RESUMO
Supraphysiological increases in serum triglycerides and cholesterol often occur during pregnancy, but their effects on vascular function are poorly understood. Intraperitoneal injection of the nontoxic surfactant poloxamer 407 (P-407) results in sustained elevation of triglycerides and cholesterol. We asked if P-407-induced hyperlipidemia during late pregnancy adversely affects mesenteric resistance artery vasodilator function. On days 13-15 of pregnancy, rats were given a single intraperitoneal injection of P-407, sterile water vehicle, or non-lipid-altering pluronic F-88 (P-88). Four days postinjection, serum triglycerides, cholesterol, free fatty acids, and the lipid peroxidation product malondialdehyde were significantly increased in P-407-treated rats. Mesenteric arteries from P-407-treated rats displayed significant increases in myogenic reactivity (constrictor responses to step increases in intraluminal pressure). The nitric oxide (NO) blocker N(alpha)-methyl-L-arginine increased the myogenic response in control but not in P-407 arteries, normalizing group differences. Endothelial removal increased myogenic reactivity beyond that of prior NO synthase inhibition in controls and potentiated myogenic reactivity in P-407 arteries such that responses again converged. Relaxation responses to the endothelium-dependent vasodilator methacholine did not differ. We conclude that that P-407-induced hyperlipidemia during pregnancy increases myogenic reactivity due to selective attenuation of an NO-mediated vasodilator component of the myogenic response.
Assuntos
Endotélio Vascular/fisiopatologia , Hiperlipidemias/fisiopatologia , Artérias Mesentéricas/fisiopatologia , Complicações na Gravidez/fisiopatologia , Sistema Vasomotor/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Colesterol/sangue , Modelos Animais de Doenças , Endotélio Vascular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Ácidos Graxos não Esterificados/sangue , Feminino , Peso Fetal/efeitos dos fármacos , Hiperlipidemias/induzido quimicamente , Malondialdeído/sangue , Artérias Mesentéricas/efeitos dos fármacos , Poloxâmero , Gravidez , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangue , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia , Sistema Vasomotor/efeitos dos fármacos , ômega-N-Metilarginina/farmacologiaRESUMO
Marked vasodilation in the kidney and other nonreproductive organs is one of the earliest maternal adaptations to occur during pregnancy. Despite the recognition of this extraordinary physiology for over four decades, the gestational hormone responsible has remained elusive. Here we demonstrate a key role for relaxin, a member of the IGF family that is secreted by the corpus luteum in humans and rodents. Using a gravid rodent model, we employ two approaches to eliminate relaxin or its biological activity from the circulation: ovariectomy and administration of neutralizing antibodies. Both abrogate the gestational elevation in renal perfusion and glomerular filtration, as well as preventing the reduction in myogenic reactivity of isolated, small renal arteries. Osmoregulatory changes, another pregnancy adaptation, are also abolished. Our results indicate that relaxin mediates the renal vasodilatory responses to pregnancy and thus may be important for maternal and fetal health. They also raise the likelihood of a role for relaxin in other cardiovascular changes of pregnancy, and they suggest that, like estrogen, relaxin should be considered a regulator of cardiovascular function.
Assuntos
Rim/fisiologia , Prenhez/fisiologia , Relaxina/fisiologia , Artéria Renal/fisiologia , Circulação Renal/fisiologia , Vasodilatação , Animais , Anticorpos/imunologia , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Masculino , Ovariectomia , Gravidez , Ratos , Ratos Long-Evans , Relaxina/imunologia , Artéria Renal/anatomia & histologiaRESUMO
Action potential (AP) prolongation typically occurs in heart disease due to reductions in transient outward potassium currents (Ito), and is associated with increased Ca2+ transients. We investigated the underlying mechanisms responsible for enhanced Ca2+ transients in normal isolated rat ventricular myocytes in response to the AP changes that occur following myocardial infarction. Normal myocytes stimulated with a train of long post-myocardial infarction (MI) APs showed a 2.2-fold elevation of the peak Ca2+ transient and a 2.7-fold augmentation of fractional cell shortening, relative to myocytes stimulated with a short control AP. The steady-state Ca2+ load of the sarcoplasmic reticulum (SR) was increased 2.0-fold when myocytes were stimulated with trains of long post-MI APs (111 +/- 21.6 micromol l(-1)) compared with short control APs (56 +/- 7.2 micromol l(-1)). Under conditions of equal SR Ca2+ load, long post-MI APs still resulted in a 1.7-fold increase in peak [Ca2+]i and a 3.8-fold increase in fractional cell shortening relative to short control APs, establishing that changes in the triggering of SR Ca2+ release are largely responsible for elevated Ca2+ transients following AP prolongation. Fractional SR Ca2+ release calculated from the measured SR Ca2+ load and the integrated SR Ca2+ fluxes was 24 +/- 3 and 11 +/- 2 % following post-MI and control APs, respectively. The fractional release (FR) of Ca2+ from the SR divided by the integrated L-type Ca2+ flux (FR/[integral]FCa,L) was increased 1.2-fold by post-MI APs compared with control APs. Similar increases in excitation-contraction (E-C) coupling gains were observed establishing enhanced E-C coupling efficiency. Our findings demonstrate that AP prolongation alone can markedly enhance E-C coupling in normal myocytes through increases in the L-type Ca2+ current (ICa,L) trigger combined with modest enhancements in Ca2+ release efficiency. We propose that such changes in AP profile in diseased myocardium may contribute significantly to alterations in E-C coupling independent of other biochemical or genetic changes.
