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Biomedical subjects

T N Hansen

Publications and source records attributed to T N Hansen.

At least 55 records · Page 3Linked to original sources

Effect of cooling rate on the survival of larvae, pupariation, and adult emergence of the gallfly Eurosta solidaginis.

Freeze-tolerant third instar larvae of the gallfly Eurosta solidaginis were cooled at 10, 5, 1, and 0.1 degrees C min-1 to -40 degrees C and then warmed to +5 degrees C at 1 degree C min-1. After cooling and warming the larvae were transferred to 21 degrees C and the survival of larvae, success of pupariation, and adult emergence were monitored at daily intervals in comparison to an uncooled control sample. The percentage emergences of flies from larvae cooled at 10, 5, 1, and 0.1 degree C min-1 and in the control were 7, 13, 37, 77, and 67%, respectively. A number of flies in each group emerged with malformed (unextended) wings and an unretracted ptilinum on the head capsule. The percentage emergences of normal flies at the four cooling rates and from the control were 3, 0, 17, 47, and 57%. At 48 hr after exposure all larvae in each treatment were alive. First mortality was observed between 48 and 72 hr after cooling and increased with time at each cooling rate. Mortality was apportioned into four phases of development: larva, pupariation, and early and late pupae. Mortality commenced earlier at the faster cooling rates; at 10 degrees C min-1, 37% of the sample died as larvae and a further 20% failed to complete pupariation, whereas at 0.1 degree C min-1, only 3% died as larvae and 97% formed a puparium.

Animals↗

Effects of arginine vasopressin on hemodynamics and lung fluid balance in lambs.

The purpose of this project was to study the effects of increased plasma concentrations of arginine vasopressin (AVP) on hemodynamics and lung fluid balance in lambs. We studied 16 unanesthetized newborn lambs during a base-line period and while infusing AVP into a hindlimb vein at 1.65 +/- 0.12 and 2.98 +/- 0.15 mU.kg-1.min-1. We measured aortic, pulmonary arterial, and left atrial pressures and heart rate continuously and cardiac output at frequent intervals. In five additional experiments, we collected samples of pure lung lymph during a base-line period and while infusing AVP at 2.02 +/- 0.15 mU.kg-1.min-1. AVP infusion increased plasma concentrations of AVP to 11.3 +/- 5.2 and 19.9 +/- 5.2 microU/ml at the low and high rates of infusion, respectively. Both aortic and left atrial pressures increased at the low rate of infusion (11 and 3 Torr, respectively) but remained unchanged at the higher rate. Systemic vascular resistance increased, and heart rate and cardiac output decreased at each rate of infusion. In fact, at the higher rate of infusion cardiac output decreased 38% when compared with base line. Neither pulmonary artery pressure nor pulmonary vascular resistance was affected by infusion of AVP. Despite the increase in left atrial pressure, the rate of lung lymph flow was not affected by the infusion of AVP, whereas the lymph-to-plasma protein ratio decreased slightly but significantly from 0.64 +/- 0.02 to 0.60 +/- 0.02.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cimetidine reduces hyperoxic lung injury in lambs.

We previously reported that pretreatment with endotoxin significantly reduced acute pulmonary O2 toxicity in lambs (J. Appl. Physiol. 65: 1579-1585, 1988). One of endotoxin's many effects is to inhibit cytochrome P-450 mono-oxygenation reactions, which are believed to produce toxic O2 species. Therefore, one possible explanation for endotoxin's beneficial effect is that it inhibited P-450-mediated O2 radical production during hyperoxia. To test this hypothesis, we administered a single dose of cimetidine, a noncompetitive inhibitor of P-450 activity, to nine lambs before continuous exposure to greater than 95% O2. Compared with six control O2-exposed lambs, the cimetidine-treated O2-exposed lambs maintained normal gas exchange for a longer period of time (P less than 0.01), accumulated lung water at a slower rate (P less than 0.01), and had normal microvascular permeability after 72 h of O2 exposure. Postmortem levels of antioxidant enzymes in blood-free lung homogenate were not increased in cimetidine-treated lambs. However, the levels of oxidized glutathione were significantly lower in cimetidine-treated lambs, and the ratio of reduced to oxidized glutathione concentrations (GSH/GSSG ratio) was sevenfold higher than the ratio measured in control O2-exposed lambs (P less than 0.001). In four lambs, pretreatment with ranitidine (a drug chemically related to cimetidine but without P-450 inhibitory activity) had no effect either on the time course of O2 injury or on postmortem antioxidants. Microsomes were isolated from blood-free lung of all study animals and P-450 activity of the form 2 isozyme was measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of alkalosis on hypoxia-induced pulmonary vasoconstriction in lungs of newborn rabbits.

