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1.
J Med Chem ; 39(22): 4361-5, 1996 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-8893830

RESUMO

Reaction of nitric oxide (NO) with L-proline in methanolic sodium methoxide yields a diazeniumdiolate product, C5H7N3O4Na2.CH3OH (PROLI/NO), that can be stabilized in basic solution but that dissociates to proline (1 mol) and NO (2 mol) with a half-life of only 1.8 s at pH 7.4 and 37 degrees C. This kinetic behavior has allowed the generation of highly localized antiplatelet and vasodilatory effects. By infusing solutions containing 4 microM PROLI/NO in 0.1 M sodium hydroxide at the rate of 1 nmol.min-1 immediately upstream from a polyester vascular graft in the unheparinized baboon circulatory system, for example, platelet deposition at the normally thrombogenic graft surface was substantially reduced relative to controls receiving only 0.1 M sodium hydroxide. In a second study, infusion of PROLI/NO into the right atrium of sheep with induced pulmonary hypertension selectively dilalated the lung vasculature, dose-dependently reducing the pulmonary arterial pressure by as much as 9 mmHg with no observable effect on the systemic arterial pressure at an infusion rate of up to 24 nmol.kg-1.min-1. PROLI/NO could also be formulated as an insoluble polymer blend that released NO smoothly for prolonged periods. The results suggest that localized delivery of diazeniumdiolates such as PROLI/NO which generate NO with extreme rapidity on entering the blood stream may hold considerable promise for inhibition of thrombus formation, selective dilation of the vasculature, and other research and clinical applications.


Assuntos
Fibrinolíticos/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacologia , Prolina/análogos & derivados , Vasodilatadores/farmacologia , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico , Animais , Sistemas de Liberação de Medicamentos , Concentração de Íons de Hidrogênio , Masculino , Óxido Nítrico/administração & dosagem , Óxidos de Nitrogênio , Nitroprussiato/farmacologia , Papio , Adesividade Plaquetária/efeitos dos fármacos , Polímeros , Prolina/administração & dosagem , Prolina/farmacologia , Endoperóxidos Sintéticos de Prostaglandinas/farmacologia , Circulação Pulmonar/efeitos dos fármacos , Ovinos , Tromboxano A2/análogos & derivados , Tromboxano A2/farmacologia , Vasoconstritores/farmacologia
2.
J Nucl Med ; 31(8): 1344-51, 1990 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2384802

RESUMO

To identify changes of ventricular performance and their relationship to myocardial glucose uptake in Sprague-Dawley rats exposed to hypobaric hypoxia, radionuclide angiocardiograms (n = 34) and 2-[14C]deoxyglucose (2-[14C]DG) autoradiography (n = 14) were performed on rats maintained either for two weeks in air at 380 mmHg (hypoxic group), two weeks in hypobaric hypoxia followed by two weeks of air (recovered group), or in air (control group). Right ventricular ejection fraction (RVEF) was 66% +/- 2% (mean +/- s.e.m.) in controls, 40% +/- 3% during hypoxia, and 60% +/- 2% in recovered rats. LVEF remained unchanged. In controls, RV 2-[14C]DG uptake was 77% +/- 3% of LV uptake. During hypoxia, 2-[14C]DG uptake increased. This increase was greater within the RV than the LV and septum (85 +/- 16% versus 51 +/- 10%, p less than 0.005). The alterations of RV 2-[14C]DG uptake correlated with systolic pulmonary artery pressure (r = 0.77, p = 0.002).


