Archive for the ‘Sepsis’ Category

Effect of Dobutamine on Lung Microvascular Fluid Flux in Sheep with “Sepsis Syndrome”: ConclusionTo further support our suggestion that dobutamine may have functionally reduced the effects of altered endothelial permeability characteristics on microvascular fluid flux in this study, Hakim et al concluded that (3-adrenergic receptors regulated pulmonary transendothelial transport of fluid and proteins since (3-adrenergic blockade with propranolol was associated with an increase in QL. Also, in the peripheral microvasculature, (3-adrenergic receptor agonists demonstrably inhibit edema formation and transmicrovascular protein flux, an observation that cannot be explained by their effects on microvascular pressure, blood flow, or surface area. The rationale underlying such a protective action of (3-adrenergic receptor agonists within the pulmonary microvasculature is purely speculative but may reflect the effects of enhanced cyclic AMP generation within the endothelium, perhaps thereby leading to relaxation of mediator-contracted endothelial cells. Read the rest of this entry »

Effect of Dobutamine on Lung Microvascular Fluid Flux in Sheep with “Sepsis Syndrome”: ObservationsNonseptic Study
The infusion of dobutamine was associated with a modest fall in the mean blood pressure at the 10μg/kg/ min dose but was without effect on the mean pulmonary arterial pressure at either dose (Table 1 ana r lg l). The cardiac output increased progressively with both doses, while the measured pulmonary arterial wedge pressure, left atrial pressure, and calculated Pmv remained unchanged. Systemic oxygen transport increased at both doses, and the Pv02 increased concurrently. Dobutamine did not signficantly affect QL or the [L/P]TP at either dose. The calculated mean 7rpmv fell with both doses (p<0.05), although the Trmv-TTpmv gradient was unchanged from baseline. Therefore, the CLP remained unchanged from baseline during the infusion of dobutamine of either dose. We found no significant relationship between changes in QL and cardiac output (CO) at either dose (5μLg/kg/min, AQL=1.3 —0.66 ACO; r= — 0.12) (10μg/kg/min, AQL = 1.70 — 0.311 ACO; r= -0.36), unlike data reported by Coates et al, where with exercise an increase in QL was significantly related to an increase in the cardiac output. Read the rest of this entry »

Specific Measurements
We collected pulmonary lymph in graduated heparinized tubes. From pooled lymph specimens, we measured total protein and albumin concentrations (in grams per deciliter) by the Biuret method using an automated system (Auto Analyzer, Technicon Instruments); duplicate samples differed by less than 5 percent. At the time of lymph collection, we also measured total protein and albumin concentration (in grams per deciliter ). With appropriate temperature corrections, we measured oxygen tension (Po2, in millimeters of mercury) (AME-1 blood gas analyzer) and oxygen saturation (So2, in percent) (Hemoximeter, Radiometer) of both arterial (eg, Pa02) and mixed venous (eg, Pv02) blood drawn from the carotid arterial line and the distal lumen of the right-heart catheter, respectively. Blood for determining gas levels was drawn into heparinized syringes and maintained in ice until determination was performed within 15 minutes of collection. Read the rest of this entry »

Effect of Dobutamine on Lung Microvascular Fluid Flux in Sheep with “Sepsis Syndrome”: Experimental ProtocolExperimental Protocol
Baseline studies were performed over a 120-minute period approximately three to four days after recovery from preliminary surgery. Pulmonary lymph was collected and measured for volume every 15 minutes; lymph was pooled at the end of the two-hour baseline period for measurement of total protein and albumin. At the midpoint of this baseline “nonseptic” study, we measured systemic and pulmonary arterial pressures, as well as cardiac output. Blood was drawn from the arterial line and distal port of the right-heart catheter for chemical analysis, hematologic studies, and measurement of arterial and central venous blood gas levels. Dobutamine (500 mg dissolved in 500 ml of 5 percent dextrose in water) was then sequentially administered at two doses (5μg/kg/min and 10μg/kg/ min) for a 60-minute infusion period with each. The first 15 to 30 minutes of infusion at each dose represented a period of equilibration. Pulmonary lymph was collected and measured for volume during each of the last two 15-minute periods of infusion; it was subsequently pooled for measurement of total protein and albumin. Blood was drawn for hematologic studies, chemical analysis, and blood gas levels at the end of each of the last two 15-minute periods of infusion. We also repeated measurement of the cardiac output, and systemic and pulmonary arterial pressures at the same time. Therefore, values reported during infusion of the drug at both doses represent the average of two measurements obtained during two timed 15-minute periods of collection.
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Experimental Preparation
Ten mature Suffolk sheep, weighing 30 to 40 kg (0.9 to 1.2 m2 of body surface area), were prepared with chronic lymph fistulae using a modification of the technique described by Staub et al. Before study the sheep were premedicated with atropine sulfate and were then anesthetized and intubated. We cannulated the aorta with a nonheparinized Silastic catheter (medical grade tubing; 0.125 outer diameter; Dow Corning) and the pulmonary artery with a No. 8 French, right-heart flow-directed thermodilution catheter (Edwards model 93A-131). The right-heart catheter position was confirmed by the presence of typical pressure recordings. With the balloon inflated, a pulmonary arterial wedge tracing was documented. The balloon was then deflated, and the catheter was flushed for the duration of the experiment with a continuous infusion of 5 percent dextrose in water, to which 1,000 units of heparin had been added (1.0 ml/hr). Read the rest of this entry »

Dobutamine had no net effect on pulmonary fluid flux in the nonseptic studies. In contrast, its effects in the septic state were inconsistent. At a dose of 5μg/kg/ min, a modest (24 percent) increase in QL was demonstrable when compared to baseline, while no significant change was evident with the 10μLg/kg/min dose; with an increase in QL, [L/P]TP ratios fell. Reasons for an increase in QL at the lower infused dose might include an effect of dobutamine to increase either the Pmv2 or the surface area of the lung s microvasculature across which fluid exchange occurs. Since we found no relationship between changes in cardiac output and Ql, we would conclude that changes in surface area were not likely to be responsible for the slight increase noted in QL Therefore, the data are most consistent with an interpretation that a “hydrostatic” effect was primarily responsible for the changes documented in pulmonary QL with low-dose dobutamine infusion. Since the pulmonary arterial wedge pressure was significantly elevated from baseline at this dose, without any concurrent change in the left atrial pressure, it is conceivable that a pressure gradient was established between the left atrium and the lungs microvascular exchanging membrane, and that such was thereby responsible for the modest increase in QL observed during low-dose dobutamine infusion. Read the rest of this entry »

Effect of Dobutamine on Lung Microvascular Fluid Flux in Sheep with “Sepsis Syndrome”: Lungs microvascularSince dobutamine has been recommended as an adrenergic receptor agonist which might be used in preference to dopamine when systemic flows require pharmacologic support in ARDS, we studied its effects on fluid flux in an animal model of peritonitis which is characterized by lung microvascular injury. This model seems more representative of early clinical sepsis than are endotoxic models, since it is characterized by a high systemic flow and low peripheral resistance state, with maintenance of systemic pressures. We evaluated the effects of dobutamine on microvascular fluid exchange in the lung of chronically cannulated sheep by using changes in the magnitude of Ql to reflect changes in water flux and using changes in the CLP to represent changes in protein flux. Read the rest of this entry »

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