The purpose of this study was to determine whether metabolic and respiratory alkalosis reduce hypoxia-induced pulmonary vasoconstriction in lungs of newborn rabbits. To accomplish this, we isolated and perfused with blood the lungs from 33 newborn rabbits, 3-14 d old. In all pairs of lungs, we first measured the magnitude of hypoxia-induced pulmonary vasoconstriction at a pH of 7.30-7.42. We then measured the effect of alkalosis on the magnitude of hypoxic pulmonary vasoconstruction by following one of two different sequences of exposure to hypoxia and alkalosis. For the first sequence, we exposed 13 lungs to hypoxia, and during the hypoxic exposure we either decreased the inspired PCO2 (respiratory alkalosis, n = 8) or infused NaHCO3 (metabolic alkalosis, n = 5) to achieve a pH of 7.50-7.65. For the second sequence, we first decreased the inspired PCO2 (n = 9) or infused NaHCO3 (n = 11) to achieve a pH of 7.50-7.65 and then exposed the lungs to hypoxia. We found that hypoxic pulmonary vasoconstriction was reduced by either respiratory or metabolic alkalosis, when alkalosis was induced during hypoxia. When respiratory or metabolic alkalosis was induced before hypoxia, the magnitude of hypoxia-induced pulmonary vasoconstriction was the same as at the normal pH. We conclude that both metabolic and respiratory alkalosis reduce ongoing hypoxic pulmonary vasoconstriction in lungs of newborn rabbits. However, neither mode of alkalosis blunts pulmonary vasoconstriction in response to subsequent exposures to hypoxia.

Alkalosis↗

Effects of an aorticopulmonary shunt on lung fluid balance in the young lamb.

We studied the effects of increased pulmonary blood flow on lung fluid balance in seven chronically instrumented lambs (18 +/- 1 d) with surgically created aorticopulmonary shunts. We measured mean pulmonary arterial and left atrial pressure (LAP), pulmonary blood flow, lung lymph flow, and lymph (CL) and plasma (CP) protein concentration with the shunt closed and opened. With the shunt partially open, a 35% increase in pulmonary blood flow resulted in an increase in pulmonary arterial pressure (15.5 +/- 1 to 19.5 +/- 1 torr) and LAP (2.0 +/- 0.5 to 3.5 +/- 0.5 torr). Lung lymph flow nearly doubled (1.53 +/- 0.28 to 2.83 +/- 0.52 mL/h) whereas the CL decreased (4.1 +/- 0.1 to 3.4 +/- 0.1 g/dL) resulting in a decrease in the CL/CP ratio (0.67 +/- 0.01 to 0.58 +/- 0.01). With the shunt fully open, pulmonary blood flow increased 65% over baseline, pulmonary arterial pressure increased from 16.5 +/- 2.0 to 26.5 +/- 5 torr, and LAP increased from 1.5 +/- 0.5 to 6.5 +/- 2.0 torr. Lung lymph flow increased (1.1 +/- 0.2 to 3.1 +/- 0.2 mL/h) whereas CL (4.1 +/- 0.1 to 3.1 +/- 0.3 g/dL) and CL/CP (0.66 +/- 0.02 to 0.51 +/- 0.05) decreased. All changes were statistically significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mechanics of the respiratory system during passive exhalation in preterm lambs.

