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

BACKGROUND: To 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. METHODS: This 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. RESULTS: 201 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. CONCLUSION: Bolus 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 REGISTRATION: Data 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).

Noradrenaline-induced changes in cerebral blood flow in health, traumatic brain injury and critical illness: a systematic review with meta-analysis.

BACKGROUND: Noradrenaline is a standard treatment for hypotension in acute care. The precise effects of noradrenaline on cerebral blood flow in health and disease remain unclear. METHODS: We systematically reviewed and synthesised data from studies examining changes in cerebral blood flow in healthy participants and patients with traumatic brain injury and critical illness. RESULTS: Twenty-eight eligible studies were included. In healthy subjects and patients without critical illness or traumatic brain injury, noradrenaline did not significantly change cerebral blood flow velocity (-1.7%, 95%CI -4.7-1.3%) despite a 24.1% (95%CI 19.4-28.7%) increase in mean arterial pressure. In patients with traumatic brain injury, noradrenaline significantly increased cerebral blood flow velocity (21.5%, 95%CI 11.0-32.0%), along with a 33.8% (95%CI 14.7-52.9%) increase in mean arterial pressure. In patients who were critically ill, noradrenaline significantly increased cerebral blood flow velocity (20.0%, 95%CI 9.7-30.3%), along with a 32.4% (95%CI 25.0-39.9%) increase in mean arterial pressure. Our analyses suggest intact cerebral autoregulation in healthy subjects and patients without critical illness or traumatic brain injury., and impaired cerebral autoregulation in patients with traumatic brain injury and who were critically ill. The extent of mean arterial pressure changes and the pre-treatment blood pressure levels may affect the magnitude of cerebral blood flow changes. Studies assessing cerebral blood flow using non-transcranial Doppler methods were inadequate and heterogeneous in enabling meaningful meta-analysis. CONCLUSIONS: Noradrenaline significantly increases cerebral blood flow in humans with impaired, not intact, cerebral autoregulation, with the extent of changes related to the severity of functional impairment, the extent of mean arterial pressure changes and pre-treatment blood pressure levels.

Adjuvant-induced arthritis promotes vascular hyporesponsiveness to phenylephrine through a nitric oxide-related mechanism.

Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced arthritis (AIA), around the 15th day post-induction. Therefore, the present study aimed to verify the effects of AIA on hyporesponsiveness to phenylephrine in rat aortas. AIA was induced by intradermal injection of Mycobacterium tuberculosis (3.8 mg/dL) in the right hind paw of male Wistar rats (n=27). Functional experiments in isolated aortas were carried out 15 days after AIA induction. Morphometric and stereological analyses of the aortas were also performed 36 days after the induction of AIA. AIA did not promote structural modifications in the aortas at any of the time points studied. AIA reduced phenylephrine-induced contraction in endothelium-intact aortas, but not in endothelium-denuded aortas. However, AIA did not change KCl-induced contraction in either endothelium-intact or denuded aortas. L-NAME (non-selective NOS inhibitor), 1400W (selective iNOS inhibitor), and ODQ (guanylyl cyclase inhibitor) reversed AIA-induced hyporesponsiveness to phenylephrine in intact aortas. 7-NI (selective nNOS inhibitor) increased the contraction induced by phenylephrine in aortas from AIA rats. In summary, the hyporesponsiveness to phenylephrine induced by AIA was endothelium-dependent and mediated by iNOS-derived NO through activation of the NO-guanylyl cyclase pathway.

Vascular Response of Triiodothyronine on Isolated Aortic Rings: Contribution of Redox Mechanisms. / Resposta Vascular da Triiodotironina sobre Anéis de Aortas Isoladas: Contribuição de Mecanismos Redox.

