E A Bacha

Massachusetts General Hospital, Boston, MA, United States

Are you E A Bacha?

Claim your profile

Publications (19)52.9 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The 2 main causes of death after thromboendarterectomy for chronic pulmonary thromboembolism are incomplete repermeabilization responsible for persistent pulmonary hypertension and acute high-permeability pulmonary edema. We wish to establish an experimental model of chronic pulmonary thromboembolism to replicate the conditions encountered during and after pulmonary thromboendarterectomy. Methods: Multiple-curled coils and tissue adhesive were embolized in 6 piglets to induce complete obstruction of the left pulmonary artery, documented by angiography. After 5 weeks, the main pulmonary artery was repermeabilized by thromboendarterectomy during circulatory arrest. The left lung was reperfused ex vivo with autologous blood at constant flow, and patency of the pulmonary artery was evaluated on a barium angiogram. The endarterectomy-reperfusion procedure was also done in 6 nonembolized piglets that served as the controls. The severity of lung injury induced by 60 minutes of reperfusion was assessed on the basis of measurements of the lung filtration coefficient and of lung myeloperoxidase activity. Results: Marked hypertrophy of the bronchial circulation was seen in the chronic pulmonary thromboembolism group. Thromboendarterectomy removed the organized obstructing thrombus that was incorporated into the arterial wall and restored patency of the pulmonary artery. Acute lung inflammation and high-permeability edema occurred after reperfusion, as indicated by a 1.5-fold increases in both lung filtration coefficient and lung myeloperoxidase values in the chronic pulmonary thromboembolism group; these 2 variables being correlated. Conclusions: Our model replicated the perioperative conditions of pulmonary thromboendarterectomy, suggesting that it may prove useful for improving the repermeabilization technique and for investigating the mechanisms and prevention of reperfusion injury. (J Thorac Cardiovasc Surg 1999;117:787-93)
    Journal of Thoracic and Cardiovascular Surgery 05/1999; · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We previously described an original transcervical approach to resect primary or secondary malignant diseases that invade the thoracic inlet (TI). The purpose of this study was to evaluate the technical aspects and long-term results of the resection and revascularization of the subclavian artery (SA). Between 1986 and 1998, 34 patients (mean age, 49 years) underwent en bloc resection of TI cancer that had invaded the SA. The surgical approach was an L-shaped transclavicular cervicotomy in 33 patients. In 14 of these patients, this approach was associated with a posterolateral thoracotomy (n = 10) or a posterior midline approach (n = 4). In one patient, the procedure was achieved with a single posterolateral thoracotomy approach. An end-to-end anastomosis was performed in 16 patients. In one patient, a subclavian-left common carotid artery transposition was performed. In one other patient, an end-to-end anastomosis was performed between the proximal innominate artery and the SA. The right carotid artery was transposed into the SA in an end-to-side fashion. In 16 patients, prosthetic revascularization with a polytetrafluoroethylene graft was performed. Thirty-three patients underwent postoperative radiation therapy. There were no cases of perioperative death, neurologic sequelae, graft infections or occlusions, or limb ischemia. There were two delayed asymptomatic polytetrafluoroethylene graft occlusions at 12 and 31 months. The 5-year patency rate was 85%. During this study, 20 patients died: 18 died of tumor recurrence (5 local and systemic and 13 systemic), one of respiratory failure, and one of an unknown cause at 74 months. The overall 5-year survival rate was 36%, and the 5-year disease-free survival rate was 18%. Tumor arterial invasion per se should not be a contraindication to TI cancer resection. This study shows that cancers that invade the SA can be resected through an L-shaped transclavicular cervicotomy, with good results with a concomitant revascularization of the SA.