Assuntos
Potenciais de Ação/fisiologia , Fibras Musculares Esqueléticas/fisiologia , Contração Miocárdica/fisiologia , Miocárdio/citologia , Animais , Cálcio/farmacocinética , Canais de Cálcio Tipo L/metabolismo , Ventrículos do Coração/citologia , Técnicas In Vitro , Masculino , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Retículo Sarcoplasmático/metabolismoRESUMO
G. Y. Oudit, Z. Kassiri, R. Sah, R. J. Ramirez, C. Zobel and P. H. Backx. The Molecular Physiology of the Cardiac Transient Outward Potassium Current (I(to)) in Normal and Diseased Myocardium. Journal of Molecular and Cellular Cardiology (2001) 33, 851-872. The Ca(2+)-independent transient outward potassium current (I(to)) plays an important role in early repolarization of the cardiac action potential. I(to)has been clearly demonstrated in myocytes from different cardiac regions and species. Two kinetic variants of cardiac I(to)have been identified: fast I(to), called I(to,f), and slow I(to), called I(to,s). Recent findings suggest that I(to,f)is formed by assembly of K(v4.2)and/or K(v4.3)alpha pore-forming voltage-gated subunits while I(to,s)is comprised of K(v1.4)and possibly K(v1.7)subunits. In addition, several regulatory subunits and pathways modulating the level and biophysical properties of cardiac I(to)have been identified. Experimental findings and data from computer modeling of cardiac action potentials have conclusively established an important physiological role of I(to)in rodents, with its role in large mammals being less well defined due to complex interplay between a multitude of cardiac ionic currents. A central and consistent electrophysiological change in cardiac disease is the reduction in I(to)density with a loss of heterogeneity of I(to)expression and associated action potential prolongation. Alterations of I(to)in rodent cardiac disease have been linked to repolarization abnormalities and alterations in intracellular Ca(2+)homeostasis, while in larger mammals the link with functional changes is far less certain. We review the current literature on the molecular basis for cardiac I(to)and the functional consequences of changes in I(to)that occur in cardiovascular disease.
Assuntos
Coração/fisiologia , Miocárdio/metabolismo , Canais de Potássio/fisiologia , Potenciais de Ação , Animais , Cálcio/metabolismo , Citoesqueleto/metabolismo , Regulação para Baixo , Eletrofisiologia , Humanos , Cinética , Camundongos , Ratos , Fatores de TempoRESUMO
Infants suffering uteroplacental insufficiency and hypoxic ischemic injury often demonstrate cerebral apoptosis. Our objective was to determine the global effects of uteroplacental insufficiency upon cerebral gene expression of the apoptosis related proteins Bcl-2 and Bax and their role in increasing vulnerability to hypoxia-induced cerebral apoptosis. We therefore caused uteroplacental insufficiency and growth retardation by performing bilateral uterine artery ligation upon pregnant rats 2 days prior to term delivery and elicited further perinatal fetal hypoxia by placing maternal rats in 14% FiO(2) 3 h prior to delivery. We quantified cerebral levels of Bcl-2 and Bax mRNA, lipid peroxidation, caspase-3 activity, and cAMP in control and growth retarded term rat pups that experienced either normoxia or hypoxia. Uteroplacental insufficiency alone caused a significant decrease in cerebral Bcl-2 mRNA levels without altering cerebral Bax mRNA levels, malondialdehyde levels, or caspase-3 activity. In contrast, uteroplacental insufficiency and subsequent fetal hypoxia significantly increased cerebral Bax mRNA levels, lipid peroxidation and caspase-3 activity; Bcl-2 mRNA levels continued to be decreased. Hypoxia alone increased cerebral cAMP levels, whereas uteroplacental insufficiency and subsequent hypoxia decreased cerebral cAMP levels. We speculate that the decrease in Bcl-2 gene expression increases the vulnerability towards cerebral apoptosis in fetal rats exposed initially to uteroplacental insufficiency and subsequent hypoxic stress.
