摘要:

Objective:Acute renal failure, frequently a consequence of renal vasoconstriction and subsequent renal ischemia, is a common problem for which no proven preventive or therapeutic agents exist. Fenoldopam is a new, selective, dopamine-1 receptor agonist that causes both systemic and renal arteriolar vasodilation. In hypertensive patients, fenoldopam rapidly decreases blood pressure, increases renal blood flow, and maintains or improves the glomerular filtration rate. We sought to determine a dose of fenoldopam that increases renal blood flow without inducing hypotension in normotensive patients and to explore the role of volume status (sodium replete vs. deplete) in these effects.Design:Randomized, double-blind, placebo-controlled, crossover study.Setting:Clinical research unit.Patients:Fourteen normal male volunteers.Interventions:Renal plasma flow (para-aminohippurate clearance) and glomerular filtration rate (inulin clearance) were measured during three fixed, escalating doses of fenoldopam (0.03, 0.1, and 0.3 μg/kg/min) on both a high-sodium and a low-sodium diet.Measurements and Main Results:Fenoldopam significantly increased renal plasma flow in a dose-dependent manner compared with placebo: 670 ± 148 vs. 576 ± 85 mL/min at 0.03 μg/kg/min; 777 ± 172 vs. 579 ± 80 mL/min at 0.1 μg/kg/min; and 784 ± 170 vs. 592 ± 165 mL/min at 0.3 μg/kg/min (p< .05 fenoldopam vs. placebo at all three doses). Glomerular filtration rate was maintained. At the lowest dose (i.e., 0.03 μg/kg/min), significant renal blood flow increases occurred without changes in systemic blood pressure or heart rate. At 0.1 and 0.3 μg/kg/min, systolic blood pressure did not change, but diastolic blood pressure was slightly lower in the fenoldopam group than in the placebo group: 62.5 ± 6.4 vs. 63.6 ± 2.6 mm Hg, respectively, at 0.3 μg/kg/min (p< .05). None of the effects of fenoldopam were altered by volume status.Conclusions:Fenoldopam increased renal blood flow in a dose-dependent manner compared with placebo, and, at the lowest dose, significantly increased renal blood flow occurred without changes in systemic blood pressure or heart rate. These findings will be useful in designing future studies exploring the role of fenoldopam in preventing or treating renal failure in patients who are not hypertensive.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objectives:After an initial vasodilator response to alkalosis, many children with pulmonary hypertension exhibit marked pulmonary vascular reactivity despite continued alkalosis therapy. This study sought to a) identify the mediator of alkalosis-induced pulmonary vasodilation in isolated lamb lungs; b) determine whether alkalosis-induced pulmonary vasodilation decreases over time in this model; and c) determine whether alkalosis enhanced vascular reactivity to subsequent pressor stimuli.Design:Prospective, interventional study.Subjects:Isolated perfused lungs from 1-month-old lambs.Interventions:Hypocarbic alkalosis, hypoxia, and infusion of the thromboxane mimetic agent U46619Measurements and Main Results:Pulmonary artery pressure was measured at constant flow, so a change in pressure reflects change in resistance. Hypoxic pulmonary artery pressure was compared after 20 and 100 mins of hypocarbic alkalosis or normocarbia in control and cyclooxygenase-inhibited lungs. Pulmonary artery dose responses to U46619 were then measured in control lungs. Responses to hypoxia and U46619 were also compared after 60-80 mins of hypocarbic or normocarbic normoxia. Hypocarbic alkalosis acutely reduced hypoxic pulmonary vascular resistance, and this was sustained for at least 100 mins. Cyclooxygenase inhibition blocked this vasodilation, suggesting that it was mediated by dilator prostaglandins. However, subsequent reactivity to U46619 was enhanced in hypoxic alkalotic lungs, and both hypoxia and U46619 caused significant vasoconstriction in normoxic alkalotic lungs.Conclusions:Alkalosis caused sustained vasodilation when pulmonary vascular resistance was high but either failed to attenuate or enhanced vascular reactivity to subsequent pressor stimuli.