BACKGROUND: Vascular dysfunction constitutes the etiology of many diseases, such as myocardial infarction and hypertension, with the disruption of redox homeostasis playing a role in the imbalance of the vasomotor control mechanism. Our group previously has shown that thyroid hormones exert protective effects on the aortic tissue of infarcted rats by improving angiogenesis signaling. OBJECTIVE: Investigate the role of triiodothyronine (T3) on vascular response, exploring its effects on isolated aortas and whether there is an involvement of vascular redox mechanisms. METHODS: Isolated aortic rings (intact- and denuded-endothelium) precontracted with phenylephrine were incubated with T3 (10-8, 10-7, 10-6, 10-5, and 10-4 M), and tension was recorded using a force-displacement transducer coupled with an acquisition system. To assess the involvement of oxidative stress, aortic rings were preincubated with T3 and subsequently submitted to an in vitro reactive oxygen species (ROS) generation system. The level of significance adopted in the statistical analysis was 5%. RESULTS: T3 (10-4 M) promoted vasorelaxation of phenylephrine precontracted aortic rings in both intact- and denuded-endothelium conditions. Aortic rings preincubated in the presence of T3 (10-4 M) also showed decreased vasoconstriction elicited by phenylephrine (1 µM) in intact-endothelium preparations. Moreover, T3 (10-4 M) vasorelaxation effect persisted in aortic rings preincubated with NG-nitro-L-arginine methylester (L-NAME, 10 µM), a nonspecific NO synthase (NOS) inhibitor. Finally, T3 (10-4 M) exhibited, in vitro, an antioxidant role by reducing NADPH oxidase activity and increasing SOD activity in the aorta's homogenates. CONCLUSION: T3 exerts dependent- and independent-endothelium vasodilation effects, which may be related to its role in maintaining redox homeostasis.

FUNDAMENTO: A disfunção vascular constitui a etiologia de diversas doenças, incluindo infarto do miocárdio e hipertensão, diante da ruptura da homeostase oxi-redutiva ("redox"), desempenhando um papel no desequilíbrio do mecanismo de controle vasomotor. Nosso grupo demonstrou anteriormente que os hormônios tireoidianos melhoram a sinalização da angiogênese, exercendo efeitos protetores sobre o tecido aórtico de ratos infartados. OBJETIVOS: Investigar o papel da triiodotironina (T3) na resposta vascular, explorando seus efeitos em aortas isoladas e a presença de mecanismos redox vasculares. MÉTODOS: Anéis aórticos isolados (endotélio intacto e desnudado) pré-contraídos com fenilefrina foram incubados com T3 (10-8, 10-7, 10-6, 10-5 e 10-4 M) e a tensão foi registrada usando um transdutor de deslocamento de força acoplado a um sistema de coleta. Para avaliar o envolvimento do estresse oxidativo, os anéis aórticos foram pré-incubados com T3 e posteriormente submetidos a um sistema de geração de espécies reativas de oxigênio (ROS) in vitro. O nível de significância adotado na análise estatística foi de 5%. RESULTADOS: A T3 (10-4 M) promoveu o vasorrelaxamento dos anéis aórticos pré-contraídos com fenilefrina em endotélio intacto e desnudado. Os anéis aórticos pré-incubados na presença de T3 (10-4 M) também mostraram diminuição da vasoconstrição provocada pela fenilefrina (1 µM) em preparações de endotélio intacto. Além disso, o efeito vasorrelaxante da T3 (10-4 M) persistiu em anéis aórticos pré-incubados com éster metílico de NG-nitro-L-arginina (L-NAME, 10 µM), um inibidor inespecífico da NO sintase (NOS). Por fim, a T3 (10-4 M) exibiu, in vitro, um papel antioxidante ao reduzir a atividade da NADPH oxidase e aumentar a atividade da SOD nos homogenatos aórticos. CONCLUSÃO: A T3 exerce efeitos dependentes e independentes de endotélio, o que pode estar relacionado ao seu papel na manutenção da homeostase redox.

The effect of vasopressor agents on pressure injury development in intensive care patients.

BACKGROUND: Vasopressors are life-saving agents that increase mean arterial pressure. The pharmacodynamic features of these agents and previous studies suggest that vasopressors may be an essential risk factor in developing pressure injuries. OBJECTIVE: This study aimed to examine the effect of vasopressors in medical-surgical intensive care patients on pressure injury development. DESIGN AND SETTINGS: This retrospective and correlational study was conducted between March 2021- May 2022. The electronic patient data were obtained from 148 surgical and medical patients exposed to vasopressor agents in the intensive care unit. Data on patients' demographic and clinical characteristics were evaluated using descriptive statistical methods (number, percentage, mean, standard deviation). Logistic regression modelling was used to assess independent relationships with pressure injury risk; results are reported as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: All patients were given norepinephrine agents, and dopamine infusion secondary to norepinephrine was found in only 28.3 % of patients (n = 42). Pressure injury incidence was 43.2 % (n = 64). Duration of norepinephrine infusion was recognized as an independent risk factor for ICU-acquired pressure injury development (OR 1.22, 95 % CI 1.11-1.35), while a medical admission diagnosis (instead of surgical) was protective against pressure injury risk (OR 0.24, 95 % CI 0.10-0.59). CONCLUSION: This study indicated that duration of norepinephrine infusion is a significant risk factor for pressure injury development. IMPLICATIONS FOR CLINICAL PRACTICE: Although norepinephrine use cannot be avoided entirely, its administration may be an early warning for nurses to increase pressure injury prevention strategies. Skin evaluation should be performed more frequently, and preventive strategies should be implemented meticulously. This study was registered on clincialtrials.gov (Identifier: NCT06163352).