Assuntos
Apoptose/fisiologia , Córtex Cerebral/anormalidades , Retardo do Crescimento Fetal/complicações , Feto/anormalidades , Hipóxia Encefálica/etiologia , Hipóxia Encefálica/fisiopatologia , Neurônios/metabolismo , Insuficiência Placentária/complicações , Animais , Caspase 3 , Caspases/metabolismo , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , AMP Cíclico/metabolismo , Feminino , Feto/metabolismo , Feto/fisiopatologia , Regulação da Expressão Gênica/fisiologia , Hipóxia Encefálica/metabolismo , Peroxidação de Lipídeos/fisiologia , Malondialdeído/metabolismo , Neurônios/patologia , Estresse Oxidativo/fisiologia , Gravidez , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2RESUMO
In the present study, 638 embryo transfers conducted over 3 yr were retrospectively examined to determine which factors (recipient, embryo and transfer) significantly influenced pregnancy and embryo loss rates and to determine how rates could be improved. On Day 7 or 8 after ovulation, embryos (fresh or cooled/transported) were transferred by surgical or nonsurgical techniques into recipients ovulating from 5 to 9 d before transfer. At 12 and 50 d of gestation (Day 0 = day of ovulation), pregnancy rates were 65.7% (419 of 638) and 55.5% (354 of 638). Pregnancy rates on Day 50 were significantly higher for recipients that had excellent to good uterine tone or were graded as "acceptable" during a pretransfer examination, usually performed 5 d after ovulation, versus recipients that had fair to poor uterine tone or were graded "marginally acceptable." Embryonic factors that significantly affected pregnancy rates were morphology grade, diameter and stage of development. The incidence of early embryonic death was 15.5% (65 of 419) from Days 12 to 50. Embryo loss rates were significantly higher in recipients used 7 or 9 d vs 5 or 6 d after ovulation. Embryos with minor morphological changes (Grade 2) resulted in more (P<0.05) embryo death than embryos with no morphological abnormalities (Grade 1). Between Days 12 and 50, the highest incidence of embryo death occurred during the interval from Days 17 to 25 of gestation. Embryonic vesicles that were imaged with ultrasound during the first pregnancy exam (5 d after transfer) resulted in significantly fewer embryonic deaths than vesicles not imaged until subsequent exams. In the present study, embryo morphology was predictive of the potential for an embryo to result in a viable pregnancy. Delayed development of the embryo upon collection from the donor or delayed development of the embryonic vesicle within the recipient's uterus was associated with a higher incidence of pregnancy failure. Recipient selection (age, day after ovulation, quality on Day 5) significantly affected pregnancy and embryo loss rates.
Assuntos
Perda do Embrião/veterinária , Transferência Embrionária/veterinária , Cavalos/fisiologia , Acepromazina/administração & dosagem , Animais , Antagonistas de Dopamina/administração & dosagem , Transferência Embrionária/métodos , Feminino , Cavalos/embriologia , Laparotomia/veterinária , Gravidez , Taxa de Gravidez , Análise de Regressão , Estudos RetrospectivosRESUMO
Dogs have been used extensively to study atrial arrhythmias, but there are no published mathematical models of the canine atrial action potential (AP). To obtain insights into the ionic mechanisms governing canine atrial AP properties, we incorporated formulations of K(+), Na(+), Ca(2+), and Cl(-) currents, based on measurements in canine atrial myocytes, into a mathematical model of the AP. The rate-dependent behavior of model APs corresponded to experimental measurements and pointed to a central role for L-type Ca(2+) current inactivation in rate adaptation. Incorporating previously described regional ionic current variations into the model largely reproduced AP forms characteristic of the corresponding right atrial regions (appendage, pectinate muscle, crista terminalis, and atrioventricular ring). When ionic alterations induced by tachycardia-dependent remodeling were incorporated, the model reproduced qualitatively the AP features constituting the cellular substrate for atrial fibrillation. We conclude that this ionic model of the canine atrial AP agrees well with experimental measurements and gives potential insights into mechanisms underlying functionally important electrophysiological phenomena in canine atrium.
