RESUMO
Covalent linkage of polyethylene glycol to superoxide dismutase prolongs the serum half-life of the enzyme and may facilitate intracellular access. We tested the myocardial protective effect of polyethylene glycol superoxide dismutase administered once, 24 hours before ischemia. Because hearts were studied ex vivo in a crystalloid perfused system, cardioprotection could be ascribed to intramyocardial or membrane-bound polyethylene glycol superoxide dismutase accumulation. Thirty isolated rabbit hearts from the four following groups were studied: (1) control: untreated rabbits (n = 7); (2) PEG-control: 24-hour intravenous preinfusion of methoxypolyethylene glycol 5000 (5 mg/kg) to examine the effect of polyethylene glycol alone, without conjugation to superoxide dismutase (n = 8); (3) PEG-SOD 10,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (10,000 U/kg) (n = 8); (4) PEG-SOD 30,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (30,000 U/kg) (n = 7). After measurement of baseline function with use of an intraventricular balloon, hearts were subjected to normothermic ischemia until a 4 mm Hg rise in intracavitary pressure was observed. Function was assessed at 15-minute intervals throughout reperfusion and expressed as percent return of developed pressure. After 60 minutes of reperfusion, recovery of function was greater for the PEG-SOD 30,000 group (85.6% +/- 2.6%) when compared with either the untreated or PEG-control group (68.9% +/- 2.3% and 71.4% +/- 2.0%, respectively). A similar difference was seen throughout reperfusion. Although an improved return of function was shown in the lower dose PEG-SOD 10,000 group, the margin of difference when compared with any of the control groups was determined to be insignificant at all times of reperfusion and at 60 minutes (75.9% +/- 3.2%). These data demonstrate that high, but not low, doses of polyethylene glycol superoxide dismutase significantly reduce reperfusion injury when administered 24 hours before initiation of global ischemia. Moreover, since the perfusate was superoxide dismutase free, this effect was most likely intramyocardial or membrane bound and therefore might be added to protection afforded by circulating superoxide dismutase.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Sequestradores de Radicais Livres , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Polietilenoglicóis/uso terapêutico , Superóxido Dismutase/uso terapêutico , Animais , Coração/efeitos dos fármacos , Isquemia Miocárdica , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/farmacologia , Pré-Medicação , Coelhos , Superóxido Dismutase/administração & dosagem , Superóxido Dismutase/farmacologia , Fatores de TempoRESUMO
Hypothyroidism is associated with profound left ventricular dysfunction. Brain-dead organ donors and patients undergoing cardiopulmonary bypass are chemically hypothyroid with significantly reduced circulating free triiodothyronine (T3). To test the hypothesis that T3 enhances left ventricular function in a hormonally deficient environment, a total of 36 healthy New Zealand White rabbit hearts were studied using a modified Langendorff preparation with Krebs-Henseleit perfusate and intra-ventricular balloon. In 9 normal rabbit hearts a cumulative dose-response curve with logarithmically increasing doses of T3 was obtained. The vehicle solution for T3 dissolution served as control (n = 9). Left ventricular function was assessed from peak developed pressure at baseline and after T3 administration. Triiodothyronine had no effect in normal hearts on peak developed pressure or end-diastolic pressure. In 18 rabbits, the acute effect of T3 administration after ischemia was investigated. Preischemic left ventricular function was measured to serve as baseline, and hearts were subjected to 37 degrees C global ischemia. Triiodothyronine (n = 9) or vehicle (n = 9) was infused during reperfusion, and left ventricular peak developed pressure was measured at 30 and 60 minutes of reperfusion. Recovery of function (expressed as percent return of left ventricular peak developed pressure) was significantly improved within 15 minutes of reperfusion (65.0% +/- 2.1% versus 80.2% +/- 4.1%) and remained significantly improved throughout the reperfusion period (p less than 0.05 by analysis of variance). These data suggest that although T3 possesses no inotropic properties, it significantly improves postischemic left ventricular function. The rapidity of the functional improvement suggests that these effects may be due to plasma membrane-mediated mechanisms.
Assuntos
Doença das Coronárias/fisiopatologia , Tri-Iodotironina/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Hemodinâmica/efeitos dos fármacos , Coelhos , Valores de ReferênciaRESUMO
We tested the hypothesis that 3,4,5,-trihydroxybenzamidoxime (VF 233), a demonstrated hydroxyl radical scavenger and an effective Fe3+ chelator, attenuates reperfusion injury and improves isovolumic left ventricular function. Eighteen isolated, perfused rabbit hearts with intracavitary balloons were subjected to normothermic, global ischemia until the initiation of ischemic contracture. Effects on the adenine nucleotide pool metabolites were determined by high-pressure liquid chromatography from right ventricular biopsy specimens before ischemia and at 15-minute intervals throughout reperfusion. In the experimental group (n = 9), a 5-mL bolus of 1 mol/L VF 233 was given immediately before reperfusion and followed by a continuous infusion (0.125 mumol/min). The control group (n = 9) received the vehicle solution at identical times. Rabbits treated with VF 233 had significant improvement in left ventricular function (expressed as percent return of left ventricular peak developed pressure) within 15 minutes of reperfusion (55.0 +/- 3.0 versus 66.2 +/- 4.1; p less than 0.05 by analysis of variance) after global ischemia and remained significantly improved throughout the reperfusion period. Myocardial adenine nucleotide pool intermediates were not significantly different between groups. These results demonstrate that administration of VF 233 significantly improves ventricular function but does not affect adenine nucleotide metabolism after ischemia and reperfusion.
