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1.
Braz J Anesthesiol ; 2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37926365

RESUMO

INTRODUCTION: Methylene Blue (MB) has been shown to attenuate oxidative, inflammatory, myocardial, and neurological lesions during ischemia-reperfusion and has great potential during cardiac arrest. This study aimed to determine the effects of MB combined with epinephrine during cardiac arrest on myocardial and cerebral lesions. METHOD: Thirty-eight male Wistar rats were randomly assigned to four groups: the sham group (SH, n = 5), and three groups subjected to cardiac arrest (n = 11/group) and treated with EPI 20 µg.kg-1 (EPI), EPI 20 µg.kg-1 + MB 2 mg.kg-1 (EPI + MB), or saline 0.9% 0.2 ml (CTL). Ventricular fibrillation was induced by direct electrical stimulation in the right ventricle for 3 minutes, and anoxia was maintained for 5 minutes. Cardiopulmonary Resuscitation (CPR) consisted of medications, ventilation, chest compressions, and defibrillation. After returning to spontaneous circulation, animals were observed for four hours. Blood gas, troponin, oxidative stress, histology, and TUNEL staining measurements were analyzed. Groups were compared using generalized estimating equations. RESULTS: No differences in the Returning of Spontaneous Circulation (ROSC) rate were observed among the groups (EPI: 63%, EPI + MB: 45%, CTL: 40%, p = 0.672). The mean arterial pressure immediately after ROSC was higher in the EPI+MB group than in the CTRL group (CTL: 30.5 [5.8], EPI: 63 [25.5], EPI+MB: 123 [31] mmHg, p = 0.007). Serum troponin levels were high in the CTL group (CTL: 130.1 [333.8], EPI: 3.70 [36.0], EPI + MB: 43.7 [116.31] ng/mL, p < 0.05). CONCLUSION: The coadministration of MB and epinephrine failed to yield enhancements in cardiac or brain lesions in a rodent model of cardiac arrest.

2.
Neurocrit Care ; 39(2): 320-330, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37535176

RESUMO

BACKGROUND: Restoration of brain tissue perfusion is a determining factor in the neurological evolution of patients with traumatic brain injury (TBI) and hemorrhagic shock (HS). In a porcine model of HS without neurological damage, it was observed that the use of fluids or vasoactive drugs was effective in restoring brain perfusion; however, only terlipressin promoted restoration of cerebral oxygenation and lower expression of edema and apoptosis markers. It is unclear whether the use of vasopressor drugs is effective and beneficial during situations of TBI. The objective of this study is to compare the effects of resuscitation with saline solution and terlipressin on cerebral perfusion and oxygenation in a model of TBI and HS. METHODS: Thirty-two pigs weighing 20-30 kg were randomly allocated into four groups: control (no treatment), saline (60 ml/kg of 0.9% NaCl), terlipressin (2 mg of terlipressin), and saline plus terlipressin (20 ml/kg of 0.9% NaCl + 2 mg of terlipressin). Brain injury was induced by lateral fluid percussion, and HS was induced through pressure-controlled bleeding, aiming at a mean arterial pressure (MAP) of 40 mmHg. After 30 min of circulatory shock, resuscitation strategies were initiated according to the group. The systemic and cerebral hemodynamic and oxygenation parameters, lactate levels, and hemoglobin levels were evaluated. The data were subjected to analysis of variance for repeated measures. The significance level established for statistical analysis was p < 0.05. RESULTS: The terlipressin and saline plus terlipressin groups showed an increase in MAP that lasted until the end of the experiment (p < 0.05). There was a notable increase in intracranial pressure in all groups after starting treatment for shock. Cerebral perfusion pressure and cerebral oximetry showed no improvement after hemodynamic recovery in any group. The groups that received saline at resuscitation had the lowest hemoglobin concentrations after treatment. CONCLUSIONS: The treatment of hypotension in HS with saline and/or terlipressin cannot restore cerebral perfusion or oxygenation in experimental models of HS and severe TBI. Elevated MAP raises intracranial pressure owing to brain autoregulation dysfunction caused by TBI.


Assuntos
Lesões Encefálicas Traumáticas , Hipotensão , Choque Hemorrágico , Humanos , Animais , Suínos , Choque Hemorrágico/tratamento farmacológico , Terlipressina/farmacologia , Terlipressina/uso terapêutico , Solução Salina , Circulação Cerebrovascular , Oximetria/efeitos adversos , Lesões Encefálicas Traumáticas/terapia , Lesões Encefálicas Traumáticas/tratamento farmacológico , Hipotensão/tratamento farmacológico , Ressuscitação , Perfusão/efeitos adversos , Hemoglobinas , Modelos Teóricos , Modelos Animais de Doenças
3.
Shock ; 60(3): 469-477, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37548627

