RESUMO
The biological mechanisms that explain how adverse early life events influence adult disease risk are poorly understood. One proposed mechanism is via the induction of accelerated biological aging, for which telomere length is considered a biomarker. We aimed to determine if maternal depression pre- and post-partum was associated with telomere length in children at 4 years of age (n = 4299). Mothers completed structured questionnaires assessing depression during pregnancy (Edinburgh Depression Scale), at 9 months (Edinburgh Depression Scale), and at 54 months postpartum (Patient Health Questionnaire 9). Regression methods were used to investigate the relationship between telomere length (DNA from saliva) and maternal depression score recorded at each stage. Significant covariates included in the final model were: maternal age at pregnancy; child sex; child ethnicity; gestational age group, and rurality group. Child telomere length was found to be longer if their mother had a higher depression score at both postpartum time points tested (9 months of age; coefficient 0.003, SE = 0.001, P = 0.01, 54 months of age; coefficient 0.003, SE = 0.002, P = 0.02). Although these findings seem paradoxical, increased telomere length may be an adaptive response to early life stressors. We propose several testable hypotheses for these results and to determine if the positive association between depression and telomere length is a developmental adaptation or an indirect consequence of environmental factors.
Assuntos
Depressão , Humanos , Feminino , Pré-Escolar , Masculino , Adulto , Gravidez , Lactente , Mães/estatística & dados numéricos , Telômero , Encurtamento do Telômero/fisiologia , Complicações na Gravidez , Depressão Pós-Parto , Escalas de Graduação PsiquiátricaRESUMO
In this study, Er-doped CoAl2O4 nanocrystals (NCs) were synthesized via co-precipitation. All the NCs were crystallized in the form of a single phase with a spinel structure and Er3+ ions replaced Al3+ ions in the formation of the CoAl2-xErxO4 alloy structure. The optical characteristics of the Er3+ ion-doped CoAl2O4 NCs were thoroughly investigated by analyzing both the UV-VIS and photoluminescence spectra, using the Judd-Ofelt theory. The effect of Er doping content on the luminescent properties of the CoAl2O4 pigment (using lasers emitting at wavelengths of 413 and 978 nm) has been studied. The values of Judd-Oflet intensity parameters (Ω2, Ω4, and Ω6) were determined from the absorption spectra using the least square fitting method. The J-O parameters were calculated and compared with those of other host materials; the values of the Ω2, Ω4, and Ω6 parameters decreased with an increase in Er concentration. This suggests that the rigidity and local symmetry of the host materials become weaker as the concentration of Er3+ ions increases. The highest value of the Ω2 parameter, when compared with Ω4 and Ω6, suggests that the vibrational frequencies in the given samples are relatively low. The upconversion fluorescence phenomenon was observed and explained in detail under an excitation wavelength of 978 nm when the excitation power was varied.
RESUMO
The aim of this study was to investigate the influence of inhalation injury on resting energy expenditure (REE) and some plasma metabolic hormones in adult burn patients. A prospective study was conducted on 16 adult burn patients admitted to the burn intensive care unit, National Burn Hospital, Vietnam. Eight patients with inhalation injury were matched with 8 non-inhalation injury patients by burn extent and age. REE measurements were obtained within 48h of admission and every week after burn. Plasma levels of epinephrine and cortisol were determined on admission and on the 7th day after burns. The results showed that, apart from REE at admission, all values of REE were significantly higher than basal metabolic rate (BMR) at all time points (p < .005). Over time, REE of both groups significantly increased and reached peak values on the 7th day after burn (1964 ± 300Kcal/m2 and 1991.8 ± 467.8Kcal/m2; REE/BMR: 1.5 vs. 1.6 respectively). These values then steadily reduced, but no remarkable differences of REE and REE/BMR were seen between the two groups at any time point (p > .05). In addition, plasma concentrations of epinephrine and cortisol were not significantly different in each group and between the two groups of patients with and without inhalation injury. In conclusion, inhalation injury may not affect metabolic response state in adult burn patients as measured by REE and metabolic hormones.
Le but de ce travail était d'étudier l'influence de l'inhalation de fumées sur la dépense énergétique de repos (DER) et le niveau plasmatique de certaines hormones « métabolique ¼ chez des adultes brûlés. Elle a été réalisée sur 16 patients hospitalisés dans le service de réanimation de l'hôpital brûlologique national du Viêt- Nam, 8 ayant inhalé de la fumée, 8 n'en ayant pas inhalé, appariés sur la surface brûlée. La DER était mesurée dans les 48 h de l'admission puis toutes les semaines. Les taux plasmatiques de cortisol et d'adrénaline étaient mesurés à l'admission et à J7. Mise part celle mesurée à l'admission, DER était systématiquement supérieure à celle calculée selon la formule de Harris- Benedict (p < 0,005), avec un pic à J7 (1964 +/- 300 Cal/m2 chez les patients avec inhalation de fumées, 1991,8 +/- 467,8 chez les autres soit 1,5 et 1,6 fois la DER supposée. Les valeurs mesurées diminuaient ensuite sans jamais qu'il y ait de différence entre les groupes. Pas plus que ne différaient les taux de cortisol ni d'adrénaline. L'inhalation de fumée semble donc de pas avoir d'impact sur la réponse métabolique, mesurée par calorimétrie ou évaluée sur les taux hormonaux.
