Air embolism-induced lung injury in isolated rat lungs

1992 ◽  
Vol 72 (4) ◽  
pp. 1235-1242 ◽  
Author(s):  
D. Wang ◽  
M. H. Li ◽  
K. Hsu ◽  
C. Y. Shen ◽  
H. I. Chen ◽  
...  
Keyword(s):  
Weight Gain ◽  
Lung Injury ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Air Embolism ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Lung Model ◽  
Lung Weight ◽  
Pulmonary Arterial

Pulmonary air embolism causes physical obstruction of microvasculature and leads to permeability changes, release of mediators, and injury to lung tissue. In this study we employed an isolated perfused rat lung model to investigate the primary and secondary effects produced by infusion of air into the pulmonary artery. Infusion of various doses of air (0.10–0.25 ml) over a 1-min period produced a dose-dependent increase in pulmonary arterial pressure and lung weight gain. In contrast, when a constant air dose was administered over various periods of time (0.25 ml over 0.5–8.0 min), the pulmonary arterial pressure rose to the same extent regardless of the infusion rate, whereas the lung weight gain increased proportionately with the rate of infusion. Total vascular resistance rose from 1.41 +/- 0.04 to 5.04 +/- 0.09 mmHg.ml-1.min in rats given 0.25 ml air over 1 min (n = 14, P less than 0.001), with greater than or equal to 90% of this increase occurring in the arterial segments. Both thromboxane B2 and endothelin concentrations also increased in the perfusate, suggesting their involvement in this increased resistance. Furthermore the pulmonary filtration coefficient increased from 0.21 +/- 0.05 to 1.28 +/- 0.26 g.min-1.cmH2O–1.100 g (n = 8, P less than 0.001), and the protein concentration in lung lavage fluid also rose, indicating lung injury. Leukocyte counts in the perfusate were unaffected by embolization, but chemiluminescent activity was increased, indicating a possible role for activated leukocytes in lung injury induced by air emboli.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary hypertension due to monocrotaline pyrrole is reduced by moderate thrombocytopenia

1988 ◽  
Vol 255 (5) ◽  
pp. H1165-H1172 ◽  
Author(s):  
P. E. Ganey ◽  
K. H. Sprugel ◽  
S. M. White ◽  
J. G. Wagner ◽  
R. A. Roth
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Injury ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Lavage Fluid ◽  
Lung Weight ◽  
Lactate Dehydrogenase Activity ◽  
Pulmonary Arterial ◽  
Series Of Experiments ◽  
Monocrotaline Pyrrole

To elucidate further the role of the platelet in the development of monocrotaline pyrrole (MCTP)-induced lung injury and pulmonary hypertension, MCTP-treated rats were made thrombocytopenic by cotreatment with an anti-rat platelet serum (PAS). Lung injury was assessed from increases in lung weight, lavage fluid protein concentration, and lactate dehydrogenase activity and from accumulation in lung tissue of 125I-labeled albumin. These indexes of injury were not different in MCTP-treated rats with normal or reduced platelet numbers at day 4,8, or 14. In MCTP-treated rats not receiving the PAS, pulmonary arterial pressure was elevated by day 8. However, pulmonary arterial pressure was the same as controls at both day 8 and day 14 in MCTP-treated rats made moderately thrombocytopenic by cotreatment with PAS. More marked reduction of platelet number abolished the protective effect of thrombocytopenia against pulmonary hypertension. In a separate series of experiments, treatment with antibodies to platelet-derived growth factor (PDGF), a potential mediator in the response to MCTP-induced injury, did not protect rats from the cardiopulmonary effects of MCTP. These data indicate that moderate reduction of the number of circulating platelets prevents MCTP-induced pulmonary hypertension but not MCTP-induced lung injury, suggesting that the platelet is involved in the pulmonary hypertensive response to MCTP-induced lung injury by unknown mechanisms.

