Regional pulmonary blood flow in the lung of the chicken.

It is known that alterations in respiratory gases in birds can cause a nonhomogenous redistribution of pulmonary blood flow between the 2 separate gas-exchanging regions of the avian lung, the paleopulmo (PALEO) and neopulmo (NEO); however, the effect of alterations in respired gas content on the distribution of pulmonary blood flow in birds, such as the chicken, that possess a highly developed NEO is not known. This study used a colorimetric microsphere method to determine the effects of hypoxia and hypercapnia on the relative distribution of pulmonary blood flow in anesthetized chickens (Gallus domesticus) during control (normoxic) and experimental (hypoxic or hypercapnic) conditions, where the relative regional distribution of blood flow in the lung is expressed as the ratio NEO/PALEO. Administration of a hypoxic gas mixture (16.0% O(2)) produced a 13.4% increase in NEO/PALEO, and, administration of a hypercapnic gas mixture (5.0% CO(2)) resulted in a 27.8% increase in NEO/PALEO. Our results are consistent with a mechanism in which the regional redistribution of pulmonary blood flow is mediated by local intrapulmonary factors.

Comparison of afferent and efferent lung lymph in the sheep.

Efferent lymph collected from the caudal mediastinal lymph node (CMN) in the sheep lung lymph fistula model has been reported to represent free pulmonary interstitial fluid. Studies that utilize this model assume that nodal transit does not alter the composition of lymph. We collected afferent lymph from the tracheobronchial node (TBN) while simultaneously collecting CMN efferent lymph in acutely prepared sheep. We compared afferent and efferent lymph protein concentrations (CA and CE) and changes in flow rates (QLA and QLE) during base line and periods of elevated left atrial pressure (Pla). As a result of elevated Pla, QLA and QLE increased and the afferent lymph-to-plasma protein concentration ratio (CA/Cp) and the efferent lymph-to-plasma protein concentration ratio (CE/Cp) fell. The CA/Cp was significantly lower than the CE/Cp during base line (0.67 vs. 0.80) and periods of elevated Pla (0.41 vs. 0.61). Although we cannot exclude regional permeability differences, the difference between CA/Cp and CE/Cp is most likely due to the concentration of lymph within the CMN. Our data suggest nodal modification of CA is correlated with the afferent lymph-to-plasma colloid osmotic pressure ratio (pi A/pi p) and further suggest that nodal alteration of lymph during elevated Pla is due to the influence of decreased pi A/pi p at the blood-to-lymph barrier. We conclude that afferent lymph is a more accurate representation of lung free interstitial fluid because collection of pulmonary afferent lymph obviates the complications introduced by the CMN. Studies utilizing efferent lymph may have overestimated lung microvascular permeability in the acute sheep preparation.

Response of air sac mesothelium to expansion of extracellular fluid volume in Gallus domesticus.

In this study, scanning electron microscopy was used to examine the effects of hydrothorax on the morphology of the air sac visceral mesothelium of Gallus domesticus. Anaesthetized chickens were subjected to acute hydrodynamic pulmonary oedema induced by expansion of the extracellular fluid volume with an infusion of Ringer's solution equal to 6.5% of body weight. Tissue samples from the visceral surface of the abdominal air sacs near their ostia were obtained and fixed after death induced by anaesthetic overdose. These were compared with similar samples from control "non-volume-loaded" birds. The air sac visceral mesothelium of the volume-loaded animals presented an increased density of bulbous or swollen microvilli. These deformations were similar to changes reported in the visceral pleura of mammals subjected to hydrothorax, suggesting a commonality with regard to the role of these mesothelia in liquid clearance during pulmonary oedema.

Effect of extracellular fluid volume expansion on the interparabronchial septum of the avian lung.

Scanning electron microscopy was used to examine the interparabronchial septa of chickens as a potential site of lymphatic drainage in the avian lung. Anaesthetized chickens were subjected to extracellular fluid volume expansion to produce pulmonary oedema as a result of increased capillary fluid flux into the interstitial spaces of the lung. In normal (control) chickens, the adjacent parabronchi were separated by a minimal septal space. In the "volume-loaded" birds, however, the interparabronchial septal spaces were measurably thickened and engorged as a result of hydrostatic pulmonary oedema. These results, which were consistent with reports of the effect of hydrostatic pulmonary oedema in mammals, suggest that the interparabronchial septum is a potential route of lymphatic drainage in the avian lung.