    Journal of Vascular Surgery 05/1999; 29(4):581-8. · 2.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: We sought to identify the long-term prognosis after surgical treatment for primary pulmonary sarcoma. Methods: Twenty-three patients were retrospectively identified as having been treated surgically for primary pulmonary sarcoma between 1981 and 1996. The records of all patients were reviewed, and the histopathology reexamined by a pathologist. Results: Fifteen patients were male and eight female; their ages ranged from 20 to 78 (mean 51) years. Tumors measured between 0.9 and 12.0 (mean 5.2) cm across the greatest diameter. The histologic diagnoses were malignant fibrous histiocytoma (8, three grade 1 or 2, two grade 3), synovial sarcoma (4), malignant schwannoma (3), leiomyosarcoma (3), and one case each of angiosarcoma, intimal sarcoma, epitheloid hemangioendothelioma, fibrosarcoma and primitive neuroectodermal tumor. Three patients were found to be unresectable. All three underwent radiation and chemotherapy. Lobectomies or bilobectomies were performed in 13 patients including two sleeve resections, one carinal resection, and one chest wall resection. Four patients underwent radical pneumonectomies. Three patients with invasion of the pulmonary artery, pulmonary veins or atrial wall underwent extended resections with the use of cardiopulmonary bypass. In two, a homograft was used to reconstruct the right ventricular outflow tract. Of the resected patients, six had a positive resection margin, and four had at least one positive lymph node in the specimen. Three patients underwent repeat pulmonary resections for recurrences. Eleven patients received postoperative chemotherapy and eight had radiation therapy. Follow-up was available on 22 patients, and ranged from 2 to 183 (mean 48) months; 14 patients are disease free, six died of disease, one died of surgical complications (operative mortality 5%), and two are alive with disease. Actuarial 3- and 5-year survival of the resected patients was 69%. Size and grade were not found to be correlated with significantly increased survival, but completeness of resection was (P<0.05). Conclusions: Resection of primary pulmonary sarcomas can produce an acceptable survival rate if the resection is complete. Cardiopulmonary bypass can be a useful adjunct when tumors involve a resectable area of the heart or great vessels.
    European Journal of Cardio-Thoracic Surgery 04/1999; · 2.67 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: We sought to identify the long-term prognosis after surgical treatment for primary pulmonary sarcoma. Methods: Twenty-three patients were retrospectively identified as having been treated surgically for primary pulmonary sarcoma between 1981 and 1996. The records of all patients were reviewed, and the histopathology reexamined by a pathologist. Results: Fifteen patients were male and eight female; their ages ranged from 20 to 78 (mean 51) years. Tumors measured between 0.9 and 12.0 (mean 5.2) cm across the greatest diameter. The histologic diagnoses were malignant fibrous histiocytoma (8, three grade 1 or 2, two grade 3), synovial sarcoma (4), malignant schwannoma (3), leiomyosarcoma (3), and one case each of angiosarcoma, intimal sarcoma, epitheloid hemangioendothelioma, fibrosarcoma and primitive neuroectodermal tumor. Three patients were found to be unresectable. All three underwent radiation and chemotherapy. Lobectomies or bilobectomies were performed in 13 patients including two sleeve resections, one carinal resection, and one chest wall resection. Four patients underwent radical pneumonectomies. Three patients with invasion of the pulmonary artery, pulmonary veins or atrial wall underwent extended resections with the use of cardiopulmonary bypass. In two, a homograft was used to reconstruct the right ventricular outflow tract. Of the resected patients, six had a positive resection margin, and four had at least one positive lymph node in the specimen. Three patients underwent repeat pulmonary resections for recurrences. Eleven patients received postoperative chemotherapy and eight had radiation therapy. Follow-up was available on 22 patients, and ranged from 2 to 183 (mean 48) months; 14 patients are disease free, six died of disease, one died of surgical complications (operative mortality 5%), and two are alive with disease. Actuarial 3- and 5-year survival of the resected patients was 69%. Size and grade were not found to be correlated with significantly increased survival, but completeness of resection was (P
    European Journal of Cardio-thoracic Surgery - EUR J CARDIO-THORAC SURG. 01/1999; 15(4):456-460.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There have been few reports on results after extended radical resection for primary mediastinal tumors invading neighboring organs. A retrospective analysis of 89 patients who underwent total or subtotal resection of a primary mediastinal tumor with resection of at least part of an adjacent structure between 1979 and 1995 was performed. Clinical data were collected from the medical records. There were 35 invasive thymomas, 12 thymic carcinomas, 17 germ cell tumors, 16 lymphomas, 3 neurogenic tumors, 3 thyroid carcinomas, 2 radiation-induced sarcomas, and 1 mediastinal mesothelioma. The tumor was located in the anterior mediastinum in 74% of patients. Residual masses after chemotherapy were excised in 14 patients with germ cell tumor and 8 with lymphoma. A median sternotomy was the most frequently used approach (79% of patients). Total resection was achieved in 79% and significantly improved survival (p < 0.01). Adjacent resected structures included 38 phrenic nerves, 21 superior venae cavae, 16 upper lobes, and 13 innominate veins, in 5 patients, a pneumonectomy was required. The complication rate was 17% and the mortality rate, 6%. With follow-up available for 86 patients, the overall 5-year survival rate was 69% for patients with thymoma, 42% for patients with thymic carcinoma, 48% for patients with germ cell tumor, and 83% for patients with lymphoma. Malignant mediastinal tumors can be safely resected even if they have invaded other mediastinal structures. Complete resection is important to achieve satisfactory long-term survival. A median sternotomy is an excellent approach, and a preoperative diagnosis by biopsy is desirable. Residual masses after chemotherapy for lymphoma or germ cell tumor should be resected. Extensive resection without a preoperative diagnosis is not indicated.
