Skip to main content
Top
Published in: Critical Care 1/2007

Open Access 01-02-2007 | Research

Effect of positive end-expiratory pressure and tidal volume on lung injury induced by alveolar instability

Authors: Jeffrey M Halter, Jay M Steinberg, Louis A Gatto, Joseph D DiRocco, Lucio A Pavone, Henry J Schiller, Scott Albert, Hsi-Ming Lee, David Carney, Gary F Nieman

Published in: Critical Care | Issue 1/2007

Login to get access

Abstract

Introduction

One potential mechanism of ventilator-induced lung injury (VILI) is due to shear stresses associated with alveolar instability (recruitment/derecruitment). It has been postulated that the optimal combination of tidal volume (Vt) and positive end-expiratory pressure (PEEP) stabilizes alveoli, thus diminishing recruitment/derecruitment and reducing VILI. In this study we directly visualized the effect of Vt and PEEP on alveolar mechanics and correlated alveolar stability with lung injury.

Methods

In vivo microscopy was utilized in a surfactant deactivation porcine ARDS model to observe the effects of Vt and PEEP on alveolar mechanics. In phase I (n = 3), nine combinations of Vt and PEEP were evaluated to determine which combination resulted in the most and least alveolar instability. In phase II (n = 6), data from phase I were utilized to separate animals into two groups based on the combination of Vt and PEEP that caused the most alveolar stability (high Vt [15 cc/kg] plus low PEEP [5 cmH2O]) and least alveolar stability (low Vt [6 cc/kg] and plus PEEP [20 cmH2O]). The animals were ventilated for three hours following lung injury, with in vivo alveolar stability measured and VILI assessed by lung function, blood gases, morphometrically, and by changes in inflammatory mediators.

Results

High Vt/low PEEP resulted in the most alveolar instability and lung injury, as indicated by lung function and morphometric analysis of lung tissue. Low Vt/high PEEP stabilized alveoli, improved oxygenation, and reduced lung injury. There were no significant differences between groups in plasma or bronchoalveolar lavage cytokines or proteases.

