To see whether histamine increases lung vascular permeability to protein, we compared the effects of steady-state histamine infusions on lung vascular pressures, lung lymph flow, and lung lymph protein content with the effects of mechanically elevated lung vascular pressures on these variables in the same unanesthetized sheep. We surgically implanted catheters in the pulmonary artery, the left atrium, the superior vena cava, and a main lung lymphatic. After the sheep had recovered from surgery, we carried out steady-state experiments without anesthesia. Histamine induced a dose-related, quickly reversible increase in lung lymph flow without affecting pulmonary artery pressure, and it caused left atrial pressure to fall. During 4-hour intravenous 4-mug/kg min-1 histamine infusions, lymph flow and lymph protein clearance (lymph flow X lymph-plasma protein concentration ratio) increased more than they did with mechanically elevated pressure even though vascular pressures fell. Lymph-plasma protein ratios decreased linearly with increasing lymph flow during increased pressure experiments, but during histamine infusions the ratios did not decrease even though lymph flow increased 2-6-fold. Lymph clearance and permeability-surface area products (PS) for eight protein fractions with molecular radii ranging from 36 to 100 A decreased with increasing molecular size in base-line, increased pressure, and histamine studies. PS values for all eight fractions were significantly higher than base line in histamine experiments but not in increased pressure experiments. Four-hour intravenous histamine infusions caused moderate increases in lung water content. Left atrial infusions had less effect on lymph flow than did intravenous infusions. We conclude that histamine causes pulmonary vascular permeability to protein to increase but that the effects on exchanging vessel porosity are more modest than those suggested for systemic microvessels. Histamine should be considered a possible mediator of increased lung vascular permeability.

To see how serotonin affects filtration from lung vessels, we measured vascular pressures, lung lymph flow, lung lymph and blood plasma protein concentrations, arterial blood gases, cardiac output, and lung water content in unanesthetized sheep before and during intravenous serotonin infusions and compared serotonin effects with the effects of inflating a balloon in the left atrium in the same sheep. Serotonin caused a dose-related increase in lung lymph flow and a dose-related decrease in lymph-plasma protein concentration ratios. Steady-state 4-hour serotonin infusions at 4 j/g/kg min" 1 caused lymph flow to increase from 5.4 ± 0.7 (SE) ml/hour to 8.3 ± 1.3 ml/hour, lymph-plasma albumin ratios to fall from 0.78 ± 0.05 to 0.72 ± 0.04, lymph-plasma globulin ratios to fall from 0.64 ± 0.02 to 0.56 ± 0.02, and pulmonary arterial and left atrial pressures to increase by 3 cm H 2 O each. Lymph clearance and permeability-surface area products for eight protein fractions ranging from 36 A to 96 A in molecular radius during steady-state serotonin infusion studies were not significantly different from those during steady-state increased pressure studies. Four-hour infusions of serotonin at 4 /ig/kg min" 1 caused a moderate fall in arterial Po 2 and a slight increase in arterial pH but did not affect cardiac output or cause pulmonary edema. We conclude that serotonin increases lung transvascular filtration primarily by increasing the transmural pressure gradient in exchanging vessels rather than by increasing vascular permeability. KEY WORDS lung lymph vasoactive mediators pulmonary edema lung water capillary permeability• Increased lung vascular permeability to protein apparently plays an important pathogenetic role in a variety of human diseases in which pulmonary edema occurs without heart failure (1). Such changes in the systemic circulation are mediated by the endogenous release of vasoactive substances (2), and serotonin has been considered to be one of these mediators (3,4). Serotonin is vasoactive in the pulmonary circulation (5-7) and may cause pulmonary edema (8), but the mechanism of its effect on lung fluid dynamics is not clear.We measured the effects of intravenous serotonin infusions on lung vascular pressures and lung lymph flow and protein content in a chronic, unanesthetized sheep preparation. We then compared the serotonin effects with the effects of steady-state mechanical increases in lung vascular pressure in the same sheep. We found that serotonin caused a dose-related increase in lung lymph flow and lymph protein transport and that these This work was supported by U. S. Public Health Service Grant HL 08195 from the National Heart and Lung Institute and by a grant from the Parker B. Francis Foundation.Received January 3, 1975. Accepted for publication March 20, 1975. changes were like those associated with increased left atrial and pulmonary arterial pressures. Methods EXPERIMENTAL PREPARATIONWe prepared sheep by a series of three thoracotomies as described by Brigham et al. (9). We fir...

A B S T R A C T To see whether antihistamines could prevent and reverse histamine-induced pulmonary edema and increased lung vascular permeability, we compared the effects of a 4-h intravenous infusion of 4 /Ag/kg per min histamine phosphate on pulmonary hemodynamics, lung lymph flow, lymph and plasma protein content, arterial blood gases, hematocrit, and lung water with the effects of an identical histamine infusion given during an infusion of diphenhydramine or metiamide on the same variables in unanesthetized sheep. Histamine caused lymph flow to increase from 6.0±0.5 to 27.0±5.5 (SEM) ml/h (P <0.05), lymph: plasma globulin concentration ratio to increase from 0.62±0.01 to 0.67±0.02 (P < 0.05), left atrial pressure to fall from 1+1 to -3±1 cm H20 (P < 0.05), and lung lymph clearance of eight protein fractions ranging from 36 to 96 A molecular radius to increase significantly. Histamine also caused increases in lung water, pulmonary vascular resistance, arterial Pco2, pH, and hematocrit, and decreases in cardiac output and arterial Po2. Diphenhydramine (3 mg/kg before histamine followed by 1.5 mg/ kg per h intravenous infusion) completely prevented the histamine effect on hematocrit, lung lymph flow, lymph protein clearance, and lung water content, and reduced histamine effects on arterial blood gases and pH. 6 mg/kg diphenhydramine given at the peak histamine response caused lymph flow and lymph: plasma protein concentration ratios to fall. Metiamide (10 mg/ Description of the preparation We used an unanesthetized, chronic sheep preparation described previously (1-4). Each animal was prepared by a series of three staged thoracotomies during which nonpulmonary contributions to a large lymph node in the posterior mediastinum (caudal mediastinal node) were resected;

No abstract

No abstract