RESUMO

ABSTRACT: Background: Approximately 50% of patients with sepsis develop acute kidney injury (AKI), which is predictive of poor outcomes, with mortality rates of up to 70%. The endothelium is a major target for treatments aimed at preventing the complications of sepsis. We hypothesized that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could attenuate tubular and endothelial injury in a porcine model of sepsis-induced AKI. Methods: Anesthetized pigs were induced to fecal peritonitis, resulting in septic shock, and were randomized to treatment with fluids, vasopressors, and antibiotics (sepsis group; n = 11) or to that same treatment plus infusion of 1 × 10 6 cells/kg of hUC-MSCs (sepsis+MSC group; n = 11). Results: At 24 h after sepsis induction, changes in serum creatinine and mean arterial pressure were comparable between the two groups, as was mortality. However, the sepsis+MSC group showed some significant differences in comparison with the sepsis group: lower fractional excretions of sodium and potassium; greater epithelial sodium channel protein expression; and lower protein expression of the Na-K-2Cl cotransporter and aquaporin 2 in the renal medulla. Expression of P-selectin, thrombomodulin, and vascular endothelial growth factor was significantly lower in the sepsis+MSC group than in the sepsis group, whereas that of Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) was lower in the former. Conclusion: Treatment with hUC-MSCs seems to protect endothelial and tubular cells in sepsis-induced AKI, possibly via the TLR4/NF-κB signaling pathway. Therefore, it might be an effective treatment for sepsis-induced AKI.


Assuntos
Injúria Renal Aguda , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Sepse , Humanos , Injúria Renal Aguda/terapia , Injúria Renal Aguda/induzido quimicamente , Células Endoteliais/metabolismo , Rim/metabolismo , Células-Tronco Mesenquimais/metabolismo , NF-kappa B/metabolismo , Sepse/complicações , Sepse/terapia , Sepse/metabolismo , Receptor 4 Toll-Like/metabolismo , Cordão Umbilical/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Suínos
4.
Braz J Anesthesiol ; 73(4): 446-454, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34118261

RESUMO

BACKGROUND: Sepsis and septic shock still represent great challenges in critical care medicine. Sildenafil has been largely used in the treatment of pulmonary arterial hypertension, but its effects in sepsis are unknown. The aim of this study was to investigate the hypothesis that sildenafil can attenuate endotoxin-induced pulmonary hypertension in a porcine model of endotoxemia. METHODS: Twenty pigs were randomly assigned to Control group (n.ß=.ß10), which received saline solution; or to Sildenafil group (n.ß=.ß10), which received sildenafil orally (100.ßmg). After 30.ßminutes, both groups were submitted to endotoxemia with intravenous bacterial lipopolysaccharide endotoxin (LPS) infusion (4.ß..g.kg-1.h-1) for 180.ßminutes. We evaluated hemodynamic and oxygenation functions, and also lung histology and plasma cytokine (TNF.., IL-1.., IL6, and IL10) and troponin I response. RESULTS: Significant hemodynamic alterations were observed after 30.ßminutes of LPS continuous infusion, mainly in pulmonary arterial pressure (from Baseline 19.ß...ß2.ßmmHg to LPS30 52.ß...ß4.ßmmHg, p.ß<.ß0.05). There was also a significant decrease in PaO2/FiO2 (from Baseline 411.ß...ß29 to LPS180 334.ß...ß49, p.ß<.ß0.05). Pulmonary arterial pressure was significantly lower in the Sildenafil group (35.ß...ß4.ßmmHg at LPS30, p.ß<.ß0.05). The Sildenafil group also presented lower values of systemic arterial pressure. Sildenafil maintained oxygenation with higher PaO2/FiO2 and lower oxygen extraction rate than Control group but had no effect on intrapulmonary shunt. All cytokines and troponin increased after LPS infusion in both groups similarly. CONCLUSION: Sildenafil attenuated endotoxin-induced pulmonary hypertension preserving the correct heart function without improving lung lesions or inflammation.


Assuntos
Endotoxemia , Hipertensão Pulmonar , Animais , Suínos , Citrato de Sildenafila/farmacologia , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Endotoxinas/farmacologia , Lipopolissacarídeos/farmacologia , Hemodinâmica
5.
Braz. J. Anesth. (Impr.) ; 73(4): 446-454, 2023. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1447616