Hyperbaric oxygen toxicity: role of thromboxane

1992 ◽  
Vol 72 (2) ◽  
pp. 416-422 ◽  
Author(s):  
J. M. Jacobson ◽  
J. R. Michael ◽  
R. A. Meyers ◽  
M. B. Bradley ◽  
A. M. Sciuto ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Injury ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Lavage Fluid ◽  
Thromboxane B2 ◽  
Lung Weight ◽  
Pulmonary Arterial

Exposing rabbits for 1 h to 100% O2 at 4 atm barometric pressure markedly increases the concentration of thromboxane B2 in alveolar lavage fluid [1,809 +/- 92 vs. 99 +/- 24 (SE) pg/ml, P less than 0.001], pulmonary arterial pressure (110 +/- 17 vs. 10 +/- 1 mmHg, P less than 0.001), lung weight gain (14.6 +/- 3.7 vs. 0.6 +/- 0.4 g/20 min, P less than 0.01), and transfer rates for aerosolized 99mTc-labeled diethylenetriamine pentaacetate (500 mol wt; 40 +/- 14 vs. 3 +/- 1 x 10(-3)/min, P less than 0.01) and fluorescein isothiocyanate-labeled dextran (7,000 mol wt; 10 +/- 3 vs. 1 +/- 1 x 10(-4)/min, P less than 0.01). Pretreatment with the antioxidant butylated hydroxyanisole (BHA) entirely prevents the pulmonary hypertension and lung injury. In addition, BHA blocks the increase in alveolar thromboxane B2 caused by hyperbaric O2 (10 and 45 pg/ml lavage fluid, n = 2). Combined therapy with polyethylene glycol- (PEG) conjugated superoxide dismutase (SOD) and PEG-catalase also completely eliminates the pulmonary hypertension, pulmonary edema, and increase in transfer rate for the aerosolized compounds. In contrast, combined treatment with unconjugated SOD and catalase does not reduce the pulmonary damage. Because of the striking increase in pulmonary arterial pressure to greater than 100 mmHg, we tested the hypothesis that thromboxane causes the hypertension and thus contributes to the lung injury. Indomethacin and UK 37,248–01 (4-[2-(1H-imidazol-1-yl)-ethoxy]benzoic acid hydrochloride, an inhibitor of thromboxane synthase, completely eliminate the pulmonary hypertension and edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary hypertension after postlavage lung injury in rabbits: possible role of polymorphonuclear leukocytes

1991 ◽  
Vol 71 (5) ◽  
pp. 1990-1995 ◽  
Author(s):  
R. Burger ◽  
A. C. Bryan
Keyword(s):  
Pulmonary Hypertension ◽  
Gas Exchange ◽  
Lung Injury ◽  
Arterial Pressure ◽  
Airway Pressure ◽  
Pulmonary Arterial Pressure ◽  
Lung Lavage ◽  
High Frequency Ventilation ◽  
Mean Airway Pressure ◽  
Pulmonary Arterial

Previous studies showed that repeated lung lavage leads to a severe lung injury with very poor gas exchange, a substantial protein leak into the alveoli with hyaline membrane formation, pulmonary hypertension, and migration of granulocytes (PMN) into the alveolar spaces. Depletion of PMN leads to a better gas exchange and a markedly decreased protein leak with only scanty hyaline membranes. In this study we show that there is sustained pulmonary hypertension after the lung lavage, but in PMN-depleted rabbits there is no postlavage increase in pulmonary arterial pressure. Changing the shunt fraction by manipulating mean airway pressure still leads to a hypoxic vasoconstriction with increase of pulmonary arterial pressure. Thus, after lung lavage, pulmonary reactivity to hypoxia is still preserved. Comparisons between high-frequency ventilation and conventional mechanical ventilation at the same mean airway pressures showed that equal mean airway pressure in these two very different modes of ventilation do not translate into the same mean functional lung volumes.