Anji white tea relaxes precontracted arteries, represses voltage-gated Ca2+ channels and voltage-gated K+ channels in the arterial smooth muscle cells: Comparison with green tea main component (-)-epigallocatechin gallate.

ETHNOPHARMACOLOGICAL RELEVANCE: Tea (Camellia sinensis) is a favorite drink worldwide. Tea extracts and green tea main component (-)-epigallocatechin gallate (EGCG) are recommended for various vascular diseases. Anji white tea is a very popular green tea. Its vascular effect profile, the mechanisms, and the contribution of EGCG to its integrated effect need elucidation. AIM: To characterize the vasomotion effects of Anji white tea and EGCG, and to explore possible involvement of voltage-gated Ca2+ channels (VGCCs) and voltage-gated K+ (Kv) channels in their vasomotion effects. MATERIALS AND METHODS: Anji white tea water soaking solution (AJWT) was prepared as daily tea-making process and concentrated to a concentration amounting to 200 mg/ml of dry tea leaves. The tension of rat arteries including aorta, coronary artery (RCA), cerebral basilar artery (CBA), intrarenal artery (IRA), intrapulmonary artery (IPA) and mesenteric artery (MA) was recorded with myographs. In arterial smooth muscle cells (ASMCs) freshly isolated from RCA, the levels of intracellular Ca2+ were measured with Ca2+-sensitive fluorescent probe fluo 4-AM, and Kv currents were recorded with patch clamp. The expressions of VGCCs and Kv channels were assayed with RT-qPCR and immunofluorescence staining. RESULTS: At 0.4-12.8 mg/ml of dry tea leaves, AJWT profoundly relaxed all tested arteries precontracted with various vasoconstrictors about half with a small transient potentiation on the precontractions before the relaxation. KCl-induced precontraction was less sensitive than precontractions induced by phenylephrine (PE), U46619 and serotonin (5-HT). IPA was less sensitive to the relaxation compared with other arteries. AJWT pretreatment for 1 h, 24 h and 72 h time-dependently inhibited the contractile responses of RCAs. In sharp contrast, at equivalent concentrations according to its content in AJWT, EGCG intensified the precontractions in most small arteries, except that it induced relaxation in PE-precontracted aorta and MA, U46619-precontracted aorta and CBA. EGCG pretreatment for 1 h and 24 h did not significantly affect RCA contractile responses. In RCA ASMCs, AJWT reduced, while EGCG enhanced, intracellular Ca2+ elevation induced by depolarization which activates VGCCs. Patch clamp study showed that both AJWT and EGCG reduced Kv currents. RT-qPCR and immunofluorescence staining demonstrated that both AJWT and EGCG reduced the expressions of VGCCs and Kv channels. CONCLUSION: AJWT, but not EGCG, consistently induces vasorelaxation. The vasomotion effects of either AJWT or EGCG vary with arterial beds and vasoconstrictors. Modulation of VGCCs, but not Kv channels, contributes to AJWT-induced vasorelaxation. It is suggested that Anji white tea water extract instead of EGCG may be a promising food supplement for vasospastic diseases.

Sodium Hydrosulfide Reverts Chronic Stress-Induced Cardiovascular Alterations by Reducing Oxidative Stress.