Assuntos
Benzamidinas/uso terapêutico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Nucleotídeos de Adenina/metabolismo , Animais , Técnicas In Vitro , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Coelhos , Função Ventricular EsquerdaRESUMO
OBJECTIVE: To determine the impact of computer-based simulations on the performance of dietetics interns in initial clinical rotations. DESIGN: Interns used either a simulation program (Care Planning Simulation System CPSS[) or a computer-based tutorial (Nutrition Care Planning Tutorial NCPT[) during their orientation. Performance of these interns on nutrition care skills was evaluated during their initial clinical rotations. SUBJECTS/SETTING: Participants were 108 dietetics interns from 8 different programs. Each internship had at least 8 interns, and none of the internships awarded a graduate degree. INTERVENTION: Subjects in the experimental group completed nutrition assessment and care planning activities for 3 simulated patients. Subjects in the control group completed a tutorial on assessment and care planning. MAIN OUTCOME MEASURES: Likert scale ratings of 31 behaviors were recorded by clinical preceptors. Behavior statements were grouped into 8 categories and average ratings for each category were determined. STATISTICAL ANALYSIS: Repeated-measures analysis of variance and linear regression were used to compare performance ratings between groups. RESULTS: There were no differences in overall evaluations of the simulation and tutorial groups for the 8-week period. Interns who started clinical rotations immediately after orientation (CPSS-I and NCPT-I groups) were rated lower in all categories than those who began their clinical rotations later (CPSS-D and NCPT-D groups). Maturation and acquisition of general skills likely influenced ratings of interns with delayed clinical rotations. For most categories of behavior the rate of improvement in rating scores was greatest for interns who used CPSS. APPLICATIONS: Computer-based simulations are a promising supplement to current techniques in didactic instruction and may be useful in both didactic and practice settings. Computer-based simulations can provide more varied practice experiences to didactic students and interns in preparation for more skilled entry-level positions in dietetics.
Assuntos
Simulação por Computador , Instrução por Computador , Dietética/educação , Internato não Médico/métodos , Adulto , Análise de Variância , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , SoftwareRESUMO
OBJECTIVE: The effects of a computer-assisted instruction (CAI) tutorial program on learning clinical reasoning skills were compared in undergraduate dietetics students. DESIGN: A drill-and-practice program to control for time on task, and tutorial program, and a simulation program, as the test vehicle, were developed. The tutorial and simulation programs presented data on a patient with cardiovascular disease. SETTING: Subjects were tested in 30 undergraduate dietetics programs. SUBJECTS: Participants were 413 undergraduate diet therapy students enrolled in a coordinated program in dietetics (CPD) or a didactic program in dietetics (DPD). INTERVENTION: After completion of lectures on cardiovascular disease, subjects were given the drill-and-practice program plus a simulation test (group 1), the tutorial plus a simulation test (group 2), or the simulation test only (group 3). MAIN OUTCOME MEASURES: Scores on the simulation test were compared. Variables included type of CAI, dietetics program, year in school, computer experience, and experience using a medical chart. Mastery of objectives related to lower- and higher-level clinical reasoning skills introduced in the tutorial program was computed. STATISTICAL ANALYSIS: One-way analysis of variance and Student-Newman Keuls tests were conducted to determine any differences among the three groups. Reliability was determined using the Kuder-Richardson Formula 20. RESULTS: The reliability coefficient of the stimulation test was 0.93. Group 2 higher on the simulation test than group 1 or group 3. As a group, the CPD students scored higher than the DPD students. When CPD and DPD students were divided into the three experimental groups, there was no significant difference between the CPD and DPD student simulation scores. Group 2 mastered all objectives for lower-level reasoning skills and the higher-level decision-making objective better than groups 1 and 3. APPLICATIONS/CONCLUSIONS: A computer tutorial program enhanced clinical reasoning skills in undergraduate dietetics students. This type of program could be used to supplement many topics taught in diet therapy and provide DPD students with experimental learning before their clinical intern practicums.
Assuntos
Instrução por Computador , Dietética/educação , Análise de Variância , Doenças Cardiovasculares/dietoterapia , Competência Clínica , HumanosRESUMO
Expandable metallic stents offer advantages over previously available techniques for treating benign tracheobronchial stenosis or obstruction. Endoluminal stent placement offers a rapid and effective means of opening up narrowed airways, and results in excellent relief of symptoms and improvement in pulmonary function. Because they are delivered in a nonexpanded state using flexible over-wire systems, they can be placed using a flexible bronchoscope and can be located in second-order bronchial branches. Metallic stents have been used to treat benign airway obstruction caused by anastomotic narrowing after lung transplantation, infection, congenital lesions, tracheobronchial malacia, inflammatory conditions including relapsing polychondritis, Wegener granulomatosis, and acquired immunodeficiency syndrome, and external compression from benign mediastinal masses or fibrosis. The stents become epithelialized, which prevents migration and permits ciliary activity to continue. Significant complications can occur, including airway inflammation, stent migration, airway erosion, and stent fracture and collapse, but more serious complications are uncommon. Computed tomography is essential in imaging patients being considered for stent placement, as it allows 1) accurate representation of airway anatomy in three dimensions. 2) measurement of airway diameter, 3) evaluation of airway anatomy distal to a narrowed segment and invisible to bronchoscopy, 4) demonstration of dynamic changes in airway morphologic features during forced exhalation in patients with airway malacia, and 5) demonstration of focal or diffuse air trapping in lung peripheral to the abnormal airway. In patients who have had stent placement, computed tomography is valuable in assessing airway morphologic features and dynamics distal to the stent, and can be valuable in assessing stent dysfunction.