help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on January 24, 2003, doi:10.1164/rccm.200207-688OC
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Online Supplement
Right arrow All Versions of this Article:
200207-688OCv1
167/8/1064    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Comellas, A. P.
Right arrow Articles by Sznajder, J. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Comellas, A. P.
Right arrow Articles by Sznajder, J. I.
American Journal of Respiratory and Critical Care Medicine Vol 167. pp. 1064-1067, (2003)
© 2003 American Thoracic Society

Original Article

Scorpion Venom Decreases Lung Liquid Clearance in Rats

Alejandro P. Comellas, Liuska M. Pesce, Zaher Azzam, Fernando J. Saldías and Jacob I. Sznajder

Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois

Correspondence and requests for reprints should be addressed to Jacob I. Sznajder, M.D., Pulmonary and Critical Care Medicine, Northwestern University, 303 East Chicago Avenue, Tarry 14-707, Chicago, IL 60611. E-mail: j-sznajder{at}nwu.edu


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
It has been reported that scorpion venom causes respiratory failure and pulmonary edema. However, the effects of this toxin on lung edema clearance have not been previously studied. We examined the effects of scorpion (Tityus serrulatus) venom on the ability of the lung to clear fluid and on alveolar epithelial Na,K-ATPase. The wet-to-dry lung weight ratio was increased in anesthetized rats injected intraperitonally with scorpion venom. Lung edema clearance decreased by up to approximately 60% in rats injected with the venom. Na,K-ATPase {alpha}1- and ß1-subunit protein abundance and activity decreased at the basolateral membranes of alveolar epithelial type II cells incubated with scorpion venom as compared with that of control animals. There was no difference in cell injury in alveolar epithelial type II cells incubated with scorpion venom for 60 minutes compared with that of control animals. We provide here the first evidence that scorpion venom decreases lung liquid clearance, probably by downregulating Na,K-ATPase in the alveolar epithelium.

Key Words: Na,K-ATPase • sodium transport • scorpion venom • alveolar epithelial cells

Human poisoning with scorpion venom is frequent and sometimes lethal in tropical and subtropical countries, with pulmonary edema present in a large proportion of the fatal cases (1). Pulmonary edema caused by scorpion venom toxins has been attributed to acute left ventricular failure and increased pulmonary vascular permeability induced by vasoactive substances released upon the venom sting (2, 3). Regardless of its pathogenesis, once the alveolar edema is established, the clearance of fluid is affected mostly by active sodium (Na+) transport across the alveolar epithelium (4–7). This occurs via the function of apical Na+ channels and the basolaterally located Na,K-ATPases, with water following isosmotically (6, 8, 9).

It has been reported that changes in lung liquid clearance paralleled the Na,K-ATPase function alveolar epithelial type II cells in normal lungs and in models of lung injury (10, 11). We set out to determine whether scorpion venom affects the ability of the rat lung to clear alveolar fluid by regulating the Na,K-ATPase.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Pathogen-free, male, Sprague-Dawley rats weighing 280 to 320 g were purchased from Harlan Sprague-Dawley, Inc. (Indianapolis, IN). Animals were handled according to National Institutes of Health guidelines, and experimental protocols were approved by institutional Animal Care and Use Committee. A total of 43 rat lungs were studied. The animals were provided food and water ad libitum and maintained on a 12 hour:12 hour light:dark cycle. Scorpion venom (from Tityus serrulatus) was purchased from Sigma Chemical Co. (St. Louis, MO). [{gamma}-32P] ATP was purchased from Amersham (Arlington Heights, IL). Antibodies against Na,K-ATPase {alpha}1 (clone 464.6 specific for {alpha}1) (12) and ß1 subunit (13) were a gift from Dr. M. Caplan (Yale University, CT) and Dr. Martin-Vasallo (University of La Laguna, Spain), respectively.

Wet-To-Dry Weight Ratio
Twelve rats were anesthetized with pentobarbital, injected intraperitoneally with normal saline (n = 4), 1.5 mg/kg (n = 4), or 2 mg/kg (n = 4) of body weight (BW) of scorpion venom 60 minutes before being killed. The wet-to-dry lung weight ratio was calculated as previously described (11).