Assuntos
Glucose/farmacocinética , Coração/fisiopatologia , Hipóxia/fisiopatologia , Miocárdio/metabolismo , Animais , Pressão Atmosférica , Autorradiografia , Doença Crônica , Desoxiglucose , Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Hipóxia/diagnóstico por imagem , Hipóxia/metabolismo , Tamanho do Órgão , Cintilografia , Ratos , Ratos Endogâmicos
3.
Chest ; 113(6): 1650-7, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9631807

RESUMO

OBJECTIVES: We evaluated the Ohmeda INOvent Nitric Oxide Delivery System, which uses an inspiratory flow sensor to inject a synchronized and proportional nitric oxide (NO) flow into the mechanical ventilator circuit. This system should deliver a constant NO concentration independent of ventilator mode, minute ventilation, fraction of inspired oxygen, or ventilator brand. It should also minimize nitrogen dioxide (NO2) formation. METHODS: NO delivery by the INOvent and a premixing NO delivery system were compared using two ventilators (Puritan-Bennett 7200 and Servo 900C). NO concentration was measured within the trachea of an attached lung model using a fast-response chemiluminescence NO analyzer. NO concentration was also measured in the inspiratory limb using the electrochemical analyzer of the INOvent. For three NO concentrations (2, 5, and 20 ppm), the ventilators were set for constant flow volume control ventilation, pressure control ventilation, and spontaneous breathing with pressure support ventilation or synchronized intermittent mandatory ventilation. Different tidal volumes (300, 500, 750, and 1,000 mL) and inspiratory times (1 and 2 s) were evaluated. NO2 formation for both ventilators and delivery systems were evaluated at 20 ppm and 95% O2-. RESULTS: Regardless of ventilatory pattern, both systems delivered a constant NO concentration. The error between the target and the delivered NO dose for the INOvent was -1.3+/-3.6% with the Puritan-Bennett 7200 and -3.9+/-4.3% with the Servo 900C. For the premixing system, the error was -5.5+/-4.8% with the Puritan-Bennett 7200 and -6.7+/-6.2% with the Servo 900C. NO2 concentrations were 0.5+/-0.1 ppm during NO delivery by the INOvent, 5.8+/-1.6 ppm when NO was premixed with air, 0.3+/-0.1 ppm when NO was premixed with N2. CONCLUSION: The INOvent provides a constant NO concentration independent of the ventilatory pattern, and NO2 formation is minimal.


Assuntos
Óxido Nítrico/administração & dosagem , Respiração Artificial/instrumentação , Administração por Inalação , Humanos , Ventilação com Pressão Positiva Intermitente , Medições Luminescentes , Pulmão/fisiologia , Modelos Estruturais , Óxido Nítrico/análise , Dióxido de Nitrogênio/análise
4.
Intensive Care Med ; 14 Suppl 2: 448-57, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-3042829

RESUMO

This paper reviews right ventricular anatomy and physiology in the critically ill patient. The role of right ventricular function during acute pulmonary artery hypertension and the effect of acute myocardial injury upon right ventricular performance are examined. Clinical methods of assessing right ventricular function at the bedside in acutely ill patients are critically reviewed.


Assuntos
Ventrículos do Coração/fisiopatologia , Doença Aguda , Ventrículos do Coração/patologia , Humanos , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Contração Miocárdica , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Volume Sistólico
5.
Surgery ; 90(2): 409-17, 1981 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7256549

RESUMO

Visual assessment of tissue staining after intravenous fluorescein is a common technique for predicting viability of questionably perfused tissue. The development of the perfusion fluorometer has permitted quantification of tissue fluorescein, providing increased precision. This study employed this instrument to calculate fluorescein elimination from rats with and without raised dorsal pedicle flaps. Control animals exhibited homogeneous patterns of fluorescein elimination consistent with first-order kinetics. Elimination in experimental animals was assessed after the animals received full back skin flaps with the cephalad pedicle remaining intact. Three distinct patterns of elimination were noted in each flap. In the cephalad portion, elimination was similar to control. At the caudad end, no elimination was noted. Midflap, fluorescein was eliminated slowly. These elimination patterns predicted ultimate viability 14 days postoperatively, as they correspond to viable, dystrophic, and transitional sections, respectively (P less than 0.001). We conclude that perfusion fluorometry can assess capillary flow in healthy and ischemic tissue by documenting elimination as well as delivery of fluorescein.