Previous studies have shown large inhomogeneities in the distributions of ventilation and perfusion of newborn infants with hyaline membrane disease. The purpose of this study was to show that measurements of lung mechanics also show evidence of lung inhomogeneities and that a multiple compartment analysis of mechanics gives a more accurate representation of passive exhalation flow and volume than single valued mechanics. We studied 10 sedated preterm lambs (130 d gestation) weighing 2.2 +/- 0.3 kg at 4 h postnatal age. Passive exhalation lung mechanics of the respiratory system were measured by obstructing gas flow near end inhalation then, after pressures within the lung reached equilibrium, allowing the animals to exhale to the atmosphere. Airway pressure and flow signals were monitored by a computer then analyzed using single and multiple compartment analyses. Single compartment analysis of time constant (tau) in s, respiratory system resistance (R) in cm H2O/L/s and quasistatic compliance (C) in mL/cm H2O yielded tau = 0.16 +/- 0.07, R = 92 +/- 17, and C = 1.8 +/- 1.1 (mean +/- SD). Multiple compartment analysis yielded "fast compartment" tau 1 = 0.10 +/- 0.04, R1 = 90 +/- 28, and C1 = 1.1 +/- 0.5 and "slow compartment" tau 2 = 0.25 +/- 0.12, R2 = 503 +/- 288, and C2 = 0.7 +/- 0.6. All of the animals studied exhibited nonlinearity in their flow-volume plots. Calculated flow-volume plots were much more accurately portrayed by the two-compartment analysis than by single valued mechanics. Multiple compartment analysis of lung mechanics may provide useful insight into the pathophysiology of the preterm lab with hyaline membrane disease.

Animals↗

Differential scanning calorimetric analysis of antifreeze protein activity in the common mealworm, Tenebrio molitor.

Antifreeze proteins (AFP) are able to inhibit the growth of ice-crystals at temperatures below the equilibrium freezing point (Tf) of hemolymph. The analysis of AFP activity has commonly involved the use of direct microscopic observation of a sample following inoculation with ice. The resulting activity, defined as the amount of thermal hysteresis observed between Tf and the subsequent rapid growth of ice, has been reported to range up to 7 degrees C. However, most studies report high level of variation, possibly due to ice-crystal size variability and the presence of non-visible ice nuclei. We describe a new method of analysis of AFP activity using differential scanning calorimetry (DSC). DSC analysis reveals much higher activity, up to 10 degrees C, with less variation observed within a sample, and is not subject to the difficulty of accurate assessment of ice-crystal volume.

Animals↗

Pulmonary O2 toxicity in lambs: physiological and biochemical effects of endotoxin infusion.

Hyperoxic adult rats have prolonged survival and reduced morphological evidence of lung injury when treated with a single dose of bacterial endotoxin; this effect is mediated by an augmentation of antioxidant enzyme activity in lung homogenate. To determine whether endotoxin would prolong survival and influence antioxidant enzyme levels in lambs whose physiological response to O2 breathing can be serially measured, we administered a single intravenous dose of endotoxin (0.75 microgram/kg body wt) to 13 lambs before exposing them to greater than 95% O2 (n = 11) or air (n = 2). Seven additional lambs were placed in O2 after receiving only saline vehicle. All lambs had been instrumented to measure pulmonary vascular pressures and cardiac output, and 10 lambs had lung lymph fistulas. O2-exposed control lambs developed noncardiogenic pulmonary edema and respiratory failure within 85 +/- 10 h (range 76-110 h); antioxidant enzymes were not increased, but reduced glutathione (GSH) levels fell and oxidized glutathione (GSSG) increased, reflecting the oxidant stress of O2 exposure. By contrast, endotoxin-treated O2-exposed lambs had a delayed increase in microvascular permeability to protein, a reduced rate of lung edema formation, normal gas exchange after 72 h in O2, and prolonged survival (136 +/- 15 h; range 90-160 h; all variables P less than 0.05). Despite prolonged survival, postmortem lung water content was no greater in the lambs that received endotoxin. Treatment with endotoxin did not increase antioxidant enzyme levels in lung homogenate, but levels of GSH relative to GSSG were significantly elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hypoxic vasoconstriction increases with postnatal age in lungs from newborn rabbits.

