Background

While there is renewed interest in lung volume reduction surgery (LVRS) for treatment of emphysema, many aspects of the operation such as patient selection and surgical end points of excision are uncertain. We studied the effects of LVRS on measured lung volumes and diffusion capacity in an animal model to investigate optimal resection volumes.

Methods

Emphysema was induced in 32 New Zealand white (NZW) rabbits using aerosolized elastase. Helium dilution lung volumes and single breath DLCO were measured concurrently at baseline, following induction of emphysema (preop), and 1 week postoperatively (postop) following LVRS. Bilateral upper and middle lobe stapled lung resections were performed through midline sternotomies with excision of variable amounts of lung tissue from 1.8 to 5.8 g.

Results

FRC increased following induction of emphysema and decreased postoperatively. DLCO improved with increasing lung tissue resection up to 3 g of tissue and then decreased as even greater amounts were removed (r = 0.54).

Conclusions

Measured lung volumes increase with development of emphysema and appropriately decrease in response to LVRS in this rabbit model. DLCO improves with moderate resection but then decreases with excessive excision of lung quantities and may help define one physiologic operative end point. In this rabbit model, excision of approximately 30% of lung volume was optimal and prevented further decrease in diffusion capacity.

Recently described surgical approaches to the treatment of emphysema, including buttressed stapled volume reduction and laser coagulation, are associated with variable clinical outcomes. We examined objective preoperative factors as predictors of response to treatment in patients enrolled in a randomized trial of staple versus laser volume-reduction surgery in order to help define patient selection criteria for these procedures. Seventy-two patients with severe symptomatic emphysema without bullae were entered into the protocol (39 staple, 33 laser). Preoperative objective variables (pulmonary function tests, smoking history, demographics, and graded chest computed tomographic [CT] scans) were evaluated as predictors of response to treatment (defined as a change in FEV1) at 3- to 6-mo follow-up, using linear and multivariate regression analysis. Follow-up pulmonary function was obtained on 90% of the 68 patients surviving at 6 mo. Overall improvement was significant only for staple-treated patients, and improved outcome correlated with greater smoking history and younger age for staple-treated patients. When physiologic variables were analyzed, greater smoking history, lower DL(CO), and younger age predicted improved outcome for laser-treated patients. Preoperative FEV1 and gas-exchange variables did not predict outcome in staple-treated patients. When CT scan grading was included in multivariate regression analysis, hyperinflation (increased thoracic gas volume) was the primary predictor of response for laser-treated patients. These findings suggest that younger patients with evidence of advanced emphysematous lung disease and hyperinflation are optimal candidates for lung-volume-reduction surgery, particularly by staple-reduction techniques. Additional studies with long-term follow-up, bilateral procedures, and assessment of other outcome measures must be performed to further define operative criteria for lung-volume-reduction surgery for emphysema.

Objective

The purpose of this study is to investigate the effects of lung volume reduction surgery on pulmonary compliance, airway flow, and helium lung volumes in an elastase-induced emphysema animal model.

Methods

A 15,000-unit bolus of elastase was aerosolized through an endotracheal tube in 14 New Zealand White rabbits to induce emphysema. Stapled lung volume reduction of bilateral upper and middle lobes was performed through a midline sternotomy at 4 weeks after induction of emphysema. Lung functions were measured at baseline before induction of emphysema, preoperatively at 4 weeks, and 1 week postoperatively.

Results

Compliance increased after induction of emphysema and decreased in response to lung volume reduction surgery. Functional residual capacity decreased after lung volume reduction surgery in proportion to the amount of excised lung tissue. Expired flows suggested improvement in response to lung volume reduction surgery. Histologic examination confirmed presence of diffuse heterogeneous emphysema in each animal at necropsy.

Conclusions

The decreased compliance and increased airway flow after volume reduction surgery in this model parallels findings in human studies and suggests that similar mechanisms of increased elastic recoil and airway support contribute to improvement.

Stapled lung volume reduction surgery (LVRS) has recently been described for treatment of emphysema. Many questions arise regarding physiologic mechanisms of response from surgical treatment of emphysema. The objective of this study was to develop an animal model for the study of lung volume reduction surgery in diffuse heterogeneous emphysema. We hypothesized that elastic recoil would increase, static respiratory system compliance would decrease, and expiratory flows would increase after lung volume reduction surgery in animals with emphysema. In the study, emphysema was induced in 31 New Zealand White rabbits (3-5 kg) with endotracheally aerosalized porcine elastase (10,000-12,000 U). Lateral thoracotomies were performed 4-6 weeks postinduction under general anesthesia and mechanical ventilatory support. Stapled volume reduction was performed on the right lower lobe using a standard multirow pediatric stapler (U.S. Surgical). Pulmonary function tests were performed at baseline (preinduction), before stapling LVRS (postemphysema induction), immediately post stapling LVRS, and 1 week poststapling. Static respiratory system compliance, flow, conductance and forced expiratory flows, and peak flows at 20 and 40 cm3 of exhaled volume were analyzed. Animals were sacrificed 1 week poststapling, and bilateral lungs were harvested for histopathology. Diffuse but heterogeneous pulmonary emphysema was seen in these animals treated with high-dose aerosolized elastase. Static compliance increased, while expiratory flows and conductance decreased after induction of emphysema. Immediately post stapled volume reduction therapy, animals had decreased static compliance. By 1 week following surgery, animals showed increased forced expiratory flows and decreased expiratory resistance, although compliance was similar to preoperative levels. In conclusion, we describe initial results in an animal model of obstructive emphysema suitable for the study of lung volume reduction surgery. Changes in pulmonary function indicate that unilateral lower lobe LVRS increases airway conductance in the rabbits. Findings from LVRS studies in animal models such as this may help explain clinical improvement following LVRS in humans.

