Increase In Pulmonary Capillary Permeability Research Articles

Increase in pulmonary capillary permeability in dogs exposed to 100% O2.

Changes in pulmonary capillary filtration induced by hyperoxia were investigated in 15 dogs. After 12 h of normobaric hyperoxic exposure, animals were anesthetized and artificially ventilated with 100% O2. A pulmonary lymphatic vessel was cannulated, and lymph flow and protein content were measured together with pulmonary and systemic hemodynamics. An increase in pulmonary capillary filtration was found when compared with reference data (normoxic dogs in similar conditions) gathered from available literature: lymph flow increased from 21.8 +/- 13.4 to 125.2 +/- 131.6 microliter/min, and the lymph-to-plasma protein concentration ratio increased from 0.67 +/- 0.08 to 0.78 +/- 0.08. To characterize the mechanisms involved, left atrial pressure was increased in two stages (approximately 10 and approximately 25 mmHg). The results clearly indicated an increase in pulmonary capillary permeability as evidenced by a decrease of the minimal estimate of the protein reflection coefficient from 0.62 +/- 0.05 to 0.42 +/- 0.05.

Effects of aerosolized methylprednisolone on experimental neurogenic pulmonary injury.

We examined the effects of graded doses of methylprednisolone sodium succinate (MPSS)--0.05 (low), 0.5 (medium), and 5 mg/kg/hour (high)--on the development of neurogenic pulmonary injury in rabbits. The aerosolized drug was administered intratracheally for 5 hours beginning 10 minutes after a 2-minute elevation of the cerebrospinal fluid pressure (Pcsf) to 250 mm Hg. Compared to untreated control animals, the percentage of increase in pulmonary capillary permeability, as determined by 51Cr-labeled ethylenediaminetetraacetic acid clearance, was significantly less in the low and high dose MPSS groups. However, high dose MPSS was also associated with a significant decrease in compliance and increase in tissue hemorrhage (quantified by visual inspection). These results indicate biphasic effect of MPSS on alveolar capillary integrity after elevated Pcsf. The low dose minimized the extent of lung hemorrhage, pulmonary capillary leakage, and loss of lung compliance. In contrast, the high dose accelerated tissue hemorrhage and compliance loss, even though pulmonary capillary permeability was maintained near base line rates.

Effects of aerosolized methylprednisolone on experimental neurogenic pulmonary injury

We examined the effects of graded doses of methylprednisolone sodium succinate (MPSS)—0.05 (low), 0.5 (medium), and 5 mg/kg/hour (high)—on the development of neurogenic pulmonary injury in rabbits. The aerosolized drug was administered intratracheally for 5 hours beginning 10 minutes after a 2-minute elevation of the cerebrospinal fluid pressure (Pcsf) to 250 mm Hg. Compared to untreated control animals, the percentage of increase in pulmonary capillary permeability, as determined by 51Cr-labeled ethylenediaminetetraacetic acid clearance, was significantly less in the low and high dose MPSS groups. However, high dose MPSS was also associated with a significant decrease in compliance and increase in tissue hemorrhage (quantified by visual inspection). These results indicate biphasic effect of MPSS on alveolar capillary integrity after elevated Pcsf. The low dose minimized the extent of lung hemorrhage, pulmonary capillary leakage, and loss of lung compliance. In contrast, the high dose accelerated tissue hemorrhage and compliance loss. even though pulmonary capillary permeability was maintained near base line rates. (Neurosurgery 19:36-40, 1986)

Increased lung capillary permeability after trauma: a prospective clinical study.

Pulmonary dysfunction and permeability were prospectively studied in a group of severely traumatized patients. Ventilatory parameters (i.e., PaO2/FiO2, dynamic compliance, per cent shunt, and A-a DO2) and extravascular lung water (EVLW) measurements were compared with scintigraphic determinations of pulmonary albumin extravasation. Albumin extravasation data demonstrated a pulmonary capillary permeability increase occurring shortly following trauma. The median albumin extravasation value in the patients within 24 hours of trauma was 3.6 X 10(-5)/sec, compared to a control value of -0.1 +/- 0.7 X 10(-5)/sec. Intermediate levels of albumin extravasation were found in patients studied within 48 hours of total hip replacement (1.6 +/- 0.9 X 10(-5)/sec). Eighty per cent of patients studied within the first 48 hours of their trauma had albumin extravasation values exceeding the upper limit of normal as determined by the control value + 2 S.D. In contrast to albumin extravasation values, the PaO2/FiO2, dynamic compliance, per cent shunt, A-a DO2, and EVLW did not begin to deteriorate significantly until at least 48 hours after trauma. We conclude that severe multiple trauma induces an early increase in pulmonary capillary permeability as measured by albumin extravasation scintigraphy. This change is not detectable with other commonly used measures.