Previous studies on the pressor response of the newborn pulmonary circulation to hypoxia have used intact animals and have reported conflicting results. Some have found an increase in responsiveness with increasing age; others have found a decrease. To circumvent many problems inherent in studies of pulmonary vascular reactivity in intact animals, we have developed methods for studying isolated, blood-perfused lungs from newborn rabbits. These methods have been used to study the influence of postnatal age on hypoxic pulmonary vasoconstriction. Two sets of experiments were performed. In the first, a stimulus response curve for hypoxic pulmonary vasoconstriction was constructed, using lungs from 19 rabbit pups that were 3-8 days old. At a constant blood flow, pulmonary artery pressure increased progressively as alveolar oxygen tension decreased so that the maximum increase from baseline (29.4 +/- 4.7%) occurred at PIO2 = 0. The pressor response to hypoxia was highly reproducible, and the entire system remained stable for over 2-3 hours. In the second set of experiments, we compared the pulmonary vascular response to hypoxia obtained using lungs from an additional 21 pups that were 3-8 days old with that obtained using lungs from 23 pups that were 10-14 days old. In response to the same hypoxic stimulus, pulmonary artery pressure increased more in lungs from older rabbit pups (56 +/- 4%) than in lungs from younger rabbit pups (34 +/- 7%) (p less than 0.001). We conclude that isolated perfused lungs from newborn rabbits exhibit a reproducible pressor response to alveolar hypoxia and that this response increases as a function of postnatal age.

Aging↗

The effects of dopamine infusion on regional blood flow in newborn lambs.

The purpose of this project was to investigate the effects of high rates of dopamine infusion on cardiac output and regional blood flow in the lamb. We studied eight unanesthetized newborn lambs (mean age 7 +/- 2 days) during a 15-min baseline period and while infusing dopamine at 5-, 20-, 80-, and 160 micrograms/kg/min. We measured cardiac output and mean aortic, pulmonary arterial and left atrial pressures, and organ blood flow using radionuclide-labeled microspheres at each rate of dopamine infusion. Cardiac output increased significantly with increasing rates of infusion up to 80 micrograms/kg/min but decreased at 160 micrograms/kg/min. Aortic, pulmonary arterial, and left atrial pressures increased at rates of infusion above 5 micrograms/kg/min. Blood flow to all organs was unchanged at the 5 micrograms/kg/min rate of infusion of dopamine while blood flow to the brain and heart increased at the 80 micrograms/kg/min rate of infusion and blood flow to the gut and kidney decreased. We conclude that dopamine is an effective inotropic agent in the newborn lamb but that an inotropic:afterload mismatch exists at high infusion rates. Despite an increase in cardiac output at low rates of infusion, dopamine did not selectively vasodilate the vascular bed of any organs tested. Furthermore, at high rates of infusion dopamine actually impaired blood flow to the gut and kidney.

Animals↗

Is chronic lung disease in low birth weight infants preventable? A survey of eight centers.

Chronic lung disease in prematurely born infants, defined as the need for increased inspired oxygen at 28 days of age, was thought to be more common in some institutions than in others. To test this hypothesis, we surveyed the experience in the intensive care nurseries at Columbia and Vanderbilt Universities, the Universities of Texas at Dallas, Washington at Seattle, and California at San Francisco, the Brigham and Women's Hospital in Boston, Texas Children's Hospital in Houston, and Mt Sinai Hospital in Toronto. The survey included 1,625 infants with birth weights of 700 to 1,500 g. We confirmed the relationship of risk to low birth weight, white race, and male sex. Significant differences in the incidence of chronic lung disease were found between institutions even when birth weight, race, and sex were taken into consideration through a multivariate logistic regression analysis. Columbia had one of the best outcomes for low birth weight infants and the lowest incidence of chronic lung disease.