ABSTRACT: Chronic stress induces a group of unrecognized cardiovascular impairments, including elevated hemodynamic variables and vascular dysfunction. Moreover, hydrogen sulfide (H 2 S), a gasotransmitter that regulates the cardiovascular system decreases under chronic stress. Thus, this study assessed the impact of sodium hydrosulfide (NaHS) (H 2 S donor) on chronic restraint stress (CRS)-induced cardiovascular changes. For that purpose, male Wistar rats were restrained for 2 hours a day in a transparent acrylic tube over 8 weeks. Then, body weight, relative adrenal gland weight, serum corticosterone, H 2 S-synthesizing enzymes, endothelial nitric oxide synthetize expression, reactive oxygen species levels, lipid peroxidation, and reduced glutathione-to-oxidized glutathione (GSH 2 :GSSG) ratio were determined in the thoracic aorta. The hemodynamic variables were measured in vivo by the plethysmograph method. The vascular function was evaluated in vitro as vasorelaxant responses induced by carbachol or sodium nitroprusside, and norepinephrine (NE)-mediated vasocontractile responses in the thoracic aorta. CRS increased (1) relative adrenal gland weight; (2) hemodynamic variables; (3) vasoconstrictor responses induced by NE, (4) reactive oxygen species levels, and (5) lipid peroxidation in the thoracic aorta. In addition, CRS decreased (1) body weight; (2) vasorelaxant responses induced by carbachol; (3) GSH content, and (4) GSH 2 :GSSG ratio. Notably, NaHS administration (5.6 mg/kg) restored hemodynamic variables and lipid peroxidation and attenuated the vasoconstrictor responses induced by NE in the thoracic aorta. In addition, NaHS treatment increased relative adrenal gland weight and the GSH 2 :GSSG ratio. Taken together, our results demonstrate that NaHS alleviates CRS-induced hypertension by reducing oxidative stress and restoring vascular function in the thoracic aorta.

Perioperative Fluid and Vasopressor Therapy in 2050: From Experimental Medicine to Personalization Through Automation.

Intravenous (IV) fluids and vasopressor agents are key components of hemodynamic management. Since their introduction, their use in the perioperative setting has continued to evolve, and we are now on the brink of automated administration. IV fluid therapy was first described in Scotland during the 1832 cholera epidemic, when pioneers in medicine saved critically ill patients dying from hypovolemic shock. However, widespread use of IV fluids only began in the 20th century. Epinephrine was discovered and purified in the United States at the end of the 19th century, but its short half-life limited its implementation into patient care. Advances in venous access, including the introduction of the central venous catheter, and the ability to administer continuous infusions of fluids and vasopressors rather than just boluses, facilitated the use of fluids and adrenergic agents. With the advent of advanced hemodynamic monitoring, most notably the pulmonary artery catheter, the role of fluids and vasopressors in the maintenance of tissue oxygenation through adequate cardiac output and perfusion pressure became more clearly established, and hemodynamic goals could be established to better titrate fluid and vasopressor therapy. Less invasive hemodynamic monitoring techniques, using echography, pulse contour analysis, and heart-lung interactions, have facilitated hemodynamic monitoring at the bedside. Most recently, advances have been made in closed-loop fluid and vasopressor therapy, which apply computer assistance to interpret hemodynamic variables and therapy. Development and increased use of artificial intelligence will likely represent a major step toward fully automated hemodynamic management in the perioperative environment in the near future. In this narrative review, we discuss the key events in experimental medicine that have led to the current status of fluid and vasopressor therapies and describe the potential benefits that future automation has to offer.

Effect of no-flow period on the vasopressor effect of initial epinephrine administration in cardiac arrest.

OBJECTIVES: Whether a longer no-flow (NF) interval affects the magnitude of response to epinephrine in the resuscitation has not been well studied. Therefore, this study aimed to evaluate the effect of NF interval on the vasopressor effect of initial epinephrine administration in a porcine model. METHODS: We enrolled 20 pigs from two randomized porcine experimental studies using a ventricular fibrillation (VF) cardiac arrest model. The first experiment subjects were resuscitated after 4 min of NF (Short NF group), followed by three cycles (6 min) of chest compression using a mechanical cardiopulmonary resuscitation device before epinephrine administration. Second experiment subjects received 6 min of NF (Long NF group), two cycles (4 min) of chest compressions, and administration of epinephrine. Defibrillation for VF was delivered 8 and 10 min after VF induction in the Short NF and Long NF groups, respectively. The mean arterial pressure (MAP) and cerebral perfusion pressure (CePP) in the 2-min resuscitation period after epinephrine administration were compared between the study groups using the Wilcoxon rank-sum test. The mean differences in the parameters between phases were also compared. RESULTS: Seven pigs in the Short NF group and 13 pigs in the Long NF group were included in the analysis. All 2-min resuscitation phases from 6 to 16 min after VF induction were compared between the study groups. The Short NF group showed higher MAP and CePP in all phases (p < 0.01). Change of mean MAP after the epinephrine administration was significantly different between the study groups: mean difference (95% confidence interval) of 16.6 (15.8-17.4) mmHg in the Short NF group and 4.2 (3.9-4.5) mmHg in the Long NF group. CONCLUSION: In the porcine VF cardiac arrest model, 6 min of NF before resuscitation may affect the vasopressor effect of the initial epinephrine administered compared to 4 min of NF. A short NF may play a role in maximizing the effect of epinephrine in advanced cardiovascular life support.