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.

Effect of Escherichia coli endotoxin on dog lung fluid balance

Endotoxin may cause an increase in pulmonary capillary permeability and thus promote edema formation. We used a gravimetric technique to estimate the pulmonary capillary filtration coefficient (KF) and the maximum capillary pressure at which the lung could maintain a constant weight (Pccritical) in dogs after intravenous administration of Escherichia coli (E. coli) endotoxin. KF should be increased and Pccritical should be decreased by an increase in permeability. Four groups of three to four dogs were given 1, 10, 1,000, or 3,000 micrograms/kg of endotoxin. A fifth group of five dogs, which served as controls, was given no endotoxin. KF was significantly (P less than 0.05) greater than control [0.049 +/- 0.031 (SD) ml . min-1 . mmHg-1] in only the 1-micrograms/kg group (0.100 +/- 0.027), indicating a possible increase in permeability. However, changes in capillary surface area may have affected KF. Pccritical was not significantly different from control (20.7 +/- 2.4 mmHg) in any of the E. coli groups. We conclude from these results that E. coli endotoxin may have caused a slight increase in permeability; however, the lung retained its ability to resist edema formation.

Lung water changes after thermal injury. The effects of crystalloid resuscitation and sepsis.

Respiratory failure after thermal injury is common, but the etiologic roles of high volume crystalloid resuscitation, hypoproteinemia, inhalation injury, or sepsis have not been specifically defined in human studies. We used the thermal-green dye double indicator dilution measurement of extravascular lung water (EVLW) to follow daily lung water changes in seven severly burned adult patients, resuscitated with only crystalloid solutions. An average weight gain of 21.3 kg, a 30% increase (p < 0.001), was present two to three days after admission. Admission EVLW for all patients was 7.9 +/- 1.2 ml/kg, (means +/- SD), and EVLW at the time of maximal weight gain was 5.9 +/- 1.4 ml/kg, a 25% decrease (p < 0.05). Admission pulmonary artery wedge pressure (PAWP) was 8 +/- 3 mmHG, which was not significantly different from PAWP of 13 +/- 4 mmHg at the time of maximal weight gain. In the three patients who died of sepsis, their terminal weight averaged 17.8 kg (27%) above their admitting weight (p < 0.01) and EVLW was 26.4 +/- 4.4 ml/kg, a 200% increase (p < 0.02) from admission. Their terminal PAWP averaged 22 +/- 2 mmHg, a 170% increase (p < 0.005). None of these patients had an increase in EVLW until clinical signs of sepsis occurred and the rise in EVLW preceded the rise in PAWP. Calculated mean plasma colloid osmotic pressure (PCOP) on admission was 20.7 +/- 4.9 mmHg; at the time of maximal weight gain, it was 8.6 +/- 1.7 mmHg (p < 0.001). The PCOP-PAWP gradient fell to -4 +/- 4 mmHg (p < 0.001) at the time of maximal weight gain and remained less than +4 mmHg throughout the study period in all patients. We conclude that massive crystalloid resuscitation while maintaining PAWP below 15 mmHg does not cause an increase in EVLW during the first four days after thermal injury. EVLW actually decreases slightly in all patients despite marked weight gain, hypoproteinemia and a negative PCOP-PAWP gradient. EVLW does not correlate with the PCOP-PAWP gradient in either septic or nonseptic periods. Three patients had severe inhalational injury and normal EVLW for the first four postburn days. It therefore appears that significant interstitial edema does not result from inhalational injury. There is also no evidence that thermal injury causes an early increase in pulmonary capillary permeability. The occurrence of sepsis, however, results in rapid accumulation of lung water, without any change in hydrostatic or osmotic forces. This study supports the primary role of sepsis in altering pulmonary capillary permeability with resulting pulmonary edema.

