco2. With the exception of maternal bradycardia, ephedrine had the highest probability of being the worst agent for all assessed outcomes. Because of the inherent imprecision when collating direct/indirect comparisons, the rank orders suggested are possibilities rather than absolute ranks. CONCLUSION: Our analysis suggests the possibility that norepinephrine and metaraminol are less likely than phenylephrine to be associated with adverse fetal acid-base status during Caesarean delivery. Our results, therefore, lay the scientific foundation for focused trials to enable direct comparisons between these agents and phenylephrine.


Assuntos
Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Teorema de Bayes , Hipotensão/prevenção & controle , Metanálise em Rede , Vasoconstritores/uso terapêutico , Cesárea , Feminino , Humanos , Hipotensão/tratamento farmacológico , Norepinefrina/uso terapêutico , Fenilefrina/uso terapêutico , Gravidez
16.
Anesth Analg ; 130(1): 187-193, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30829668

RESUMO

BACKGROUND: Prophylactic IV infusion of phenylephrine has been recommended to prevent hypotension during spinal anesthesia for cesarean delivery. However, the optimal infusion dose is unknown. This study aimed to determine the infusion dose of phenylephrine that would be effective in preventing hypotension in 50% (ED50) and 90% (ED90) of patients when administered as a prophylactic infusion at a fixed rate based on the individual body weight. METHODS: Eighty parturients scheduled for elective cesarean delivery were randomly allocated to receive IV infusion of prophylactic phenylephrine at 0.25, 0.375, 0.5, or 0.625 µg/kg/min (n = 20 per group) started immediately after intrathecal injection of 10 mg hyperbaric bupivacaine and 5 µg sufentanil using a combined spinal-epidural technique. An effective dose was defined by the occurrence of no hypotension (defined as a decrease in systolic blood pressure by ≥20% below baseline and to <90 mm Hg) during the interval from the initiation of spinal anesthesia to delivery of the infant. Values for ED50 and ED90 of prophylactic phenylephrine were calculated using probit analysis. RESULTS: Hypotension occurred in 13/20, 8/20, 2/20, and 1/20 patients in the groups that received phenylephrine infusion at 0.25, 0.375, 0.5, or 0.625 µg/kg/min, respectively. The calculated values for ED50 and ED90 were 0.31 (95% CI, 0.24-0.36) and 0.54 (95% CI, 0.46-0.76) µg/kg/min, respectively. No difference was found in the incidence of adverse effects and neonatal outcomes among groups. CONCLUSIONS: Under the conditions of this study, when phenylephrine was given as a fixed-rate prophylactic infusion during spinal anesthesia for cesarean delivery to prevent hypotension, the values for ED50 and ED90 were 0.31 (95% CI, 0.24-0.36) and 0.54 (95% CI, 0.46-0.76) µg/kg/min, respectively.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Anestesia Obstétrica , Raquianestesia , Pressão Sanguínea/efeitos dos fármacos , Cesárea , Hipotensão/prevenção & controle , Parto , Fenilefrina/administração & dosagem , Vasoconstritores/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Anestesia Epidural/efeitos adversos , Raquianestesia/efeitos adversos , Peso Corporal , Cesárea/efeitos adversos , China , Relação Dose-Resposta a Droga , Método Duplo-Cego , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Hipotensão/diagnóstico , Hipotensão/etiologia , Hipotensão/fisiopatologia , Infusões Intravenosas , Fenilefrina/efeitos adversos , Gravidez , Fatores de Tempo , Resultado do Tratamento , Vasoconstritores/efeitos adversos
18.
BMJ Case Rep ; 12(12)2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31811105

RESUMO

We describe the case of a 25-year-old parturient who presented sudden onset and short-lived severe headache caused by reversible cerebral vasoconstriction syndrome (RCVS) during an emergency caesarean section. The syndrome was triggered by phenylephrine administered intravenously to correct arterial hypotension following spinal anaesthesia. RCVS is a clinical and radiological syndrome attributed to transient disturbance in the control of cerebral arterial tone resulting in vasospasms. The syndrome can be precipitated by several triggers, including vasoactive drugs, often used during spinal anaesthesia, illicit drugs, pregnancy and postpartum state. Diagnosis and management can be challenging during pregnancy, peripartum or post partum, since many medications commonly used during these periods must be avoided to prevent triggering RCVS. The aim of this report is to raise the awareness, particularly for anaesthesiologists and obstetricians, of this rare and potentially serious syndrome. We discuss diagnosis, triggers, pathogenesis, clinical course and complications, as well as coordinated multidisciplinary management plans.