Pulmonary hypertension and ECG changes from monocrotaline pyrrole in the rat

1983 ◽  
Vol 245 (2) ◽  
pp. H300-H306 ◽  
Author(s):  
L. H. Bruner ◽  
K. S. Hilliker ◽  
R. A. Roth
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Frontal Plane ◽  
Lavage Fluid ◽  
Male Rats ◽  
Lung Weight ◽  
Lactate Dehydrogenase Activity ◽  
Pulmonary Arterial ◽  
Monocrotaline Pyrrole

Chemically synthesized monocrotaline pyrrole (MCTP) was administered to adult male rats at a dose of 5 mg/kg in the tail vein. Controls received an equivalent volume of dimethylformamide vehicle. Rats were killed at 3, 5, 7, 10, and 14 days after treatment. Bronchopulmonary lavage fluid lactate dehydrogenase activity and lung weight were significantly elevated at 4 and 7 days, respectively, after MCTP, indicating that pulmonary damage had occurred. White blood cell count was elevated 7 days after treatment. Mean pulmonary arterial pressure was also first elevated in treated (22 +/- 3 mmHg) compared with control (16 +/- 1 mmHg) animals 7 days after treatment. Right ventricle-to-left ventricle plus septum weight ratios were significantly increased in treated (0.429 +/- 0.015) vs. control (0.320 +/- 0.015) animals 14 days after treatment. Development of right heart enlargement correlated with a shift in the QRS complex mean electrical axis in the frontal plane of the electrocardiogram. These results indicate that MCTP produces effects similar to that caused by monocrotaline, that pulmonary arterial pressure increases from control levels between 5 and 7 days after treatment, and that measurement of mean electrical axis of the electrocardiogram may be a useful, noninvasive method to monitor MCTP-induced cardiac changes in vivo.

Lymph flow and lung weight in isolated sheep lungs

1986 ◽  
Vol 61 (5) ◽  
pp. 1830-1835 ◽  
Author(s):  
W. Mitzner ◽  
J. T. Sylvester
Keyword(s):  
Weight Gain ◽  
Arterial Pressure ◽  
Left Atrial ◽  
Pulmonary Arterial Pressure ◽  
Lymph Flow ◽  
Atrial Pressure ◽  
Left Atrial Pressure ◽  
Lung Water ◽  
Lung Weight ◽  
Pulmonary Arterial

To study the relationship between lung weight and lymph flow, we used an in situ, isolated sheep lung preparation that allowed these two variables to be measured simultaneously. All lungs were perfused for 4.5 h at a constant rate of 100 ml X min-1 X kg-1. In control lungs, the left atrial pressure (Pla) was kept at atmospheric pressure. In experimental lungs, Pla was kept atmospheric except for a 50-min elevation to 18 mmHg midway through the perfusion. During this period of left atrial hypertension, pulmonary arterial pressure rose from 18 to 31 mmHg, lymph flow rose from 3 to 12 ml/h, and the lymph-to-plasma oncotic pressure ratio (pi L/pi P) fell from 0.7 to 0.48. After left atrial pressure was returned to control, pulmonary arterial pressure, lymph flow, and pi L/pi P all returned to control levels. The rate of weight gain after the return of left atrial pressure to control was also the same as that in the control group. However, during the period of left atrial hypertension 135 ml of fluid were filtered into the lung, and this large increase in lung weight remained after the pressure was lowered. The presence of this substantial excess lung water despite control values for vascular pressures, lymph flow, rate of weight gain, and pi L/pi P suggests that the absolute amount of lung water has little influence on the dynamic aspects of lung fluid balance. These results are consistent with a two-compartment model of the interstitial space, where only one of the compartments is readily drained by the lymphatics.