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.

Medical Measures in Hypertensives Considered Resistant.

BACKGROUND: Patients with resistant hypertension are the group of hypertensive patients with the highest cardiovascular risk. METHODS: All rules and guidelines for treatment of hypertension should be followed strictly to obtain blood pressure (BP) control in resistant hypertension. The mainstay of treatment of hypertension, also for resistant hypertension, is pharmacological treatment, which should be tailored to each patient's specific phenotype. Therefore, it is pivotal to assess nonadherence to pharmacological treatment as this remains the most challenging problem to investigate and manage in the setting of resistant hypertension. RESULTS: Once adherence has been confirmed, patients must be thoroughly worked-up for secondary causes of hypertension. Until such possible specific causes have been clarified, the diagnosis is apparent treatment-resistant hypertension (TRH). Surprisingly few patients remain with true TRH when the various secondary causes and adherence problems have been detected and resolved. Refractory hypertension is a term used to characterize the treatment resistance in hypertensive patients using ≥5 antihypertensive drugs. All pressor mechanisms may then need blockage before their BPs are reasonably controlled. CONCLUSIONS: Patients with resistant hypertension need careful and sustained follow-up and review of their medications and dosages at each term since medication adherence is a very dynamic process.

Hypoxia-inducible factors activator, roxadustat, increases pulmonary vascular resistance in rats.

Activators of hypoxia inducible factors (HIFs), such as roxadustat, are promising agents for anemia treatment. However, since HIFs are also involved in the regulation of the pulmonary circulation, we hypothesized that roxadustat increases pulmonary vascular resistance and vasoconstrictor reactivity. Using isolated, cell-free solution perfused rat lungs, we found perfusion pressure-flow curves to be shifted to higher pressures by 2 weeks of roxadustat treatment (10 mg/kg every other day), although not as much as by chronic hypoxic exposure. Vasoconstrictor reactivity to angiotensin II and acute hypoxic challenges was not altered by roxadustat. Since roxadustat may inhibit angiotensin-converting enzyme 2 (ACE2), we also tested a purported ACE2 activator, diminazene aceturate (DIZE, 0.1 mM). It produced paradoxical, unexplained pulmonary vasoconstriction. We conclude that the risk of serious pulmonary hypertension is not high when roxadustat is given for 14 days, but monitoring is advisable.

Relación entre la presión arterial durante el destete de fármacos vasopresores y la supervivencia hospitalaria: análisis de los valores objetivo del tratamiento vasopresor / Association between blood pressure during vasopressor weaning and in-hospital survival: an analysis of vasopressor targets

Objetivos. Analizar la relación entre la presión arterial (PA) durante el destete de fármacos vasopresores y la mortalidad intrahospitalaria en pacientes ingresados en una unidad de cuidados intensivos (UCI).Método. Estudio de cohorte observacional, retrospectivo y unicéntrico. Incluyó pacientes del registro MIMIC-IV. La variable de resultado fue la mortalidad intrahospitalaria. Se utilizaron splines cúbicos restringidos (SCR) para estudiar la relación entre la PA durante el destete de los vasopresores [sistólica (DPAS), diastólica (DPAD), media (DPAM)] y lamortalidad. Los pacientes se clasificaron en diferentes subgrupos según sus cifras de DPAS, DPAD y DPAM. Se realizó un análisis de sensibilidad mediante regresión de Cox.Resultados. Se analizaron 8.294 pacientes. El SCR mostró que DPAS, DPAD y DPAM tenían una relación no lineal, en forma de “U”, con la mortalidad intrahospitalaria. Basándose en los puntos de intersección de los valores de referencia, los pacientes se clasificaron en los siguientes grupos: DPAS < 110, 110-150 y > 150 mmHg; DPAD < 60, 60-85 y > 85 mmHg; y DPAM < 75, 75-110 y > 110 mmHg. En comparación con el grupo de PA más baja, de DPAS entre 110-150 mmHg tenía una hazard ratio (HR) de 0,59 (IC 95% 0,52-0,66), DPAD entre 60-85 mmHg una HR de 0,62 (IC 95% 0,55-0,70) y DPAM entre 75-110 mmHg una HR de 0,64 (IC 95% 0,57-0,72). El análisis de subgrupos diagnósticos mostró que la PA durante el destete interactuaba con la enfermedad vascular cerebral y con la enfermedad pulmonar crónica.Conclusiones. Valores altos de PA durante el destete de los fármacos vasopresores se asocian a una mayor supervivencia intrahospitalaria en pacientes ingresados en una UCI. Los valores óptimos son: DPAS 110-150 mmHg, DPAD 60-85 mmHg y DPAM 75-110 mmHg. La PA óptima puede ser diferente en función del diagnóstico del paciente. (AU)

