• Journal of Chest Surgery
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• v.31 no.2
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• pp.108-112
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• 1998

Experimental trials of unilateral lung transplantation in dogs have been attempted and satisfactory results were obtained without any noticeable difficulty in surgical techniques. Fourteen dogs with the body weight of around 25 kg were anesthesized by 20~30 mg/kg of intravenous Entobar,; one was sacrificed to make available blood for use during transplantation for the recipient dog. A mid-sternotomy incision was performed and 20 mg/kg of Prostaglandin E1 was infused through the pulmonary artery and Euro-Collin's(E-C) preservation solution, cooled down to 4$^{\circ}C$, was perfused at the rate of 70cc/kg by a pressure of 30 cmH2O. The heart-lung block was then resected out and promptly immersed in the prepared preservation solution at 4$^{\circ}C$. One lung preserved in the EC solution at 4$^{\circ}C$ was anastomosed to the recipient dog in the order of the pulmonary vein, bronchus then pulmomary artery and the thoracotomy incision was closed after the bleeding control and tube thoracostomy. Then the pneumonectomy in the opposite side was perfomed in the same manner and the tailored lung was transplanted in the order of the pulmonary vein, bronchus, then pulmonary artery. We conclude that in the bilateral sequential lung transplantation, the right lung transplantation should precede to better expose the operative field and to prevent reperfusion injury; also, the cardiopulmonary bypass should be consider for certain appropriate cases.

• Journal of Nutrition and Health
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• v.32 no.3
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• pp.318-326
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• 1999

Apoptotic cell death, characterized by DNA fragmentation and morphological changes, has previously been shown to occur in vascular endothelial cells cultured with hydrogen peroxide. The present study examined the induction of apoptosis by hydrogen peroxide and whether pyruvate, a key glycolytic intermediate and $\alpha$-keto-monocarboxylate, can inhibit the apoptotic effects in bovine pulmonary artery endothelial cells(BPAECs). Culture with 500uM hydrogen peroxide resulted in 30% cell death and induced morphological changes and DNA fragmentation. Cell injury was inhibited by the treatment with pyruvate. Pyruvate(0.1-5.0mM), and cell viability increased in a dose-dependent manner. In the presence of pyruvate(10~20mM), the viability was improved to over 95%. In contrast, treatment with lactate, a reduced form of phyuvate, did not protect against cell death oxidative stress-induced loss of viability and apoptosis was examined with $\alpha$-cyano-3-hydroxycinnarmate(COHC) as a selective mitochondrial monocarboxylate transport blocker. Incubation with COHC(500uM) did not significantly affect cell viability in the presence of hydrogen peroxide. The cytoprotection by pyruvate(3mM)against hydrogen peroxide stress was abolished by COHC. This indicates that the cytoprotection by pyruvate against oxidative stress in endothelial cells is mediated, at least in part, by mitochondrial pyruvate uptake and hence endothelial enerygetics. However, cytosolic mechanisms related, at least in part, by mitochondrial pyruvate uptake and hence endothelial energetics. However, cytosolic mechanisms related to the glutathione system may also contribute. The results suggest that pyruvate has therapeutic potential in the treatment of oxidative stress-induced cytotoxicity associated with increased apoptosis.

• Journal of Chest Surgery
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• v.32 no.5
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• pp.413-421
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• 1999

