Static Inflation Attenuates Ischemia/Reperfusion Injury in an Isolated Rat Lung In Situ

doi:10.1378/chest.126.2.552

Chest

Volume 126, Issue 2, August 2004, Pages 552-558

https://doi.org/10.1378/chest.126.2.552 Get rights and content

Study objectives:

Ischemia (I)/reperfusion (R) lung injury is an important clinical issue in lung transplantation. In the present study, we observed the effects of lung static inflation, different perfusates, and ventilatory gas with nitrogen or oxygen on the I/R-induced pulmonary damage.

Design and setting:

A total of 96 male Sprague-Dawley rats were used. The lung was isolated in situ.

Methods:

In an isolated lung, the capillary filtration coefficient (Kfc), lung weight gain (LWG), lung weight (LW)/body weight (BW) ratio, and protein concentration in BAL fluid (PCBAL) were measured or calculated to evaluate the degree of lung injury. Histologic examinations with hematoxylin-eosin staining were performed.

Results:

I/R caused lung injury, as reflected by increases in Kfc, LWG, LW/BW, and PCBAL. The histopathologic picture revealed the presence of hyaline membrane formation and the infiltration of inflammatory cells. These values were significantly attenuated by static lung inflation. The I/R lung damage appeared to be less in the lung perfused with whole blood than in the lung perfused with an isotonic solution. Therapy with ventilatory air (ie, nitrogen or oxygen) did not alter the I/R lung damage.

Conclusions:

The data suggest that lung inflation is protective to I/R injury, irrespective of the type of ventilatory air used for treatment. The preservation of the lung for transplantation is better kept at a static inflation state and perfused with whole blood instead of an isotonic physiologic solution.

Section snippets

Preparation of the Isolated Lung

The preparation of an isolated rat lung in situ model has been described previously.⁹¹⁶¹⁷¹⁸ In brief, a total of 96 male Sprague-Dawley rats weighing 250 to 350 g were anesthetized intraperitoneally with sodium pentobarbital (30 mg/kg) and were intubated with an endotracheal tube. A rodent ventilator provided ventilation with a mixture of 95% room air and 5% carbon dioxide. The respiratory rate was set at 60 to 65 breaths/min, and tidal volume was set at 2 to 3 mL. The inspiratory pressure and

Kfc

Figure 1illustrates Kfc changes by I/R in the isolated lung perfused with whole blood or KHS. I/R caused a marked increase in Kfc. Static lung inflation significantly attenuated the increase in Kfc. The mean Kfc change in the lung perfused with whole blood (1.54 ± 0.46 g/min/cm H₂O per 100 g) was lower than that in the lung perfused with KHS (2.31 ± 0.18 g/min/cm H₂O per 100 g; p < 0.05).

LWG and LW/BW Ratio

Figure 2shows that I/R increased LWG during the R period for 50 min. Static inflation significantly reduced

Discussion

Previous studies have reported an association between the state of lung inflation and I/R injury. Puskas and coworkers¹⁰ noted that donor lung storage in the inflated state during organ perfusion improved the outcome. Stevens et al¹¹ also reported improved lung preservation by prevention of lung collapse. However, there have also been conflicting reports¹²¹³ indicating that hyperinflation of the preserved lung led to a worse outcome. In fact, Aoe et al¹⁴ showed that immediate postpreservation

ACKNOWLEDGMENT

The authors are grateful to Liu Yen Chin for his excellent assistance in the technique used, to Lucy Chen from Simon Fraser University (Burnaby, BC, Canada) for improving the English writing, to Dr. Y. W. Lee for her help in the statistical analysis, and to C. C. Chang for the preparation of this manuscript.

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: This study was supported in part by grants from the National Science Council (90–2320-B-320–002, 90–2316-B-320–004, and NSC 91–2320-B-320–008), and by the Shin Kong Wu-Ho Su Memorial Foundation and the Outstanding Scholarship Development Foundation (1996–2001).

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Chest

Laboratory and Animal InvestigationsStatic Inflation Attenuates Ischemia/Reperfusion Injury in an Isolated Rat Lung In Situ

Study objectives:

Design and setting:

Methods:

Results:

Conclusions:

Section snippets

Preparation of the Isolated Lung

Kfc

LWG and LW/BW Ratio

Discussion

ACKNOWLEDGMENT

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Surg Res

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Heart Lung Transplant

Reperfusion pulmonary edema after pulmonary artery thromboendarterectomy

Am Rev Respir Dis

Reperfusion pulmonary edema after thrombolytic therapy of massive pulmonary embolism

Am Rev Respir Dis

Pulmonary reimplantation response in single-lung transplantation

Eur Respir J

Early function as the principal correlate of graft survival

Transplantation

The influence of preservation injury on rejection in the hepatic transplant recipient

Transplantation

Ischemia-reperfusion lung injury in rabbits: mechanisms of injury and protection

Am J Physiol

Vascular distension and continued ventilation are protective in lung ischemia/reperfusion

Am J Respir Crit Care Med

Protective effect of mepacrine on hypoxia-reoxygenation-induced acute lung injury in rats

J Appl Physiol

Intermittent positive-pressure hyperventilation with high inflation pressures produces pulmonary microvascular injury in rats

Am Rev Respir Dis

O2radicals mediate reperfusion lung injury in ischemic O2-ventilated canine pulmonary lobe

J Appl Physiol

Laboratory and Animal Investigations
Static Inflation Attenuates Ischemia/Reperfusion Injury in an Isolated Rat Lung In Situ

O₂radicals mediate reperfusion lung injury in ischemic O₂-ventilated canine pulmonary lobe