Conclusion

A ventilatory strategy employing high Vt and low PEEP causes alveolar instability, and to our knowledge this is the first study to confirm this finding by direct visualization. These studies demonstrate that low Vt and high PEEP work synergistically to stabilize alveoli, although increased PEEP is more effective at stabilizing alveoli than reduced Vt. In this animal model of ARDS, alveolar instability results in lung injury (VILI) with minimal changes in plasma and bronchoalveolar lavage cytokines and proteases. This suggests that the mechanism of lung injury in the high Vt/low PEEP group was mechanical, not inflammatory in nature.
Appendix
Available only for authorised users
Literature
1.
go back to reference Artigas A, Bernard GR, Carlet J, Dreyfuss D, Gattinoni L, Hudson L, Lamy M, Marini JJ, Matthay MA, Pinsky MR, et al.: The American-European Consensus Conference on ARDS, part 2. Ventilatory, pharmacologic, supportive therapy, study design strategies and issues related to recovery and remodeling. Intensive Care Med 1998, 24: 378-398. 10.1007/s001340050585CrossRefPubMed Artigas A, Bernard GR, Carlet J, Dreyfuss D, Gattinoni L, Hudson L, Lamy M, Marini JJ, Matthay MA, Pinsky MR, et al.: The American-European Consensus Conference on ARDS, part 2. Ventilatory, pharmacologic, supportive therapy, study design strategies and issues related to recovery and remodeling. Intensive Care Med 1998, 24: 378-398. 10.1007/s001340050585CrossRefPubMed
2.
go back to reference Boussarsar M, Thierry G, Jaber S, Roudot-Thoraval F, Lemaire F, Brochard L: Relationship between ventilatory settings and barotrauma in the acute respiratory distress syndrome. Intensive Care Med 2002, 28: 406-413. 10.1007/s00134-001-1178-1CrossRefPubMed Boussarsar M, Thierry G, Jaber S, Roudot-Thoraval F, Lemaire F, Brochard L: Relationship between ventilatory settings and barotrauma in the acute respiratory distress syndrome. Intensive Care Med 2002, 28: 406-413. 10.1007/s00134-001-1178-1CrossRefPubMed
3.
go back to reference Finfer S, Rocker G: Alveolar overdistension is an important mechanism of persistent lung damage following severe protracted ARDS. Anaesth Intensive Care 1996, 24: 569-573.PubMed Finfer S, Rocker G: Alveolar overdistension is an important mechanism of persistent lung damage following severe protracted ARDS. Anaesth Intensive Care 1996, 24: 569-573.PubMed
4.
go back to reference Rouby JJ, Lherm T, Martin de Lassale E, Poete P, Bodin L, Finet JF, Callard P, Viars P: Histologic aspects of pulmonary barotrauma in critically ill patients with acute respiratory failure. Intensive Care Med 1993, 19: 383-389. 10.1007/BF01724877CrossRefPubMed Rouby JJ, Lherm T, Martin de Lassale E, Poete P, Bodin L, Finet JF, Callard P, Viars P: Histologic aspects of pulmonary barotrauma in critically ill patients with acute respiratory failure. Intensive Care Med 1993, 19: 383-389. 10.1007/BF01724877CrossRefPubMed
5.
go back to reference Vieira SR, Puybasset L, Lu Q, Richecoeur J, Cluzel P, Coriat P, Rouby JJ: A scanographic assessment of pulmonary morphology in acute lung injury. Significance of the lower inflection point detected on the lung pressure-volume curve. Am J Respir Crit Care Med 1999, 159: 1612-1623.CrossRefPubMed Vieira SR, Puybasset L, Lu Q, Richecoeur J, Cluzel P, Coriat P, Rouby JJ: A scanographic assessment of pulmonary morphology in acute lung injury. Significance of the lower inflection point detected on the lung pressure-volume curve. Am J Respir Crit Care Med 1999, 159: 1612-1623.CrossRefPubMed
6.