RESUMO
Brain dopamine-serotonin vesicular transport disease is a rare disease caused by autosomal recessive mutations in the SLC18A2 gene, which encodes the VMAT2 protein. VMAT2 is a membrane protein responsible for vesicular transport of monoamines, and its disruption negatively affects neurotransmission. This results in a severe neurodevelopmental disorder affecting motor skills and development, and causes muscular hypotonia. The condition was initially described in a consanguineous Saudi Arabian family with affected siblings homozygous for a P387L mutation. We subsequently found a second mutation in a New Zealand family (homozygous P237H), which was later also identified in an Iraqi family. Pramipexole has been shown to have some therapeutic benefit. Transgenic Caenorhabditis elegans were developed to model the P237H and P387L mutations. Investigations into dopamine- and serotonin-related C. elegans phenotypes, including pharyngeal pumping and grazing, showed that both mutations cause significant impairment of these processes when compared with a non-transgenic N2 strain and a transgenic containing the wild-type human SLC18A2 gene. Preliminary experiments investigating the therapeutic effects of serotonin and pramipexole demonstrated that serotonin could successfully restore the pharyngeal pumping phenotype. These analyses provide further support for the role of these mutations in this disease.
Assuntos
Encéfalo/metabolismo , Caenorhabditis elegans/metabolismo , Dopamina/metabolismo , Modelos Biológicos , Serotonina/metabolismo , Vesículas Transportadoras/patologia , Animais , Animais Geneticamente Modificados , Sequência de Bases , Transporte Biológico , Humanos , Faringe/patologia , Fenótipo , Vesículas Transportadoras/metabolismoRESUMO
OBJECTIVES: The reported long-term safety of kidney donation is inconsistent with the impairment of kidney function observed following nephrectomy for renal cell cancer. We aimed to investigate if indication for nephrectomy (kidney cancer vs. living donation) was an independent risk factor for kidney function deterioration. MATERIALS AND METHODS: Between 1985 and 2008, 124 patients with localized renal cell carcinoma who meet the criteria used for living donation, underwent radical nephrectomy (group 1) at our institution. Group 1 was retrospectively compared with 124 consecutive living donor nephrectomies (group 2) performed from 2004 to 2008. Kidney function evaluation was performed preoperatively and at 1, 2, 3, and 4 years postoperatively with calculation of estimated glomerular filtration rate through the Modification of Diet in Renal Disease (MDRD-eGFR) and the adjusted Cockroft and Gault (CG-eGFR) formula. Multivariate logistic regression included patients' characteristics and indication for nephrectomy as predictors of kidney function deterioration. RESULTS: Mean decrease in MDRD-eGFR was 30.4% and 32.4% in groups 1 and 2 (P = 0.30). Prevalence of chronic kidney disease (CKD), defined by MDRD-eGFR < 60 mL/min/m(2), varied from 42.3% to 71% in group 1 and from 41.6% to 56% in group 2 at different time points (P = 0.073). Prevalence of CKD at 4 years defined by MDRD-eGFR < 45 mL/min/m(2) was significantly increased in group 1 compared with group 2 (16.2% and 5.3%, P < 0.005, respectively). Linear regression analysis showed only baseline kidney function and patient age predicted a significant decrease in postoperative kidney function (P < 0.001 and P = 0.04). CONCLUSIONS: Renal cell carcinoma is not an independent risk factor for kidney function impairment following nephrectomy. Selected kidney cancer patients with few morbidities face the same deterioration of meanly 30% of kidney function compared with living donors, but their lower baseline function results in an increased risk for CKD.
Assuntos
Taxa de Filtração Glomerular , Rim/fisiologia , Rim/fisiopatologia , Nefrectomia/métodos , Adulto , Idoso , Carcinoma de Células Renais/fisiopatologia , Carcinoma de Células Renais/cirurgia , Estudos de Coortes , Feminino , Humanos , Neoplasias Renais/fisiopatologia , Neoplasias Renais/cirurgia , Doadores Vivos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nefrectomia/efeitos adversos , Período Pós-Operatório , Período Pré-Operatório , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologiaRESUMO
PURPOSE: The purpose of this multicenter study was to determine the doses received by patients during interventional neuroradiology procedures and to consider establishing reference standards. MATERIALS AND METHODS: A retrospective study of nine interventional neuroradiology departments was conducted. Seven diagnostic (cerebral and spinal angiography) and therapeutic (embolization and vertebroplasty) procedures were reviewed. For each procedure, three dosimetric parameters were recorded: dose-area product (DAP), fluoroscopy time, and number of images. RESULTS: Results showed interdepartment variations, up to four-fold for diagnostic procedures and seven-fold for therapeutic procedures. However, applying the 75th percentile method to the entire dataset, reference standards can be proposed for six types of procedures including diagnostic cerebral angiography (230 Gycm(2)), follow-up selective cerebral angiography (80 Gycm(2)), aneurysm embolization (350 Gycm(2)), AVM embolization (440 Gycm(2)). Reference standards are also proposed with regards to fluoroscopy time and number of images. CONCLUSION: Such standards are useful for clinicians to evaluate and improve their practices.