Objectives. To analyze the association between blood pressure during vasopressor weaning and in-hospital mortality in patients admitted to an intensive care unit (ICU).Methods. Observational retrospective single-center study including patient data registered in the Medical Information Mart for Intensive Care, version 4. The outcome was in-hospital mortality. We used restricted cubic spline (RCS) functions to analyze the associations between mortality and systolic and diastolic blood pressures and mean arterial pressure (SBP, DBP, and MAP, respectively) during weaning from vasopressors. The data was stratified according to SBP, DBP, and MAP, and sensitivity was assessed with Cox regression analysis.Results. Data for 8294 patients were analyzed. The RCS functions showed that SBP, DBP, and MAP values had nonlinear U-shaped associations with in-hospital mortality. Patients were classified into the following subgroups according to points of intersection of SBP, DBP, and MAP reference values: SBP <110, 110-150, or >150 mmHg; DBP <60, 60-85, or >85 mmHg; and MAP <75, 75-110, or >110 mmHg. In the lowest blood pressure group the hazard ratio was 0.59 (95% CI, 0.52-0.66) for SBP in the 110-150 mmHg range; 0.62 (95% CI, 0.55-0.70) for DBP in the 60-85 mmHg range; and 0.64 (95% CI, 0.57-0.72) for MAP in the 75-110 mmHg range during weaning. The analysis of subgroups also indicated that blood pressures during weaning interacted with cerebral vascular disease and chronic obstructive pulmonary disease.Conclusions. Higher blood pressures during vasopressor weaning are associated with longer in-hospital survival in ICU patients. The optimum pressure ranges are SBP, 110-150 mmHg; DBP, 60-85 mmHg; and MAP, 75-110 mmHg. Blood pressures may behave differently according to diagnosis. (AU)

Cardioprotective solutions exposure for 1 hour in hypoxia and low temperatures affects vascular reactivity differently

Abstract Introduction: Heart preservation benefits cardiac performance after operations decreasing morbidity but the contribution of the vascular reactivity has been neglected. Objective: We evaluated whether cardioprotective solutions, Krebs-Henseleit (KH), Bretschneider-HTK (BHTK), St. Thomas No. 1 (STH-1), and Celsior (CEL), affect vascular reactivity. Methods: Aortic rings from Wistar rats were used in two protocols. First, the rings were exposed to BHTK, STH-1 or CEL for 1 hour of hypoxia at 37 °C. Second, the rings were exposed to 10 °C or 20 °C for 1 hour under hypoxia. After treatment, the rings were immersed in KH at 37 °C, endothelial integrity was tested and concentration-response curves to phenylephrine were performed. Results: In the first protocol, the solutions did not damage the endothelium; CEL and BHTK reduced KCl-induced contractions but not STH-1; only CEL and BHTK reduced vascular reactivity; there was a positive correlation between Rmax and KCl concentration. At 20 °C, 1 hour under hypoxia, the solutions produced similar KCl-induced contractions without endothelial damage. CEL, BHTK and STH-1 decreased vascular reactivity. At 10 °C, STH-1 increased reactivity but CEL and BHTK decreased. After 1 hour under hypoxia in CEL or BHTK solutions, reactivity was similar at different temperatures. At 20 °C, endothelial damage after exposure to STH-1 produced more vasoconstriction than CEL and BHTK. However, at 10 °C, endothelial damage after CEL and BHTK exposure elicited more vasoconstriction while STH-1 showed a small vasoconstrictor response, suggesting endothelial damage. Conclusion: STH-1 decreased reactivity at 20 °C and increased at 10 °C. CEL promoted greater endothelial modulation at 10 °C than at 20 °C, while STH-1 promoted higher modulation at 20 °C than at 10 °C. Vascular tone was reduced by CEL and BHTK exposure, also depending on the KCl concentration.