Background: Ischemia reperfusion injury is known to contribute to the major causes of the early graft failure in lung transplantation. Triiodothyronine (T3) has been suggested to ameliorate ischemia reperfusion injury from both in vivo and in vitro experiments of various organs. Prospecting its beneficial effect for pulmonary allograft preservation, we made a new solution by adding T3 into the extracellular type dextran solution. Material and Method: Twelve adult mongrel dogs underwent left lung allotransplantation. Six donor dogs were flushed with the new solution(Group 1, n=6), and the remaining six were flushed with Euro-Collins solution to serve as controls(Group 2, n=6). Allografts were stored in each preservation solution for 20 hours at 4$^{\circ}C$. Left single lung transplantations were performed. The right pulmonary artery and the right main bronchus were clamped at 15 minutes after the reperfusion and maintained throughout the experiment to evaluate the transplanted left lung function. Result: Arterial carbon dioxide tension was better in group 1 than in group 2 throughout the experiment period and the difference was statistically significant at 2 hours after reperfusion(28.0${\pm}$3.0 mmHg and 53.1${\pm}$17.4 mmHg, p<0.05). The differences of arterial oxygen partial pressure, peak airway pressure and pulmonary vascular resistance showed no statistical significance. The malondialdehyde(MDA) level, measured from tissue obtained at 120 minutes after reperfusion showed no statistically significant difference. The tissue wet/dry ratio of group 1(649${\pm}$27 %) was significantly lower than that of group 2(686${\pm}$71 %, p<0.05). The microscopic examination revealed varying degrees of injury represented mainly by findings such as perivascular neutrophil infiltration, capillary hemorrhage and interstitial congestion. These findings were less severe in group 1 than those in group 2. Conclusion: The new solution demonstrated superior allograft preservation after 20 hour ischemia compared to Euro-Collins solution in canine single left lung transplantation model, these results suggest that T3 might be a promising agent for pulmonary allograft preservation.

• Journal of Chest Surgery
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• v.35 no.7
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• pp.501-510
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• 2002

Background: The various pathogeneses of acute respiratory distress syndrome have been suggested but not established yet. In the present study, the role of group II phospholipase $A_2$($PLA_2$) in the pathogenesis of gut ischemia-reperfusion(I/R) induced acute lung injury (ALI), especially in the pulmonary oxidative stress with infiltration of neutrophils was investigated. Material and Method: To induce ALI, reperfusion of mesentery was done for 120 min after clamping of superior mesenteric artery for 60 min in Sprague-Dawley rats that weighed about 300g. To exmaine the role of group II $PLA_2$ in ALI, especially endothelial injury associated with the action of neutrophils, lung myeloperoxidase activity, lung leak index, bronchoalveolar lavage fluid protein were measured, and pulmonary $PLA_2$ activity changes in gut I/R were also measured. The role of group II $PLA_2$in the neutrophilic generation of free radicals was assessed by inhibiting group II $PLA_2$ with rutin, manoalide and scalaradial. Furthermore, to verify the oxidative stress in the lung, histologic and free radical detecting cytochemical electron microscopy were done. Result: After reperfusion, ALI was developed with accumulation of neutrophils in the lung, which was confirmed by the increase of myeloperoxidase activity, lung leak index and bronchoalveolar lavage protein (p<0.001). The pulmonary and intestinal group II $PLA_2$ activities significantly increased after gut I/R which were reversed by rutin(p<0.001). In vitro, cytochrome-c reduction assay denoted the inhibitory effects of rutin, scalaradial and manoalide on the production of free radicals from isolated human neutrophils. Histologically, neutrophilic accumulation and pericapillary edema in the lung after gut I/R was detected by light microscopy which was suppressed by rutin. In $CeCl_3$ cytochemical electron microscopy, the increased production of hydrogen peroxide in the lung after gut I/R was confirmed and also the production of hydrogen peroxide was decreased by rutin. Conclusion: On the basis of these experimental results, the inhibition of group II $PLA_2$ seemed to mitigate gut I/R-induced ALI by suppressing the production of free radicals from the infiltrated neutrophils. Collectively, group II $PLA_2$ seems to play a crucial role in gut I/R-induced ALI by neutrophilic oxidative stress.

• Journal of Korean Neurosurgical Society
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• v.46 no.2
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• pp.99-102
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• 2009

Objective: Cardiac dysfunction after aneurysmal subarachnoid hemorrhage (SAH) is associated with elevation of serum cardiac troponin I (cTnl) levels. Elevation of cTnl predicts cardiopulmonary and neurological complications, and poor outcome. Methods: We retrospectively reviewed the medical and radiologic records of 114 (male: 30, female: 84) patients who developed aneurysmal SAH between January 2006 and June 2007 and had no history of previous cardiac problems. We evaluated their electrocardiography and cTnl level, which had been measured at admission. A cTnl level above 0.5 $\mu$g/L was defined as an indicator of cardiac injury following SAH. We examined various clinical factors for their association with cTnl elevation and analyzed data using chi-square test, t-test and logistic regression test with SPSS version 12.0. The results were considered significant at p< 0.05. Results: The following parameters shows a correlation with cTnl elevation: higher Hunt-Hess (H-H) grade (p = 0.000), poor Glasgow Outcome Scale (GOS) score (p = 0.000), profound pulmonary complication (p = 0.043), higher heart rate during initial three days following SAH (p = 0.029), ruptured aneurysm on communicating segment of internal carotid artery (p = 0.025), incidence of vasospasm (p = 0.421), and duration of hyperdynamic therapy for vasospasm (p = 0.292). A significant determinants for outcome were cTnl elevation (p = 0.046) and H-H grade (p = 0.000) in a multivariate study. Conclusion: A cTnl is a good indicator for cardiopulmonary and neurologic complications and outcome following SAH. Consideration of variable clinical factors that related with cTnl elevation may be useful tactics for treatment of SAH and concomitant complications.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.263-273
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• 1999