Assuntos
Neurorradiografia/normas , Doses de Radiação , Radiografia Intervencionista/normas , Humanos , Estudos RetrospectivosRESUMO
We report a case of carotid endarterectomy and clipping of an ipsilateral internal carotid artery aneurysm in a patient with complete contralateral carotid stenosis. The patient developed an ischaemic electroencephalographic (EEG) tracing on temporary carotid clamping and bypass shunt was contraindicated. We used thiopentone titrated to EEG burst suppression for pharmacological cerebral protection during the subsequent prolonged carotid clamp necessary for carotid endarterectomy. We review the use of thiopentone for this purpose, in particular the evidence for efficacy, mechanism of action and optimal dosage and timing of administration.
Assuntos
Artéria Carótida Interna/cirurgia , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Hipnóticos e Sedativos/administração & dosagem , Aneurisma Intracraniano/cirurgia , Fármacos Neuroprotetores/administração & dosagem , Tiopental/administração & dosagem , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Isquemia Encefálica/prevenção & controle , Estenose das Carótidas/complicações , Constrição , Eletroencefalografia , Feminino , Humanos , Aneurisma Intracraniano/complicações , Complicações Intraoperatórias , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Epinephrine administration for hemostasis during burn wound excision may produce potential anesthetic risks. Two patient groups were studied to determine the absorption of either topical concentrated epinephrine or exogenously injected dilute epinephrine. METHODS: For the topical group (10 patients, 10 procedures), excision of wounds under tourniquet was performed, followed by epinephrine (1 mg/10 mL) gauze with pressure wrapping. For the clysis group (9 patients, 12 procedures), donor sites were injected with 0.5 mg epinephrine/1,000 mL lactated Ringer's solution before harvest. Nine intraoperative serum samples were collected and frozen during each procedure for epinephrine and norepinephrine assay. RESULTS: Concentrated epinephrine (67 mL) was topically applied to excise 1,362 cm2. Dilute epinephrine (1,350 mL) was clysed to obtain 1,950 cm2 autograft. No significant increases in the serum catecholamines or changes in the cardiovascular profiles occurred. CONCLUSION: The administration of either topical or clysed epinephrine during acute burn excision does not cause any side effects for safe anesthetic management; there were no detectable increased plasma levels of epinephrine or norepinephrine. Epinephrine provides the burn surgeon with two safe methods for controlling intraoperative blood loss.
Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Queimaduras/cirurgia , Epinefrina/administração & dosagem , Epinefrina/sangue , Norepinefrina/sangue , Vasoconstritores/administração & dosagem , Vasoconstritores/sangue , Administração Cutânea , Adulto , Feminino , Humanos , Injeções Subcutâneas , Período Intraoperatório , Masculino , Pessoa de Meia-IdadeRESUMO
Small-volume resuscitation using hypertonic saline (7.5%) is effective for various types of shock. Recently, hypertonic saline has been proposed for fluid management in patients with impaired cardiovascular function. Whether hypertonic saline is safe in the compromised heart during coronary occlusion is not known. We examined the effects of hypertonic saline at 4 mL.kg-1 on myocardial function and blood flow during acute coronary occlusion. In anesthetized dogs, the left ventricle (LV) was instrumented with pressure and ultrasonic dimension transducers. Myocardial contractility was assessed using percent of systolic shortenings measured in both normal or ischemic regions. Blood flow distribution was measured using radioactive microspheres. Percent of systolic shortening and blood flow in the normal myocardium, unaltered by coronary occlusion, increased significantly after hypertonic saline from 11.0 +/- 1.1% to 13.7 +/- 1.4% and from 120 +/- 13 mL.min-1.100 g-1 to 169 +/- 13 mL.min-1.100 g-1, respectively. In the ischemic myocardium, occlusion of the left anterior descending coronary artery markedly decreased percent of systolic shortening from 13.0 +/- 1.2% to 9.3 +/- .9% and blood flow from 98 +/- 13 mL.min-1.100 g-1 to 19 +/- 10 mL.min-1.100 g-1. At peak effect of hypertonic saline contractility and blood flow in the ischemic myocardium decreased to 7.4 +/- .8% and 12 +/- 5 mL.min-1.100 g-1, respectively. Five of the nine dogs developed premature ventricular beats during hypertonic saline infusion. However, no significant changes were observed when normal saline was given at equivalent volumes to hypertonic saline in six dogs. Hypertonic saline was associated with significant increases in heart rate (from 116 +/- 3 beats.min-1 to 129 +/- 5 beats.min-1) and cardiac output (from 2.54 +/- .17 L.min-1 to 3.32 +/- .26 L.min-1). Except for an improved perfusion in the skin, hepatic arterial, and coronary beds, blood flow to the muscle, spleen, jejunum, kidney, and brain was not significantly altered by hypertonic saline. Our data demonstrates variant effects of hypertonic saline on either normal or ischemic myocardium. Whereas contractile function and blood flow in the normal myocardium were improved after hypertonic saline infusion, further decreases in blood flow and contractile function in region distal to coronary occlusion could lead to worsening of ischemic injury. These data suggest that hypertonic saline may be deleterious in hearts with impaired contractile function caused by ischemia.