Assessment of postpreservation rat lung function using a new model for extended venous reperfusion

1993 ◽  
Vol 75 (4) ◽  
pp. 1890-1896 ◽  
Author(s):  
K. N. DeCampos ◽  
T. K. Waddell ◽  
A. S. Slutsky ◽  
M. Post ◽  
G. A. Patterson
Keyword(s):  
Weight Gain ◽  
Lung Function ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Suitable Model ◽  
Rat Lung ◽  
Lung Dysfunction ◽  
Pulmonary Arterial ◽  
Group 3 ◽  
Group 1

Understanding the physiological significance of biochemical events after lung preservation in rats has been hampered by the lack of a suitable model for physiological assessment. We have developed an ex vivo paracorporeal rat lung perfusion model that permits hemodynamic and gas exchange evaluation of lung function. After anesthesia and heparinization, the heart-lung block was removed and the left lung was reperfused for 1 h at a constant flow of 4 ml/min with homologous venous blood drained from the inferior vena cava of the paracorporeal (host) rat. The lung effluent was returned at the same flow rate to the host distal aorta. The model was validated by the assessment of lung function after room temperature ischemia. Animals were allocated into three groups (n = 6) according to the ischemic interval (group 1, 20 min; group 2, 3 h; group 3, 4 h). In groups 1 and 2, PO2, PCO2, mean airway pressure, and pulmonary arterial pressure were within the normal ranges and stable throughout the experiment. In contrast, lungs in group 3 demonstrated higher pulmonary arterial pressure and lower blood effluent PO2 than were found in either group 1 or 2. A significant weight gain during reperfusion was observed only in group 3 (4.23 +/- 0.9 g; P < 0.002). For each lung, the final blood effluent PO2 correlated with the weight gain (R2 = 0.81; P < 0.0001). Our results indicate that this model can be used reliably to detect lung dysfunction after ischemic injury.

Thromboxane does not mediate pulmonary hypertension in phorbol ester-induced acute lung injury in dogs

1990 ◽  
Vol 69 (1) ◽  
pp. 345-352 ◽  
Author(s):  
A. H. Stephenson ◽  
R. S. Sprague ◽  
T. E. Dahms ◽  
A. J. Lonigro
Keyword(s):  
Pulmonary Hypertension ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Pressor Response ◽  
H2 Receptor Antagonist ◽  
Arterial Blood ◽  
Pulmonary Arterial ◽  
The Relationship

Thromboxane (Tx) has been suggested to mediate the pulmonary hypertension of phorbol myristate acetate- (PMA) induced acute lung injury. To test this hypothesis, the relationship between Tx and pulmonary arterial pressure was evaluated in a model of acute lung injury induced with PMA in pentobarbital sodium-anesthetized male mongrel dogs. Sixty minutes after administration of PMA (20 micrograms/kg iv, n = 10), TxB2 increased 10-fold from control in both systemic and pulmonary arterial blood and 8-fold in bronchoalveolar lavage (BAL) fluid. Concomitantly, pulmonary arterial pressure (Ppa) increased from 14.5 +/- 1.0 to 36.2 +/- 3.5 mmHg, and pulmonary vascular resistance (PVR) increased from 5.1 +/- 0.4 to 25.9 +/- 2.9 mmHg.l-1.min. Inhibition of Tx synthase with OKY-046 (10 mg/kg iv, n = 6) prevented the PMA-induced increase in Tx concentrations in blood and BAL fluid but did not prevent or attenuate the increase in Ppa. OKY-046 pretreatment did, however, attenuate but not prevent the increase in PVR 60 min after PMA administration. Pretreatment with the TxA2/prostaglandin H2 receptor antagonist ONO-3708 (10 micrograms.kg-1.min-1 iv, n = 7) prevented the pressor response to bolus injections of 1-10 micrograms U-46619, a Tx receptor agonist, but did not prevent or attenuate the PMA-induced increase in Ppa. ONO-3708 also attenuated but did not prevent the increase in PVR. These results suggest that Tx does not mediate the PMA-induced pulmonary hypertension but may augment the increases in PVR in this model of acute lung injury.