go back to reference Steinberg J, Schiller HJ, Halter JM, Gatto LA, Dasilva M, Amato M, McCann UG, Nieman GF: Tidal volume increases do not affect alveolar mechanics in normal lung but cause alveolar overdistension and exacerbate alveolar instability after surfactant deactivation. Crit Care Med 2002, 30: 2675-2683. 10.1097/00003246-200212000-00011CrossRefPubMed Steinberg J, Schiller HJ, Halter JM, Gatto LA, Dasilva M, Amato M, McCann UG, Nieman GF: Tidal volume increases do not affect alveolar mechanics in normal lung but cause alveolar overdistension and exacerbate alveolar instability after surfactant deactivation. Crit Care Med 2002, 30: 2675-2683. 10.1097/00003246-200212000-00011CrossRefPubMed
7.
go back to reference Dreyfuss D, Soler P, Saumon G: Mechanical ventilation-induced pulmonary edema. Interaction with previous lung alterations. Am J Respir Crit Care Med 1995, 151: 1568-1575.CrossRefPubMed Dreyfuss D, Soler P, Saumon G: Mechanical ventilation-induced pulmonary edema. Interaction with previous lung alterations. Am J Respir Crit Care Med 1995, 151: 1568-1575.CrossRefPubMed
8.
go back to reference Dreyfuss D, Soler P, Basset G, Saumon G: High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis 1988, 137: 1159-1164.CrossRefPubMed Dreyfuss D, Soler P, Basset G, Saumon G: High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis 1988, 137: 1159-1164.CrossRefPubMed
9.
go back to reference Webb HH, Tierney DF: Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures. Protection by positive end-expiratory pressure. Am Rev Respir Dis 1974, 110: 556-565.PubMed Webb HH, Tierney DF: Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures. Protection by positive end-expiratory pressure. Am Rev Respir Dis 1974, 110: 556-565.PubMed
10.
go back to reference Taskar V, John J, Evander E, Robertson B, Jonson B: Surfactant dysfunction makes lungs vulnerable to repetitive collapse and reexpansion. Am J Respir Crit Care Med 1997, 155: 313-320.CrossRefPubMed Taskar V, John J, Evander E, Robertson B, Jonson B: Surfactant dysfunction makes lungs vulnerable to repetitive collapse and reexpansion. Am J Respir Crit Care Med 1997, 155: 313-320.CrossRefPubMed
11.
go back to reference Tschumperlin DJ, Oswari J, Margulies AS: Deformation-induced injury of alveolar epithelial cells. Effect of frequency, duration, and amplitude. Am J Respir Crit Care Med 2000, 162: 357-362.CrossRefPubMed Tschumperlin DJ, Oswari J, Margulies AS: Deformation-induced injury of alveolar epithelial cells. Effect of frequency, duration, and amplitude. Am J Respir Crit Care Med 2000, 162: 357-362.CrossRefPubMed
12.
go back to reference Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS: Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA 1999, 282: 54-61. 10.1001/jama.282.1.54CrossRefPubMed Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS: Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA 1999, 282: 54-61. 10.1001/jama.282.1.54CrossRefPubMed
13.
go back to reference Vlahakis NE, Schroeder MA, Limper AH, Hubmayr RD: Stretch induces cytokine release by alveolar epithelial cells in vitro. Am J Physiol 1999, 277: L167-L173.PubMed Vlahakis NE, Schroeder MA, Limper AH, Hubmayr RD: Stretch induces cytokine release by alveolar epithelial cells in vitro. Am J Physiol 1999, 277: L167-L173.PubMed
14.
go back to reference Tremblay LN, Slutsky AS: Ventilator-induced injury: from barotrauma to biotrauma. Proc Assoc Am Physicians 1998, 110: 482-488.PubMed Tremblay LN, Slutsky AS: Ventilator-induced injury: from barotrauma to biotrauma. Proc Assoc Am Physicians 1998, 110: 482-488.PubMed
15.
go back to reference Quinn DA, Moufarrej RK, Volokhov A, Hales CA: Interactions of lung stretch, hyperoxia, and MIP-2 production in ventilator-induced lung injury. J Appl Physiol 2002, 93: 517-525.CrossRefPubMed Quinn DA, Moufarrej RK, Volokhov A, Hales CA: Interactions of lung stretch, hyperoxia, and MIP-2 production in ventilator-induced lung injury. J Appl Physiol 2002, 93: 517-525.CrossRefPubMed