Assuntos
Doença das Coronárias/tratamento farmacológico , Coração/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Solução Salina Hipertônica/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Circulação Coronária/efeitos dos fármacos , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiopatologia , Modelos Animais de Doenças , Cães , Ecocardiografia/métodos , Feminino , Coração/fisiopatologia , Masculino , Contração Miocárdica/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , PerfusãoRESUMO
Resuscitation using small volumes (3-5 mL/kg) of 7.5% hypertonic saline (HTS) is effective for hemorrhagic shock. Whether HTS is beneficial for the initial resuscitation of burn injury is not clear. We compared the hemodynamic effects of HTS versus lactated Ringer's solution (LR) and examined organ tissue perfusion during burn resuscitation (R). Full thickness scald burn (35% of total body surface area) was induced in pentobarbital-anesthetized rats. Regional blood flows were measured using radioactive microspheres before and 30 min after burn, and after R with either HTS (4 mL/kg) or LR (at a dose required for equivalent restoration of arterial blood pressure). Data from the HTS-or LR-resuscitated groups were compared to those from a nonresuscitated group (n = 10 in each group). Mean arterial pressure decreased 30% after burn (from 120 +/- 4 to 84 +/- 5 mm Hg, mean +/- SEM) and returned toward baseline (112 +/- 7 mm Hg) at 10 min after R with HTS (4 mL/kg) or LR (22.6 +/- 0.7 mL/kg), but subsequently decreased to 100 +/- 7 mm Hg with HTS and 105 +/- 5 mm Hg with LR at 30 min. In contrast to LR, resuscitation using HTS was associated with tachycardia. Blood flows to the skin and muscle of the normal or burn regions did not change after fluid resuscitation as compared to a nonresuscitated group. Fluid resuscitation transiently increased intestinal perfusion. Similar improvements in blood flow to the spleen were observed with HTS and LR at 10 min after R (from 128 +/- 10 to 156 +/- 15 and from 113 +/- 10 to 145 +/- 26 mL.min-1 x 100 g-1, respectively). However, at 30 min after R, splenic perfusion in the LR group was not different from that in the nonresuscitated group. Blood flows to the brain and kidney increased 39% and 42%, respectively, with HTS. HTS was also associated with pronounced improvements in blood flows to the heart (from 346 +/- 20 to 631 +/- 37 mL.min-1 x 100 g-1), liver (from 36 +/- 2 to 62 +/- 4 mL.min-1 x 100 g-1), and testis (from 29 +/- 2 to 43 +/- 2 mL.min-1 x 100g-1). Resuscitation using HTS was associated with rapid improvement in organ tissue perfusion in anesthetized rats subjected to burn injury. In comparison to LR, greater increases in blood flows to the heart, kidney, liver, and testis were observed with HTS. The results suggest that significant improvement in blood flow distribution can be achieved using HTS at less than one fifth the volume of LR for the initial treatment of burn shock.
Assuntos
Circulação Sanguínea , Queimaduras/terapia , Hidratação/métodos , Soluções para Reidratação/uso terapêutico , Solução Salina Hipertônica/uso terapêutico , Animais , Pressão Sanguínea , Superfície Corporal , Queimaduras/patologia , Queimaduras/fisiopatologia , Circulação Cerebrovascular , Circulação Coronária , Intestinos/irrigação sanguínea , Soluções Isotônicas/administração & dosagem , Soluções Isotônicas/uso terapêutico , Circulação Hepática , Masculino , Microesferas , Músculo Esquelético/irrigação sanguínea , Radioisótopos , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional , Soluções para Reidratação/administração & dosagem , Circulação Renal , Ressuscitação , Lactato de Ringer , Solução Salina Hipertônica/administração & dosagem , Choque Hemorrágico/terapia , Pele/irrigação sanguínea , Baço/irrigação sanguínea , Taquicardia/etiologia , Testículo/irrigação sanguíneaRESUMO
OBJECTIVE: To develop a method of measuring end-systolic elastance from information obtained outside the ventricle and thereby simplify its transduction. DESIGN: Prospective, within-animal comparative analysis. SETTING: University-based laboratory study. PARTICIPANTS: Six mixed-breed dogs. INTERVENTIONS: Instrumentation included minor axis sonomicrometry, ascending aortic flow probe, aortic and ventricular pressure transducers, and constricting cuffs on the vena cavae and aorta. MEASUREMENTS AND MAIN RESULTS: Elastance was determined from the equation PES = EES (VED - VES), where VED - VES is stroke volume and PES is end-systolic arterial pressure. EES was derived from both preload and afterload manipulation. Cardiac performance indices were calculated automatically by computer under conditions of varying load and inotropy. This extraventricular method of elastance calculation was compared by linear regression and analysis of variance to preload recruitable stroke work, traditional EES determination (using ventricular dimension instead of volume), and LVdP/dt at 50 mmHg. EES measured from the aortic sites correlated well with the other contractility indicators (p < 0.003 in all cases) and demonstrated more sensitivity and stability under loading manipulation than traditional EES. A strong relationship between the change in stroke volume and end-systolic ventricular diameter during acute aortic constriction (r = 0.924, p < 0.0001) was observed, and the mean r value for the individual outflow elastance measurements was 0.97 +/- 0.02. CONCLUSIONS: In this study, measurement of EES from the ventricular outflow tract during progressive aortic constriction produced results more consistent and descriptive than EES by traditional techniques and has the potential for obtaining elastance measurements from possibly less invasive techniques.