Assuntos
Função Atrial , Cães/fisiologia , Modelos Cardiovasculares , Potenciais de Ação/fisiologia , Adaptação Fisiológica , Animais , Eletrofisiologia , Frequência Cardíaca/fisiologia , Tempo de Reação/fisiologia , Taquicardia/fisiopatologiaRESUMO
INTRODUCTION: The anti-inflammatory and anticoagulant effects of ibuprofen and heparin may enhance skin perfusion in cutaneous scald burns. To test this hypothesis, skin perfusion and edema formation in scald burned rabbit ears were measured. METHOD: Eighteen rabbits (3.5-4.5 kg) received partial-thickness scald burns to one ear and then were given normal saline, n = 6, 20 mg/kg ibuprofen, n = 6, or 700 IU/kg heparin, n = 6. Skin perfusion, blood flow and edema formation in the burned ear were measured with laser Doppler, ultrasound flowmeter and skin calipers, respectively. Statistical analysis was performed using repeated measures ANOVA with post hoc Scheffe's test for comparison between groups. RESULTS: Blood flow to the scald burned ear increased 10-15 times that of baseline with tissue perfusion increasing by 70% within 0.5 h compared to pre-burn. Ibuprofen maintained the elevated tissue perfusion for 5 h while the heparin and saline groups showed decreases to 95 and 35% of pre-burn values, respectively. The heparin and ibuprofen groups demonstrated significant increases in ear perfusion at 4 and 5 h postburn. Ibuprofen also showed a significant difference within the first hour postburn, p<0.01. Wet to dry weight ratios in burned ear tissue were greater in rabbits receiving saline or heparin compared to ibuprofen at 3.6+/-0.2 and 2.9+/-0.3 vs. 2.1+/-0.1, respectively (p<0.001). CONCLUSION: Ibuprofen increases tissue perfusion and reduces edema formation in scald burned rabbit ears.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Queimaduras/fisiopatologia , Ibuprofeno/uso terapêutico , Pele/lesões , Análise de Variância , Animais , Anticoagulantes/uso terapêutico , Queimaduras/diagnóstico por imagem , Queimaduras/patologia , Orelha Externa/irrigação sanguínea , Orelha Externa/diagnóstico por imagem , Orelha Externa/efeitos dos fármacos , Orelha Externa/lesões , Edema/diagnóstico por imagem , Edema/patologia , Edema/fisiopatologia , Seguimentos , Heparina/uso terapêutico , Fluxometria por Laser-Doppler , Coelhos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Pele/irrigação sanguínea , Pele/diagnóstico por imagem , Pele/efeitos dos fármacos , Cloreto de Sódio , UltrassonografiaRESUMO
Numerous studies have shown estrogen to be vasoactive in various circulations. Our objective was to determine the effect of estrogen on isolated bovine coronary arteries and the possible mechanism. Bovine coronary arteries, precontracted with thromboxane mimetic U46619 were given doses (0.01-30 microM) of 17B-estradiol in the presence and absence of endothelium and these inhibitors: 10 microM indomethacin (cyclooxygenase inhibitor), 10 microM methylene blue (inhibits soluble guanylate cyclase), 100 microM nitro-L-arginine (inhibits nitric oxide synthesis), 100 microM isobutylmethylxanthine (phosphodiesterase inhibitor) and 30 microM mifepristone (Ru38486 steroid receptor antagonist). Our results indicated that, estrogen, in the highest concentration used (30 microM), elicited an acute dose-dependent relaxation of bovine coronary arteries from 4%-68% (n = 15). No major difference in relaxation was observed between coronary arteries with or without endothelium, indicating that the mechanism was endothelium-independent. Indomethacin, nitro-L-arginine and methylene blue did not alter this relaxation, suggesting that relaxant prostaglandins, l-arginine products and cGMP are not involved (n = 11-16), isobutylmethylxanthine enhanced relaxation from 20%-40% (n = 15 p < 0.01), suggests a role for cAMP. Furthermore, mifepristone reduced the relaxation by more than 50% (n = 15 p < 0.05) consistent with the role for estrogen receptors. Based on our study, estrogen causes a dose-dependent relaxation of bovine coronary arteries that does not appear to utilize endothelium, prostaglandins, cGMP or arginine products, but may involve cAMP and estrogen receptors. This study may help justify treating myocardial ischemia with estrogen.