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To test propofol and the solvent of propofol on leukocyte function in the presence of endothelial cell monolayers. The interactions of leukocytes with endothelial cells play a tremendous role during inflammation. Previous studies have investigated the influence of propofol on leukocytes.Design:Prospective, controlled study.Setting:University research laboratories.Subjects:Seven independent experiments were performed to investigate the influence of propofol (0.4, 4, and 40 ng/mL) on the migration of human leukocytes through human endothelial cell monolayers. Moreover, the authors tested the solvent of propofol on leukocyte migration.Interventions:Human endothelial cell monolayers and/or human leukocytes were preincubated with clinically relevant higher and lower concentrations of propofol. The amount of leukocyte migration after 3 hrs was measured with a fluorometer.Measurements and Main Results:Human endothelial cells isolated from umbilical veins were cultured on microporous membranes until they formed an endothelial cell monolayer. Leukocytes were separated by standard procedures. The migration of leukocytes through monolayers of endothelial cells using the clinically relevant concentration of propofol was reduced to 93% ± 3.8% (SD;p< .05) when the leukocytes but not the endothelial cell monolayers were preincubated with propofol. Leukocyte migration was reduced to 80% ± 5.9% (p< .05) when only monolayers of endothelial cells were treated with propofol, and was reduced to 73% ± 10.4% (p< .05) when both leukocytes and monolayers of endothelial cells were treated with propofol. The higher and lower concentrations showed a dose-dependent effect. The solvent of propofol had no significant effect.Conclusion:The authors investigated the influence of propofol and its solvent on the interaction between both cell systems-leukocytes and endothelial cells. Propofol is able to reduce significantly the migration of leukocytes through endothelial cell monolayers. The use of different doses revealed a dose-dependent effect. The current model allowed treatment of one cell type: leukocyte or endothelial cell. The results of this investigation indicate that the influence of propofol on leukocyte migration affects endothelial cells more than leukocytes.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To assess the effects of continuous venovenous hemofiltration (CVVH) on global and regional hemodynamics, plasma lactate, and tumor necrosis factor-α (TNF-α) levels during endotoxic shock in dogs.Methods:Thirty pentobarbital-anesthetized and mechanically ventilated dogs were divided into six groups of five dogs each. Group 1 served as a control, undergoing CVVH at 3 L/hr without endotoxin. Group 2 served as the endotoxin-alone time-matching group. Group 3 received CVVH 1 hr after endotoxin at 3 L/hr for 270 mins. Group 4 received CVVH 1 hr after endotoxin at 3 L/hr for 150 mins and at 6 L/hr for an additional 120 mins. Group 5 and group 6 received the ultrafiltrate from group 1 and group 3, respectively.Measurements and Main Results:Three hours after endotoxin challenge, dogs treated with CVVH at 3 L/hr had a higher cardiac output (4.9 ± 0.6 vs. 2.9 ± 0.6 L/min;p< .05) and stroke volume (35 ± 7 vs. 20 ± 4 mL;p< .05) and a lower pulmonary vascular resistance (116 ± 26 vs. 331 ± 126 dyne·sec/cm5;p< .05) than the endotoxin-alone group. Five hours after endotoxin, dogs treated with CVVH at 6 L/hr also had higher hepatic (464 ± 164 vs. 126 ± 75 mL/min;p< .05) and femoral (95 ± 46 vs. 30 ± 34 mL/min;p< .05) blood flow. Moreover, dogs treated with CVVH at 6 L/hr had higher mean arterial blood pressure (84 ± 24 vs. 40 ± 15 mm Hg;p< .05) and left ventricular stroke work index (1.1 ± 0.6 vs. 0.2 ± 0.2 g/kg;p< .05) than the endotoxin-alone group. Plasma lactate levels were lower in the CVVH group at 6 L/hr (2.7 ± 1.1 mmol/L) than in the endotoxin-alone group (4.4 ± 0.6 mmol/L;p< .05). Plasma TNF-α levels were unaffected, and only minor amounts of TNF-α were found in the ultrafiltrate.Conclusion:In this acute endotoxic shock model, CVVH at 3 L/hr improved cardiac performance and decreased pulmonary vasoconstriction. Moreover, CVVH at 6 L/hr also increased arterial blood pressure and left ventricular stroke work, increased hepatic and femoral arterial blood flow, and decreased blood lactate levels. These effects were not attributable to TNF-α removal.