RESUMO

Abstract Background Sepsis and septic shock still represent great challenges in critical care medicine. Sildenafil has been largely used in the treatment of pulmonary arterial hypertension, but its effects in sepsis are unknown. The aim of this study was to investigate the hypothesis that sildenafil can attenuate endotoxin-induced pulmonary hypertension in a porcine model of endotoxemia. Methods Twenty pigs were randomly assigned to Control group (n = 10), which received saline solution; or to Sildenafil group (n = 10), which received sildenafil orally (100 mg). After 30 minutes, both groups were submitted to endotoxemia with intravenous bacterial lipopolysaccharide endotoxin (LPS) infusion (4 µg.kg-1.h-1) for 180 minutes. We evaluated hemodynamic and oxygenation functions, and also lung histology and plasma cytokine (TNFα, IL-1β, IL6, and IL10) and troponin I response. Results Significant hemodynamic alterations were observed after 30 minutes of LPS continuous infusion, mainly in pulmonary arterial pressure (from Baseline 19 ± 2 mmHg to LPS30 52 ± 4 mmHg, p< 0.05). There was also a significant decrease in PaO2/FiO2 (from Baseline 411 ± 29 to LPS180 334 ± 49, p< 0.05). Pulmonary arterial pressure was significantly lower in the Sildenafil group (35 ± 4 mmHg at LPS30, p< 0.05). The Sildenafil group also presented lower values of systemic arterial pressure. Sildenafil maintained oxygenation with higher PaO2/FiO2 and lower oxygen extraction rate than Control group but had no effect on intrapulmonary shunt. All cytokines and troponin increased after LPS infusion in both groups similarly. Conclusion Sildenafil attenuated endotoxin-induced pulmonary hypertension preserving the correct heart function without improving lung lesions or inflammation.


Assuntos
Animais , Endotoxemia , Hipertensão Pulmonar/tratamento farmacológico , Suínos , Lipopolissacarídeos/farmacologia , Endotoxinas/farmacologia , Citrato de Sildenafila/farmacologia , Hemodinâmica , Hipertensão Pulmonar/induzido quimicamente
6.
Sci Rep ; 12(1): 20443, 2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443404

RESUMO

Hemorrhagic shock (HS), a major cause of trauma-related mortality, is mainly treated by crystalloid fluid administration, typically with lactated Ringer's (LR). Despite beneficial hemodynamic effects, such as the restoration of mean arterial pressure (MAP), LR administration has major side effects, including organ damage due to edema. One strategy to avoid such effects is pre-hospitalization intravenous administration of the potent vasoconstrictor terlipressin, which can restore hemodynamic stability/homeostasis and has anti-inflammatory effects. Wistar rats were subjected to HS for 60 min, at a target MAP of 30-40 mmHg, thereafter being allocated to receive LR infusion at 3 times the volume of the blood withdrawn (liberal fluid management); at 2 times the volume (conservative fluid management), plus terlipressin (10 µg/100 g body weight); and at an equal volume (conservative fluid management), plus terlipressin (10 µg/100 g body weight). A control group comprised rats not subjected to HS and receiving no fluid resuscitation or treatment. At 15 min after fluid resuscitation/treatment, the blood previously withdrawn was reinfused. At 24 h after HS, MAP was higher among the terlipressin-treated animals. Terlipressin also improved post-HS survival and provided significant improvements in glomerular/tubular function (creatinine clearance), neutrophil gelatinase-associated lipocalin expression, fractional excretion of sodium, aquaporin 2 expression, tubular injury, macrophage infiltration, interleukin 6 levels, interleukin 18 levels, and nuclear factor kappa B expression. In terlipressin-treated animals, there was also significantly higher angiotensin II type 1 receptor expression and normalization of arginine vasopressin 1a receptor expression. Terlipressin associated with conservative fluid management could be a viable therapy for HS-induced acute kidney injury, likely attenuating such injury by modulating the inflammatory response via the arginine vasopressin 1a receptor.


Assuntos
Injúria Renal Aguda , Choque Hemorrágico , Ratos , Animais , Terlipressina/uso terapêutico , Choque Hemorrágico/complicações , Choque Hemorrágico/tratamento farmacológico , Ratos Wistar , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Lactato de Ringer , Receptores de Vasopressinas , Arginina Vasopressina
7.
Acta Cir Bras ; 37(7): e370703, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36383809

RESUMO

PURPOSE: To determine whether dexmedetomidine aggravates hemodynamic, metabolic variables, inflammatory markers, and microcirculation in experimental septic shock. METHODS: Twenty-four pigs randomized into: Sham group (n = 8), received saline; Shock group (n = 8), received an intravenous infusion of Escherichia coli O55 (3 × 109 cells/mL, 0.75 mL/kg, 1 hour); Dex-Shock group (n = 8), received bacteria and intravenous dexmedetomidine (bolus 0.5 mcg/kg followed by 0.7 mcg/kg/h). Fluid therapy and/ornorepinephrine were administered to maintain a mean arterial pressure > 65 mmHg. Hemodynamic, metabolic, oxygenation, inflammatory markers, and microcirculation were assessed at baseline, at the end of bacterial infusion, and after 60, 120, 180, and 240 minutes. RESULTS: Compared to Shock group, Dex-Shock group presented a significantly increased oxygen extraction ratio at T180 (23.1 ± 9.7 vs. 32.5 ± 9.2%, P = 0.0220), decreased central venous pressure at T120 (11.6 ± 1 vs. 9.61 ± 1.2 mmHg, P = 0.0214), mixed-venous oxygen saturation at T180 (72.9 ± 9.6 vs. 63.5 ± 9.2%, P = 0.026), and increased plasma lactate (3.7 ± 0.5 vs. 5.5 ± 1 mmol/L, P = 0.003). Despite the Dex-Shock group having a better sublingual vessel density at T240 (12.5 ± 0.4 vs. 14.4 ± 0.3 mL/m2; P = 0.0003), sublingual blood flow was not different from that in the Shock group (2.4 ± 0.2 vs. 2.4 ± 0.1 mL/kg, P = 0.4418). CONCLUSIONS: Dexmedetomidine did not worsen the hemodynamic, metabolic, inflammatory, or sublingual blood flow disorders resulting from septic shock. Despite inducing a better sublingual vessel density, dexmedetomidine initially and transitorily increased the mismatch between oxygen supply and demand.