Bronchopulmonary Dysplasia↗

Effect of hypoproteinemia on lung fluid balance in awake newborn lambs.

To study the influence of plasma protein concentration on fluid balance in the newborn lung, we measured pulmonary arterial and left atrial pressures, lung lymph flow, and concentrations of protein in lymph and plasma of eight lambs, 2-3 wk old, before and after we reduced their plasma protein concentration from 5.8 +/- 0.3 to 3.6 +/- 0.6 g/dl. Each lamb underwent two studies, interrupted by a 3-day period in which we drained protein-rich systemic lymph through a thoracic duct fistula and replaced fluid losses with feedings of a protein-free solution of electrolytes and glucose. Each study consisted of a 2-h control period followed by 4 h of increased lung microvascular pressure produced by inflation of a balloon in the left atrium. Body weight and vascular pressures did not differ significantly during the two studies, but lung lymph flow increased from 2.6 +/- 0.1 ml/h during normoproteinemia to 4.1 +/- 0.1 ml/h during hypoproteinemia. During development of hypoproteinemia, the average difference in protein osmotic pressure between plasma and lymph decreased by 1.6 +/- 2 Torr at normal left atrial pressure and by 4.9 +/- 2.2 Torr at elevated left atrial pressure. When applied to the Starling equation governing microvascular fluid balance, these changes in liquid driving pressure were sufficient to account for the observed increases in lung fluid filtration; reduction of plasma protein concentration did not cause a statistically significant change in calculated filtration coefficient. Protein loss did not influence net protein clearance from the lungs nor did it accentuate the increase in lymph flow associated with left atrial pressure elevation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Optimal constant positive airway pressure assessed by arterial alveolar difference for CO2 in hyaline membrane disease.

In a group of infants with hyaline membrane disease, the level of optimal constant positive airway pressure (CPAP) was assessed by raising CPAP in small steps from an initial low value, and after each change measuring the arterial alveolar difference for CO2 (aADCO2) and transmission of airway pressure to the esophagus. Below optimal CPAP there was a progressive increase in mixed alveolar partial pressure of CO2 (PACO2) and no change in arterial partial pressure of CO2 (PaCO2), so that aADCO2 declined and reached a lowest value at optimal CPAP. Correspondingly, transmission of airway pressure increased progressively and reached a highest value at optimal CPAP. Between 1 step below and optimal CPAP, PACO2 rose from 30.9 to 34.0 torr, and aADCO2 declined from 16.6 to 12.7 torr. Between optimal and 1 step above optimal CPAP, PaCO2 increased from 46.7 to 51.0 torr, PACO2 rose slightly, and aADCO2 increased from 12.7 to 15.6 torr. Thus, the aADCO2 was an excellent index of optimal CPAP. In five patients with measurements of PaO2 at constant fractional inspired oxygen, calculated values for arterial oxygen saturation changed from 80.8 to 91.5 to 92.2%, and calculated values for venous admixture changed from 0.61 to 0.48 to 0.46 as CPAP was raised from 1 step below through optimal to 1 step above optimal CPAP. The results are interpreted to mean a progressive improvement in perfusion of well ventilated lung units as CPAP increased to optimal levels, but a significant reduction of both ventilation and perfusion above optimal CPAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Dioxide↗

Effects of dopamine and nifedipine infusions on the pulmonary circulation of the lamb.