Isolated Lung Studies
Fifteen rats were anesthetized with pentobarbital and studied in the isolated–perfused rat lung model in three groups: (1) the sham group, in which rats were injected intraperitoneally with 1 cc of 0.9 normal saline (n = 7); (2) experimental group 1, which were rats injected intraperitoneally with 1.5 mg/kg of BW of scorpion venom for 60 minutes (n = 4); and (3) experimental group 2, in which rats were injected intraperitoneally with 2 mg/kg of BW of scorpion venom for 60 minutes (n = 4).

The isolated lung preparation was performed as previously described (5, 10). Additional details on the methods and calculations for these measurements are provided in an online supplement.

Cell Isolation and Culture
Alveolar epithelial type II (ATII) cells were isolated from pathogen-free male Sprague-Dawley rats (n = 16) (200–225 g), as previously described (14, 15) according to the method of Dobbs and colleagues (16). Additional detail on the method for making these measurements is provided in an online supplement.

Basolateral Membrane Isolation and Western Blotting
ATII cells were incubated in the presence or absence of scorpion venom (10 µg/ml) for 60 minutes at 37°C. Basolateral membranes (BLMs) were isolated using a percoll gradient as previously described by Hammond and Verroust (17). Additional detail on the method for making these measurements is provided in an online supplement.

Determination of Na,K-ATPase Activity in ATII Cells
ATII cells were incubated in the presence or absence of scorpion venom (10 µg/ml) for 60 minutes at 37°C; Na,K-ATPase activity was determined as described before (14). Additional detail on the method for these measurements is provided in the online supplement.

Measurement of Cell Injury
We assayed cell injury in ATII cells incubated with and without scorpion venom (10 µg/ml) for 60 minutes at 37°C by measuring lactate dehydrogenase activity in culture supernatants with a cytotoxicity detection kit (Roche Molecular Biochemicals, Indianapolis, IN) according to the manufacturer's protocol.

Data Analysis
Data are presented as mean values ± SEM, and n represents the number of animals in each experimental group. When comparisons were made between two experimental groups an unpaired Student's t-test was used. When multiple comparisons were made a one-way analysis of variance was used, followed by a multiple comparison test (Tukey) when the F statistic indicated significance. Results were considered significant when p < 0.05.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Wet-to-Dry Lung Weight Ratio
As shown in Figure 1 , the wet-to-dry lung weight ratio, a gravimetric estimate of pulmonary edema, increased somewhat with 1.5 mg/kg of BW of scorpion venom, being statistically significant after 2 mg/kg of BW of scorpion venom as compared with control rats.



View larger version (32K):
[in this window]
[in a new window]
  		Figure 1. Wet-to-dry lung weight ratio. Bars represent means ± SEM. *p < 0.05 compared with control animals. CT = control; scorpion venom = 1.5 mg/kg and scorpion venom 2 mg/kg T. serrulatus venom.

 
Lung Liquid Clearance
As depicted in Figure 2 , control rat lungs were instilled with 5 ml of buffered salt albumin solution and cleared approximately 10% of the instilled volume within 1 hour (0.52 ± 0.02 ml/hour). Rats injected with 1.5 mg/kg of scorpion venom had a slight (nonstatistically significant) decrease in lung liquid clearance of approximately 15% (0.44 ± 0.01 ml/hour), whereas those injected with 2 mg/kg of scorpion venom had decreased lung liquid clearance by approximately 60% (0.22 ± 0.04 ml/hour). Perfusate flow did not change in any experimental group (data not shown).



View larger version (24K):
[in this window]
[in a new window]
  		Figure 2. Scorpion venom (T. serrulatus) injected intraperitoneally, 1.5 and 2 mg/kg. The latter dose decreased lung liquid clearance in isolated rat lungs. Scorpion venom was injected 1 hour before isolating lung. Bars represent means ± SEM. ***p < 0.0001 compared with control animals. CT = control; scorpion venom = 1.5 and 2 mg/kg T. serrulatus venom.

 
Lung Permeability in Rats Injected With scorpion venom
As depicted in Figure 3A , the lung permeability to small solutes (22Na+ and 3H-mannitol) increased slightly, but not significantly, in rats injected intraperitoneally with 1.5 and 2 mg/kg BW as compared with control rats. The movement of fluorescein isothiocyanate–albumin from the pulmonary circulation into rat airspace was not changed in rats injected with scorpion venom, independently of the dose (Figure 3B).