Assuntos
Circulação Sanguínea , Fluoresceínas/metabolismo , Fluorometria/métodos , Retalhos Cirúrgicos , Animais , Fluorometria/instrumentação , Cinética , Masculino , Ratos , Pele/irrigação sanguínea
6.
J Appl Physiol (1985) ; 78(4): 1288-95, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7615435

RESUMO

Inhaled nitric oxide (NO) has been shown to selectively dilate the pulmonary vasculature. Zaprinast, an inhibitor of guanosine 3',5'-cyclic monophosphate-specific phosphodiesterase, augments smooth muscle relaxation induced by endothelium-dependent vasodilators. The present study was designed to determine whether intravenous administration of Zaprinast potentiates the vasodilating effects or prolongs the duration of action of intermittent NO inhalation. Eight awake lambs with U-46619-induced pulmonary hypertension breathed three concentrations of NO (5, 10, and 20 ppm) in a random order before and during an intravenous Zaprinast infusion (0.1 mg.kg-1.min-1). Inhaled NO decreased pulmonary arterial pressure (PAP) in a dose-dependent fashion, with mean PAP reduction at 5, 10, and 20 ppm NO inhalation of 6 +/- 1, 7 +/- 1, and 9 +/- 1 (SE) mmHg, respectively. Although the Zaprinast infusion did not change the magnitude of mean PAP reduction, it caused a statistically significant reduction of pulmonary vascular resistance and prolonged the duration of action of inhaled NO (half-times of vasodilator response to 5, 10, and 20 ppm NO inhalation: 1.9 +/- 0.1, 2.1 +/- 0.2, and 2.1 +/- 0.2 min, respectively; half-times of NO inhalation with Zaprinast: 9.7 +/- 1.7, 11.5 +/- 2.2, and 12.3 +/- 2.0, respectively). Plasma concentrations as well as the transpulmonary differences of guanosine 3',5'-cyclic monophosphate were increased by the Zaprinast infusion during NO inhalation. A stable level of pulmonary vasodilation was demonstrated in four additional lambs by combining intermittent NO breathing with an intravenous infusion of Zaprinast.


Assuntos
GMP Cíclico/sangue , Óxido Nítrico/antagonistas & inibidores , Artéria Pulmonar/efeitos dos fármacos , Purinonas/farmacologia , Resistência Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico , Administração por Inalação , Animais , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/fisiopatologia , Infusões Intravenosas , Endoperóxidos Sintéticos de Prostaglandinas , Artéria Pulmonar/fisiopatologia , Ovinos , Tromboxano A2/análogos & derivados , Resistência Vascular/fisiologia
7.
J Appl Physiol (1985) ; 84(2): 435-41, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9475849

RESUMO

Sodium 1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA/NO; Et2N-[N(O)NO]Na) is a compound that spontaneously generates nitric oxide (NO). Because of its short half-life (2.1 min), we hypothesized that inhaling DEA/NO aerosol would selectively dilate the pulmonary circulation without decreasing systemic arterial pressure. We compared the pulmonary selectivity of this new NO donor with two other reference drugs: inhaled NO and inhaled sodium nitroprusside (SNP). In seven awake sheep with pulmonary hypertension induced by the infusion of U-46619, we compared the hemodynamic effects of DEA/NO with those of incremental doses of inhaled NO gas. In seven additional awake sheep, we examined the hemodynamic effects of incremental doses of inhaled nitroprusside (i.e., SNP). Inhaled NO gas selectively dilated the pulmonary vasculature. Inhaled DEA/NO produced nonselective vasodilation; both systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were reduced. Inhaled SNP selectively dilated the pulmonary circulation at low concentrations (< or = 10(-2)M), inducing a decrease of PVR of up to 42% without any significant decrease of SVR(-5%), but nonselectively dilated the systemic circulation at larger doses (> 10(-2)M). In conclusion, despite its short half-life, DEA/NO is not a selective pulmonary vasodilator compared with inhaled NO. Inhaled SNP appears to be selective to the pulmonary circulation at low doses but not at higher levels.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Óxido Nítrico/farmacologia , Pró-Fármacos/farmacologia , Circulação Pulmonar/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/toxicidade , Doença Aguda , Administração por Inalação , Aerossóis , Animais , Hemodinâmica/efeitos dos fármacos , Hidrazinas/administração & dosagem , Hidrazinas/farmacologia , Hipertensão Pulmonar/induzido quimicamente , Óxido Nítrico/administração & dosagem , Óxidos de Nitrogênio , Nitroprussiato/administração & dosagem , Nitroprussiato/farmacologia , Pró-Fármacos/administração & dosagem , Ovinos , Vasoconstritores/toxicidade , Vasodilatadores/administração & dosagem
8.
J Appl Physiol (1985) ; 79(4): 1148-55, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8567556