Protamine sulfate causes pulmonary hypertension and edema in isolated rat lungs

1987 ◽  
Vol 62 (4) ◽  
pp. 1363-1367 ◽  
Author(s):  
R. P. Fairman ◽  
C. N. Sessler ◽  
M. Bierman ◽  
F. L. Glauser
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Weight Ratio ◽  
Dry Weight ◽  
Protamine Sulfate ◽  
Pulmonary Vasculature ◽  
Lung Weight ◽  
Control Value ◽  
Pulmonary Arterial ◽  
Vascular Beds

The polycation protamine sulfate increases microvascular permeability in the kidney by reducing glomerular charge. We have exposed the pulmonary vasculature to protamine sulfate to determine whether electrical charges play a role in protein permeability in lung vascular beds. In anephric rats, protamine sulfate increased hematocrit approximately 25%. With protamine sulfate doses of 0.08 and 0.04 mg/g body wt, lung blood-free wet-to-dry weight ratios were increased (5.24 +/- 0.8 and 4.89 +/- 0.7) compared with control (3.85 +/- 0.3) (P less than 0.05). In isolated, ventilated, and perfused lungs 0.04 mg/g body wt protamine sulfate increased pulmonary arterial pressure from 5.2 +/- 1.4 to 16.3 +/- 3.9 mmHg (P less than 0.01). These lungs gained weight and lung wet-to-dry weight ratios were significantly increased (15.33 +/- 4.26 compared with 6.04 +/- 0.24 for control lungs). Poly-L-lysine, another polycation, also caused significant increases in pulmonary arterial pressure, lung weight, and lung wet-to-dry weight ratios. The addition of diphenhydramine to the perfusate 10 min before the addition of protamine sulfate did not prevent these changes. Heparin (90 U/mg protamine sulfate) reversed the abnormalities. Pulmonary arterial pressure (7.0 +/- 1.1 mmHg) was not significantly different from the control value, lung weight did not increase, and the lung wet-to-dry weight ratio was 6.24 +/- 0.23 (P greater than 0.05). We conclude that polycations have a significant effect on pulmonary vascular resistance and perhaps on permeability.

Modulation by endogenous opioids of pulmonary vasoconstrictor response to acute lung injury

1988 ◽  
Vol 64 (5) ◽  
pp. 1823-1828 ◽  
Author(s):  
A. T. Scardella ◽  
J. A. Neubauer ◽  
N. H. Edelman ◽  
T. V. Santiago
Keyword(s):  
Blood Pressure ◽  
Cardiac Output ◽  
Lung Injury ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Endogenous Opioids ◽  
Pulmonary Perfusion ◽  
Base Line ◽  
Injured Lung ◽  
Pulmonary Arterial

The effects of endogenously generated opioids on distribution of pulmonary perfusion (as assessed by radiolabeled microspheres) and overall gas exchange in acute acid-induced lung injury were studied. In 14 anesthesized dogs, sufficient acid was given to one lung to double shunt fraction (Qs/Qt) from 14.2 +/- 0.8 to 32.4 +/- 2.6% (SE). This resulted in a significant decrease in Po2 from 495 +/- 9 to 136 +/- 21 Torr, cardiac output from 2.47 +/- 0.27 to 1.46 +/- 0.15 1/min, and blood pressure from 139 +/- 3 to 116 +/- 5 mmHg and a significant rise in pulmonary arterial pressure from 9.6 +/- 0.8 to 14.9 +/- 0.8 mmHg. After acid instillation, microsphere distribution to the injured lung segments decreased to 50% of the base-line value. At the same time, microsphere distribution in the normal segments increased to 160% of base line. In 7 of the 14 dogs the effects of naloxone (1 mg/kg) given after lung injury were compared with the other 7 animals that were given saline. Naloxone administration caused a significant redistribution of regional pulmonary perfusion such that microsphere distribution in the injured lung segments increased by a factor of 2 at 35 min compared with the animals given saline. Consistent with this finding, Qs/Qt in the naloxone group increased to 34.7 +/- 5.0% at 35 min, whereas that of the saline group decreased to 28.2 +/- 2.5%. The difference between the two groups was significant at 35 min. These changes occurred without further alterations in cardiac output, pulmonary arterial pressure, or systemic blood pressure in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

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