The role of phospholipase $A_2\;(PLA_2)$ in acute lung leak induced by intestinal ischemia was investigated in association with neutrophilic respiratory burst. To induce lung leak, we generated intestinal ischemia for 60 min prior to the 120 min reperfusion by clamping superior mesenteric artery in Sprague-Dawley rats. Acute lung leak was confirmed by the increased lung leak index and protein content in bronchoalveolar fluid. These changes were inhibited by mepacrine, the non-specific $PLA_2$ inhibitor. The lung myeloperoxidase (MPO) activity denoting the pulmonary recruitment of neutrophils was increased by intestinal I/R, but decreased by mepacrine. Simultaneously, the number of leukocytes in bronchoalveolar fluid was increased by intestinal ischemia/reperfusion (I/R) and decreased by mepacrine. Gamma glutamyl transferase activity, an index of oxidative stress in the lung, was increased after intestinal I/R but decreased by mepacrine, which implicates that $PLA_2$ increases oxidative stress caused by intestinal I/R. The $PLA_2$ activity was increased after intestinal I/R not only in the intestine but also in the lung. These changes were diminished by mepacrine. In the cytochemical electron microscopy to detect hydrogen peroxide, intestinal I/R increased the generation of the hydrogen peroxide in the lung as well as in the intestine. Expression of interleukin-1 (IL-1) in the lung was investigated through RT-PCR. The expression of IL-1 after intestinal I/R was enhanced, and again, the inhibition of $PLA_2$ suppressed the expression of IL-1 in the lung. Taken together, intestinal I/R seems to induce acute lung leak through the activation of $PLA_2$, the increase of IL-1 expression associated with increased oxidative stress by neutrophilic respiratory burst.

• Journal of Chest Surgery
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• v.34 no.9
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• pp.672-679
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• 2001

Background: Surgical correction of partial anomalous pulmonary venous connection to the superior vena cava has been associated with postoperative venous obstruction and sinus node dysfunction. In this paper we describe our current approach and its short-term results. Material and Method: Between April 1999 and January 2000, 5 consecutive patients, ranging from 2 months to 66 years old, underwent corrective operation for partial anomalous pulmonary venous connection to the superior vena cava at Sejong General Hospital and Daegu Catholic University Medical Center. Surgical correction involved diversion of the pulmonary venous drainage to the left atrium using a right atrial flap(2 patients) or prosthetic patch(3 patients) with division of the superior vena cava superior to the restore site of the pulmonary veins and reimplantation on the right atrial appendage to restore systemic venous drainage. Result: All patients were discharged between postoperative day 9 and 15 without complications. One Russian boy returned to his country, therefore, he was lost to follow-up after discharge. Remaining 4 patients were asymptomatic and in normal regular sinus rhythm at a mean follow-up of 17.75$\pm$4.27 months. Follow-up echocardiographic study (range, 12 to 24 months) revealed no incidence of narrowing of the venous pathways or of residual shunt. Conclusion: Our current approach is relatively simple and reproducible in achieving unobstructive pulmonay venous and SVC pathways. By avoiding incision across the cavoatrial junction, surgical injury to the sinus node and its artery may be minimized. The presented surgical technique can be safely and effectively applied to the selected patients.

• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.516-521
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• 2003

The Aspergillus species produces metabolic products that play a significant role in the destructive processes in the lung. We experienced a case of chronic necrotizing pulmonary aspergillosis caused by an Aspergillus niger infection, which contained numerous calcium oxalate crystals in the necrotic lung tissue. A 46-year-old man, who had a history of pulmonary tuberculosis, presented with high fever, intermittent hemoptysis and pulmonary infiltrations with a cavity indicated by the chest radiograph. Despite being treated with several antibiotics and anti-tuberculosis regimens, the high fever continued. The sputum cultures yielded A. niger repeatedly, and intravenous amphotericin B was then introduced. The pathological specimen obtained by a transbronchial lung biopsy revealed numerous calcium oxalate crystals in a background of acute inflammatory exudates with no identification of the organism. Intravenous amphotericin B was continued at a total dose of 1600 mg, and at that time he was afebrile, although the intermittent hemoptysis continued. On the $63^{rd}$ hospital day, a massive hemoptysis (about 800 mL) developed, which could not be controlled despite embolizing the left bronchial artery. He died of respiratory failure the next day. It is believed that the oxalic acid produced by A. niger was the main cause of the patient's pulmonary injury and the ensuing massive hemoptysis.

• Journal of Chest Surgery
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• v.36 no.8
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• pp.576-582
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• 2003

During the Off-Pump Coronary Arterial Bypass surgery (OPCAB), the manipulation of the heart can depress cardiac contractility and cause hemodynamic instability. In this study, hemodynamic parameters were measured during operation and the laboratory and clinical data were investigated to evaluate their effects on postoperative outcome. Material and Method: From March 2001 to August 2002, 50 consecutive patients who underwent OPCAB were included in this study. During the same period, total number of CABG was 71 The blood pressure, pulmonary artery pressure, mixed venous oxygen saturation, and cardiac index were measured before manipulation, after application of stabilizer, and at the end of anastomosis. Postoperatively, we measured the cardiac enzymes such as CK-MB, troponin 1 and checked the amount of inotropes required, chest tube drainage, the amount of transfusion, duration of ventilator support, and duration of ICU stay. Result: The number of mean distal anastomoses was 2.8$\pm$0.9 per patient. On elevation and stabilization of the heart, systolic blood pressure was depressed and pulmonary artery pressure was elevated significantly, but during each anastomosis no significant changes were detected. The peak level of cardiac markers was 29.2$\pm$46.7 for CK-MB, 0.69$\pm$0.86 for troponin 1 on postoperative day f. Among the intraoperative hemodynamic parameters, the ischemic change of EKG and bolus injection of inotropes significantly affected the posteroperative cardiac enzymes. But, no difference other than the level of cardiac enzymes between the two groups with or without the ischemic change of EKG and bolus injection of inotropes was noticed. Conclusion: The significant hemodynamic changes occurred when the heart was elevated and stabilized, however during anastomoses there were no significant changes. Serum cardiac enzymes rose significantly in the group that showed the ischemic charge of EKG or needed the bolus injection of inotropes for maintaining hemodynamic stability intraoperatively, but it did not affect the postoperative outcome. In conclusion, the ischemic change of EKG and the need for bolus injection of intropes during operation may be very indicative for probable ischemia.

• Tuberculosis and Respiratory Diseases
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• v.54 no.5
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• pp.532-541
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• 2003

Background : Phospholipase $A_2$ ($PLA_2$) has been known to be involved in the pathogenesis of acute lung injury (ALI) including ARDS. Since doxycycline has the property of inhibiting secretory group II $PLA_2$, the therapeutic effect of doxycycline hyclate was investigated for gut ischemia/reperfusion (I/R)-induced ALI in Sprague-Dawley rats. Methods : ALI was induced in Sprague-Dawley rats by clamping of the superior mesenteric artery for 60 min, followed by 120 min of reperfusion. To confirm the pathogenetic mechanisms of this ALI associated with neutrophilic oxidative stress, we measured bronchoalveolar lavage (BAL) protein content and lung MPO, and performed cyto-chemical electron microscopy for detection of free radicals, assay of $PLA_2$ activity and cytochrome-c reduction assay. Results : In gut I/R-induced ALI rats, protein leakage, pulmonary neutrophil accumulation, free radical production and lung $PLA_2$ activity were all increased. These effects were reversed by doxycycline hyclate. Conclusion : Doxycycline appears to be effective in ameliorating the gut I/R-induced ALI by inhibiting $PLA_2$, thereby decreasing the production of free radicals from neutrophils.