RESUMO

Although the consumption of myoglobin-bound O2 (MbO2) stores in seal muscles has been demonstrated in seal muscles during laboratory simulations of diving, this may not be a feature of normal field diving in which measurements of heart rate and lactate production show marked differences from the profound diving response induced by forced immersion. To evaluate the consumption of muscle MbO2 stores during unrestrained diving, we developed a submersible dual-wavelength laser near-infrared spectrophotometer capable of measuring MbO2 saturation in swimming muscle. The probe was implanted on the surface of the latissimus dorsi of five subadult male Weddell seals (Leptonychotes weddelli) released into a captive breathing hole near Ross Island, Antarctica. Four seals had a monotonic decline of muscle O2 saturation during free diving to depths up to 300 m with median slopes of -5.12 +/- 4.37 and -2.54 +/- 1.95%/min for dives lasting < 17 and > 17 min, respectively. There was no correlation between the power consumed by swimming and the desaturation rate. Two seals had occasional partial muscle resaturations late in dives, indicating transfer of O2 from circulating blood to muscle myoglobin. Weddell seals partially consume their MbO2 stores during unrestrained free diving.


Assuntos
Mergulho/fisiologia , Músculos/irrigação sanguínea , Mioglobina/metabolismo , Focas Verdadeiras/fisiologia , Animais , Frequência Cardíaca/fisiologia , Lactatos/sangue , Ácido Láctico , Lasers , Masculino , Modelos Biológicos , Consumo de Oxigênio/fisiologia , Esforço Físico/fisiologia , Reflexo/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Músculos Respiratórios/irrigação sanguínea , Espectrofotometria Infravermelho
9.
J Appl Physiol (1985) ; 69(3): 932-6, 1990 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2246181

RESUMO

Major increases of hemoglobin concentration and hematocrit, possibly secondary to splenic contraction, have been noted during diving in the Weddell seal. We sought to learn whether this component of the diving response could be present in professional human breath-hold divers. Splenic size was measured ultrasonically before and after repetitive breath-hold dives to approximately 6-m depth in ten Korean ama (diving women) and in three Japanese male divers who did not routinely practice breath-hold diving. Venous hemoglobin concentration and hematocrit were measured in nine of the ama and all Japanese divers. In the ama, splenic length and width were reduced after diving (P = 0.0007 and 0.0005, respectively) and calculated splenic volume decreased 19.5 +/- 8.7% (mean +/- SD, P = 0.0002). Hemoglobin concentration and hematocrit increased 9.5 +/- 5.9% (P = 0.0009) and 10.5 +/- 4% (P = 0.0001), respectively. In Japanese male divers, splenic size and hematocrit were unaffected by repetitive breath-hold diving and hemoglobin concentration increased only slightly over baseline (3.0 +/- 0.6%, P = 0.0198). Splenic contraction and increased hematocrit occur during breath-hold diving in the Korean ama.