16.
go back to reference Imanaka H, Shimaoka M, Matsuura N, Nishimura M, Ohta N, Kiyono H: Ventilator-induced lung injury is associated with neutrophil infiltration, macrophage activation, and TGF-beta 1 mRNA upregulation in rat lungs. Anesth Analg 2001, 92: 428-436. 10.1097/00000539-200102000-00029CrossRefPubMed Imanaka H, Shimaoka M, Matsuura N, Nishimura M, Ohta N, Kiyono H: Ventilator-induced lung injury is associated with neutrophil infiltration, macrophage activation, and TGF-beta 1 mRNA upregulation in rat lungs. Anesth Analg 2001, 92: 428-436. 10.1097/00000539-200102000-00029CrossRefPubMed
17.
go back to reference Dos Santos CC, Slutsky AS: Invited review: mechanisms of ventilator-induced lung injury: a perspective. J Appl Physiol 2000, 89: 1645-1655.PubMed Dos Santos CC, Slutsky AS: Invited review: mechanisms of ventilator-induced lung injury: a perspective. J Appl Physiol 2000, 89: 1645-1655.PubMed
18.
go back to reference The Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000, 342: 1301-1308. 10.1056/NEJM200005043421801CrossRef The Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000, 342: 1301-1308. 10.1056/NEJM200005043421801CrossRef
19.
go back to reference Cereda M, Foti G, Musch G, Sparacino ME, Pesenti A: Positive end-expiratory pressure prevents the loss of respiratory compliance during low tidal volume ventilation in acute lung injury patients. Chest 1996, 109: 480-485.CrossRefPubMed Cereda M, Foti G, Musch G, Sparacino ME, Pesenti A: Positive end-expiratory pressure prevents the loss of respiratory compliance during low tidal volume ventilation in acute lung injury patients. Chest 1996, 109: 480-485.CrossRefPubMed
20.
go back to reference Richard JC, Brochard L, Vandelet P, Breton L, Maggiore SM, Jonson B, Clabault K, Leroy J, Bonmarchand G: Respective effects of end-expiratory and end-inspiratory pressures on alveolar recruitment in acute lung injury. Crit Care Med 2003, 31: 89-92. 10.1097/00003246-200301000-00014CrossRefPubMed Richard JC, Brochard L, Vandelet P, Breton L, Maggiore SM, Jonson B, Clabault K, Leroy J, Bonmarchand G: Respective effects of end-expiratory and end-inspiratory pressures on alveolar recruitment in acute lung injury. Crit Care Med 2003, 31: 89-92. 10.1097/00003246-200301000-00014CrossRefPubMed
21.
go back to reference Amato MB, Barbas CS, Medeiros DM, Schettino Gde P, Lorenzi Filho G, Kairalla RA, Deheinzelin D, Morais C, Fernandes Ede O, Takagaki TY, et al.: Beneficial effects of the 'open lung approach' with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation. Am J Respir Crit Care Med 1995, 152: 1835-1846.CrossRefPubMed Amato MB, Barbas CS, Medeiros DM, Schettino Gde P, Lorenzi Filho G, Kairalla RA, Deheinzelin D, Morais C, Fernandes Ede O, Takagaki TY, et al.: Beneficial effects of the 'open lung approach' with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation. Am J Respir Crit Care Med 1995, 152: 1835-1846.CrossRefPubMed
22.
go back to reference Schiller HJ, McCann UG II, Carney DE, Gatto LA, Steinberg JM, Nieman GF: Altered alveolar mechanics in the acutely injured lung. Crit Care Med 2001, 29: 1049-1055. 10.1097/00003246-200105000-00036CrossRefPubMed Schiller HJ, McCann UG II, Carney DE, Gatto LA, Steinberg JM, Nieman GF: Altered alveolar mechanics in the acutely injured lung. Crit Care Med 2001, 29: 1049-1055. 10.1097/00003246-200105000-00036CrossRefPubMed
23.
go back to reference McCann UG II, Schiller HJ, Carney DE, Gatto LA, Steinberg JM, Nieman GF: Visual validation of the mechanical stabilizing effects of positive end-expiratory pressure at the alveolar level. J Surg Res 2001, 99: 335-342. 10.1006/jsre.2001.6179CrossRefPubMed McCann UG II, Schiller HJ, Carney DE, Gatto LA, Steinberg JM, Nieman GF: Visual validation of the mechanical stabilizing effects of positive end-expiratory pressure at the alveolar level. J Surg Res 2001, 99: 335-342. 10.1006/jsre.2001.6179CrossRefPubMed