Passive Cigarette Smoking Impact on Blood Pressure Response to Epinephrine and Felypressin in 1K1C Hypertensive Rats Treated or not with Atenolol / Impacto do Tabagismo Passivo na Resposta Pressórica à Epinefrina e Felipressina em Ratos Hipertensos 1K1C Tratados ou não com Atenolol

Abstract Background: Cigarette smoking is usually associated with hypertension and may modify vasoconstrictor response. Objective: The present study aimed to analyze and compare the interaction of passive cigarette smoking and hypertension on epinephrine and felypressin blood pressure effects after intravascular injection. Method: 45-day male Wistar rats had the main left renal artery partially constricted and the right kidney removed (1K1C model). Rats were placed in the chamber for exposition to passive cigarette smoking (10 cigarettes) during 10 min (6 days a week). Hypertensive rats received atenolol (90 mg/kg/day) by gavage for two weeks. Hypotensive and hypertensive response, response duration and heart rate were recorded from direct blood pressure values. The significance level was 5%. Results: Passive cigarette smoking increased maximal hypertensive response to epinephrine in normotensive and 1K1C-atenolol treated rats and to felypressin only in 1K1C-atenolol treated rats; it also reduced epinephrine hypotensive response. Epinephrine increased heart rate in normotensive and hypertensive passive smokers or non-smoker rats. Comparing the two vasoconstrictors, epinephrine showed greater hypertensive response in normotensive smokers, 1K1C-atenolol treated smokers and non-smokers. However, in normotensive-nonsmoker rats, felypressin showed a greater and longer hypertensive effect. Conclusions: Our results suggest that passive cigarette smoking may reduce epinephrine vasodilation and increase hypertensive response when compared to felypressin. Therefore, felypressin may be safe for hypertensive patients to avoid tachycardia and atenolol interaction, but for normotensive and non-smoker patients, epinephrine may be safer than felypressin.

Resumo Fundamento: O tabagismo geralmente está associado à hipertensão e pode modificar a resposta vasoconstritora. Objetivo: O presente estudo teve como objetivo analisar e comparar a interação do tabagismo passivo e hipertensão sobre os efeitos da epinefrina e felipressina na pressão arterial após injeção intravascular. Métodos: Ratos Wistar machos de 45 dias tiveram a artéria renal principal esquerda parcialmente obstruída e o rim direito removido (modelo 1K1C). Os ratos foram colocados na câmara para exposição ao tabagismo passivo (10 cigarros) durante 10 minutos (6 dias por semana). Ratos hipertensos receberam atenolol (90 mg/kg/dia) por gavagem durante duas semanas. A resposta hipotensora e hipertensiva, a duração da resposta e a frequência cardíaca foram registradas a partir da medida dos valores diretos da pressão arterial. O nível de significância foi de 5%. Resultados: O tabagismo passivo aumentou a resposta hipertensiva máxima à epinefrina em ratos normotensos e ratos 1K1C tratados com atenolol e à felipressina apenas em ratos 1K1C tratados com atenolol; também reduziu a resposta hipotensiva à epinefrina. A epinefrina aumentou a frequência cardíaca em ratos fumantes passivos ou não-fumantes, normotensos e hipertensos. Comparando os dois vasoconstritores, a epinefrina apresentou maior resposta hipertensiva em fumantes normotensos, ratos 1K1C fumantes e não fumantes tratados com atenolol. No entanto, em ratos normotensos e não fumantes, a felipressina apresentou um efeito hipertensivo maior e mais prolongado. Conclusões: Nossos resultados sugerem que o tabagismo passivo pode reduzir a vasodilatação da epinefrina e aumentar a resposta hipertensiva quando comparado à felipressina. Portanto, a felipressina pode ser segura para pacientes hipertensos, com o objetivo de evitar a interação entre taquicardia e atenolol, mas para pacientes normotensos e não-fumantes, a epinefrina pode ser mais segura que a felipressina.

Evaluation of relaxant responses properties of cinnamon essential oil and its major component, cinnamaldehyde on human and rat corpus cavernosum