Assuntos
Mergulho/efeitos adversos , Respiração , Baço/fisiologia , Adulto , Feminino , Hematócrito , Hemoglobinas/metabolismo , Humanos , Japão , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Baço/anatomia & histologia , Baço/diagnóstico por imagem , Ultrassonografia
10.
J Appl Physiol (1985) ; 80(1): 298-306, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8847318

RESUMO

The spleen of the Weddell seal (Leptonychotes weddelli) may contract and inject red blood cells (RBCs) into the peripheral circulation during diving, but evidence for this hypothesis is indirect. Accordingly, we measured splenic dimensions by ultrasonography, plasma catecholamine concentrations, hemoglobin concentration, and hematocrit in five Weddell seals before and after intravenous epinephrine during halothane anesthesia and while awake at the surface after voluntary dives. Spleen size was reduced immediately after epinephrine injection or after the seal surfaced. Within the first 2 min after the seal surfaced, cephalocaudal splenic length was 71 +/- 2% (mean +/- SD; P < 0.05) and splenic thickness was 71 +/- 4% (P < 0.05) of the maximal resting values. Splenic size increased (half-time = 6-9 min) after the seal surfaced and was inversely correlated with plasma epinephrine and norepinephrine concentrations. Hemoglobin concentration increased from 17.5 +/- 5.3 g/dl (measured during general anesthesia) to 21.9 +/- 3.7 g/dl (measured in the first 2 min after surfacing). At these same times, the hematocrit increased from 44 +/- 12 to 55 +/- 8%. These values decreased (half-time = 12-16 min) after the seal surfaced. We estimate 20.1 liters of RBCs were sequestered at rest, presumably in the spleen, and released either on epinephrine injection or during diving. Catecholamine release and splenic contraction appear to be an integral part of the voluntary diving response of Weddell seals.


Assuntos
Volume Sanguíneo/fisiologia , Catecolaminas/metabolismo , Mergulho/fisiologia , Focas Verdadeiras/fisiologia , Baço/fisiologia , Animais , Epinefrina/sangue , Epinefrina/farmacologia , Hematócrito , Hemoglobinas/metabolismo , Masculino , Contração Muscular/fisiologia , Músculo Liso Vascular/fisiologia , Norepinefrina/sangue , Oxigênio/sangue , Baço/anatomia & histologia , Baço/diagnóstico por imagem , Ultrassonografia , Vasoconstritores/sangue , Vasoconstritores/farmacologia
11.
J Appl Physiol (1985) ; 75(1): 285-93, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8376276

RESUMO

Korean female unassisted divers (cachido ama) breath-hold dive > 100 times to depths of 3-7 m during a work day. We sought to determine the extent of arterial hypoxemia during normal working dives and reasonable time limits for breath-hold diving by measuring radial artery blood gas tensions and pH in five cachido ama who dove to a fixed depth of 4-5 m and then continued to breath hold for various times after their return to the surface. Eighty-two blood samples were withdrawn from indwelling radial artery catheters during 37 ocean dives. We measured compression hyperoxia [arterial PO2 = 141 +/- 24 (SD) Torr] and hypercapnia (arterial PCO2 = 46.6 +/- 2.4 Torr) at depth. Mean arterial PO2 near the end of breath-hold dives lasting 32-95 s (62 +/- 14 s) was decreased (62.6 +/- 13.5 Torr). Mean arterial PCO2 reached 49.9 +/- 5.4 Torr. Complete return of these values to their baseline did not occur until 15-20 s after breathing was resumed. In dives of usual working duration (< 30 s), blood gas tensions remained within normal ranges. Detailed analysis of hemoglobin components and intrinsic oxygenation properties revealed no evidence for adaptive changes that could increase the tolerance of the ama to hypoxic or hypothermic conditions associated with repetitive diving.


Assuntos
Dióxido de Carbono/sangue , Mergulho , Oxigênio/sangue , Respiração/fisiologia , 2,3-Difosfoglicerato , Adulto , Contagem de Células Sanguíneas , Ácidos Difosfoglicéricos/sangue , Eletroforese , Feminino , Hemoglobinas/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Hipóxia/fisiopatologia , Focalização Isoelétrica , Coreia (Geográfico) , Pessoa de Meia-Idade
12.
Ann Thorac Surg ; 66(6): 1894-902, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9930465