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To assess the possible benefits of sympatholytics on uncontrolled hemorrhage in unanesthetized rats.Design:A randomized laboratory study using rats to test the effects of sympatholytics on uncontrolled hemorrhage.Setting:Research laboratory.Subjects:Forty female Sprague-Dawley rats, randomly assigned into four groups according to the treatment: untreated (Control); α-adrenergic blockade with phenoxybenzamine (Alpha); β-adrenergic blockade with propranolol (Beta); and a combined α- and β-adrenergic blockade by phenoxybenzamine and propranolol (Alpha/Beta).Intervention:After cannulation under light ether, the rats were allowed to awaken. A baseline blood sample was withdrawn. The uncontrolled hemorrhage was initiated by tail resection and allowed to continue without intervention for the duration of the experiment. After 15 mins, 80 mL/kg isotonic saline fluid was infused at 4.4 mL/min. At 60 mins, another blood sample was drawn; changes in mean arterial pressure, hematocrit, blood loss, and mortality were observed for up to 180 mins.Main Outcome Measure:Survival, mortality, blood loss (amount, prevalence, and rate), and hemodynamic variables (mean arterial pressure, pulse rate, hematocrit).Results:In the Alpha group, there was a reduction in spontaneous blood loss compared with the control group (2.9 vs. 10.6 mL/kg, respectively) and 100% survival. In contrast, the Beta group exhibited an increase in tail blood loss (21.1 mL) and a decreased survival (10%). Despite the enhanced hemorrhage in the Alpha/Beta group (17.0 mL/kg) compared with controls, the survival rate in both of these groups was 60%. In all groups, no significant increase in tail blood loss was observed after 60 mins.Conclusions:An α-adrenergic blockade increased survival in uncontrolled hemorrhage by significantly reducing spontaneous blood loss. Conversely, a β-adrenergic blockade significantly decreased survival and increased blood loss, whereas a combined blockade significantly increased blood loss without affecting survival.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To observe pulmonary edema resulting from intestinal ischemia-reperfusion injury. We used a newly developed laser confocal microscope to observe the subpleural capillary network and the superficial alveoli under intravital conditions, and created three-dimensional images of the pulmonary microcirculation to analyze the time course and spatial pattern of pulmonary exudative changes during intestinal ischemia-reperfusion injuryin vivo.Design:Prospective, randomized, unblinded study.Setting:Laboratory of a university hospital.Subjects:Male Sprague-Dawley rats.Interventions:The rats were injected intravenously with bovine serum albumin labeled with fluorescein isothiocyanate and subjected to 60 mins of intestinal ischemia, followed by 180 mins of reperfusion. During mechanical ventilation, the upper lobe of the right lung was examined in the intravital state using a high-speed confocal fluorescence microscope.Measurements and Main Results:Interstitial edema and alveolar leakage were recognized as changes of interstitial fluorescence in the subpleural capillary network and as changes of alveolar fluorescence in the alveolar cross-sectional view. Although exudative changes in the interstitium and alveoli were observed during intestinal ischemia, there was a marked increase in both interstitial edema and alveolar leakage after intestinal reperfusion.Conclusion:We observed pulmonary edema under intravital conditions and demonstrated the utility of a newly developed laser confocal microscope. This system not only enabled us to analyze the development of pulmonary edema three-dimensionally, but also allowed us to evaluate the pulmonary microcirculation.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objectives:To monitor PO2, PCO2, and pH in the interstitium of skeletal muscle (PmO2, PmCO2, and pHm) during hemorrhage, shock, and resuscitation using fiber-optic sensors and to compare PCO2and pH in the interstitium of gastric mucosa (PrCO2and pHi) obtained using gastric CO2tonometry.Design:Prospective, controlled observational study in an acute experimental preparation.Setting:Physiology laboratory in a university medical school.Subjects:Nine mongrel dogs (20 to 35 kg).Interventions:Anesthesia was induced with pentobarbital (25 mg/kg iv) and maintained (10 mg/hr) after hemorrhagic shock. Mechanical ventilation was established to maintain baseline PaCO2≈ 35 torr. Arterial, venous, and pulmonary artery catheters were placed. Blood flow probes were placed around the right femoral artery and vein. A probe (0.5 mm in diameter) with fiber-optic PO2, PCO2, and pH sensors was placed percutaneously in the adductor muscle of the right thigh. A gastric tonometer catheter was placed in the stomach lumen. After baseline data collection, controlled hemorrhage to mean arterial pressure (MAP) of 45 to 50 mm Hg was maintained for 1 hr. Shed blood was then reinfused. Blood gas, hemodynamic, and gastric tonometric data were collected during shock and reinfusion at 