View larger version (19K):
[in this window]
[in a new window]
  		Figure 3. Increase passive 22Na+ and 3H-mannitol movement (A). The movement of albumin (B) from the pulmonary circulation into the air space did not increase. Bars are means ± SEM. CT = control; scorpion venom = 1.5 and 2 mg/kg T. serrulatus venom.

 
Effect of Scorpion Venom on Alveolar Epithelial Cell Na,K-ATPase
Na,K-ATPase {alpha}1 and ß1 -subunit protein abundance was determined by Western blot analysis at the BLMs of ATII cells incubated with 10 µg/ml of scorpion venom for 60 minutes. This concentration was as an estimate of the distribution of the venom concentration present in the extracellular space of a rat injected with 2 mg/kg BW of scorpion venom. As shown in Figure 4A , scorpion venom decreased the Na,K-ATPase {alpha}1 and ß1-subunit protein in the BLMs of ATII cells compared with control animals. Also, the Na,K-ATPase activity in ATII cells incubated with 10 µg/ml for 60 minutes was decreased by 50% as compared with that in control animals (Figure 4B).




View larger version (59K):
[in this window]
[in a new window]
  		Figure 4. (A) Na,K-ATPase {alpha}1- and ß1-subunit abundance in basolateral membranes of ATII cells. Cells were incubated for 60 minutes with 10-µg/ml T. serrulatus venom. Equal amounts of protein were loaded in each lane. (Bottom) Representative Western blot of Na,K-ATPase {alpha}1- and ß1-subunit abundance. (Top) quantitative densitometric scans of 3 different experiments. scorpion venom decreased Na,K-ATPase {alpha}1- and ß1-subunit protein abundance at the cell BLMs. Bars represent means ± SEM. **p < 0.001; ***p < 0.0001 compared with control animals. CT = control, scorpion venom = 10-µg/ml T. serrulatus venom. (B) Na,K-ATPase activity in cultured ATII cells incubated with scorpion venom (10 µg/ml) for 60 minutes decreased Na+ pump activity. Bars represent means ± SEM. *p < 0.05 as compared with the control group. CT = control; scorpion venom = 10-µg/ml T. serrulatus venom.

 
Cell Injury
The percentage of cell injury in ATII cells was not different between cells incubated with scorpion venom for 60 minutes and control cells (data not shown).


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Of the six families of scorpions, only those of the Buthidae family are dangerous to humans because of their potent venom (18). The Tityinae subfamily is found in South America; the venom of one species of this subfamily, T. serrulatus, is among the most potent and lethal, causing cardiac arrhythmias, hypertension, and pulmonary edema (18, 19). It is still unclear as to the mechanisms contributing to pulmonary edema during scorpion envenomation. Animal studies have suggested that pulmonary edema may be caused either by changes of the alveolocapillary barrier or by a surge of sympathetic release resulting in cardiogenic pulmonary edema (1, 20, 21).

Pathologic examination of a patient stung by a scorpion revealed findings compatible with acute lung injury and increased pulmonary vascular permeability several hours (approximately 16 hours) after being stung (22). We also found that after 1 hour, the most edema (assessed as wet-to-dry lung weight ratio) was observed in rats injected with the higher dose of scorpion venom (see Figure 1). Although the paradigm that hydrostatic and/or oncotic pressure changes across the alveolocapillary barrier are important in driving fluid into the alveoli is well described during lung injury, a less recognized fact is that the balance between edema formation and edema clearance is of critical importance for the patient to recover from lung injury (6, 7, 23).