RESUMO

BACKGROUND: The adult respiratory distress syndrome (ARDS) developing after pulmonary resection is usually a lethal complication. The etiology of this serious complication remains unknown despite many theories. Intubation, aspiration bronchoscopy, antibiotics, and diuresis have been the mainstays of treatment. Mortality rates from ARDS after pneumonectomy have been reported as high as 90% to 100%. METHODS: In 1991, nitric oxide became clinically available. We instituted an aggressive program to treat patients with ARDS after pulmonary resection. Patients were intubated and treated with standard supportive measures plus inhaled nitric oxide at 10 to 20 parts/million. While being ventilated, all patients had postural changes to improve ventilation/perfusion matching and management of secretions. Systemic steroids were given to half of the patients. RESULTS: Ten consecutive patients after pulmonary resection with severe ARDS (ARDS score = 3.1+/-0.04) were treated. The mean ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen at initiation of treatment was 95+/-13 mm Hg (mean +/- SEM) and improved immediately to 128+/-24 mm Hg, a 31%+/-8% improvement (p<0.05). The ratio improved steadily over the ensuing 96 hours. Chest x-rays improved in all patients and normalized in 8. No adverse reactions to nitric oxide were observed. CONCLUSIONS: We recommend the following treatment regimen for this lethal complication: intubation at the first radiographic sign of ARDS; immediate institution of inhaled nitric oxide (10 to 20 parts per million); aspiration bronchoscopy and postural changes to improve management of secretions and ventilation/perfusion matching; diuresis and antibiotics; and consideration of the addition of intravenous steroid therapy.


Assuntos
Óxido Nítrico/administração & dosagem , Pneumonectomia , Complicações Pós-Operatórias/terapia , Síndrome do Desconforto Respiratório/terapia , Vasodilatadores/administração & dosagem , Administração por Inalação , Estudos de Casos e Controles , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/uso terapêutico , Complicações Pós-Operatórias/diagnóstico , Postura , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/etiologia , Vasodilatadores/uso terapêutico
13.
Pharmacotherapy ; 17(5): 1023-6, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9324192

RESUMO

Current fluconazole dosing recommendations are based on pharmacokinetic parameters calculated from serum concentration data in subjects and patients of normal weight. These recommendations may be inaccurate when applied to obese individuals due to the physiologic changes of obesity that may influence drug pharmacokinetics. A 39-year-old morbidly obese man (BMI 48.3 kg/m2) was treated with fluconazole 1200 mg/day infused over 6 hours. After 14 days of therapy, blood samples were obtained at 0, 1, 2, 4, 8, 12, 18, and 24 hours after infusion and steady-state serum concentrations were determined using a bioassay. Pharmacokinetic parameters calculated were area under the concentration-time curve (AUC(0-24)) 574.9 mg/L x hour, average steady-state serum concentration 23.9 mg/L, and fluconazole clearance 139.4 ml/minute. Compared with published data, our patient had a lower area under the curve and increased fluconazole clearance. These changes may be due to the drug's increased volume of distribution. Based on these data and the favorable toxicity profile of fluconazole, we recommend considering higher dosages in such morbidly obese patients.


Assuntos
Antifúngicos/sangue , Antifúngicos/farmacocinética , Fluconazol/sangue , Fluconazol/farmacocinética , Obesidade Mórbida/metabolismo , Adulto , Área Sob a Curva , Meia-Vida , Humanos , Masculino
14.
Crit Care Clin ; 10(4): 831-43, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8000929

RESUMO

Local custom continues to dictate the clinical use of NMBDs in critically ill patients with respiratory failure. The safety of long-term administration of NMBDs to critically ill patients remains of great concern. Studies that clearly delineate the cause of severe myopathies and neuropathies in critically ill paralyzed patients remain to be performed. Because it appears these disorders may be related to the administration of drugs with steroidal structure, we believe it is prudent to avoid such drugs, if possible, in critically ill patients. We therefore continue to use curare, a nonsteroidal drug with a long history of safety, for long-term paralysis in these patients. Similarly, we believe that it is prudent to monitor the efficacy of NMBDs via the routine use of ulnar nerve stimulation. Patient movement in the face of adequate neuromuscular blockade as assessed by ulnar nerve stimulation then can be treated by deepening the level of sedation rather than by continually increasing the dose of the NMBD.