Objective

To determine the relative efficacy and morbidity of Ho:YAG versus Nd:YAG laser treatment of bullous lung disease in an animal model.

Summary background data

Laser coagulation procedures for treatment of emphysematous pulmonary bullae and heterogeneous emphysema continue to evolve. The role of lasers in lung volume reduction surgery remains controversial due to issues of relative efficacy and morbidity. The Nd:YAG laser is most commonly used for these procedures. We hypothesized that the shallower penetration of the Ho:YAG laser may be better suited for laser bullae coagulation and emphysema lung volume reduction with increased efficacy and reduced lung injury.

Methods

Thirty New Zealand White rabbits (15 normal rabbits; 15 with bullous lung disease) were evaluated with Ho:YAG compared to Nd:YAG laser exposures. Bullae were coagulated by either Ho:YAG or Nd:YAG treatment. In all animals (bullous-induced and normals), unaffected lung tissue in the upper lobes and contralateral lungs were treated with 5 spot exposures of Nd:YAG and Ho:YAG, each to assess depth of lung injury. Animals were sacrificed at Days 0, 7, and 21 and their lungs were examined histologically.

Results

Ho:YAG and Nd:YAG exposures caused equivalent lung injury to normal lung tissue. In the acute phase, parenchymal necrosis depth was similar for both Ho:YAG and Nd:YAG (850 +/- 273 microns vs. 900 +/- 270 microns respectively, p = 0.7). By Day 7, lung necrosis depth was 925 +/- 133 microns Ho:YAG vs. 1225 +/- 235 microns Nd:YAG (p = 0.33), and lung fibrosis depth was 300 +/- 134 microns Ho:YAG vs. 558 +/- 127 microns Nd:YAG (p = 0.11). By Day 21, pulmonary parenchymal necrosis was not seen. Pleural fibrosis depth was maximal at Day 21, reaching 250 +/- 102 microns for Ho:YAG vs. 300 +/- 156 microns Nd:YAG (P = 0.88). Pleural necrosis depth was 67 +/- 42 microns Ho:YAG vs 48 +/- 34 microns Nd:YAG (p = 0.42) on Day 7 and resolved by Day 21. During surgical coagulation procedures, the Ho:YAG laser was dramatically more efficient in coagulating bullae. The Ho:YAG laser required less exposure at equivalent power and resulted in immediate desiccation of bullae, in sharp contrast to the Nd:YAG laser.

Conclusions

Because the Ho:YAG was more effective and did not result in more acute lung injury than the standard Nd:YAG laser in this study, Ho:YAG lasers may have improved potential for laser treatment of bullae or lung volume reduction surgery (LVRS) compared to Nd:YAG lasers.

Lung volume reduction surgery (LVRS) has shown promising results in severe emphysema. However, intraoperative indicators are needed to define optimal resection volumes. Diffusing capacity (DLCO) worsens with larger LVRS and may correlate with pulmonary artery (PA) pressure. We hypothesized that there would be a greater increase in PA pressures with larger volume LVRS in an inhaled elastase animal emphysema model. Twenty-one rabbits were induced with 15,000 units of elastase via an endotracheal tube. Four weeks later, bilateral LVRS was performed through a median sternotomy using an endoscopic stapler. PA pressures were measured prior to LVRS, immediately after LVRS, and at sacrifice. Single-breath DLCO, static pressure-volume relationships, and forced expiratory flows were measured prior to induction and at corresponding times to PA pressures. Systolic PA pressures increased in both groups immediately after LVRS (small: 2. 67 +/- 9.2 mm Hg, ANOVA, P = 0.023; large: 3.8 +/- 8.5 mm Hg, P = 0. 002), and then decreased at time of sacrifice 1 week later (small: 9. 43 +/- 4.8 mm Hg, ANOVA, P = 0.053; large: 5.2 +/- 7.3 mm Hg, P = 0. 552). The decrease, at sacrifice, in PA pressures was greater for small LVRS animals than large LVRS animals. The mortality rate (MR) for the small resection group was 0%, whereas that for the large resection group was 24%. The MR associated with larger LVRS was appreciably greater than that associated with small LVRS. These studies suggest that PA pressures may prove to be a useful intraoperative indicator for limits of resection.