Equilibration of intravascular albumin with lung lymph in unanesthetized sheep.

In 16 unanesthetized sheep with chronic lung lymph fistulas we measured pulmonary vascular pressures, lymph flow, lymph and plasma total protein and albumin concentration. We determined the rate of equilibration of radioiodinated albumin between plasma and lung interstitial fluid (lung lymph) in three steady-state conditions; baseline (n = 14), increased pulmonary microvascular pressure (n = 9) and increased microvascular permeability (n = 4). The tracer protein equilibration proceeded according to single compartment wash-in kinetics in all experiments. Lung lymph flow averaged 5.3 +/- 2.8 (S.D.)ml/h under baseline conditions, 16.1 +/- 10.6 ml/h during increased pressure and 37.3 +/- 29.4 ml/h during increased permeability. The half time of equilibration averaged 2.9 +/- 1.0 h, 2.2 +/- 1.0 h and 0.7 +/- 0.2 h, respectively. Lung interstitial fluid equilibrates with plasma proteins more rapidly than most other organs. The marked difference between increased permeability and the other conditions demonstrates the sensitivity of this method. No evidence was obtained that any tracer protein entered lung lymph within the caudal mediastinal lymph node.

Vascular responses in the equine digit.

The digital circulation was isolated in 12 ponies under pentobarbital anesthesia. Blood flow was either controlled by a pump or measured under natural perfusion. The responses to rapid changes and stoppages of blood flow indicated no evidence of autoregulation or reactive hyperemia. Local administration of acetylcholine, histamine, and prostaglandins E1 and E2 decreased prevenous resistance, whereas epinephrine and serotonin caused prevenous constriction. Large doses of epinephrine and serotonin decreased venous caliber. The effects of prostaglandins A1 and F2alpha were variable. The equine digital vasculature responds to changes in flow and to vasoactive agents like the canine forelimb skin vasculature.

Effect of hydrostatic pulmonary edema on the interparabronchial septum of the chicken lung.

Scanning electron microscopy (SEM) was utilized to examine the interparabronchial septum as a potential site of lymphatic drainage in the lungs of anesthetized chickens (Gallus domesticus). Birds were subjected to extracellular fluid volume expansion in order to produce hydrostatic pulmonary edema via increased pulmonary capillary fluid flux into the interstitial spaces of the lung. Micrographs obtained from freeze-dried lungs of volume-loaded birds were compared with similarly prepared lungs from normal control chickens, which were not volume loaded. The adjacent parabronchi of the control lungs were closely opposed by a minimal septal space, whereas the interparabronchial septal space of the volume-loaded birds was measurably thickened and appeared to be engorged as a result of hydrostatic pulmonary edema. The results of this study are consistent with observations of the lungs of mammals subjected to hydrostatic pulmonary edema and suggest that the interparabronchial septum may be a potential route of lymphatic drainage in the avian lung.

Effects of Monastral blue on pulmonary arterial blood pressure and lung and liver particle retention in chickens.

The effects of intravenous administration of the vascular tracer Monastral blue (MB) on pulmonary arterial blood pressure and the retention of MB by lung and liver were assessed in anesthetized White Leghorn cocks. Pulmonary arterial blood pressure and systemic blood pressure were measured by direct cannulation. Administration of MB alone had no effect on either pulmonary arterial blood pressure or systemic arterial blood pressure; however, following pretreatment with endotoxin (ENDO), infusion of MB caused a rapid and transient increase in pulmonary arterial blood pressure. Histological examination of lungs and liver from these animals showed a greater accumulation of MB in liver than in lung, in which virtually no MB was observed by light microscopy. The relative amounts of MB in lung and liver were measured by atomic emission spectrophotometry in animals given MB alone and following ENDO pretreatment. In either case the total amount of MB retained by the lungs was less than 2% of the injected dose, whereas liver retention of MB was approximately 88% in those birds given MB alone and 80% in those pretreated with ENDO. The results of this study suggest that chickens do not possess reactive pulmonary intravascular macrophages (PIMS), as, in those species in which reactive PIMS are present, injection of MB alone causes a marked increase in pulmonary arterial blood pressure and substantial lung retention of the tracer.