The purpose of this study was to test the hypothesis that nifedipine when given with dopamine will lower pulmonary vascular resistance in hypoxic lambs without altering systemic vascular resistance. We studied six unanesthetized lambs (ranging in age from 13 to 35 days) as they breathed air or on a separate day as they breathed 10% O2 and 3% CO2 in nitrogen. First, we infused dopamine at progressively higher rates (10, 20, 40, 80, and 160 micrograms/kg/min) while measuring mean aortic, pulmonary arterial, and left atrial pressures and heart rate continuously and cardiac output and arterial blood gas tensions at frequent intervals. Then, while maintaining the dopamine infusion at 160 micrograms/kg/min, we infused boluses of nifedipine intravenously (10 micrograms/kg) every 5 min until a cumulative dose of 50 micrograms/kg had been administered. In both groups of lambs, cardiac output increased with increasing rates of dopamine infusion (baseline to maximum dopamine: 260 +/- 20 ml/kg/min to 420 +/- 60 ml/kg/min for normoxic lambs and 400 +/- 50 ml/kg/min to 560 +/- 80 ml/kg/min for hypoxic lambs). While systemic vascular resistance and pulmonary vascular resistance did not change significantly in either group during dopamine infusion, the ratio of pulmonary vascular resistance to systemic vascular resistance increased at low rates of infusion and decreased at high rates. The peak in this ratio occurred at a rate of infusion of 20-40 micrograms/kg/min in normoxic lambs and 40-80 micrograms/kg/min in hypoxic lambs. Infusion of nifedipine did not affect cardiac output in normoxic lambs but decreased it significantly in hypoxic lambs. Nifedipine infusion did not affect pulmonary vascular resistance in the normoxic lambs and increased pulmonary vascular resistance in the hypoxic lambs. We conclude that nifedipine, even when given with high doses of dopamine, is not a specific pulmonary vasodilator.

Acidosis↗

Hypoxia and angiotensin II infusion redistribute lung blood flow in lambs.

To assess the effects of alveolar hypoxia and angiotensin II infusion on distribution of blood flow to the lung we performed perfusion lung scans on anesthetized mechanically ventilated lambs. Scans were obtained by injecting 1-2 mCi of technetium-labeled albumin macroaggregates as the lambs were ventilated with air, with 10-14% O2 in N2, or with air while receiving angiotensin II intravenously. We found that both alveolar hypoxia and infusion of angiotensin II increased pulmonary vascular resistance and redistributed blood flow from the mid and lower lung regions towards the upper posterior region of the lung. We assessed the effects of angiotensin II infusion on filtration pressure in six lambs by measuring the rate of lung lymph flow and the protein concentration of samples of lung lymph. We found that angiotensin II infusion increased pulmonary arterial pressure 50%, lung lymph flow 90%, and decreased the concentration of protein in lymph relative to plasma. These results are identical to those seen when filtration pressure increases during alveolar hypoxia. We conclude that alveolar hypoxia and angiotensin II infusion both increase fluid filtration in the lung by increasing filtration pressure. The increase in filtration pressure may be the result of a redistribution of blood flow in the lung with relative overperfusion of vessels in some areas and transmission of the elevated pulmonary arterial pressure to fluid-exchanging sites in those vessels.

Angiotensin II↗

Inspiratory airway obstruction does not affect lung fluid balance in lambs.

The purpose of this study was to examine the effects of inspiratory airway obstruction on lung fluid balance in newborn lambs. We studied seven 2- to 4-wk-old lambs that were sedated with chloral hydrate and allowed to breathe 30-40% O2 spontaneously through an endotracheal tube. We measured lung lymph flow, lymph and plasma protein concentrations, pulmonary arterial and left atrial pressures, mean and phasic pleural pressures and airway pressures, and cardiac output during a 2-h base-line period and then during a 2- to 3-h period of inspiratory airway obstruction produced by partially occluding the inspiratory limb of a nonrebreathing valve attached to the endotracheal tube. During inspiratory airway obstruction, both pleural and airway pressures decreased 5 Torr, whereas pulmonary arterial and left atrial pressures each decreased 4 Torr. As a result, calculated filtration pressure remained unchanged. Inspiratory airway obstruction had no effect on steady-state lung lymph flow or the lymph protein concentration relative to that of plasma. We conclude that in the spontaneously breathing lamb, any decrease in interstitial pressure resulting from inspiratory airway obstruction is offset by a decrease in microvascular hydrostatic pressure so that net fluid filtration remains unchanged.