Assuntos
Bloqueadores Neuromusculares/uso terapêutico , Insuficiência Respiratória/terapia , Protocolos Clínicos , Humanos , Monitorização Fisiológica/métodos , Bloqueadores Neuromusculares/administração & dosagem , Planejamento de Assistência ao Paciente
15.
J Neurosurg Anesthesiol ; 1(3): 249-55, 1989 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15815281

RESUMO

Because of the physiologic and metabolic changes that occur during acclimatization, we hypothesized that LCGU may be normal during prolonged hypoxia. We exposed five Sprague-Dawley rats to hypoxia (air at 380 mm Hg) for 2 weeks (hypoxic group) and six rats to 2 weeks of hypoxia followed by 2 weeks of recovery in room air (recovered group). Six control rats breathed room air (control group). Regional brain glucose utilization was measured in awake animals by using 2-[C]deoxyglucose autoradiography. Glucose utilization was comparable in the control and recovered groups and in most brain regions of hypoxic animals. Glucose utilization was decreased slightly in 10 of 12 gray matter regions examined and was 20 to 25% lower (p <0.05) in the olfactory and auditory cortices, the caudate nucleus, and the superior olive of the hypoxic group. White matter glucose utilization was unchanged. Hypoxic rats, compared to controls, had a lower PaO2 (53 +/- 3 vs. 76 +/- 3 mm Hg, mean SEM, respectively), a lower PaCO2 (22 +/- 1 vs. 36 +/- 2 mm Hg), and a higher mean pulmonary artery pressure (46 +/- 3 vs. 14 +/- 3 mm Hg) and hematocrit (61 +/- 2% vs. 48 +/- 1%; p <0.005 for all comparisons). Pulmonary hypertension and polycythemia persisted in recovered rats. Arterial pressure, pH, and plasma glucose were unaffected. Therefore, while acute hypoxia may increase glucose utilization in most brain structures, prolonged exposure does not.

16.
Comp Biochem Physiol B Biochem Mol Biol ; 112(2): 361-75, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7584864

RESUMO

Subadult male Weddell seals were instrumented with microcomputer-based backpacks and were then monitored during voluntary diving and recovery periods in McMurdo Sound, Antarctica. Depth and duration of diving, swim speed, and dive pattern were routinely monitored. An indwelling venous catheter was used to collect plasma samples at various time periods before and following diving episodes, so that changes in plasma concentrations of hormones and of metabolites could be measured. Adrenergic and nitroxidergic regulatory effects were assessed indirectly by measuring concentration changes in catecholamine and cyclic guanosine monophosphate (cGMP), respectively. The studies found that (i), except for dives of less than several minutes, epinephrine and norepinephrine both increased as a function of diving duration, then rapidly decreased during recovery (with a half time of about 10 min), (ii) that the changes in catecholamine concentrations correlated with splenic contraction and an increase in circulating red blood cell mass (hematocrit), (iii) that the changes in catecholamines, especially [epinephrine], were inversely related to insulin/glucagon ratios, which mediated a postdiving hyperglycemia, and (iv) that in long dives (but not short ones) the changes in catecholamines correlated with increasing reliance on anaerobic metabolism, indicated by increased plasma lactate concentrations. These diving-catecholamine relationships during voluntary diving at sea were similar to those observed during enforced submergence (simulated diving) under controlled laboratory conditions. At the end of diving, even while catecholamine concentrations were still high, many of the above effects were rapidly reversed and the reversal appeared to correlate with accelerated nitric oxide production, indirectly indicated by increased plasma cGMP concentrations. Taken together, the data led to the hypothesis of important adrenergic regulation of the diving response in seals, with rapid reversal at the end of diving and during recovery being regulated by nitroxidergic mechanisms.