30-min intervals and hourly after reinfusion for 4 hrs. Normothermia was maintained.Measurements and Main Results:PmO2decreased rapidly from 42 ± 13 torr (mean ± SD) to 13 ± 9 torr within 15 mins and to 6 ± 4 torr within 30 mins of MAP reaching 45 mm Hg, and it recovered to baseline with reinfusion. pHm decreased gradually from 7.23 ± 0.09 to 6.89 ± 0.25 during the 1-hr shock period and increased slowly toward baseline after reinfusion. pHi decreased from 7.43 ± 0.14 to 6.91 ± 0.23, and on average it returned to baseline 2 hrs after reinfusion. PmCO2increased from 50 ± 12 to 113 ± 49 torr, increased further to 124 ± 73 torr during reinfusion, and returned slowly toward baseline after reinfusion, PrCO2increased from 35 ± 8 to 60 ± 19 torr and returned to baseline within 15 mins after reinfusion. During shock and reinfusion, oxygen delivery, mixed venous PO2, mixed venous oxygen saturation, and PmO2responded with similar time courses. After reinfusion, on average, PmO2exceeded baseline PmO2and mixed venous PO2, and oxygen availability exceeded demand, suggesting an oxygen consumption defect. On average, PmCO2and pHm did not return to baseline values 4 hrs after reinfusion, suggesting the persistence of anaerobic metabolic effects in skeletal muscle beyond the relatively short time that is required to reestablish baseline MAP, blood flow rates, oxygen delivery, PrCO2, and pHi.Conclusions:PmO2, PmCO2, and pHm, monitored simultaneously using fiber-optic sensors in a single, small probe placed percutaneously, appear to indicate greater severity of shock and more prolonged resuscitation than conventional systemic or gastric tonometric variables.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To compare normative ventilatory and gas-exchange data and anesthetic requirements in male and female rats subjected to critical care conditions.Design:Prospective study.Setting:Critical care research laboratory in a hospital.Subjects:Twenty-two age-matched young male and female rats (Sprague-Dawley, Long Evans strain).Interventions:Anesthesia was induced with 65 and 45 mg/kg pentobarbital in male and female rats, respectively. The rats were then tracheostomized and cannulated in one femoral vein and artery. Anesthesia was maintained using 8-15 mg/kg/hr pentobarbital (iv) and controlled by continuous hemodynamic monitoring.Measurements and Main Results:Normoxic baselines for breathing frequency, tidal volume, minute volume, inspiratory-to-expiratory ratio, inspiratory drive (tidal volume/inspiratory time), respiratory system compliance, peak airway pressure, and gas-exchange profiles were established. Ventilatory and gas-exchange responses to oxygen and CO2were then determined by exposure to 10 mins of hyperoxia (100% oxygen), two levels of mild and severe hypercapnic hyperoxia (inspired PCO2of 30 and 60 torr; 4 and 8 kPa), and two levels of mild and severe normocapnic hypoxia (inspired PO2of 81 and 48 torr; 10.7 and 6.3 kPa). The average anesthetic requirement (during a 5- to 6-hr experiment) was 30% less in the female rats than in the male rats (p< .05). Female rats showed significantly lower breathing frequency, minute volume (mL/min/kg), and inspiratory drive (mL/kg/sec) during hyperoxia, mild and severe hypercapnia, and mild hypoxia. Pulmonary peak airway pressure was significantly lower in the female rats, consistent with a significantly higher weight-indexed compliance during all exposures. The female rats also had significantly higher inspiratory-to-expiratory ratio and higher PaCO2with lower pH during normoxia, hyperoxia, and mild hypercapnia. These gender differences had no effect on PaO2, which was similar in all exposures.Conclusions:There are significant gender differences in ventilation, gas exchange, and anesthetic requirements in rats subjected to critical care conditions. The gas-exchange values observed in these spontaneously breathing rats may represent the optimal levels attainable during pentobarbital anesthesia with normal lungs. They may serve as standards for ventilator settings in the rat models used for critical care studies.