Lung edema clearance is the consequence of active Na+ transport and water after osmotic gradients generated by the vectorial Na+ flux (24). Active Na+ transport across the alveolar epithelium and hence edema clearance is predominantly dependent on the functions of the alveolar apical Na+ channels and the basolaterally located Na,K-ATPase (4–8, 25). It has been reported that Na,K-ATPase is inhibited during lung injury. In patients with lung injury and animal models such as ventilator-induced lung injury, hyperoxia, hypoxia, and acute increase in left atrial pressure, the alveolar fluid clearance is impaired (10, 11, 23, 26, 27). In this study, lung liquid clearance was decreased by approximately 60% 1 hour after injecting intraperioneally 2 mg/kg (but not 1.5 mg/kg) of scorpion venom to anesthetized rats. Permeability to small solutes (Na+ and Mannitol) were slightly but not significantly increased at the higher dose, and permeability to albumin did not change at either dose, suggesting that the venom did not have a severe damaging effect to the alveolocapillary barrier within the 1st hour. We conducted our studies in anesthetized animals before being injected with this toxin. It is well known that scorpion venom causes significant pain, distress, and a catecholamine surge, as discussed by Taylor in a recent editorial (28). It is known that catecholamines increase alveolar fluid clearance (24, 29–33); therefore, we reason that when animals or humans are stung by a scorpion, there is a rapid increase in alveolar fluid reabsorption, which could compensate and protect the lungs from flooding, but after the catecholamine surge resolves, it is possible that there is a decrease in the ability to clear edema contributing to the overall pulmonary edema.

We have also observed that the {alpha}-1 and ß-1 Na,K-ATPase protein abundance was decreased at the BLMs of alveolar epithelial cells in parallel with a decrease in Na,K-ATPase activity in ATII cells incubated with scorpion venom as compared with control animals, suggesting endocytosis of the Na+ pump from the plasma membrane into intracellular compartments. Endocytosis of the Na+ pump has been reported in different tissues in response to G-protein receptor activation and injurious stimuli, resulting in decreased Na,K-ATPase function. Because we measured Na, K-ATPase activity at Vmax the decrease in activity can only be due to a decrease in the number of Na+ pumps at the plasma membrane, which corresponds with the Western blot data (see Figures 4A and 4B). To exclude the possibility that the scorpion venom was causing gross increase in cell injury, we measured the release of lactate dehydrogenase in cells incubated in the absence or presence of the scorpion venom, which did not reveal differences in the percentage of cell injury after 60 minutes of incubation. This assay does not exclude some loss of cell junction integrity and barrier function which could have been affected by the scorpion venom.

To our knowledge, there are no studies that describe the effect of scorpion venom on the ability of the lungs to clear lung edema, and further research is warranted to determine the pathways by which the scorpion venom is causing the decrease of Na,K-ATPase protein abundance at the BLMs (12, 16). scorpion venom has several fractions that could be involved in regulating this phenomenon (34–37). These fractions can bind Na+ and K+ channels, which could potentially regulate the Na,K-ATPase trafficking. Also, this toxin could potentially bind to a membrane receptor involved in the regulation of the Na,K-ATPase in alveolar epithelial cells.

Our data provides new information that warrants further studies to determine the effects of the scorpion venom on the signal transduction pathways involved in the endocytosis of the Na+ pump in this model.

This first report provides evidence that scorpion venom decreases lung liquid clearance, probably by downregulating the Na,K-ATPase in alveolar epithelial cells, which could contribute to the morbidity and mortality of patients that develop pulmonary edema after scorpion venom sting.


   FOOTNOTES
 
Supported in part by HL48129.

This article has an online supplement, which is accessible from this issue's table of contents online at www.atsjournals.org