Assuntos
Vasos Coronários/efeitos dos fármacos , Estradiol/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Bovinos , Vasos Coronários/fisiologia , Inibidores de Ciclo-Oxigenase/farmacologia , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Estradiol/uso terapêutico , Guanilato Ciclase/antagonistas & inibidores , Antagonistas de Hormônios/farmacologia , Técnicas In Vitro , Isquemia Miocárdica/tratamento farmacológico , Óxido Nítrico Sintase/antagonistas & inibidores , Inibidores de Fosfodiesterase/farmacologia , Receptores de Estrogênio/fisiologiaRESUMO
UNLABELLED: Recent advances in molecular electrophysiology have made possible the development of more selective ion channel blockers for therapeutic use. However, more information is needed about the effects of blocking specific channels on repolarization in normal human atrium and in atrial cells of patients with atrial fibrillation (AF). AF-induced electrical remodeling is associated with reductions in transient outward current (Ito), ultrarapid delayed rectifier current (IKur), and L-type calcium current (ICa,L). Direct evaluation of the results of ion channel depression is limited by the nonspecificity of the available pharmacological probes. OBJECTIVES: Using a mathematical model of the human atrial action potential (AP), we aimed to: (1) evaluate the role of ionic abnormalities in producing AP changes characteristic of AF in humans and (2) explore the effects of specific channel blockade on the normal and AF-modified AP (AFAP). METHODS: We used our previously developed mathematical model of the normal human atrial AP (NAP) based on directly measured currents. We constructed a model of the AFAP by incorporating experimentally-measured reductions in Ito (50%), IKur (50%), and ICa,L (70%) current densities observed in AF. RESULTS: The AFAP exhibits the reductions in AP duration (APD) and rate-adaption typical of AF. The reduction in ICa,L alone can account for most of the morphological features of the AFAP. Inhibition of Ito by 90% leads to a reduction in APD measured at -60 mV in both the NAP and AFAP. Inhibition of the rapid component of the delayed rectifier (IKr) by 90% slows terminal repolarization of the NAP and AFAP and increases APD by 38% and 34%, respectively. Inhibition of IKur by 90% slows early repolarization and increases plateau height, activating additional IK and causing no net change in APD at 1 Hz in the NAP. In the presence of AF-induced ionic modifications, IKur inhibition increases APD by 12%. Combining IKur and IKr inhibition under both normal and AF conditions synergistically increases APD. In the NAP, altering the model parameters to reproduce other typical measured AP morphologies can significantly alter the response to K(+)-channel inhibition. CONCLUSIONS: (1) The described abnormalities in Ito, IKur and ICa,L in AF patients can account for the effects of AF on human AP properties; (2) AP prolongation by IKur block is limited by increases in plateau height that activate more IK; (3) Blockers of IKur may be more effective in prolonging APD in patients with AF; 4) Inhibition of both IKur and IKr produces supra-additive effects on APD. These observations illustrate the importance of secondary current alterations in the response of the AP to single channel blockade, and have potentially important implications for the development of improved antiarrhythmic drug therapy for AF.
Assuntos
Potenciais de Ação/efeitos dos fármacos , Fibrilação Atrial/tratamento farmacológico , Transporte Biológico Ativo/efeitos dos fármacos , Simulação por Computador , Modelos Cardiovasculares , Antiarrítmicos/farmacologia , Fibrilação Atrial/metabolismo , Fibrilação Atrial/fisiopatologia , Canais de Cálcio/efeitos dos fármacos , Humanos , Transporte de Íons , Canais de Potássio/efeitos dos fármacosRESUMO
BACKGROUND: Recombinant human growth hormone (rhGH) has been shown to favorably modulate the acute-phase response and may improve the clinical outcome. OBJECTIVE: To examine whether rhGH attenuates the elevated tumor necrosis factor alpha (TNF-alpha) levels that correlate with increased multiorgan failure and mortality in burned adults and children. DESIGN: Twenty children with burns of greater than 40% of the total body surface area were randomly divided into 2 groups to receive placebo (n = 10) or rhGH, 0.2 mg/kg per day intramuscularly (n = 10). SETTING: Pediatric burn hospital. MAIN OUTCOME MEASURE: Serum TNF-alpha levels by enzyme-linked immunoassay at baseline (day 0) and at 21 and 42 days after injury. For statistical analysis, we used the Kruskal-Wallis and Friedman tests. RESULTS: No significant differences in age (mean +/- SD, 6.2+/-1.6 vs 5.0+/-1.2 years) or percentage of total body surface area burn (mean +/- SD, 65.1%+/-8.2% vs 57.1%+/-5.2%) could be shown between the groups given rhGH and placebo. Baseline TNF-alpha levels were elevated from reference values in both groups. Twenty-one and 42 days after rhGH administration, serum TNF-alpha levels were significantly decreased from those at baseline (P<.05). No significant decrease in TNF-alpha levels was observed in the placebo group (P = .5). CONCLUSIONS: Recombinant human growth hormone significantly lowers serum TNF-alpha levels after burn injury. This is consistent with the beneficial effect that rhGH has on the acute-phase response.