The efffect of sustained +Gz acceleration on extravascular lung water content in domestic fowl.

In order to examine the effects of sustained acceleration on pulmonary fluid balance, chickens were centrifuged at low sustained +G acceleration (LSG) intensities of +3Gz or +4Gz or high sustained +G acceleration (HSG) at +6Gz for varying periods. Animals were exposed to acceleration on a hydraulic-driven centrifuge. Controls (Group I) were not centrifuged. The vascular lungs were rapidly excised after centrifugation, and the extravascular lung water content (EVLW) was measured. EVLW in Group I animals = 2.19 +/- 0.38 g/g. Results indicate that positive acceleration elevated in animals exposed to +4Gz for 60 min (Group III). In this group, EVLW = 3.01 +/- 1.07 g/g. This increase is largely attributable to an elevated EVLW in those animals which died as a result of centrifugation, in which EVLW = 3.90 +/- 1.04 g/g. Exposure to +3Gz for 120 min (Group II) or +6Gz for periods up to 50 min (Group IV) did not produce significant elevations in EVLW in either group as a whole, but EVLW in those Group II animals which died as a result of centrifugation was significantly elevated. EVLW in these animals = 2.87 +/- 0.21 g/g. We conclude that pulmonary edema caused by centrifugation is dependent on both magnitude and duration of G force.

Regional blood flow in the domestic fowl immediately following chronic acceleration.

In order to examine the effects of chronic low G acceleration on blood flow distribution and cardiac output, chickens (N=10) were centrifuged at +2Gz for 30-61 d. Controls (N=12) were not centrifuged. The animals were anesthetized with sodium pentobarbital after removal from the centrifuge and surgically prepared in order to measure cardiac output and regional blood flows by the reference sample method with 85Sr labeled microspheres (15 +/- 5 mum diam.). Both brachial arteries were cannulated to withdraw timed, paired blood samples at a known rate. The chest was opened and a cannula inserted into the left ventricle for administration of microspheres. Tissue samples were taken after completion of experimental procedures and their radioactivity was determined. The cardiac outputs in the two groups were not significantly different. Regional blood flows to the kidney, eyes, and skeletal muscle were significantly increased in the animals subjected to chronic +2Gz. While the mechanism by which these increases in blood flow occurred is not known, results indicate that chronic exposure to hyperdynamic gravitational fields can alter circulatory dynamics. We conclude that the cardiovascular system is directly involved in the process of adaptation to chronic positive acceleration.

Effects of indomethacin on pulmonary hemodynamics and extravascular lung water in sheep after pulmonary microembolism.

Since the role of prostaglandins (PGs) in the response of the lung to pulmonary microembolism is unclear, this study examined the effects of indomethacin (INDO), an inhibitor of PG synthesis, on pulmonary hemodynamics and lung fluid balance in normal sheep and in sheep subjected to pulmonary microembolism. Anesthetized, ventilated ewes were given either INDO (5 mg/kg in saline) or emboli (Sephadex G-25, 0.1 ml/kg in saline) via a cannulated jugular vein. Pulmonary arterial (Ppa) and left atrial (Pla) pressures were measured. The ratio of extravascular lung water content to dry weight of the blood-free lung (Qwl/dQl) was measured. Animals were given either INDO 1 hr prior to embolism (Group IV), emboli only (Group III), INDO only (Group II), or were saline controls (Group I). While INDO had little effect in normal animals, Ppa was significantly attenuated in those pretreated with INDO prior to embolism (Group IV) as compared to those embolized only (Group III), and while Qwl/dQl for Group III was significantly elevated compared to Group I, it was not in Group IV. Results suggest that INDO attenuates the pulmonary hypertension caused by microembolism via inhibition of a vasoconstrictor PG, which may in part mediate embolism-induced edemogenesis.

Low levels of inorganic mercury damage the corneal endothelium.