Assuntos
Pressão Sanguínea , Contração Miocárdica , Volume Sistólico , Análise de Variância , Animais , Aorta/fisiologia , Débito Cardíaco , Constrição , Cães , Elasticidade , Frequência Cardíaca , Ventrículos do Coração/anatomia & histologia , Modelos Lineares , Manometria/instrumentação , Micromanipulação , Estudos Prospectivos , Sístole , Transdutores de Pressão , Ultrassonografia/instrumentação , Veias Cavas/fisiologia , Pressão VentricularRESUMO
The spinal cord is an important site where inhaled anesthetics suppress movement in response to noxious stimuli. Inhaled anesthetics also act in peripheral tissues, although it is unclear whether these actions influence anesthetic requirements. In six isoflurane-anesthetized mongrel dogs, we placed Y cannulas in the lower aorta and vena cava, allowing us to divert blood to, and infuse blood from, a bubble oxygenator/roller pump system or to maintain normal blood flow. This technique permits a greatly diminished isoflurane concentration at the site of the noxious stimulus (tail), while maintaining isoflurane in the remainder of the body. After baseline minimum alveolar anesthetic concentration (MAC1) was determined, venous blood from the lower body was diverted to the bubble oxygenator and reinfused into the lower body via the aortic cannula; MAC2 was determined with isoflurane in the lower body at approximately 0.2%, and MAC3 was determined with isoflurane in the lower body matched to the end-tidal isoflurane. Bypass was terminated, the native circulation established, and MAC4 determined. MAC1, 2, 3, and 4 were (mean +/- SD) 1.3 +/- 0.3%, 1.2 +/- 0.1%, 1.2 +/- 0.2%, and 1.1 +/- 0.2%, respectively (P > 0.05). We conclude that the peripheral effects of isoflurane do not influence the response to a noxious stimulus.
Assuntos
Isoflurano/administração & dosagem , Isoflurano/farmacologia , Nervos Periféricos/efeitos dos fármacos , Anestesia por Inalação , Animais , Aorta , Axônios/efeitos dos fármacos , Axônios/fisiologia , Circulação Sanguínea , Cateterismo/instrumentação , Cães , Membro Posterior , Isoflurano/sangue , Nociceptores/efeitos dos fármacos , Nociceptores/fisiologia , Oxigenadores , Dor/fisiopatologia , Nervos Periféricos/fisiopatologia , Alvéolos Pulmonares , Medula Espinal/efeitos dos fármacos , Cauda , Volume de Ventilação Pulmonar , Veia Cava InferiorRESUMO
We examined the relationship between nicotine-induced vasoconstriction in pregnant rat dams and fetal growth during the third trimester of pregnancy. Pregnant rats were continuously treated between days 13 and 19 of gestation with either nicotine (9.6, 4.8 or 2.4 mg/kg/day), epinephrine (0.72 microgram/kg/day), or saline via continuous infusion from a subcutaneously implanted osmotic minipump. Placental weights in rats treated with high dose nicotine and dams' body weights were severely reduced. However, fetal weights were not affected. Blood flows in uterus and placenta were quantified by measurement of tissue content of 85Sr-labelled microspheres injected via a carotid artery catheter. Both nicotine and epinephrine caused a significant reduction (> 40%) in uterine and placental blood flow. We conclude that vasoconstriction alone as a result of nicotine or epinephrine administration during the last trimester of gestation does not necessarily reduce nutrient supply to the fetus and does not affect fetal growth in rats.