Assuntos
Queimaduras/sangue , Hormônio do Crescimento Humano/uso terapêutico , Fator de Necrose Tumoral alfa/biossíntese , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Hormônio do Crescimento Humano/farmacologia , Humanos , Masculino , Fator de Necrose Tumoral alfa/análiseRESUMO
BACKGROUND: The relationship of the burn wound flora to microbial pathogens in the tracheobronchial tree has important implications for antimicrobial therapy in the severely burned patient. Management of septic complications is bolstered by surveillance quantitative wound cultures (QWC) and bronchial lavage fluid (BLF) cultures. OBJECTIVES: To compare the organisms present in BLF with those found in QWC and to determine if QWC can predict BLF results. DESIGN: Results of BLF cultures from all patients who underwent bronchial lavage from January 1, 1996, to December 31, 1996, at our institution were compared with QWC data from the same date. Criteria for a positive match included an identical antibiotic susceptibility pattern and biotype. Match rates were calculated qualitatively and quantitatively. RESULTS: In 30 (48%) of the 62 BLF cultures, there was a match between the organism identified in the BLF and the QWC. When strict quantitative criteria were applied, the match rate was only 9 (14%) of 62. Burn size and inhalation injury had no significant effect on match rate. CONCLUSIONS: Whereas the microbial pathogens were similar in the QWC and BLF, linear regression showed no value of QWC in predicting BLF culture results. The difference between qualitative and quantitative match rates suggests cross-colonization between the burn wound and tracheobronchial tree, but little to no cross-infection. The QWC and BLF cultures must be performed independently in determining antimicrobial specificity in the burned patient.
Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Queimaduras/microbiologia , Adolescente , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Escala de Gravidade do Ferimento , MasculinoRESUMO
Septic episodes in thermal injuries are usually hallmarked by a series of physiologic parameters that include tachypnea, prolonged paralytic ileus, hyperthermia or hypothermia, altered mental status, thrombocytopenia, leukocytosis or unexplained leukopenia, acidosis, and hyperglycemia. Recent studies with polycystic kidney disease have clearly indicated that the limulus amebocyte lysate (LAL) assays were predictive of fungal infections in this patient population. Because both bacteria and fungi produce lipopolysaccharide that can be identified with the LAL assay, we randomly assayed sequential sera of 45 patients with major thermal injuries for positivity in the LAL assay, with use of the QCL-1000 kit (BioWhittaker, Walkersville, Md). The average burn size of this patient population was 63.43% total body surface area. The average age of the patient was 6.2 years. The sex distribution included 30 males and 15 females. The infectious agents included gram-positive cocci and gram-negative rods, and 14 patients had concomitant fungal infections. Eighty-five percent of the patients tested were positive for endotoxin, with levels ranging from < 0.1 EU/mL to > 1.0 EU/mL. The predominant organism isolated before or on the date the serum was drawn was Pseudomonas aeruginosa (51%), followed by Klebsiella pneumoniae (15%). The remaining 34% were a variety of Enterobacteriaceae. Of the 14 patients who yielded a fungus, 3 had negative LAL assays. Two patients with an elevated LAL grew only Staphylococcus epidermidis in the bloodstream and the wounds. These data clearly indicate that the LAL assay cannot be relied on as the sole predictor of septic episodes; however, it can be an adjunctive test to confirm sepsis when the other parameters have been considered.