Assuntos
Transtornos Cerebrovasculares/diagnóstico , Hipertensão/diagnóstico , Complicações Intraoperatórias/diagnóstico , Fenilefrina/efeitos adversos , Vasoconstritores/efeitos adversos , Vasoespasmo Intracraniano/diagnóstico , Adulto , Raquianestesia/efeitos adversos , Transtornos Cerebrovasculares/induzido quimicamente , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico por imagem , Cesárea , Diagnóstico Diferencial , Feminino , Cefaleia/etiologia , Humanos , Hipertensão/induzido quimicamente , Hipertensão/complicações , Hipertensão/diagnóstico por imagem , Complicações Intraoperatórias/induzido quimicamente , Fenilefrina/administração & dosagem , Fatores Desencadeantes , Gravidez , Vasoconstritores/administração & dosagem , Vasoespasmo Intracraniano/induzido quimicamente , Vasoespasmo Intracraniano/complicações , Vasoespasmo Intracraniano/diagnóstico por imagem
19.
Medicina (Kaunas) ; 55(12)2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31817916

RESUMO

Background and Objectives: The potent, endothelium-independent, vasorelaxant effect of ethyl rosmarinate, an ester derivative of rosmarinic acid, makes it of interest as an alternative therapeutic agent for use in hypertension. This study was designed to investigate the effect of ethyl rosmarinate on Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Materials and Methods: L-NAME was given orally to male Wistar rats for 6 weeks to induce hypertension concurrently with treatment of ethyl rosmarinate at 5, 15, or 30 mg/kgor enalapril at 10 mg/kg Systolic blood pressure (SBP), heart rate, and body weight of all experimental groups were recorded weekly, while the vascular sensitivity and histological changes of the aorta were evaluated at the end of the experiment. Results: For all treatment groups, the data indicated that ethyl rosmarinate significantly attenuated the SBP in hypertensive rats induced by L-NAME, with no significant differences in heart rate and body weight. In addition, the response of vascular sensitivity to acetylcholine (ACh) was improved but there was no significant difference in the response to sodium nitroprusside (SNP). Furthermore, the sensitivity of the aorta to phenylephrine (PE) was significantly decreased. The thickness of the aortic wall did not differ between groups but the expression of endothelial nitric oxide synthase (eNOS) was increased in ethyl rosmarinate- and enalapril-treated groups compared with the hypertensive group. Conclusions: Ethyl rosmarinate is an interesting candidate as an alternative treatment for hypertension due to its ability to improve vascular function and to increase the expression of eNOS similar to enalapril which is a drug commonly used in hypertension.


Assuntos
Cinamatos/farmacologia , Depsídeos/farmacologia , Endotélio Vascular/efeitos dos fármacos , Inibidores Enzimáticos/efeitos adversos , Hipertensão/induzido quimicamente , NG-Nitroarginina Metil Éster/efeitos adversos , Acetilcolina/farmacologia , Administração Oral , Agonistas de Receptores Adrenérgicos alfa 1/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Cinamatos/uso terapêutico , Depsídeos/uso terapêutico , Enalapril/farmacologia , Endotélio Vascular/fisiopatologia , Inibidores Enzimáticos/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , NG-Nitroarginina Metil Éster/administração & dosagem , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Fenilefrina/farmacologia , Ratos , Ratos Wistar , Vasodilatadores/farmacologia
20.
Vestn Otorinolaringol ; 84(5): 61-67, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31793529

RESUMO

The aim of the study was proof of efficacy and safety of the drug Frinozol nasal spray in patients with acute respiratory infection (acute rhinitis). PATIENTS AND METHODS: A randomized open-label study with active control included 134 ambulatory patients: men and women aged 18 to 65 years with acute upper respiratory tract infection (acute rhinitis) lasting no more than 48 hours before inclusion into the study. Patients were randomized in two groups: group 1 took Frinozol nasal spray 2 sprays per each nostril three times a day for 7 days, subjects randomized to the group 2 took Vibrocil at the same dose and treatment regimen. The primary efficacy endpoint in the study was assessment of the dynamics of symptoms such as nasal congestion, rhinorrhea, itching in the nose and hyposmia using 10 cm VAS in 1 day after the start of treatment compared to the baseline. Secondary endpoints included assessment of the dynamics of nasal symptoms after 7 days of treatment, changes in the values of the Congestion Quantifier 5, CQ-5 questionnaire and evaluation of the effectiveness by the investigator. Safety analysis was carried out throughout the study and included the assessment of adverse events, laboratory data, vital signs, ECG assessment. RESULTS: According to the results of the study and comparative analysis of the primary (assessment of the dynamics of nasal symptoms on a 10 cm visual analogue scale 1 day after the start of treatment) and secondary efficacy endpoints as well as a comprehensive safety analysis, it can be concluded that the study drug is not inferior to the reference drug. Thus, the new combination Frinozol nasal spray is an effective and safe treatment for patients with acute respiratory infections.


Assuntos
Sprays Nasais , Fenilefrina/uso terapêutico , Infecções Respiratórias , Administração Intranasal , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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