Assuntos
Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Epinefrina/farmacologia , Nicotina/farmacologia , Placenta/efeitos dos fármacos , Circulação Placentária/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Animais , Cotinina/sangue , Epinefrina/administração & dosagem , Feminino , Feto/irrigação sanguínea , Bombas de Infusão Implantáveis , Troca Materno-Fetal , Nicotina/administração & dosagem , Nicotina/sangue , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
We examined the hypothesis that the coronary vasomotor responses to etomidate (ETO), propofol (PRO), and sodium thiopental (STP) are mediated through contrasting effects on the resting nitric oxide (NO)-dependent vasodilator tone that opposes adrenergic vasoconstrictor activity in the intact dog. Circumflex flow (CxF) responses to randomized intracoronary microinjections (0.3 mL) of normal saline (NS), alkalinized saline (AS), intralipid (IL), adenosine (ADE, 17 micrograms), acetylcholine (ACh, 1.25 micrograms), ETO (6, 12, 60 micrograms), PRO (30, 60, 300 micrograms), and STP (75, 150, 750 micrograms) were quantified in eight isoflurane-anesthetized dogs with fixed ventricular rates (100 bpm). Injections were repeated during intravenous (IV) infusion (50 mg/kg + 1 mg.kg-1.min-1) of NG-nitro-L-arginine methyl ester (L-NAME). ADE and ACh transiently increased CxF to 305% +/- 20% (P < 0.001) and 310% +/- 29% (P < 0.001) of resting values, respectively. ETO had no effect, whereas PRO (300 micrograms) provoked small transient increases in CxF to 135% +/- 4% (P < 0.05) of control. Responses to STP (750 micrograms) were characterized by momentary decreases to 74% +/- 4% (P < 0.001), followed immediately by increases to 183% +/- 11% (P < 0.001) of resting values; NS AS, and IL had no effect. The momentary decreases with STP (750 micrograms) were significantly augmented during NO inhibition with CxF declining to 49% +/- 7% (P < 0.001) of resting values, whereas the secondary increase was unchanged. With L-NAME, CxF responses to ACh were attenuated to 32% +/- 3% (P < 0.001) of control, whereas responses to ADE, ETO, and PRO were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Circulação Coronária/efeitos dos fármacos , Etomidato/farmacologia , Óxido Nítrico/fisiologia , Propofol/farmacologia , Tiopental/farmacologia , Acetilcolina/farmacologia , Anestesia , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiologia , Cães , Feminino , Masculino , NG-Nitroarginina Metil Éster , Óxido Nítrico/antagonistas & inibidores , Vasoconstrição/efeitos dos fármacosRESUMO
During acute myocardial ischaemia, the function of the unaffected muscle is the primary determinant of residual cardiac performance. We compared six methods of measuring regional function in the remaining non-ischaemic segment after acute ligation of the left anterior descending (LAD) coronary artery in 16 dogs. Preparation included left ventricular micromanometers, regional sonomicrometer transducers to measure segment length and wall thickness, caval occluders and left atrial catheters for injection of radioactive microspheres to measure regional blood flow. Pulmonary artery, central venous and systemic arterial pressures were measured and regional coronary venous blood was collected for direct myocardial oxygen consumption (VO2) calculations. Under basal high-dose fentanyl-neuromuscular blocker anaesthesia, the LAD was occluded after addition of halothane or isoflurane at 0.5 or 1.5 MAC concentrations. Regional myocardial function of the non-ischaemic segment was assessed by the following computer-derived indices: percent systolic wall thickening (% WT), velocity of shortening (vs), percent systolic shortening (%SS), regional stroke work (RSW), regional preload recruitable stroke work (RPRSW) and regional end-systolic elastance (Ees). No index demonstrated enhanced function in the non-ischaemic segment after LAD ligation and all monitors, except Ees, were sensitive to depression of function represented by a decrease in values after administration of halothane and isoflurane (P < 0.05). Ees values increased with the addition of isoflurane and remained constant with halothane. Circulating concentrations of catecholamines were unchanged after ischaemia, while inhalation agents caused a decrease in the concentrations of adrenaline and dopamine (P < 0.05), but not noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Halotano/farmacologia , Coração/fisiopatologia , Isoflurano/farmacologia , Isquemia Miocárdica/fisiopatologia , Animais , Modelos Animais de Doenças , Cães , Dopamina/sangue , Epinefrina/sangue , Feminino , Coração/efeitos dos fármacos , Testes de Função Cardíaca/métodos , Hemodinâmica/efeitos dos fármacos , Masculino , Isquemia Miocárdica/sangue , Norepinefrina/sangueRESUMO