Assuntos
Dexmedetomidina , Sepse , Choque Séptico , Animais , Dexmedetomidina/farmacologia , Hemodinâmica , Microcirculação , Oxigênio/farmacologia , Choque Séptico/tratamento farmacológico , Suínos
8.
J Trauma Acute Care Surg ; 93(6): 838-845, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35393381

RESUMO

BACKGROUND: Trauma-induced secondary cardiac injury has been associated with significant adverse cardiovascular events. Speckle tracking echocardiography is a novel technology that allows an accurate and reproducible cardiac structure and function assessment. We evaluated the left ventricle (LV) myocardial deformation by speckle tracking echocardiography in a hemorrhagic shock (HS) swine model. METHODS: Seven healthy male Landrace pigs were included in this study. Severe HS was reached through three sequentially blood withdraws of 20% of estimated blood volume, and it was maintained for 60 minutes. Volume resuscitation was performed using all precollected blood volume. A 1.8- to 4.2-MHz phased-array transducer was used to acquire the two-dimensional echocardiography images. Strain measurements were obtained semiautomatically by wall motion tracking software. Results are presented as medians and interquartile ranges and compared using Wilcoxon rank-sum test. A p value of <0.05 was considered statistically significant. RESULTS: The median weight was 32 (26.1-33) kg, and the median total blood volume withdrawn was 1,100 (1,080-1,190) mL. During the severe HS period, the median arterial systemic pressure was 39 (36-46) mm Hg, and the cardiac index was 1.7 (1.6-2.0) L/min/m 2 . There was statistically significant absolute decrease in the global longitudinal strain 2 hours postresuscitation comparing with the basal measurements (-9.6% [-10.7 to -8.0%] vs. -7.9% [-8.1 to -7.4%], p = 0.03). There were no statistically significant differences between the basal and 2 hours postresuscitation assessments in the invasive/noninvasive hemodynamic, other two-dimensional echocardiogram (LV ejection fraction, 49.2% [44-54.3%] vs. 53.2% [51.5-55%]; p = 0.09), and circumferential strain (-10.6% [-14.4 to -9.0%] vs. -8.5% [-8.6 to -5.2%], p = 0.06) parameters. CONCLUSION: In this experimental swine model of controlled HS, LV global longitudinal strain analysis accurately characterizes the timing and magnitude of subclinical cardiac dysfunction associated with trauma-induced secondary cardiac injury.


Assuntos
Ecocardiografia Tridimensional , Choque Hemorrágico , Masculino , Suínos , Animais , Ventrículos do Coração/diagnóstico por imagem , Ecocardiografia Tridimensional/métodos , Choque Hemorrágico/diagnóstico por imagem , Reprodutibilidade dos Testes , Ecocardiografia/métodos
9.
Acta cir. bras ; 37(7): e370703, 2022. tab, graf, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1402969

RESUMO

Purpose: To determine whether dexmedetomidine aggravates hemodynamic, metabolic variables, inflammatory markers, and microcirculation in experimental septic shock. Methods: Twenty-four pigs randomized into: Sham group (n = 8), received saline; Shock group (n = 8), received an intravenous infusion of Escherichia coli O55 (3 × 109 cells/mL, 0.75 mL/kg, 1 hour); Dex-Shock group (n = 8), received bacteria and intravenous dexmedetomidine (bolus 0.5 mcg/kg followed by 0.7 mcg/kg/h). Fluid therapy and/ornorepinephrine were administered to maintain a mean arterial pressure > 65 mmHg. Hemodynamic, metabolic, oxygenation, inflammatory markers, and microcirculation were assessed at baseline, at the end of bacterial infusion, and after 60, 120, 180, and 240 minutes. Results: Compared to Shock group, Dex-Shock group presented a significantly increased oxygen extraction ratio at T180 (23.1 ± 9.7 vs. 32.5 ± 9.2%, P = 0.0220), decreased central venous pressure at T120 (11.6 ± 1 vs. 9.61 ± 1.2 mmHg, P = 0.0214), mixed-venous oxygen saturation at T180 (72.9 ± 9.6 vs. 63.5 ± 9.2%, P = 0.026), and increased plasma lactate (3.7 ± 0.5 vs. 5.5 ± 1 mmol/L, P = 0.003). Despite the Dex-Shock group having a better sublingual vessel density at T240 (12.5 ± 0.4 vs. 14.4 ± 0.3 mL/m2; P = 0.0003), sublingual blood flow was not different from that in the Shock group (2.4 ± 0.2 vs. 2.4 ± 0.1 mL/kg, P = 0.4418). Conclusions: Dexmedetomidine did not worsen the hemodynamic, metabolic, inflammatory, or sublingual blood flow disorders resulting from septic shock. Despite inducing a better sublingual vessel density, dexmedetomidine initially and transitorily increased the mismatch between oxygen supply and demand.


