American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Aug 1995
Effects of an antibody to interleukin-5 in a monkey model of asthma.
To investigate the role of interleukin-5 (IL-5) on airway hyperreactivity and pulmonary inflammation in nonhuman primate airways, the effect of a neutralizing monoclonal antibody to murine IL-5 (TRFK-5) was investigated in a cynomolgus monkey model of allergic asthma. Anesthetized Ascaris-sensitive monkeys underwent bronchoalveolar lavage (BAL) to assess the granulocyte content of this fluid before and 24 h after aerosolized Ascaris suum extract inhalation. Airway reactivity was assessed by the concentration of inhaled histamine required to produce a 40% reduction in dynamic lung compliance (Cdyn40). ⋯ In contrast, only small nonsignificant changes in airway reactivity and granulocyte influx into the BAL occurred after aerosolized saline as a sham challenge. When the monkeys were treated 1 h before Ascaris challenge with the TRFK-5 antibody (0.3 mg/kg, intravenously), there was no increase in airway reactivity after Ascaris challenge (Cdyn40 = 0.032 +/- 0.016% before Ascaris; Cdyn40 = 0.217 +/- 0.196% after Ascaris) and there were only small increases in the number of eosinophils and neutrophils in the BAL after Ascaris challenge. The inhibition of this pulmonary eosinophilia and bronchial hyperresponsiveness by TRFK-5 was seen for up to 3 mo after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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Total venous return decreases with positive end-expiratory pressure (PEEP). It is likely that the liver plays an important role in this response, either through the development of an increase in venous resistance or through an increase in the venous backpressure at the outflow end of the liver. In addition, hepatic arterial flow is reported to be selectively decreased by the application of PEEP. ⋯ Ppvback and right atrial pressure (Pra) increased equally (from 5.1 +/- 0.3 to 9.9 +/- 0.4 mm Hg, p < 0.05, and from 4.0 +/- 0.2 to 8.6 +/- 0.5 mm Hg, p < 0.05, respectively, at PEEP 15). The reduction in portal venous flow was related to an increase in the backpressure to flow (as a result of an increase in Pra) and to an increase in liver venous resistances that may cause blood pooling in the splanchnic compartment and decrease venous return through the liver. PEEP increased Phaback (from 11.2 +/- 0.9 to 14.5 +/- 0.7 mm Hg at PEEP 15, p < 0.05) but did not change hepatic arterial resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
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The aim of the study was to determine whether closing pressures or vascular distensibility can be used to describe liver venous hemodynamics when right atrial pressure is raised. The study was performed using a vascularly isolated pig liver preparation that allowed the independent control of portal vein and hepatic artery inflows and of outflow pressure (Pout). Pressure-flow (P-Q) relationships of both liver vessels were generated at multiple levels of Pout. ⋯ The behavior of the liver vein system is characterized by a zero flow pressure mimicking a classic vascular waterfall and by distensibility, once the waterfall is exceeded. Both factors act to minimize the reduction in venous return with an increased central venous pressure. Flow through the hepatic artery is affected by an increase in backpressure occurring upstream from the sinusoids, reducing arterial inflow for a constant perfusion pressure.
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Am. J. Respir. Crit. Care Med. · Aug 1995
Role of nitric oxide in endotoxin-induced metabolic and vascular dysregulation of the canine diaphragm.
We assessed the role of nitric oxide (NO) in the regulation of diaphragmatic O2 uptake (Vo2di) and phrenic vascular resistance during endotoxemia in anesthetized, mechanically ventilated dogs. Left diaphragmatic vasculature was isolated and briefly pump perfused with arterial blood at a normal flow rate, at a high rate (50% higher than normal), and at low rat (60 to 70% lower than normal). At each rate, Vo2di and phrenic perfusion pressure (Pphr) were measured. ⋯ Serum arterial and phrenic venous NO concentrations measured in separate groups of animals increased significantly after endotoxin infusion, whereas saline infusion had no effect on these parameters. These results indicate that enhanced NO release plays a significant role in endotoxin-induced phrenic and systemic vasodilation. However, the increase in Vo2di in the endotoxin group does not seem to be mediated by NO release.