24.
go back to reference Carney DE, Bredenberg CE, Schiller HJ, Picone AL, McCann UG, Gatto LA, Bailey G, Fillinger M, Nieman GF: The mechanism of lung volume change during mechanical ventilation. Am J Respir Crit Care Med 1999, 160: 1697-1702.CrossRef Carney DE, Bredenberg CE, Schiller HJ, Picone AL, McCann UG, Gatto LA, Bailey G, Fillinger M, Nieman GF: The mechanism of lung volume change during mechanical ventilation. Am J Respir Crit Care Med 1999, 160: 1697-1702.CrossRef
26.
go back to reference Lim S-C, Adams AB, Simonson DA, Dries DJ, Broccard AF, Hotchkiss JR, Marini JJ: Intercomparison of recruitment maneuver efficacy in three models of acute lung injury. Crit Care Med 2004, 32: 2371-2377. 10.1097/01.CCM.0000147445.73344.3ACrossRefPubMed Lim S-C, Adams AB, Simonson DA, Dries DJ, Broccard AF, Hotchkiss JR, Marini JJ: Intercomparison of recruitment maneuver efficacy in three models of acute lung injury. Crit Care Med 2004, 32: 2371-2377. 10.1097/01.CCM.0000147445.73344.3ACrossRefPubMed
27.
go back to reference Steinberg J, Schiller HJ, Halter JM, Gatto LA, Lee H-M, Pavone LA, Nieman GF: Alveolar instability causes early ventilator-induced lung injury independent of neutrophils. Am J Respir Crit Care Med 2004, 159: 57-63.CrossRef Steinberg J, Schiller HJ, Halter JM, Gatto LA, Lee H-M, Pavone LA, Nieman GF: Alveolar instability causes early ventilator-induced lung injury independent of neutrophils. Am J Respir Crit Care Med 2004, 159: 57-63.CrossRef
28.
go back to reference Crotti S, Mascheroni D, Caironi P, Pelosi P, Ronzoni G, Mondino M, Marini JJ, Gattinoni L: Recruitment and derecruitment during acute respiratory failure: a clinical study. Am J Respir Crit Care Med 2001, 164: 131-140.CrossRefPubMed Crotti S, Mascheroni D, Caironi P, Pelosi P, Ronzoni G, Mondino M, Marini JJ, Gattinoni L: Recruitment and derecruitment during acute respiratory failure: a clinical study. Am J Respir Crit Care Med 2001, 164: 131-140.CrossRefPubMed
29.
go back to reference Pelosi P, Cadringher P, Bottino N, Panigada M, Carrieri F, Riva E, Lissoni A, Gattinoni L: Sigh in acute respiratory distress syndrome. Am J Respir Crit Care Med 1999, 159: 872-880.CrossRefPubMed Pelosi P, Cadringher P, Bottino N, Panigada M, Carrieri F, Riva E, Lissoni A, Gattinoni L: Sigh in acute respiratory distress syndrome. Am J Respir Crit Care Med 1999, 159: 872-880.CrossRefPubMed
30.
go back to reference Richard JC, Maggiore SM, Jonson B, Mancebo J, Lemaire F, Brochard L: Influence of tidal volume on alveolar recruitment. Respective role of PEEP and a recruitment maneuver. Am J Respir Crit Care Med 2001, 163: 1609-1613.CrossRefPubMed Richard JC, Maggiore SM, Jonson B, Mancebo J, Lemaire F, Brochard L: Influence of tidal volume on alveolar recruitment. Respective role of PEEP and a recruitment maneuver. Am J Respir Crit Care Med 2001, 163: 1609-1613.CrossRefPubMed
31.
go back to reference Frank JA, Gutierrez JA, Jones KD, Allen L, Dobbs L, Matthay MA: Low tidal volume reduces epithelial and endothelial injury in acid-injured rat lungs. Am J Respir Crit Care Med 2002, 165: 242-249.CrossRefPubMed Frank JA, Gutierrez JA, Jones KD, Allen L, Dobbs L, Matthay MA: Low tidal volume reduces epithelial and endothelial injury in acid-injured rat lungs. Am J Respir Crit Care Med 2002, 165: 242-249.CrossRefPubMed
32.
go back to reference Muscedere JG, Mullen JB, Gan K, Slutsky AS: Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med 1994, 149: 1327-1334.CrossRefPubMed Muscedere JG, Mullen JB, Gan K, Slutsky AS: Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med 1994, 149: 1327-1334.CrossRefPubMed