Received in original form July 11, 2002; accepted in final form January 17, 2003


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Gueron M, Adolph RJ, Grupp IL, Gabel M, Grupp G, Fowler NO. Hemodynamic and myocardial consequences of scorpion venom. Am J Cardiol 1980;45:979–986.[CrossRef][Medline]
  2. Amaral CF, de Rezende NA, Freire-Maia L. Acute pulmonary edema after Tityus serrulatus scorpion sting in children. Am J Cardiol 1993;71:242–245.[CrossRef][Medline]
  3. Amaral CF, Rezende NA. Both cardiogenic and non-cardiogenic factors are involved in the pathogenesis of pulmonary oedema after scorpion envenoming. Toxicon 1997;35:997–998.[Medline]
  4. Saumon G, Basset G. Electrolyte and fluid transport across the mature alveolar epithelium. J Appl Physiol 1993;74:1–15.[Abstract/Free Full Text]
  5. Rutschman DH, Olivera W, Sznajder JI. Active transport and passive liquid movement in isolated perfused rat lungs. J Appl Physiol 1993;75:1574–1580.[Abstract/Free Full Text]
  6. Matthay MA, Folkesson HG, Verkman AS. Salt and water transport across alveolar and distal airway epithelia in the adult lung. Am J Physiol 1996;270:L487–L503.
  7. Sznajder JI. Alveolar edema must be cleared for the acute respiratory distress syndrome patient to survive. Am J Respir Crit Care Med 2001;163:1293–1294.[Free Full Text]
  8. Matalon S, O'Brodovich H. Sodium channels in alveolar epithelial cells: molecular characterization, biophysical properties, and physiological significance. Annu Rev Physiol 1999;61:627–661.[CrossRef][Medline]
  9. Skou JC, Esmann M. The Na,K-ATPase. J Bioenerg Biomembr 1992;24:249–261.[Medline]
  10. Olivera WG, Ridge KM, Sznajder JI. Lung liquid clearance and Na,K-ATPase during acute hyperoxia and recovery in rats. Am J Respir Crit Care Med 1995;152:1229–1234.[Abstract]
  11. Lecuona E, Saldias F, Comellas A, Ridge K, Guerrero C, Sznajder JI. Ventilator-associated lung injury decreases lung ability to clear edema in rats. Am J Respir Crit Care Med 1999;159:603–609.[Abstract/Free Full Text]
  12. Gottardi CJ, Caplan MJ. Delivery of Na+,K(+)-ATPase in polarized epithelial cells. Science 1993;260:552–554; discussion 554–556.[Free Full Text]
  13. Gonzalez-Martinez LM, Avila J, Marti E, Lecuona E, Martin-Vasallo P. Expression of the beta-subunit isoforms of the Na,K-ATPase in rat embryo tissues, inner ear and choroid plexus. Biol Cell 1994;81:215–222.[CrossRef][Medline]
  14. Bertorello AM, Ridge KM, Chibalin AV, Katz AI, Sznajder JI. Isoproterenol increases Na+-K+-ATPase activity by membrane insertion of alpha-subunits in lung alveolar cells. Am J Physiol 1999;276:L20–L27.
  15. Ridge KM, Rutschman DH, Factor P, Katz AI, Bertorello AM, Sznajder JL. Differential expression of Na-K-ATPase isoforms in rat alveolar epithelial cells. Am J Physiol 1997;273:L246–L255.
  16. Dobbs LG, Gonzalez R, Williams MC. An improved method for isolating type II cells in high yield and purity. Am Rev Respir Dis 1986;134:141–145.[Medline]
  17. Hammond TG, Verroust PJ. Heterogeneity of endosomal populations in the rat renal cortex: light endosomes. Am J Physiol 1994;266:C1783–C1794.
  18. Correa MM, Sampaio scorpion venom, Lopes RA, Mancuso LC, Cunha OA, Franco JJ, Giglio JR. Biochemical and histopathological alterations induced in rats by Tityus serrulatus scorpion venom and its major neurotoxin tityustoxin-I. Toxicon 1997;35:1053–1067.[Medline]
  19. Borges CM, Silveira MR, Aparecida M, Beker CL, Freire-Maia L, Teixeira MM. Scorpion venom-induced neutrophilia is inhibited by a PAF receptor antagonist in the rat. J Leukoc Biol 2000;67:515–519.[Abstract]
  20. Rossi MA, Ferreira AL, Paiva SM. Fine structures of pulmonary changes induced by Brazilian scorpion venom. Arch Pathol 1974;97:284–288.[Medline]
  21. D'Suze G, Comellas A, Pesce L, Sevcik C, Sanchez-de-Leon R. Tityus discrepans venom produces a respiratory distress syndrome in rabbits through an indirect mechanism. Toxicon 1999;37:173–180.[Medline]
  22. Amaral CF, Barbosa AJ, Leite VH, Tafuri WL, de Rezende NA. Scorpion sting-induced pulmonary oedema: evidence of increased alveolocapillary membrane permeability. Toxicon 1994;32:999–1003.[Medline]