Assuntos
Catecolaminas/sangue , Focas Verdadeiras/fisiologia , Animais , Mergulho/fisiologia , Glucagon/metabolismo , Hematócrito , Insulina/metabolismo , Masculino
17.
Otolaryngol Head Neck Surg ; 91(2): 151-5, 1983 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-6408571

RESUMO

The fluorescein test is widely used to assess perfusion in skin flaps but tends to underestimate skin viability when visual inspection under ultraviolet light is employed. Fiberoptic dermofluorometry, which has recently been introduced, more accurately assesses fluorescein distribution in skin flaps than does visual inspection. Viability of the back flap in rats receiving ionizing radiation was evaluated by dermofluorometry. This technique was highly accurate in predicting viability and has great applicability for studying blood flow in irradiated tissues.


Assuntos
Fluorometria/métodos , Radioterapia/efeitos adversos , Retalhos Cirúrgicos , Cicatrização/efeitos da radiação , Animais , Ratos , Ratos Endogâmicos , Pele/irrigação sanguínea , Pele/efeitos da radiação
18.
J Clin Anesth ; 6(5): 434-6, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7986519

RESUMO

We present the case of a patient with Charcot-Marie-Tooth (CMT) disease who required prolonged ventilatory support following a thoracotomy due to respiratory muscle weakness. Although CMT was traditionally believed to affect only skeletal muscles, recent evidence suggests that respiratory involvement is relatively common, even in the absence of pulmonary symptoms. Assessment of respiratory muscle strength using measurements of vital capacity and negative inspiratory force is helpful in evaluating pulmonary reserve in patients with CMT.


Assuntos
Doença de Charcot-Marie-Tooth/complicações , Insuficiência Respiratória/etiologia , Toracotomia/efeitos adversos , Adulto , Doença de Charcot-Marie-Tooth/fisiopatologia , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Capacidade Inspiratória/fisiologia , Respiração Artificial , Insuficiência Respiratória/terapia , Músculos Respiratórios/fisiopatologia , Capacidade Vital/fisiologia
19.
Respir Care Clin N Am ; 3(3): 357-69, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9390916

RESUMO

Nitric oxide is produced by nitric oxide synthase enzymes, which cleave the amino acid L-arginine to form nitric oxide and the amino acid L-citrulline. Many of the biologic actions of nitric oxide occur because nitric oxide activates guanylate cyclase, which in turn synthesizes a second-messenger molecule, cyclic guanosine 3',5'-monophosphate (cGMP). The increased concentration of cGMP activates cGMP-dependent protein kinase, reducing intracellular concentrations of calcium and relaxing smooth muscle. Nitric oxide also has many important effects that may not be mediated through increases of pulmonary cGMP activity. These include the ability to scavenge oxygen free radicals, reduce oxygen toxicity, and inhibit platelet and leukocyte aggregation. Nitric oxide is metabolized and excreted via a number of diverse pathways that may modify the toxicity of the molecule.


Assuntos
Exposição por Inalação , Óxido Nítrico/metabolismo , Animais , Humanos , Pneumopatias Obstrutivas/terapia , Óxido Nítrico/farmacologia , Óxido Nítrico/fisiologia , Óxido Nítrico/uso terapêutico , Fenômenos Fisiológicos Respiratórios , Sistema Respiratório/efeitos dos fármacos
20.
Respir Care Clin N Am ; 3(3): 437-58, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9390919

RESUMO

Inhalation of low inspired concentration of nitric oxide reduces pulmonary hypertension and increases arterial oxygen tension in patients with acute respiratory distress syndrome (ARDS), and appears to be safe. Research on the physiologic mechanisms regulating the action of inhaled nitric oxide may provide clinicians with ways to further potentiate and prolong its beneficial effects.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Óxido Nítrico/uso terapêutico , Síndrome do Desconforto Respiratório/complicações , Administração por Inalação , Animais , Bovinos , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Cães , Humanos , Hipertensão Pulmonar/etiologia , Recém-Nascido , Leucócitos/efeitos dos fármacos , Óxido Nítrico/efeitos adversos , Óxido Nítrico/farmacologia , Adesividade Plaquetária/efeitos dos fármacos , Prognóstico , Mecânica Respiratória/efeitos dos fármacos , Suínos
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