Assuntos
Animais , Choque Séptico/tratamento farmacológico , Suínos/fisiologia , Dexmedetomidina/análise , Microcirculação , Biomarcadores Farmacológicos/análise , Hemodinâmica
10.
Animals (Basel) ; 10(12)2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33287159

RESUMO

The neonatal period is a challenging phase for calves, and during this phase constant adaptations are required. The aim of the present study was to evaluate the invasive hemodynamics with the Swan-Ganz catheter in neonate calves to understand adaptive changes during the first 30 days of life. A prospective and observational study was conducted with 10 Holstein calves. Assessments of the right atrial pressure (RAP), right ventricular pressure (RVP), pulmonary artery pressure (PAP), pulmonary capillary pressure (PW), cardiac output (CO), heart rate (HR), pulmonary vascular resistance (PVR), and blood gas levels were performed. The analyses of PAP, PVR, PW, HR, sO2, and arterial blood gases differed (p < 0.05) between the evaluated periods. Our results indicated transient pulmonary artery hypertension during the process of extrauterine adaptation during the first 30 days of life. This hypertension must be considered as physiological and consequent to the neonatal adaptation process.

11.
Vet Ophthalmol ; 23(2): 358-367, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32048792

RESUMO

OBJECTIVE: Optical coherence tomography (OCT) measurement of adult blue-fronted parrots (Amazona aestiva), free from infectious, inflammatory or neoplastic systemic diseases and from any ophthalmological illness, aim at its characterization, as well as to standardize the examination technique for the species. PROCEDURE: Pupillary dilation was achieved with rocuronium bromide (5 mg/mL) at 0, 2, 15, 17, 30, and 32 minutes. The animals were sedated with midazolam maleate (0.5 mg/kg/IM) and anesthetized with propofol (5.0 mg/kg/IV). Measurements were made to evaluate the thickness of the total retina (TR), sensorineural retinal (SR), and ganglion cell complex (GCC), 2 millimeters (mm) from the pecten toward the fovea. OCT data were compared to measurements of retinal histological slides from enucleated eyes of blue-fronted parrots, scanned in automatic fluorescence microscope and measured with by the VS-ASW® software. RESULTS: Averages of measurements from the 43 retinas evaluated by OCT were TR: 279.40 micrometers (µm), SR: 255.90 µm, and GCC: 138.60 µm, respectively, and the measurements of six retinas using fluorescence microscopy were 260.30 µm for TR, 238.20 µm for SR, and 129.30 µm for GCC, demonstrating a high correlation coefficient between all measurements (r = .8698, P < .0001). It is also possible to evaluate the anatomy of the retina and to identify its layers, variations and abnormalities using OCT images. Variations were found between the different areas of the retina, both in the images of the histological slides and in the images of the OCT. CONCLUSION: Optical coherence tomography is a valuable technique for in vivo evaluation of retinal structures in blue-front parrots, providing detailed and accurate images. This method improves the understanding of retinal diseases, monitoring the beginning, progression and therapy of retinal diseases, in the same individuals during longitudinal studies. In comparison to histological investigations, OCT enables imaging in vivo, therefore reducing the number of euthanized animals or enucleated eyes.


Assuntos
Amazona/anatomia & histologia , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica/veterinária , Animais , Feminino , Masculino , Retina/anatomia & histologia
12.
Anesthesiology ; 132(6): 1516-1527, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32053565

