A preclinical animal study to evaluate the operability and safety of domestic one-way endobronchial valves

Abstract

Purpose: To evaluate the operability and safety of bronchoscopic domestic one-way endobronchial valves (EBV) on animals.

Methods: Nine pigs were randomly assigned (2:1) to receive domestic one-way EBV (the experimental group, n = 6) and Zephyr^® EBV (the control group, n = 3). Routine blood tests, arterial blood gases, and CT scans of the lungs were performed 1 day pre-procedure in addition to 1 week and 1 month post-procedure to assess changes in blood markers and lung volumes. At 1 month post-procedure, the animals were sacrificed, followed by removal of all valves via bronchoscopy. Pathological examinations of critical organs were subsequently performed.

Results: A total of 15 valves were placed in the experimental group and 6 valves were placed in the control group, without serious complications. Routine blood tests and arterial blood gas examinations at 1 day pre-procedure, 1 week post-procedure, and 1 month post-procedure did not differ significantly in both groups. No EBV displacement was noted under bronchoscopy, and the valve was smoothly removable by bronchoscope at 1 month post-procedure. At 1 week post-procedure, varying degrees of target lung lobe volume reduction were observed on lung CT in both groups. Lung volume reduction was achieved at 1 month post-procedure in both groups, without significant statistical difference. Although 3 cases in the experimental group and 1 case in the control group developed varying degrees of pneumonia, the inflammatory response did not increase over time during the experimental period. Pathological examination revealed no significant abnormal changes in the critical organs for both groups.

Conclusion: Our results demonstrate that domestic EBV is safe and reliable for endobronchial application in general-grade laboratory white pigs. The safety of domestic EBV is similar to that of Zephyr^® EBV, with good ease of use and operability. This kind of domestic EBV can meet the safety evaluation requirements for animal testing.

Keywords: animal; bronchoscopy; emphysema; lung volume reduction; one-way endobronchial valve; operability; safety.

Figure 1

Comparison of two groups of endobronchial valves (EBV) styles. (A) The EBV of experimental group with 6-segment waveform structure at the near end. (B) The EBV of control group with 5-segment waveform structure at the near end.

Figure 2

Bronchoscopic views of the experimental (No. P-1536, A–C) and control (No. P-1538, D–F) groups at different time points after the product placement. (A,D) Placement in the left lower lobe during surgery; (B,E) Condition around the valve opening 1 month post-surgery; (C,F) Smooth removal at 1 month post-surgery.

Figure 3

Lung CT (A–C) and 3D reconstruction (D–F): Blue, yellow, and green section represent the right upper lobe (RUL), right middle lobe (RML), and right lower lobe (RLL), respectively images of the lungs of the experimental group at different time points after product placement in animal No. P-1542: (A) 1 day pre-surgery; (B) Visible volume reduction in the RML at 7 days post-surgery; (C) Visible volume reduction in the RML at 1 month post-surgery; (D) The volume of RML was 65.8 mL 1 day pre-surgery; (E) The volume of RML was 0 mL at 7 days post-surgery; (F) The volume of RML was 2.9 mL at 1 month post-surgery.

Figure 4

Lung CT (A–C) and lobe segmentation (D–F): Yellow-green, blue and green section represent the right upper lobe (RUL), right middle lobe (RML), and right lower lobe (RLL), respectively images of the lungs of the control group at different time points after product placement in animal No. P-1535: (A) 1 day pre-surgery; (B) Visible volume reduction in the RML at 7 days post-surgery; (C) Visible volume reduction in the RML at 1 month post-surgery; (D) The volume of RML was 53.8 mL 1 day pre-surgery (RUL and RLL were mostly consolidated); (E) The volume of RML was 0 mL at 7 days post-surgery; (F) The volume of RML was 12.6 mL at 1 month post-surgery.

Figure 5

Pathological specimens of organs in the experimental (No. P-1536, A–E) and control (No. P-1523, F–J) groups were presented in the order of heart, liver, kidney, brain, and spleen from left to right.