The effect of inorganic mercury on the integrity of the endothelium of isolated bullfrog (Rana catesbeiana) corneas was examined by spectrophotometric analysis of corneal uptake of the vital stain Janus green, and by both transmission (TEM) and scanning (SEM) electron microscopy. The uptake of Janus green by the endothelium is dose related between 1.0 and 30.0 microM HgCl2. The effect of mercury is not altered by changes in external calcium concentration, nor is it influenced by the calcium ionophore A23187, indicating that inorganic mercury damages the corneal endothelium through a mechanism which does not involve competition with external calcium or interaction with calcium channels. TEM and SEM demonstrate significant ultrastructural damage to the endothelium exposed to inorganic mercury, including cellular swelling, increased vacuolization, focal denuding of Descemet's membrane, and diminished integrity at the intercellular junctions.

A comparison of the effects of aspirin and histamine of fluid balance in the recruited lung.

Salicylate administration has been reported to increase the flow of protein-rich lymph from the lungs of animals, however, the mechanism of this response is unclear. In the present study we measured pulmonary hemodynamics and lung fluid and protein flux in anesthetized sheep, surgically prepared for the collection of lung lymph, in order to examine the possible effect of aspirin (ASP) on lung vascular permeability. ASP was given during recruitment of pulmonary microvascular surface area induced by sustained elevation of left atrial pressure (Pla) (Group 1) or continuous infusion of adenosine triphosphate (ATP) (Group 2). We compared the results of ASP administration to those found in similarly prepared animals given histamine (H) during like periods of increased Pla (Group 3) or ATP infusion (Group 4). ASP administration resulted in increased lymphatic protein clearance (Cp) in both Groups 1 and 2. In Group 1, following the characteristic increase in lung lymph flow (Q1) and fall in the ratio of lung lymph to plasma protein concentration (L/P) produced by Pla elevation, ASP administration resulted in a further increase in Q1 and a significant increase in L/P. The results found in ASP animals are qualitatively similar to those observed in Groups 3 and 4 after H. While we cannot specifically rule out a hemodynamic effect of the drug, our results suggest the increased protein flux observed following ASP administration was mediated at least in part through an increase in lung microvascular permeability.

Effects of temperature and elevated intracranial pressure on peripheral and brain stem auditory responses in dogs.

Far-field recordings of central (P2 through P4) and peripheral (cochlear microphonic; and compound action potential of the eighth nerve) auditory responses were used to assess changes in auditory function resulting from elevated intracranial pressure. Normative data for eight dogs were obtained. The relationship between response latency and core temperature was examined. A mean slope of -0.17 ms/degrees C resulted for the temperature range of 35.0 to 40.0 degrees C. Systemic arterial pressure was measured in order to identify the cerebral ischemic response. Responses were not altered significantly unless the intracranial pressure approached within 15 to 30 mm Hg of mean systemic arterial pressure. Changes in the response consisted of both enhancement and deterioration during intracranial pressure elevation and were accompanied by increases in systemic arterial pressure during that elevation. Supernormal amplitudes of the action potential also occurred during recovery periods. Results suggest that: (i) during elevated intracranial pressure, changes in both central and peripheral auditory function result from ischemia rather than pressure-induced distortion of the cochlea or central neural assemblies. (ii) Far-field auditory responses may include an O2-dependent cochlear microphonic. (iii) An unknown process causing enhancement of central and peripheral neural responses exists and operates in connection with intracranial hypertension. Possible mechanisms underlying enhancement of response components are discussed.

Low levels of cadmium chloride damage the corneal endothelium.

The effect of cadmium chloride on the integrity of the endothelium of isolated bullfrog (Rana catesbeiana) corneas was examined by spectrophotometric analysis of corneal uptake of the vital stain Janus green and by scanning electron microscopy (SEM). The uptake of Janus green by the endothelium was dose related between 1.0 and 100.0 microM CdCl2. The effect of cadmium was significantly attenuated by the calcium channel blocker SKF 96365 and was augmented by the calcium ionophore A23187, indicating that cadmium influx through calcium channels is an important determinant of its cellular effect. The effect of cadmium was not altered by changes in the external calcium concentration, indicating that the mechanism does not involve competitive inhibition by calcium. SEM demonstrated significant structural damage to the corneal endothelium exposed to cadmium chloride, including focal disruption and denuding of the apical endothelial membrane.