33.
go back to reference van Kaam AH, de Jaegere A, Haitsma JJ, Van Aalderen WM, Kok JH, Lachmann B: Positive pressure ventilation with the open lung concept optimizes gas exchange and reduces ventilator-induced lung injury in newborn piglets. Pediatr Res 2003, 53: 245-253. 10.1203/01.PDR.0000047520.44168.22CrossRefPubMed van Kaam AH, de Jaegere A, Haitsma JJ, Van Aalderen WM, Kok JH, Lachmann B: Positive pressure ventilation with the open lung concept optimizes gas exchange and reduces ventilator-induced lung injury in newborn piglets. Pediatr Res 2003, 53: 245-253. 10.1203/01.PDR.0000047520.44168.22CrossRefPubMed
34.
go back to reference Corbridge TC, Wood LD, Crawford GP, Chudoba MJ, Yanos J, Sznajder JI: Adverse effects of large tidal volume and low PEEP in canine acid aspiration. Am Rev Respir Dis 1990, 142: 311-315.CrossRefPubMed Corbridge TC, Wood LD, Crawford GP, Chudoba MJ, Yanos J, Sznajder JI: Adverse effects of large tidal volume and low PEEP in canine acid aspiration. Am Rev Respir Dis 1990, 142: 311-315.CrossRefPubMed
35.
go back to reference Mancini M, Zavala E, Mancebo J, Fernandez C, Barbera JA, Rossi A, Roca J, Rodriguez-Roisin R: Mechanisms of pulmonary gas exchange improvement during a protective ventilatory strategy in acute respiratory distress syndrome. Am J Respir Crit Care Med 2001, 164: 1448-1453.CrossRefPubMed Mancini M, Zavala E, Mancebo J, Fernandez C, Barbera JA, Rossi A, Roca J, Rodriguez-Roisin R: Mechanisms of pulmonary gas exchange improvement during a protective ventilatory strategy in acute respiratory distress syndrome. Am J Respir Crit Care Med 2001, 164: 1448-1453.CrossRefPubMed
36.
go back to reference Nieman GF, Bredenberg CE, Clark WR, West NR: Alveolar function following surfactant deactivation. J Appl Physiol 1981, 51: 895-904.PubMed Nieman GF, Bredenberg CE, Clark WR, West NR: Alveolar function following surfactant deactivation. J Appl Physiol 1981, 51: 895-904.PubMed
37.
go back to reference DiRocco JD, Pavone LA, Carney DE, Lutz CJ, Gatto LA, Landas SK, Nieman GF: Dynamic alveolar mechanics in four models of lung injury. Intensive Care Med 2006, 32: 140-148. 10.1007/s00134-005-2854-3CrossRefPubMed DiRocco JD, Pavone LA, Carney DE, Lutz CJ, Gatto LA, Landas SK, Nieman GF: Dynamic alveolar mechanics in four models of lung injury. Intensive Care Med 2006, 32: 140-148. 10.1007/s00134-005-2854-3CrossRefPubMed
38.
go back to reference Broccard AF, Hotchkill JR, Vannay C, Market M, Sauty A, Feihl F, Schaller MD: Protective effects of hypercapnic acidosis on ventilator-induced lung injury. Am J Respir Crit Care Med 2001, 164: 802-806.CrossRefPubMed Broccard AF, Hotchkill JR, Vannay C, Market M, Sauty A, Feihl F, Schaller MD: Protective effects of hypercapnic acidosis on ventilator-induced lung injury. Am J Respir Crit Care Med 2001, 164: 802-806.CrossRefPubMed
39.
go back to reference Ricard JD, Dreyfuss D, Saumon G: Production of inflammatory cytokines in ventilator induced lung injury: a reappraisal. Am J Respir Crit Care Med 2001, 163: 1176-1180.CrossRefPubMed Ricard JD, Dreyfuss D, Saumon G: Production of inflammatory cytokines in ventilator induced lung injury: a reappraisal. Am J Respir Crit Care Med 2001, 163: 1176-1180.CrossRefPubMed
Metadata
Title
Effect of positive end-expiratory pressure and tidal volume on lung injury induced by alveolar instability
Authors
Jeffrey M Halter
Jay M Steinberg
Louis A Gatto
Joseph D DiRocco
Lucio A Pavone
Henry J Schiller
Scott Albert
Hsi-Ming Lee
David Carney
Gary F Nieman
Publication date
01-02-2007
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2007
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc5695

Other articles of this Issue 1/2007

Critical Care 1/2007 Go to the issue