TRANSVASCULAR FLUID AND PROTEIN DYNAMICS IN THE LUNG FOLLOWING HEMORRHAGIC SHOCK

Although many factors have been implicated in the development of the syndrome of post traumatic pulmonary insufficiency, the role of hemorrhagic shock remains in doubt [2]. Several groups have reported hemorrhagic and congestive changes in the lungs of dogs after treatment for hemorrhagic shock [3, 231, but the documentation of any functional pulmonary deterioration has been less impressive [3, 171. A universal finding in post traumatic respiratory insufficiency is an increase in pulmonary extra-vascular water which may appear as either interstitial and/or alveolar pulmonary edema [16]. The most frequently recognized cause of increased pulmonary extra-vascular water is an elevation of pulmonary microvascular pressure due to left ventricular failure. When pulmonary edema occurs in the absence of cardiac failure, it is usually ascribed to either an increase in permeability of the lung capillaries to fluid and protein [19] or to a severe decrease in plasma colloid pressure with altered microvascular driving forces in the Starling Equation of transcapillary exchange which has been shown to apply to the lung [ll]. Some studies have suggested that an increase in pulmonary capillary permeability occurs as a result of hemorrhagic shock [6, 141, while others have failed to observe any changes in the protein transport properties of the pulmonary capillary following a period of hemorrhagic shock [5,9].

PULMONARY CAPILLARY PERMEABILITY—TRANSFUSION LESION

Massive transfusion of bank blood has been implicated as a major etiologic factor in the evolution of pulmonary insufficiency after injury. In spite of the demonstration of significant debris, including aggregates, in stored blood, a precise and reproducible pulmonary effect of transfusion has not previously been demonstrated. Since clinical pulmonary insufficiency is frequently accompanied by increased lung water, these experiments were designed to measure pulmonary capillary permeability and its response to transfusion of blood and blood components in rats. These experiments demonstrate that: 1) the rat lung is a target organ with regard to blood transfusion; 2) the lung lesion with transfusion is attributable, at least in part, to a selective and acute increase in pulmonary capillary permeability; 3) pulmonary capillary permeability is highly responsive to viable platelets; 4) prolonged storage of blood in polyvinyl chloride containers may enhance its ability to induce pulmonary capillary permeability; 5) increased capillary permeability with transfusion is largely eliminated when platelets and buffy coat are eliminated.

Transvascular fluid and protein dynamics in the lung following hemorrhagic shock

Although many factors have been implicated in the development of the syndrome of post traumatic pulmonary insufficiency, the role of hemorrhagic shock remains in doubt [2]. Several groups have reported hemorrhagic and congestive changes in the lungs of dogs after treatment for hemorrhagic shock [3, 231, but the documentation of any functional pulmonary deterioration has been less impressive [3, 171. A universal finding in post traumatic respiratory insufficiency is an increase in pulmonary extra-vascular water which may appear as either interstitial and/or alveolar pulmonary edema [16]. The most frequently recognized cause of increased pulmonary extra-vascular water is an elevation of pulmonary microvascular pressure due to left ventricular failure. When pulmonary edema occurs in the absence of cardiac failure, it is usually ascribed to either an increase in permeability of the lung capillaries to fluid and protein [19] or to a severe decrease in plasma colloid pressure with altered microvascular driving forces in the Starling Equation of transcapillary exchange which has been shown to apply to the lung [ll]. Some studies have suggested that an increase in pulmonary capillary permeability occurs as a result of hemorrhagic shock [6, 141, while others have failed to observe any changes in the protein transport properties of the pulmonary capillary following a period of hemorrhagic shock [5,9].

Neurohemodynamics of pulmonary edema. II. The role of sympathetic pathways in the elevation of pulmonary and stemic vascular pressures following the intracisternal injection of fibrin.

The authors criticize the concept of "neurogenic pulmonary edema" as resulting from an increase in pulmonary capillary permeability mediated by nerve impulses to those vessels. They show that one of the methods used to produce "neurogenic pulmonary edema" markedly elevates systemic and pulmonary vascular pressures, the latter to levels high enough to produce pulmonary edema. Vagotomy and/or upper thoracic sympathectomy do not prevent the elevation of pulmonary vascular pressures. Blockade of the sympathetic innervation to the systemic vascular bed lowers the systemic vascular pressures and brings the pulmonary vascular pressures back to normal. The control of pulmonary vascular pressures by sympathetic impulses to the systemic vascular bed is demonstrated.