RESUMO

BACKGROUND: Intravenous vancomycin is used to treat ventilator-associated pneumonia caused by methicillin-resistant Staphylococcus aureus, but achieves high rates of failure. Vancomycin nebulization may be efficient to provide high vancomycin lung tissue concentrations. The aim of this study was to compare lung tissue and serum concentrations of vancomycin administered intravenously and by aerosol in mechanically ventilated and anesthetized healthy piglets. METHODS: Twelve female piglets received a single intravenous dose of vancomycin (15 mg/kg) and were killed 1 (n = 6) or 12 h (n = 6) after the end of administration. Twelve piglets received a single nebulized dose of vancomycin (37.5 mg/kg) and were killed 1 (n = 6) or 12 h (n = 6) after the end of the aerosol administration. In each group, vancomycin lung tissue concentrations were assessed on postmortem lung specimens using high-performance liquid chromatography. Blood samples were collected for serum vancomycin concentration measurement 30 min and 1, 2, 4, 6, 8, and 12 h after the end of vancomycin administration. Pharmacokinetics was analyzed by nonlinear mixed effect modeling. RESULTS: One hour after vancomycin administration, lung tissue concentrations in the aerosol group were 13 times the concentrations in the intravenous group (median and interquartile range: 161 [71, 301] µg/g versus 12 [4, 42] µg/g; P < 0.0001). Twelve hours after vancomycin administration, lung tissue concentrations in the aerosol group were 63 (23, 119) µg/g and 0 (0, 19) µg/g in the intravenous group (P < 0.0001). A two-compartment weight-scaled allometric model with first-order absorption and elimination best fit serum pharmacokinetics after both routes of administration. Area under the time-concentration curve from 0 to 12 h was lower in the aerosol group in comparison to the intravenous group (56 [8, 70] mg · h · l vs. 121 [103, 149] mg · h · l, P = 0.002). Using a population model, vancomycin bioavailability was 13% (95% CI, 6 to 69; coefficient of variation = 85%) and absorption rate was slow (absorption half life = 0.3 h). CONCLUSIONS: Administration of vancomycin by nebulization resulted in higher lung tissue concentrations than the intravenous route.


Assuntos
Antibacterianos/administração & dosagem , Pulmão/metabolismo , Nebulizadores e Vaporizadores , Respiração Artificial/métodos , Vancomicina/administração & dosagem , Administração por Inalação , Administração Intravenosa , Animais , Antibacterianos/metabolismo , Feminino , Modelos Animais , Suínos , Vancomicina/metabolismo
13.
Sci Rep ; 9(1): 14975, 2019 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-31628390

RESUMO

Data on predictors of intraoperative cardiac arrest (ICA) outcomes are scarce in the literature. This study analysed predictors of poor outcome and their prognostic value after an ICA. Clinical and laboratory data before and 24 hours (h) after ICA were analysed as predictors for no return of spontaneous circulation (ROSC) and 24 h and 1-year mortality. Receiver operating characteristic curves for each predictor and sensitivity, specificity, positive and negative likelihood ratios, and post-test probability were calculated. A total of 167,574 anaesthetic procedures were performed, including 158 cases of ICAs. Based on the predictors for no ROSC, a threshold of 13 minutes of ICA yielded the highest area under curve (AUC) (0.867[0.80-0.93]), with a sensitivity and specificity of 78.4% [69.6-86.3%] and 89.3% [80.4-96.4%], respectively. For the 1-year mortality, the GCS without the verbal component 24 h after an ICA had the highest AUC (0.616 [0.792-0.956]), with a sensitivity of 79.3% [65.5-93.1%] and specificity of 86.1 [74.4-95.4]. ICA duration and GCS 24 h after the event had the best prognostic value for no ROSC and 1-year mortality. For 24 h mortality, no predictors had prognostic value.


Assuntos
Parada Cardíaca/epidemiologia , Parada Cardíaca/mortalidade , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/mortalidade , Adulto , Idoso , Anestesia Geral , Área Sob a Curva , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Probabilidade , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade
14.
Clinics (Sao Paulo) ; 74: e937, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291390

RESUMO

OBJECTIVE: Despite advances in diffuse peritonitis treatment protocols, some cases develop unfavorably. With the advent of vacuum therapy, the use of laparostomy to treat peritonitis has gained traction. Another treatment modality is continuous peritoneal lavage. However, maintaining this technique is difficult and has been associated with controversial results. We propose a new model of continuous peritoneal lavage that takes advantage of the features and benefits of vacuum laparostomy. METHOD: Pigs (Landrace and Large White) under general anesthesia were submitted to laparostomy through which a multiperforated tube was placed along each flank and exteriorized in the left and lower right quadrants. A vacuum dressing was applied, and intermittent negative pressure was maintained. Peritoneal dialysis solution (PDS) was then infused through the tubes for 36 hours. The stability of peritoneostomy with intermittent infusion of fluids, the system resistance to obstruction and leakage, water balance, hemodynamic and biochemical parameters were evaluated. Fluid disposition in the abdominal cavity was analyzed through CT. RESULTS: Even when negative pressure was not applied, the dressing maintained the integrity of the system, and there were no leaks or blockage of the catheters during the procedure. The aspirated volume by vacuum laparostomy was similar to the infused volume (9073.5±1496.35 mL versus 10165±235.73 mL, p=0.25), and there were no major changes in hemodynamic or biochemical analysis. According to CT images, 60 ml/kg PDS was sufficient to occupy all intra-abdominal spaces. CONCLUSION: Continuous peritoneal lavage with negative pressure proved to be technically possible and may be an option in the treatment of diffuse peritonitis.