ABSTRACT Cinnamomum cassia (Cinnamon) is a well-known traditional medicine with therapeutic benefits for centuries. We evaluated the effects of cinnamon essential oil (CEO) and its main component cinnamaldehyde (CA) on human corpus cavernosum (HCC) and rat CC. The essential oil of cinnamon was analyzed for the confirmation of the oil profile. HCC specimens from patients undergoing penile prosthesis surgery (age 48-69 years) were utilized for functional studies. In addition, erectile responses in anesthetized control and diabetic rats were evaluated in vivo after intracavernosal injection of CEO and CA, and rat CC strips were placed in organ baths. After precontraction with phenylephrine (10µM), relaxant responses to CEO and CA were investigated. CA (96.9%) was found as the major component. The maximum relaxation responses to CEO and CA were 96.4±3.5% and 96.0±5.0% in HCC and 97.5±5.5% and 96.8±4.8% in rat CC, respectively. There was no difference between control and diabetic rats in relaxation responses to CEO and CA. The relaxant responses obtained with essential oil and CA were not attenuated in the presence of nitric oxide synthase (NOS) inhibitor, and soluble guanylate cyclase inhibitor (sGS) in CC. In vivo, erectile responses in diabetic rats were lower than in control rats, which was restored after intracavernosal injection of CEO and CA. CEO and CA improved erectile function and relaxation of isolated strips of rat CC and HCC by a NO/cGMP-independent mechanism. Further investigations are warranted to fully elucidate the restorative effects of CEO and CA on diabetic erectile dysfunction.

The antimicrobial activity of ephedrine and admixture of ephedrine and propofol: an in vitro study / A atividade antimicrobiana de efedrina e da combinação de efedrina e propofol: um estudo in vitro

Abstract Introduction Propofol and Ephedrine are commonly used during anesthesia maintenance, the former as a hypnotic agent and the later as a vasopressor. The addition of propofol to ephedrine or administration of ephedrine before propofol injection is useful for decreasing or preventing propofol related hemodynamic changes and vascular pain. This in vitro study evaluated the antibacterial effect on common hospital-acquired infection pathogens of ephedrine alone or combined with propofol. Material and method The study was performed in two stages. In the first, the Minimum Inhibitory Concentration of propofol and ephedrine alone and combined was calculated for Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa, and a clinical isolate of Acinetobacter spp. at 0, 6, 12 and 24 h, using the microdilution method. In the second stage, the same drugs and combination were used to determine their effect on bacterial growth. Bacterial solutions were prepared at 0.5 MacFarland in sterile 0.9% physiological saline and diluted at 1/100 concentration. Colony numbers were measured as colony forming units.mL-1 at 0, 2, 4, 6, 8, 10 and 12th hours. Results Ephedrine either alone or combined with propofol did not have an antimicrobial effect on Escherichia coli, Enterococcus faecium, or Pseudomonas aeruginosa and this was similar to propofol. However, ephedrine alone and combined with propofol was found to have an antimicrobial effect on Staphylococcus aureus and Acinetobacter species at 512 mcg.mL-1 concentration and significantly decreased bacterial growth rate. Conclusion Ephedrine has an antimicrobial activity on Staphylococcus aureus and Acinetobacter species which were frequently encountered pathogens as a cause of nosocomial infections.

Resumo Introdução Propofol e efedrina são fármacos comumente usados durante a manutenção da anestesia, o primeiro como agente hipnótico e o segundo como vasopressor. A adição de propofol à efedrina ou a administração de efedrina antes da injeção de propofol é útil para diminuir ou prevenir alterações hemodinâmicas e dor vascular relacionadas ao propofol. Este estudo in vitro avaliou o efeito antibacteriano de efedrina, isolada ou em combinação com propofol, em patógenos comuns implicados em infecção hospitalar. Material e método O estudo foi feito em duas etapas. Na primeira, a concentração inibitória mínima (CIM) de propofol e de efedrina isolada e em combinação foi calculada para Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa e um isolado clínico de Acinetobacter spp às 0, 6, 12 e 24 horas, com o método de microdiluição. Na segunda etapa, o mesmo fármaco e sua combinação foram usados para determinar seus efeitos no crescimento bacteriano. As soluções bacterianas foram preparadas em soro fisiológico a 0,9% em 0,5 McFarland e diluídas a uma concentração de 1/100. Os números das colônias foram medidos como ufc.mL-1 às 0, 2, 4, 6, 8, 10 e 12 horas. Resultados Efedrina isolada ou em combinação com propofol não apresentou efeito antimicrobiano sobre E. coli, E. faecium ou P. aeruginosa, um resultado semelhante ao de propofol. Porém, efedrina isolada e em combinação com propofol apresentou efeito antimicrobiano sobre Staphylococcus aureus e Acinetobacter spp, em concentração de 512 mcg.mL-1, e redução significativa da taxa de crescimento bacteriano. Conclusão Efedrina tem atividade antimicrobiana em S. aureus e Acinetobacter spp, patógenos frequentemente identificados como causa de infecções nosocomiais.