Effects of sequential periods of intracranial hypertension on lung fluid balance.

Pulmonary hemodynamics and fluid and protein exchange were examined in dogs subjected to three successive periods of intracranial hypertension. Results indicate that the alteration in lung fluid balance is due to increased microvascular surface area following capillary recruitment. The relationship to the mechanism of neurogenic pulmonary edema is discussed.

Influence of indomethacin on cation excretion after acute unilateral nephrectomy in dogs.

Acute unilateral nephrectomy (AUN) causes functional changes in the remaining kidney. Since renal prostaglandins (PGs) may participate in this response, we investigated the effect of the PG synthetase inhibitor, indomethacin (INDO), on the function of the remaining kidney after AUN. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), filtration fraction (FF), sodium excretion, and potassium excretion were measured for 1 hr prior to and 3 hr after AUN in dogs anesthetized with sodium pentobarbital. Group I and II animals underwent AUN. A third group was sham-operated (Group III). Group I received INDO (2 mg/kg) before and 2 hr after AUN, while Groups II and III received a buffered saline vehicle. AUN alone (Group II) had no effect on GFR, ERPF, FF, or sodium excretion, while potassium excretion was increased. In animals administered INDO prior to AUN (Group I), the increase in potassium excretion was abolished, FF rose and sodium excretion, while potassium excretion was increased. In animals administered INDO prior to AUN (Group I), the increase in potassium excretion was abolished, FF rose and sodifore and 2 hr after AUN, while Groups II and III received a buffered saline vehicle. AUN alone (Group II) had no effect on GFR, ERPF, FF, or sodium excretion, while potassium excretion was increased. In animals administered INDO prior to AUN (Group I), the increase in potassium excretion was abolished, FF rose and sodium excretion was decreased. Results suggest that renal PGs participate in the compensatory response of the remaining kidney to AUN and may specifically play a role in increased cation excretion following AUN.

The effects of temperature and acute alcohol intoxication on brain stem auditory evoked potentials in the cat.

The effects of core temperature changes (less than 1 degree C) and acute ethanol intoxication (100-400 mg%) on brain stem auditory evoked potentials in cats were studied independently--then together--to distinguish between a putative direct pharmacological action of ethanol on brain stem auditory neurons, as reflected in reported BAEP latency changes, and in indirect action of ethanol mediated through slight changes in central temperatures. The results suggest that the reported BAEP latency effects are attributable, largely if not entirely, to the second mechanism above. No significant temperature-independent BAEP latency alterations occurred at any sublethal blood ethanol concentration or in one dosage that subsequently proved fatal. These findings do not exclude a direct ethanol effect on brain stem auditory neurons but provide no evidence for a temperature-independent effect. Knowledge of secondary BAEP temperature effects associated with drug administration is crucial to proper interpretation of BAEPs in both experimental and clinical applications.

Effect of histamine on tracheobronchial afferent and caudal mediastinal efferent lymph.

We prepared nine sheep with acute tracheobronchial afferent (TBN) and caudal mediastinal efferent (CMN) lymph fistulas. After a baseline period (B) in 3 sheep, we administered histamine (H) continuously for 4 h. In six sheep, we elevated left atrial pressure (PLA) and reestablished steady-state conditions prior to H administration. The afferent lymph to plasma protein concentration ratio (CA/CP) was significantly lower than the efferent ratio (CE/CP) during periods of B, H, elevated PLA, and elevated PLA with H. H administration increased lymph flow rates (QlA and QlE) and both CA/CP and CE/CP, albeit insignificantly. During elevated PLA, QlA and QlE increased, while CA/CP and CE/CP fell. QlE increased, while QlA did not change during elevated PLA with H. CE/CP increased from its PLA level. CA/CP did not increase. Afferent data suggest that histamine may increase pulmonary microvascular surface area, but does not alter the permeability of the pulmonary circulation. While we cannot exclude the possibility of an increase in pulmonary microvascular permeability from efferent results, the difference between TBN afferent and CMN efferent results likely represent the action of histamine at the CMN.