Assuntos
Laparotomia/métodos , Tratamento de Ferimentos com Pressão Negativa/métodos , Lavagem Peritoneal/métodos , Peritônio/cirurgia , Animais , Modelos Animais , Peritônio/diagnóstico por imagem , Suínos , Tomografia Computadorizada por Raios X , Vácuo
15.
Eur J Neurosci ; 49(1): 51-61, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30402917

RESUMO

The aim of the present study was to investigate changes in glucose metabolism in male Wistar rats induced by the anesthetics isoflurane and ketamine combined with xylazine via 18 F-fluorodeoxyglucose-positron emission tomography. We analyzed the differential effects of the anesthetics on 18 F-fluorodeoxyglucose uptake and pharmacokinetics in 33 rats using quantification methods: (a) the standardized uptake value, (b) voxel-based analyses, and (c) kinetic analysis. Both anesthetics reduced glucose uptake in the entire brain. The voxel-based analyses detected smaller uptake reductions in the bilateral primary somatosensory system cortex and part of the limbic system in the ketamine-xylazine (KX) group and in the vestibular nucleus in the isoflurane group. Through kinetic analysis, we found that the volume of distribution and the membrane transport rate K1 were reduced in the KX group. Through various methods of 18 F-fluorodeoxyglucose-positron emission tomography quantification, the present study found that anesthesia with the ketamine-xylazine combination induced a global reduction of glucose metabolism compared with isoflurane; this reduction of metabolism was relatively lower in the primary somatosensory cortex and part of the limbic system. The volume of distribution of 18 F-fluorodeoxyglucose and its Glut1-mediated transport across the brain membranes (K1 ) were decreased in the KX group.


Assuntos
Anestésicos Gerais/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Glucose/metabolismo , Isoflurano/farmacologia , Ketamina/farmacologia , Xilazina/farmacologia , Animais , Fluordesoxiglucose F18 , Hipnóticos e Sedativos/farmacologia , Masculino , Tomografia por Emissão de Pósitrons , Ratos Wistar
16.
Clinics ; 74: e937, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1011913

RESUMO

OBJECTIVE: Despite advances in diffuse peritonitis treatment protocols, some cases develop unfavorably. With the advent of vacuum therapy, the use of laparostomy to treat peritonitis has gained traction. Another treatment modality is continuous peritoneal lavage. However, maintaining this technique is difficult and has been associated with controversial results. We propose a new model of continuous peritoneal lavage that takes advantage of the features and benefits of vacuum laparostomy. METHOD: Pigs (Landrace and Large White) under general anesthesia were submitted to laparostomy through which a multiperforated tube was placed along each flank and exteriorized in the left and lower right quadrants. A vacuum dressing was applied, and intermittent negative pressure was maintained. Peritoneal dialysis solution (PDS) was then infused through the tubes for 36 hours. The stability of peritoneostomy with intermittent infusion of fluids, the system resistance to obstruction and leakage, water balance, hemodynamic and biochemical parameters were evaluated. Fluid disposition in the abdominal cavity was analyzed through CT. RESULTS: Even when negative pressure was not applied, the dressing maintained the integrity of the system, and there were no leaks or blockage of the catheters during the procedure. The aspirated volume by vacuum laparostomy was similar to the infused volume (9073.5±1496.35 mL versus 10165±235.73 mL, p=0.25), and there were no major changes in hemodynamic or biochemical analysis. According to CT images, 60 ml/kg PDS was sufficient to occupy all intra-abdominal spaces. CONCLUSION: Continuous peritoneal lavage with negative pressure proved to be technically possible and may be an option in the treatment of diffuse peritonitis.


Assuntos
Animais , Peritônio/cirurgia , Lavagem Peritoneal/métodos , Tratamento de Ferimentos com Pressão Negativa/métodos , Laparotomia/métodos , Peritônio/diagnóstico por imagem , Suínos , Vácuo , Tomografia Computadorizada por Raios X , Modelos Animais
17.
Acta Cir Bras ; 32(6): 467-474, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28700008

RESUMO

PURPOSE:: To establish and evaluate the feasibility of continuous peritoneal lavage with vacuum peritoneostomy in an animal model. METHODS:: Eight pigs aged 3-4 months, females, were anesthetized and submitted to laparotomy and installation of a continuous peritoneal lavage with vacuum peritoneostomy. The sta-bility of the system, the physiological effects of washing with NaCl 0.9% and the sys-tem clearance were evaluated. RESULTS:: Stability of vacuum peritoneostomy was observed, with no catheter leaks or obstructions and the clearance proved adequate, however, the mean volume of fluids aspirated by the peritoneostomy at the end of the experiment was higher than the volume infused by the catheters (p=0.02). Besides that, the animals presented a progressive increase in heart rate (p=0.04) and serum potassium (p=0.02). CONCLUSION:: The continuous peritoneal lavage technique with vacuum peritoneostomy is feasible and presents adequate clearance.