  23. Ware LB, Matthay MA. Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med 2001;163:1376–1383.[Abstract/Free Full Text]
  24. Factor P. Role and regulation of lung Na,K-ATPase. Cell Mol Biol (Noisy-le-grand) 2001;47:347–361.[Medline]
  25. Sznajder JI. Strategies to increase alveolar epithelial fluid removal in the injured lung. Am J Respir Crit Care Med 1999;160:1441–1442.[Free Full Text]
  26. Saldias FJ, Azzam ZS, Ridge KM, Yeldandi A, Rutschman DH, Schraufnagel D, Sznajder JI. Alveolar fluid reabsorption is impaired by increased left atrial pressures in rats. Am J Physiol Lung Cell Mol Physiol 2001;281:L591–L597.[Abstract/Free Full Text]
  27. Wodopia R, Ko HS, Billian J, Wiesner R, Bartsch P, Mairbaurl H. Hypoxia decreases proteins involved in epithelial electrolyte transport in A549 cells and rat lung. Am J Physiol Lung Cell Mol Physiol 2000;279:L1110–L1119.[Abstract/Free Full Text]
  28. Taylor AE. Cardiovascular responses to scorpion venom. Crit Care Med 1999;27:250.[CrossRef][Medline]
  29. Azzam ZS, Saldias FJ, Comellas A, Ridge KM, Rutschman DH, Sznajder JI. Catecholamines increase lung edema clearance in rats with increased left atrial pressure. J Appl Physiol 2001;90:1088–1094.[Abstract/Free Full Text]
  30. Barnard ML, Olivera WG, Rutschman DM, Bertorello AM, Katz AI, Sznajder JI. Dopamine stimulates sodium transport and liquid clearance in rat lung epithelium. Am J Respir Crit Care Med 1997;156:709–714.[Abstract/Free Full Text]
  31. Barnard ML, Ridge KM, Saldias F, Friedman E, Gare M, Guerrero C, Lecuona E, Bertorello AM, Katz AI, Sznajder JI. Stimulation of the dopamine 1 receptor increases lung edema clearance. Am J Respir Crit Care Med 1999;160:982–986.[Abstract/Free Full Text]
  32. McGraw DW, Fukuda N, James PF, Forbes SL, Woo AL, Lingrel JB, Witte DP, Matthay MA, Liggett SB. Targeted transgenic expression of beta(2)-adrenergic receptors to type II cells increases alveolar fluid clearance. Am J Physiol Lung Cell Mol Physiol 2001;281:L895–L903.[Abstract/Free Full Text]
  33. Saldias F, Lecuona E, Friedman E, Barnard ML, Ridge KM, Sznajder JI. Modulation of lung liquid clearance by isoproterenol in rat lungs. Am J Physiol 1998;274:L694–L701.
  34. Arantes EC, Sampaio scorpion venom, Vieira CA, Giglio JR. What is tityustoxin? Toxicon 1992;30:786–789.[Medline]
  35. Arantes EC, Riccioppo Neto F, Sampaio scorpion venom, Vieira CA, Giglio JR. Isolation and characterization of TsTX-V, a new neurotoxin from Tityus serrulatus scorpion venom which delays the inactivation of Na+ channels. Biochim Biophys Acta 1994;1199:69–75.[Medline]
  36. Teixeira CE, Bento AC, Lopes-Martins RA, Teixeira SA, von Eickestedt V, Muscara MN, Arantes EC, Giglio JR, Antunes E, de Nucci G. Effect of Tityus serrulatus scorpion venom on the rabbit isolated corpus cavernosum and the involvement of NANC nitrergic nerve fibres. Br J Pharmacol 1998;123:435–442.[CrossRef][Medline]
  37. Borges A, Tsushima RG, Backx PH. Antibodies against Tityus discrepans venom do not abolish the effect of Tityus serrulatus venom on the rat sodium and potassium channels. Toxicon 1999;37:867–881.[Medline]



This article has been cited by other articles:


Home page
 Am. J. Respir. Crit. Care Med.Home page
P. M. Myrianthefs, A. Briva, E. Lecuona, V. Dumasius, D. H. Rutschman, K. M. Ridge, G. J. Baltopoulos, and J. I. Sznajder
Hypocapnic but Not Metabolic Alkalosis Impairs Alveolar Fluid Reabsorption
Am. J. Respir. Crit. Care Med., June 1, 2005; 171(11): 1267 - 1271.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. J. Tobin
Critical Care Medicine in AJRCCM 2003
Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 239 - 253.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Online Supplement
Right arrow All Versions of this Article:
200207-688OCv1
167/8/1064    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Comellas, A. P.
Right arrow Articles by Sznajder, J. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Comellas, A. P.
Right arrow Articles by Sznajder, J. I.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2003 American Thoracic Society