Assuntos
Queimaduras/complicações , Endotoxinas/análise , Fungemia/diagnóstico , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Positivas/diagnóstico , Teste do Limulus/métodos , Sepse/diagnóstico , Adolescente , Criança , Pré-Escolar , Feminino , Fungemia/epidemiologia , Fungemia/etiologia , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/etiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/etiologia , Humanos , Incidência , Lactente , Escala de Gravidade do Ferimento , Masculino , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Sepse/epidemiologia , Sepse/etiologiaRESUMO
Survival after a major thermal burn is precarious and fraught with difficult complications associated with hypermetabolism, gut or respiratory dysfunction, and infection. Clinicians must be cognizant of a new threat to the patient with burn injuries--the emergence of vancomycin-resistant enterococci (VRE). In an analysis of 31 clinical isolates obtained during acute burn hospitalization, an optimal antimicrobial therapy for VRE has been identified. All VRE cultures were inoculated to the MicroScan Gram-Positive Breakpoint Combo Panel #8 (Dade Microscan, Inc, Sacramento, Calif), which speciates the enterococci, provides antimicrobial susceptibility patterns (including vancomycin) and a biotype, and examines streptomycin and gentamicin synergy. Eleven (35.5%) of the 31 isolates were identified as E faecium and 20 (64.5%) as E faecalis. All isolates were susceptible to chloramphenicol and tetracycline, whereas only half were sensitive to gentamicin synergy screen. All other antimicrobials screened against VRE were either ineffective or of limited effect. Our preliminary data supports the initiation of chloramphenicol therapy when a VRE burn wound infection is encountered or suspected.
Assuntos
Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Queimaduras/complicações , Cloranfenicol/uso terapêutico , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Vancomicina/farmacologia , Infecção dos Ferimentos/microbiologia , Queimaduras/microbiologia , Cloranfenicol/farmacologia , Resistência Microbiana a Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Infecção dos Ferimentos/tratamento farmacológicoRESUMO
OBJECTIVE: To determine the safety and efficacy of recombinant human growth hormone (rhGH) in the treatment of children who are severely burned. SUMMARY BACKGROUND DATA: During the last decade, we have used recombinant human growth hormone (rhGH; 0.2 mg/kg/day s.q.) to successfully treat 130 children with more than 40% total body surface area (TBSA) burns to enhance wound healing and decrease protein loss. A significant increase in the mortality of adult patients in the intensive care unit who were given rhGH has recently been reported in two large European trials which questions the therapeutic safety of rhGH. METHODS: The records of 263 children who were burned were reviewed. Patients receiving either rhGH at 0.2 mg/kg/day subcutaneously as part of a randomized clinical trial (n = 48) or therapeutically (n = 82) were compared with randomized placebo-administered controls (n = 54), contiguous matched controls (n = 48), and matched patients admitted after August 1997, after which no patients were treated with rhGH (n = 31). Morbidity and mortality, which might be altered by rhGH therapy, were considered with specific attention to organ function or failure, infection, hemodynamics, and calcium, phosphorous, and albumin balance. RESULTS: A 2% mortality was observed in both rhGH and saline placebo groups in the controlled studies, with no differences in septic complications, organ dysfunction, or heart rate pressure product identified. In addition, no difference in mortality could be shown for those given rhGH therapeutically versus their controls. No patient deaths were attributed to rhGH in autopsies reviewed by observers blinded to treatment. Hyperglycemic episodes and exogenous insulin requirements were higher among rhGH recipients, whereas exogenous albumin requirements and the development of hypocalcemia was reduced. CONCLUSIONS: Data indicate that rhGH used in the treatment of children who were severely burned is safe and efficacious.
Assuntos
Queimaduras/tratamento farmacológico , Hormônio do Crescimento/uso terapêutico , Adolescente , Queimaduras/complicações , Queimaduras/mortalidade , Queimaduras/fisiopatologia , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Lactente , Masculino , Estudos ProspectivosRESUMO
The mechanisms underlying many important properties of the human atrial action potential (AP) are poorly understood. Using specific formulations of the K+, Na+, and Ca2+ currents based on data recorded from human atrial myocytes, along with representations of pump, exchange, and background currents, we developed a mathematical model of the AP. The model AP resembles APs recorded from human atrial samples and responds to rate changes, L-type Ca2+ current blockade, Na+/Ca2+ exchanger inhibition, and variations in transient outward current amplitude in a fashion similar to experimental recordings. Rate-dependent adaptation of AP duration, an important determinant of susceptibility to atrial fibrillation, was attributable to incomplete L-type Ca2+ current recovery from inactivation and incomplete delayed rectifier current deactivation at rapid rates. Experimental observations of variable AP morphology could be accounted for by changes in transient outward current density, as suggested experimentally. We conclude that this mathematical model of the human atrial AP reproduces a variety of observed AP behaviors and provides insights into the mechanisms of clinically important AP properties.