BACKGROUND: As part of studies aimed at better defining the effects of anesthetics at different anatomic sites, we have developed a model of preferentially delivering inhaled anesthetics to the in situ goat brain, using a bubble oxygenator and roller pump. We tested the hypotheses that (1) this model excludes the cerebral circulation from the body; (2) the concentration of halothane in the oxygenator exhaust correlates with the concentration of halothane in the oxygenator arterial blood. METHODS: After ligation of the occipital arteries in six halothane-anesthetized goats, we used a bubble oxygenator to perfuse the brain preferentially (exclusive of the body) via a carotid artery, draining cranial venous blood back into the oxygenator via the isolated jugular veins. (In goats, the vertebral arteries do not directly contribute to the cerebral circulation, and internal jugular veins and extracranial internal carotid arteries are absent). The extent of isolation was determined with radioactive microspheres injected into the left atrium during the following periods: (1) baseline; (2) during bypass when the blood pressure in the head equalled that in the body; (3) during bypass when the blood pressure in the body exceeded that in the head by approximately 30-35 mmHg; (4) when the bypass roller pump was stopped. We also measured the concentration of halothane in the arterial blood of the bypass unit. In three animals, systemic metocurine was administered during bypass to detect the presence of venous contamination. RESULTS: Baseline cerebral blood flow was 74 +/- 32 ml.100 g-1.min-1 (mean +/- SD). During bypass, cerebral blood flow originating from the systemic circulation was less than 1 ml.100 g-1.min-1, and isolation extended to the caudal medulla during periods 3 and 4, and to the first 1-cm segment of the spinal cord during period 2. The concentration of halothane in the oxygenator exhaust correlated reasonably well with the arterial halothane concentration (r = 0.82, P < 0.001). Systemic arterial metocurine concentrations peaked at 1 min (27 +/- 3.7 micrograms/ml) and decreased to 10.6 +/- 2.3 micrograms/ml at 10 min; head venous metocurine plasma concentrations gradually increased to 3.1 +/- 0.4 micrograms/ml at 10 min. CONCLUSIONS: This technique permits selective perfusion and delivery of inhaled anesthetics to the in situ goat brain, but is not adequate for selective delivery of fixed intravenous anesthetics.
Assuntos
Anestesia por Inalação/métodos , Pressão Sanguínea , Encéfalo/irrigação sanguínea , Circulação Cerebrovascular , Halotano/administração & dosagem , Anestesia por Inalação/instrumentação , Animais , Artérias Carótidas , Cabras , Halotano/sangue , Veias Jugulares , Fármacos Neuromusculares Despolarizantes/sangue , Especificidade de Órgãos , Oxigênio/sangue , Perfusão/instrumentação , Perfusão/métodos , Fluxo Sanguíneo Regional , Tubocurarina/análogos & derivados , Tubocurarina/sangueRESUMO
The present study examined the postulate that the quotient of mean systemic arterial pressure and heart rate predicts the severity of myocardial ischemia during occlusion of the left anterior descending coronary artery. Studies were performed in open-chest fentanyl-anesthetized dogs before and during halothane (n = 8) or isoflurane (n = 8) anesthesia. The pressure-rate quotient (PRQ) decreased significantly in both groups during incremental increases in halothane or isoflurane to 68% and 57% of control values at 0.5 MAC and to 41% and 38% at 1.5 MAC for halothane and isoflurane, respectively. Myocardial lactate production was unchanged from the ischemic region, and no correlation between the PRQ and myocardial lactate production was observed. In contrast, heart rate correlated significantly (r = 0.376; P less than 0.05) with lactate production. The product of systolic systemic arterial pressure and heart rate (rate-pressure product) correlated with blood flow (r = 0.493; P less than 0.001) and with oxygen consumption (r = 0.571; P less than 0.001) in the normal myocardium. A weak correlation (r = 0.330; P less than 0.05) of rate-pressure product with myocardial lactate production from the ischemic region was observed. There were no correlations between the PRQ and myocardial lactate production from the ischemic region or indices of blood flow distribution (i.e., inner/outer ratio in the ischemic region or ischemic/normal ratio). The relationship of hemodynamic variables to measurements of regional myocardial metabolism was independent of background anesthetic agent of depth of anesthesia. The current data suggest that heart rate changes are weakly predictive of severity of myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Pressão Sanguínea/fisiologia , Doença das Coronárias/fisiopatologia , Frequência Cardíaca/fisiologia , Anestesia , Animais , Artérias/fisiologia , Temperatura Corporal , Doença das Coronárias/etiologia , Doença das Coronárias/metabolismo , Vasos Coronários/fisiologia , Cães , Feminino , Halotano/farmacologia , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Hemoglobinas/análise , Concentração de Íons de Hidrogênio , Isoflurano/farmacologia , Masculino , Miocárdio/metabolismo , Oxigênio/fisiologia , Consumo de Oxigênio/efeitos dos fármacos , Consumo de Oxigênio/fisiologia , Valor Preditivo dos Testes , Prognóstico , Fatores de RiscoRESUMO