Airway Obstruction↗

Effect of endotoxin on lung fluid balance in unanesthetized sheep.

We used a gravimetric technique to test for increased pulmonary capillary permeability after Escherichia coli endotoxin infusion in unanesthetized sheep. The sheep were chronically prepared with cannulas placed into the left atrium and pulmonary artery 1-2 wk before the experiments. We estimated pulmonary capillary pressure (Pc) as the average of pulmonary arterial and left atrial pressures, and used the modified method of Pierce to estimate the ratio of extravascular fluid weight (EVF) to blood-free dry weight. In 15 sheep we inflated a left atrial balloon to raise Pc to -10.7, 5, 10, or 15 mmHg above plasma oncotic pressure (IIc) for 3 h, then measured EVF. EVF averaged 4.0 +/- 0.2 (base line), 4.3 +/- 0.1, 4.5 +/- 0.1, and 5.1 +/- 0.5 (SD), respectively, for the four levels of Pc - IIc. We gave seven additional sheep 1 microgram/kg of E. coli endotoxin (0127:B8) and measured EVF after 3 h of stable Pc. Endotoxin increased Pc in each sheep. EVF was higher than control for the endotoxin sheep with Pc - IIc greater than -1. This finding is consistent with an increase in pulmonary capillary permeability caused by endotoxin. However, EVF was not elevated in the endotoxin sheep with Pc - IIc less than 1 mmHg. This shows that the increased permeability was insufficient to cause edema unless Pc was elevated. Thus endotoxin may cause edema by two mechanisms, 1) an increase in capillary permeability, and 2) an increase in Pc.

Animals↗

Effects of asphyxia on lung fluid balance in baby lambs.

The purpose of this study was to assess the effects of combined hypoxia and hypercapnia and of severe asphyxia on lung water balance and protein transport in newborn lambs. We studied ten 2-4-wk-old anesthetized lambs which were mechanically ventilated first with air for 2-3 h, then with 10-12% oxygen in nitrogen for 2-4 h, and then with 10-12% oxygen and 10-12% carbon dioxide in nitrogen for 2-4 h. Next we stopped their breathing for 1-2 min to produce severe asphyxia, after which we followed their recovery in air for 2-4 h. In 5 of the 10 lambs we intravenously injected radioactive albumin and measured its turnover time between plasma and lymph during the baseline period and after recovery from asphyxia. During alveolar hypoxia alone, mean pulmonary arterial pressure increased 60% and lung lymph flow increased 74%, whereas lymph protein concentration decreased from 3.47 +/- 0.13 to 2.83 +/- 0.15 g/dl. Cardiac output, left atrial pressure, and plasma protein concentration did not change. When carbon dioxide was added to the inspired gas mixture, pulmonary arterial pressure increased 22%, cardiac output increased 13%, lung lymph flow increased 33%, and lymph protein concentration decreased from 2.83 +/- 0.15 to 2.41 +/- 0.13 g/dl. Left atrial pressure and plasma protein concentration did not change. After 60-90 s of induced asphyxia, vascular pressures and lung lymph flow rapidly returned to values the same as those obtained during the baseline period. The turnover time for radioactive albumin between plasma and lymph was the same between the baseline and recovery periods (185 +/- 16 vs. 179 +/- 12 min). The ratio of albumin to globulin in lymph relative to the same ratio in plasma did not change during any phase of these experiments. Five lambs killed after recovery from asphyxia had significantly less blood and extravascular water in their lungs than control lambs had. We conclude that in the newborn lamb both alveolar hypoxia and alveolar hypoxia with hypercapnia increase lung lymph flow by increasing filtration pressure in the microcirculation, but neither hypoxia with hypercapnia nor brief severe asphyxia alters the protein permeability of the pulmonary microcirculation.

Animals↗