Assuntos
Potenciais de Ação/fisiologia , Função Atrial/fisiologia , Coração/fisiologia , Modelos Cardiovasculares , Modelos Teóricos , Canais de Cálcio/fisiologia , Canais de Cálcio Tipo L , Células Cultivadas , Átrios do Coração , Humanos , Cinética , Miocárdio/citologia , Canais de Potássio/fisiologia , Canais de Sódio/fisiologia , Trocador de Sódio e Cálcio/antagonistas & inibidores , Trocador de Sódio e Cálcio/metabolismoRESUMO
Children with spina bifida, cerebral palsy, mental retardation, developmental delays, and seizure states are handicapped with sensorimotor deficits, including gait or coordination instability, temperature insensitivity, and mental simplicity. These handicaps make this distinct and unpretentious population more susceptible to lethal burns. A 30-year review was conducted in a pediatric burn center to examine the relationships between pediatric sensorimotor deficit and burn injury. Of the 4874 acute burn admissions, 66 children were identified with preexisting sensorimotor deficits. Data indicate that children with sensorimotor deficit are more prone to burn injury from both their physical impairment and poorly supervised environments. In addition to extended hospitalizations, these children bear significantly higher mortality risks. Had the special supervisions and protection required by such handicapped children been provided, 80% of the burn injuries could have been prevented. Results emphasize that the future of these special children with sensorimotor deficits relies on health care providers playing a greater role in educating parents and caregivers.
Assuntos
Queimaduras/epidemiologia , Crianças com Deficiência , Desempenho Psicomotor , Queimaduras/etiologia , Cuidadores , Paralisia Cerebral , Criança , Deficiências do Desenvolvimento , Feminino , Humanos , Deficiência Intelectual , Masculino , Mortalidade , Estudos Retrospectivos , Fatores de Risco , Convulsões , Disrafismo EspinalRESUMO
GH is a potent anabolic agent that offers distinct advantages to the hypercatabolic paediatric burns patient. GH can be administered with minimal risk of untoward side-effects in this patient group. GH reduces the catabolic effects of trauma, both directly and indirectly, through stimulation of protein synthesis. Accelerated wound healing and reduction in tissue-wasting effects are clear benefits that reduce the overall morbidity associated with burn injury in children. Further applications of GH treatment will stem from ongoing investigations that are examining alternative delivery methods, long-term treatment beyond the acute hospitalization phase, and combination therapy with beta-blockers, antiglucocorticoids or other growth factors.
Assuntos
Queimaduras/tratamento farmacológico , Hormônio do Crescimento Humano/uso terapêutico , Reação de Fase Aguda/imunologia , Queimaduras/imunologia , Queimaduras/metabolismo , Coração/efeitos dos fármacos , Coração/fisiologia , Hemodinâmica/efeitos dos fármacos , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/farmacologia , Humanos , Imunocompetência/efeitos dos fármacos , Imunocompetência/imunologia , Cicatrização/efeitos dos fármacosRESUMO
OBJECTIVE: To determine the effects of growth hormone (GH) on the hepatic acute-phase response (APR) in a burned rat model. SETTING: Laboratory. MATERIAL: Male Sprague-Dawley rats (weight, 300-350 g). INTERVENTIONS: Rats underwent a 40% total body surface area burn injury and received GH or saline solution daily by subcutaneous injection. Unburned rats served as controls. MAIN OUTCOME MEASURES: Hepatic messenger RNA (mRNA) expression and serum levels of alpha 1-acid glycoprotein and albumin were determined 2, 7, and 14 days after injury. RESULTS: The serum alpha 1-acid glycoprotein levels in GH-treated animals did not increase on days 2 and 7, whereas saline-treated animals showed a major increase. Hepatic mRNA expression increased dramatically on day 2 for burned groups; however, the mRNA pool levels of GH-treated animals showed a faster rate of decline to control levels on days 7 and 14. The albumin mRNA pool levels of GH-treated and control animals did not show significant differences, whereas the negative APR, indicated by loss of albumin mRNA, was more pronounced on day 7 in the saline-treated animals. By day 14, mRNA levels were comparable in all 3 groups. CONCLUSION: Growth hormone attenuated the positive APR, as indicated by a decrease in alpha 1-acid glycoprotein expression and production, and prevented the negative APR, as seen by an absence of a decline of albumin mRNA pool levels and serum concentration. We conclude that the beneficial effects of GH on thermal injury may be due in part to a modification of the APR.