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To examine the hypothesis that mixed venous oxygen saturation (S&OV0456;O2) values, which reflect the residual oxygen after tissue oxygen extraction, would be similar during hypoxic and anemic hypoxia.Design:S&OV0456;O2values, oxygen delivery, arterial oxygen content, and fractional oxygen extraction were compared, and critical values were determined based on lactate, the lactate/pyruvate ratio, and oxygen consumption during hypoxic and anemic hypoxia.Setting:Laboratory of physiology at a university hospital.Subjects:Two groups of eight piglets, 8 to 12 days old.Interventions:Piglets were anesthetized, tracheotomized, intubated, and ventilated. A thoracotomy was performed and a fiberoptic catheter was placed in the pulmonary artery to monitor S&OV0456;O2. A transit time ultrasound flow probe was positioned around the ascending aorta to measure aorta flow. Progressive hypoxic hypoxia was induced by decreasing FIO2from baseline (0.30-0.75) to 0.21, 0.15, and 0.10. Progressive anemic hypoxia was induced by a repeated isovolemic exchange transfusion with 50 mL of pasteurized plasma.Measurements and Main Results:Fifteen or 30 mins after each intervention, samples were taken from the carotid artery for blood gases, hemoglobin, lactate, and pyruvate and from the pulmonary artery for blood gases and hemoglobin. Hemodynamic, arterial oxygen saturation, and S&OV0456;O2measurements were made. The calculated oxygen delivery and oxygen consumption decreased in both hypoxic and anemic hypoxia. At the lowest oxygen delivery level of anemic hypoxia, the decrease in S&OV0456;O2was less than that in hypoxic hypoxia (−26% vs. −55%). The range of critical values for S&OV0456;O2calculated for each individual piglet below which lactate, the lactate/pyruvate ratio, and oxygen consumption rapidly changed from baseline value was significantly lower in hypoxic hypoxia (11% to 24%) than in anemic hypoxia (26% to 48%). Fractional oxygen extraction increased significantly but not with a change as high as in hypoxic hypoxia 0.31 (range, 0.20-0.41)vs.0.49 (range, 0.41-0.54).Conclusions:In comparison with hypoxic hypoxia, critical values of S&OV0456;O2are higher in anemic hypoxia, indicating that oxygen unloading from blood to tissues is impaired in anemic hypoxia. These characteristics in oxygen transport and capillary hemodynamics should be taken into consideration when S&OV0456;O2is used in clinical critical care.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Objective:To compare the efficacy of four methods of simulated single-rescuer bystander cardiopulmonary resuscitation (CPR) in a clinically relevant swine model of prehospital pediatric asphyxial cardiac arrest.Design:Prospective, randomized study.Subjects:Thirty-nine anesthetized domestic piglets.Interventions:Asphyxial cardiac arrest was produced by clamping the endotracheal tubes of the piglets. For 8 mins of simulated bystander CPR, animals were randomly assigned to the following groups: group 1, chest compressions and simulated mouth-to-mouth ventilation (FIO2= 0.17, FICO2= 0.04) (CC+V); group 2, chest compressions only (CC); group 3, simulated mouth-to-mouth ventilation only (V); and group 4, no CPR (control group). Standard advanced life support was then provided, simulating paramedic arrival. Animals that were successfully resuscitated received 1 hr of intensive care support and were observed for 24 hrs.Measurements and Main Results:Electrocardiogram, aortic blood pressure, right atrial blood pressure, and end-tidal CO2were monitored continuously until the intensive care period ended. Arterial and mixed venous blood gases were measured at baseline, 1 min after cardiac arrest, and 7 mins after cardiac arrest. Minute ventilation was determined during each minute of bystander CPR. Survival and neurologic outcome were determined. Twenty-four-hour survival was attained in eight of 10 group 1 (CC+V) piglets vs. three of 14 group 2 (CC) piglets (p≤ .01), one of seven group 3 (V) piglets (p≤ .05), and two of eight group 4 (control) piglets (p≤ .05). Twenty-four-hour neurologically normal survival occurred in seven of 10 group 1 (CC+V) piglets vs. one of 14 group 2 (CC) piglets (p≤ .01), one of seven group 3 (V) piglets (p≤ .05), and none of eight group 4 (control) piglets (p≤ .01). Arterial oxygenation and pH were markedly better during CPR in group 1 than in group 2. Within 5 mins of bystander CPR, six of 10 group 1 (CC+V) piglets attained sustained return of spontaneous circulation vs. only two of 14 group 2 (CC) piglets and none of the piglets in the other two groups (p≤ .05 for all groups).Conclusions:In this pediatric asphyxial model of prehospital single-rescuer bystander CPR, chest compressions plus simulated mouth-to-mouth ventilation improved systemic oxygenation, coronary perfusion pressures, early return of spontaneous circulation, and 24-hr survival compared with the other three approaches.

ISSN:0090-3493    

出版商:OVID    

年代:1999

数据来源: OVID