A total of 60 patients were enrolled in this study, however, three patients were excluded from the data analysis. The final analyses included 28 patients in group O and 29 patients in group C (Fig. 1).
Patients’ characteristics and surgical conditions, postoperative pulmonary complications were not different between two groups (P> 0.05) (Table 1).
Table 1 Patient characteristics
Variable
|
Group O (n=28)
|
Group C (n=29)
|
Sex (M/F)
|
13/16
|
13/15
|
Age(years)
|
63.42±5.34
|
65.88±4.80
|
Height(cm)
|
162.16±6.90
|
163.125±7.08
|
Weight(kg)
|
63.48±7.47
|
64.34±5.46
|
ASA class I/II
|
13/15
|
12/17
|
Preoperative pulmonary function (normal / abnormal)
|
21/10
|
16/16
|
Anesthesia time (min)
|
254.03±58.69
|
260.69±55.48
|
Operation time (min)
|
202.10±50.63
|
210.01±48.56
|
OLV time (min)
|
172.71±51.15
|
170.21±47.44
|
Hospitalization time (d)
|
16.45±3.42
|
18.65±3.22
|
Postoperative hospital stay (d)
|
9.03±2.11
|
9.21±2.06
|
Second intubation
|
0
|
0
|
Chest tube indwelling time (d)
|
6.26±1.75
|
6.34±1.73
|
The data are expressed as the mean ± SD values or the number of patients. ASA, American Society of Anesthesiologists
The levels of arterial and venous blood gas analysis are given in table 2. The results of statistical analysis are presented in Fig. 2, from which we can see at T2-4, the PaO2 levels were significantly higher in group O than in group C (127±4.2 vs 90±2.2, 180±8 vs 92±2.1, 196±7.7 vs 91±2.2). At T2-3, the PaCO2 levels were significantly lower in group O than in group C (41.7±4.4 vs 45.9±3.4, 40.5±5.7 vs 44.2±3.2). At T2-3, the PvO2 levels were significantly higher in group O than in group C (61±1.7 vs 42±1.3, 58±1.7 vs 46±2.4). At T2-4, the PvCO2 levels were significantly lower in group O than in group C. (50±0.5 vs 57±0.6, 50±0.6 vs 62±0.9, 46±0.8 vs 59±0.7).
Table 2 Blood gas analysis
Variable
|
Group
|
T1
|
T2
|
T3
|
T4
|
PaO2(mmHg)
|
O(n=28)
|
337±10.4
|
127±4.2*
|
180±8*
|
196±7.7*
|
|
C(n=29)
|
318±4.9
|
90±2.2
|
92±2.1
|
91±2.2
|
PaCO2(mmHg)
|
O(n=28)
|
40.9±5.6
|
41.7±4.4*
|
40.5±5.7*
|
43.3±5.5
|
|
C(n=29)
|
35.6±1.4
|
45.9±3.4
|
44.2±3.2
|
43.0±3.4
|
PvO2(mmHg)
|
O(n=28)
|
54±3.1
|
61±1.7*
|
58±1.7*
|
58±1.6
|
|
C(n=29)
|
53±2.7
|
42±1.3
|
46±2.4
|
48±2.6
|
PvCO2(mmHg)
|
O(n=28)
|
47±1.1
|
50±0.5*
|
50±0.6*
|
46±0.8*
|
|
C(n=29)
|
51±0.9
|
57±0.6
|
62±0.9
|
59±0.7
|
The data are expressed as the mean ± SD values. *P < 0.05 compared with group C
The levels of SOD, MDA and the expression levels of HO-1in the lung tissue are given in table 3. The results of statistical analysis and the image of western-blotting are presented in Fig. 3, from which we can see that the levels of MDA were lower in group O than in group C (8.09±3.30 vs 17.39±8.40); however, the HO-1 expression levels were higher in group O than in group C (0.76±0.49 vs 0.21±0.15) (table3)
Table 3 MDA, SOD levels and expression of HO-1
Variable
|
Group O(n=28)
|
Group C(n=29)
|
SOD (U/mgprot)
|
13.46±2.97
|
17.69±1.65
|
MDA (nmol/mgprot)
|
8.09±1.30*
|
17.39±2.40
|
HO-1 expression
|
0.76±0.09*
|
0.21±0.05
|
The data are expressed as the mean ± SD values. *P < 0.05 compared with group C
Discussion
Temporary, one lung ventilation (OLV) is an anesthetic procedure performed to facilitate thoracic surgeries. While this procedure is medically necessary, there is ample evidence to suggest that OLV procedures can lead to lung injury through various mechanisms. These include hypoxia, ischemia/reperfusion, mechanical injury in the collapsed lung, hyperperfusion of the ventilated lung (due in part to its gravitationally dependent positioning during surgery and in part to pulmonary shunting and over distension of alveoli), and oxidative injury from high FiO2[1,10], which are causes of ALI after surgery. Protective ventilation is essential to reduce lung injury. Therefore, protective ventilation (including tidal volume, respiratory frequency and PEEP) was applied before OLV and for the ventilated lung during OLV to reduce the influence of non-research factors on the observed factors.