This study determined the effect of cardiopulmonary bypass (CPB) on canine enflurane minimum alveolar concentration (MAC). Fourteen dogs were anesthetized with enflurane in N2O and O2, and after tracheal intubation, the N2O was discontinued. Femoral arterial and pulmonary arterial catheters were placed, and MAC was determined with the tail-clamp method. CPB was initiated via the femoral artery-vein route, with additional venous return obtained from an external jugular vein. Partial CPB was used in the first 10 dogs. In 4 dogs, a membrane oxygenator (group 1) was used, and in the next 6 dogs a bubble oxygenator (group 2) was used. In 4 additional dogs (group 3), using bubble oxygenators, total CPB was achieved by occlusion of the pulmonary artery via a left thoracotomy. The CPB circuit was primed with Ringer's lactate, and circuit blood flows were 70-125 ml.kg-1.min-1, with mean arterial pressures maintained at 50-110 mmHg. MAC was determined again after termination of CPB. In 10 dogs, MAC was also measured during CPB. In 5 dogs MAC was measured after administration of protamine. MAC in all 14 dogs did not change (2.2 +/- 0.3 vs. 2.3 +/- 0.3). MAC remained constant in group 1 (2.4 +/- 0.3 vs. 2.3 +/- 0.4), group 2 (2.2 +/- 0.2 vs. 2.3 +/- 0.3), and group 3 (2.2 +/- 0.1 vs. 2.3 +/- 0.1). Similarly, MAC was unchanged during CPB (2.2 +/- 0.2 vs. 2.2 +/- 0.2) and after protamine (2.3 +/- 0.2 vs. 2.2 +/- 0.3). Temperature was 38.3 +/- 1.2 prebypass and 37.9 +/- 0.9 postbypass.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Anestesia por Inalação , Ponte Cardiopulmonar , Enflurano/administração & dosagem , Animais , Cães , OxigenadoresRESUMO
Protamine sulfate (PS), used to neutralize the anticoagulant effect of heparin, is often associated with systemic hypotension. Whether this hypotension is secondary to a depression of myocardial function is not clear. The present study tested the hypothesis that systemic hypotension was accompanied by a depression in myocardial function and examined the possible role of histamine in mediating the cardiovascular response to PS. Seven conditioned dogs were chronically instrumented with pressure and ultrasonic dimension transducers. Studies were conducted under halothane anesthesia 7 to 10 days after instrumentation. Cardiac contractility was assessed using the slope, Ees, of the linear regression of the left ventricular end-systolic pressure-diameter relationship. Intravenous infusion of PS, 5 mg/kg, when given in periods of less than 30 seconds, decreased systemic arterial pressure by 45% (from 101 +/- to 54 +/- 5 mm Hg) without change in heart rate. Cardiac output decreased by 22% from control and the slope Ees decreased by 37% (from 14.5 +/- 1.2 to 8.7 +/- 1.4 mm Hg/mm). Systemic vascular resistance decreased by 34% (from 2581 +/- 121 to 1712 +/- 200 dyne.s.cm-5). The cardiovascular depression caused by PS was transient and could not be reproduced by a repeated dose given within a 60-minute period. Antagonists of histamine (diphenhydramine and cimetidine) could not attenuate the PS-induced cardiovascular depression. This depression was independent of preheparinization and did not occur when PS was infused slowly over a 2-minute period. The data clearly demonstrate negative inotropic and vasodilator effects of PS following rapid administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Anestesia por Inalação , Halotano , Hipotensão/induzido quimicamente , Protaminas/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Depressão Química , Cães , Feminino , Humanos , Infusões Intravenosas , Protaminas/administração & dosagem , Fatores de Tempo , Resistência Vascular/efeitos dos fármacosRESUMO
Fenoldopam, a selective dopamine1 receptor agonist, has been recommended for induced hypotension because it effectively lowers arterial blood pressure and improves renal perfusion. We examined cardiovascular functions during hypotension induced by fenoldopam or sodium nitroprusside. In eight halothane-anesthetized dogs, the left ventricle (LV) was instrumented with pressure and ultrasonic dimension transducers for the assessment of LV contractility using the analysis of the pressure-diameter relationship. Blood flow distribution was measured by radioactive microspheres. Doses of fenoldopam and nitroprusside were titrated to reduce mean arterial blood pressure to 60 mm Hg. After 40 min of hypotension, fenoldopam and nitroprusside caused similar increases in heart rate (17% +/- 4% vs 19% +/- 10%, respectively) and decreases in systemic vascular resistance (-24% +/- 5% vs -27% +/- 4%). Hypotension induced by fenoldopam was associated with higher LV end-diastolic pressure (4.4 +/- 0.6 vs 2.5 +/- 1.1 mm Hg) and end-systolic meridional wall stress (33.0 +/- 4.3 vs 17.8 +/- 2.1 g/cm2) when compared with nitroprusside. There were no significant changes in cardiac output and cardiac contractility as expressed by the slope (Ees) of the LV end-systolic pressure-diameter relationship, velocity of shortening of the diameter, and percentage of wall thickening of the LV. In contrast to nitroprusside, which decreased renal blood flow from 197 +/- 19 to 163 +/- 15 mL/min, renal blood flow increased during fenoldopam-induced hypotension from 187 +/- 20 to 239 +/- 18 mL/min. The increase in renal perfusion was similar in upper, middle, and lower regions of the kidney; however, it was more in the medulla compared with the cortex (37% +/- 17% vs 25% +/- 7%).(ABSTRACT TRUNCATED AT 250 WORDS)