Assuntos
Lavagem Peritoneal/métodos , Peritônio/cirurgia , Animais , Estudos de Viabilidade , Feminino , Modelos Animais , Suínos
18.
Acta cir. bras ; 32(6): 467-474, June 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-886203

RESUMO

Abstract Purpose: To establish and evaluate the feasibility of continuous peritoneal lavage with vacuum peritoneostomy in an animal model. Methods: Eight pigs aged 3-4 months, females, were anesthetized and submitted to laparotomy and installation of a continuous peritoneal lavage with vacuum peritoneostomy. The sta-bility of the system, the physiological effects of washing with NaCl 0.9% and the sys-tem clearance were evaluated. Results: Stability of vacuum peritoneostomy was observed, with no catheter leaks or obstructions and the clearance proved adequate, however, the mean volume of fluids aspirated by the peritoneostomy at the end of the experiment was higher than the volume infused by the catheters (p=0.02). Besides that, the animals presented a progressive increase in heart rate (p=0.04) and serum potassium (p=0.02). Conclusion: The continuous peritoneal lavage technique with vacuum peritoneostomy is feasible and presents adequate clearance.


Assuntos
Animais , Feminino , Peritônio/cirurgia , Lavagem Peritoneal/métodos , Suínos , Estudos de Viabilidade , Modelos Animais
19.
Acta Cir Bras ; 31(5): 338-45, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27275856

RESUMO

PURPOSE: To investigate the myocardial ischemia-reperfusion with sevoflurane anesthetic preconditioning (APC) would present beneficial effects on autonomic and cardiac function indexes after the acute phase of a myocardial ischemia-reperfusion. METHODS: Twenty Wistar rats were allocated in three groups: control (CON, n=10), myocardial infarction with sevoflurane (SEV, n=5) and infarcted without sevoflurane (INF, n=5). Myocardial ischemia (60 min) and reperfusion were performed by temporary coronary occlusion. Twenty-one days later, the systolic and diastolic function were evaluated by echocardiography; spectral analysis of the systolic arterial pressure (SAPV) and heart rate variability (HRV) were assessed. After the recording period, the infarct size (IS) was evaluated. RESULTS: The INF group presented greater cardiac dysfunction and increased sympathetic modulation of the SAPV, as well as decreased alpha index and worse vagal modulation of the HRV. The SEV group exhibited attenuation of the systolic and diastolic dysfunction and preserved vagal modulation (square root of the mean squared differences of successive R-R intervals and high frequency) of HRV, as well as a smaller IS. CONCLUSION: Sevoflurane preconditioning better preserved the cardiac function and autonomic modulation of the heart in post-acute myocardial infarction period.


Assuntos
Anestésicos Inalatórios/farmacologia , Sistema Nervoso Autônomo/efeitos dos fármacos , Precondicionamento Isquêmico Miocárdico/métodos , Éteres Metílicos/farmacologia , Infarto do Miocárdio/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Animais , Sistema Nervoso Autônomo/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Ecocardiografia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Masculino , Modelos Animais , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/etiologia , Pulso Arterial , Distribuição Aleatória , Ratos Wistar , Sevoflurano , Fatores de Tempo
20.
Acta cir. bras ; 31(5): 338-345, May 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-783802

RESUMO

ABSTRACT PURPOSE: To investigate the myocardial ischemia-reperfusion with sevoflurane anesthetic preconditioning (APC) would present beneficial effects on autonomic and cardiac function indexes after the acute phase of a myocardial ischemia-reperfusion. METHODS: Twenty Wistar rats were allocated in three groups: control (CON, n=10), myocardial infarction with sevoflurane (SEV, n=5) and infarcted without sevoflurane (INF, n=5). Myocardial ischemia (60 min) and reperfusion were performed by temporary coronary occlusion. Twenty-one days later, the systolic and diastolic function were evaluated by echocardiography; spectral analysis of the systolic arterial pressure (SAPV) and heart rate variability (HRV) were assessed. After the recording period, the infarct size (IS) was evaluated. RESULTS: The INF group presented greater cardiac dysfunction and increased sympathetic modulation of the SAPV, as well as decreased alpha index and worse vagal modulation of the HRV. The SEV group exhibited attenuation of the systolic and diastolic dysfunction and preserved vagal modulation (square root of the mean squared differences of successive R-R intervals and high frequency) of HRV, as well as a smaller IS. CONCLUSION: Sevoflurane preconditioning better preserved the cardiac function and autonomic modulation of the heart in post-acute myocardial infarction period.


Assuntos
Animais , Masculino , Sistema Nervoso Autônomo/efeitos dos fármacos , Isquemia Miocárdica/fisiopatologia , Anestésicos Inalatórios/farmacologia , Precondicionamento Isquêmico Miocárdico/métodos , Éteres Metílicos/farmacologia , Infarto do Miocárdio/fisiopatologia , Pulso Arterial , Sistema Nervoso Autônomo/fisiologia , Fatores de Tempo , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Ecocardiografia , Distribuição Aleatória , Ratos Wistar , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/diagnóstico por imagem , Modelos Animais , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/diagnóstico por imagem
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