As for collapsed lung, protective OLV results in reduced ALI, critical care admissions, and hospital length of stay[11]. Continuous Positive Airway Pressure(CPAP) should be considered as one of the protective ventilation during OLV for collapsed lung to avoid dense atelectasis and minimize the shunt fraction. The incomplete lung collapse associated with CPAP is compatible with many chest wall and peripheral lung procedures. Even during thoracoscopic procedures, low-level CPAP of 2 cm H2O has been shown to be feasible without impairing surgical exposure[5]. This approach has been shown to reduce hypoxic pulmonary vasoconstriction(HPV) and attenuate inflammatory cytokine release during clinical esophagectomy[12]. The impact of recruitment maneuvers on the alveolar−capillary membrane may be minimized by the use of slow airway pressure increases[13] and cycling maneuvers[14]. The use of lower FiO2 during recruitment maneuvers may reduce the creation of reactive oxygen species, but this has not been studied in the OLV setting[15]. Therefore, we applied the continuous administration of low-medium flow oxygen (1-4L/min) and maintain the pressure between 1-2 cmH2O for NVL to simulate CPAP in our study. Our result showed that compared with group C, the PaO2 levels increased at T2-4 in group O, the PaCO2 levels decreased at T2,3, the PvO2 levels increased at T2,3, the PvCO2 levels decreased at T2-4, implying that the continuous administration of low-medium flow oxygen for NVL during OLV may improve partial pressure of oxygen (PO2) and lower partial pressure of carbon dioxide (PCO2) to improve abnormal ventilation / blood flow ratio in NVL and thus play a role in lung protection.
Chow CW et al reported that lung parenchyma is one of the largest accumulations of neutrophils, monocytes and macrophages, and is also an important organ for oxidative stress reaction[16]. (After Ipsilateral lung recover ventilation and, but a large number of oxygen molecules into the tissues release large amounts of oxygen free radicals and cause tissue damage). Once ipsilateral lung ventilation recovers and low blood perfusion lung/hypoxia improves, excessive oxygen molecules in the tissues will release large amounts of oxygen free radicals and cause tissue damage. SOD is an oxygen free radical scavenger, widely presenting in the lung and having a protective effect on lung injury[17]. MDA is the final product of lipid peroxidation, directly reflecting the level of free radicals. The MDA content level is an important sign of tissue damage[18]. HO-1, the heme-degrading enzyme, has shown anti-inflammatory effects in several models of pulmonary diseases. HO-1 attenuates lung edema by inhibiting the oxidation of lipid membranes and scavenging free radicals, the expression level of which increases when hypoxia, ischemia or other noxious stimulations occurs[19]. Almolki A et al confirmed that upregulation of the HO pathway has a significant protective effect against oxidative stress response[20]. The result showed that The MDA levels in the lung tissue were lower in group O than in group C; however, the HO-1 expression levels were higher in group O than in group C, which implied that the administration of continuous low-medium flow oxygen for NVL during OLV may inhibit lung tissue oxidative stress response, resulting in the role of lung protection. The possible mechanism is as follows: 1. Improvement of hypoxia can directly affect the SOD content: Studies have shown that hypoxia can directly inhibit the generation of endogenous SOD. Improving the hypoxia can increase the content of SOD, accelerate the elimination of oxygen free radicals to inhibit oxidative stress[21-22]. The results of this study showed no significant difference in lung tissue SOD content between the two groups of patients. It may be related to the smaller sample size, also related to the decrease of antioxidant ability in patients with cancer. Misthos P et al founded that patients with cancer have a higher oxidative burden and may have less antioxidant capacity[8]. 2. Improvement of changes in the pulmonary circulation (HPV) caused by hypoxia in NVL can reduce the formation of oxygen free radicals: The existing research has shown that HPV is directly related to the generation of oxygen free radicals and oxidative stress response[23]. As HPV causes relatively insufficient perfusion in lung tissue, it directly causes the generation of oxygen free radicals and the destruction of vascular structure, and indirectly causes the release of various vasoactive factors and inflammatory factors, resulting in the occurrence of oxidative stress response. Cheng YD et al founded that during OLV in NVL, acute HPV is produced with increased systemic MDA, suggesting an increased oxidative stress response[6]. Therefore, the administration of continuous low-medium flow oxygen for NVL during OLV can improve the acute HPV occurrence in NVL in order to inhibit oxidative stress. 3. Ischemia-reperfusion injury: Acute HPV during OLV causes increased pressure on the pulmonary circulation, decreased blood flow and oxygen supply in NVL tissue, abnormalities in the production or inactivation of vasoactive substances in the tissue, which may cause or exacerbate pulmonary vascular endothelial cell damage such as cell swelling, interstitial edema or vascular wall permeability changes. Liu R et al have confirmed such pathophysiological process on rat-OLV model[24]. After reoxygenation, while hypoperfusion and hypoxia improve in NVL, a large number of oxygen molecules influx into the tissue, releasing a large number of oxygen free radicals, thus causing oxidative stress response, and then lung tissue damage. After clinically relevant durations of lung collapse in rat models[25] and patients, as reventilation after a period of clinical OLV substantially increased exhaled hydrogen peroxide concentrations in breath condensate, myeloperoxidase levels in bronchoalveolar lavage samples, and systemic markers of oxidative stress[8-9,26]. So the administration of continuous low-medium flow oxygen for NVL during OLV may inhibit the occurrence of ischemia-reperfusion injury to a certain extent. 4. Upregulation of HO-1 gene expression: Studies have shown that HO-1, one of the most important endogenous protective protein in the body, has a variety of physiological regulatory functions, such as anti-oxidation, anti-inflammatory response, anti-necrosis and cell protection[27]. HO-1 and its metabolites have strong antioxidant effects[28]. Our results showed that the expression of HO-1 was up-regulated in the lung tissues of the patients with continuous low-medium flow oxygen supply for the NVL during OLV compared with that in the control group, indicating that HO-1 could play a role in lung protection.