    The Annals of Thoracic Surgery 08/1998; 66(1):234-9. · 3.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Experimental studies reveal that inhaled nitric oxide (NO) can prevent, worsen, or have no effect on lung injury in the setting of ischemia-reperfusion (I-R). We tested the hypothesis that these disparate effects could be related to differences in the timing of administration and/or concentration of inhaled NO during I-R. Isolated rat lungs were subjected to 1-h periods of ischemia followed by 1-h periods of blood reperfusion. We investigated the effects of NO (30 ppm) given during ischemia, NO (30 or 80 ppm) begun immediately at reperfusion, or NO (30 ppm) given 15 min after the beginning of reperfusion, on total pulmonary vascular resistance (PVR), the coefficient of filtration (Kfc), the lung wet/dry weight ratio (W/D) of lung tissue, and lung myeloperoxidase activity (MPO). A control group did not receive NO. NO given during ischemia had no effect on Kfc or MPO, but decreased PVR. NO (30 ppm) during reperfusion (early or delayed) decreased PVR, W/D, Kfc and MPO. NO at 80 ppm decreased PVR and MPO but not W/D or Kfc. In conclusion, NO at 30 ppm, given immediately or in a delayed fashion during reperfusion, attenuates I-R-induced lung injury. NO at 30 ppm given during ischemia or at 80 ppm during reperfusion is not protective.
    American Journal of Respiratory and Critical Care Medicine 09/1997; 156(2 Pt 1):454-8. · 11.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Non-heartbeating-donor (NHBD) lung transplantation could help reduce the current organ shortage. Polymorphonuclear neutrophil (PMN) activation plays a pivotal role in ischemia-reperfusion injury (I-R), and can be inhibited by nitric oxide (NO). We hypothesized that inhaled NO might be beneficial in NHBD lung transplantation. The effect of inhaled NO on PMNs was studied by measuring in vivo PMN lung sequestration (myeloperoxidase activity) and adhesion of recipient circulating PMNs to cultured pulmonary artery endothelial cells (PAECs) in vitro. Pigs were randomly assigned to an NO or a control group (n=9 each). In the NO group, cadavers and recipients were ventilated with oxygen and 30 parts per million of NO. After 3 hr of postmortem in situ warm ischemia and 2 hr of cold ischemia, left allotransplantation was performed. The right pulmonary artery was ligated, and hemodynamic and gas exchange data were recorded hourly for 9 hr. Recipient PMN adherence to tumor necrosis factor-alpha- and calcium ionophore-stimulated PAECs was measured before and after reperfusion, and lung PMN sequestration was determined after death. NO-treated animals exhibited lowered pulmonary vascular resistance (P<0.01), as well as improved oxygenation (P<0.01) and survival (P<0.05). Adhesion of PMNs to PAECs was inhibited in the NO group before (P<0.001) and after reperfusion (P<0.0001). Lung PMN sequestration was reduced by NO (P<0.05). Inhaled NO attenuates I-R injury after NHBD lung transplantation. This is likely due to the prevention of I-R-induced pulmonary vasoconstriction and to the direct effect on peripheral blood PMN adhesion to endothelium, which results in reduced sequestration and tissue injury.
    Transplantation 06/1997; 63(10):1380-6. · 3.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In non-heart-beating donor lung transplantation, postmortem warm ischemia poses a special challenge. Inhaled nitric oxide and pentoxifylline have been shown to attenuate ischemia-reperfusion injury after lung transplantation. We hypothesized that concomitant administration of inhaled nitric oxide and pentoxifylline would result in a synergistic effect on ischemia-reperfusion lung injury. Lungs were harvested from non-heart-beating donors after 30 minutes of in situ warm ischemia, flushed, and stored for 2 hours at 4 degrees C before left lung transplantation in rats. Inhaled nitric oxide (30 ppm) was added during cadaver ventilation and reperfusion; pentoxifylline was given intravenously throughout reperfusion. The following groups were studied (n = 8 each): control, pentoxifylline, nitric oxide, and nitric oxide+pentoxifylline. Hemodynamic indices and arterial blood gases were obtained after ligation of the right pulmonary artery. Lung myeloperoxidase and wet/dry ratio were measured after death. All rats that did not receive nitric oxide died within 10 minutes after ligation. Inhaled nitric oxide significantly decreased pulmonary vascular resistance and improved recipient survival. Nitric oxide + pentoxifylline improved pulmonary vascular resistance, arterial oxygen tension, and survival even further and reduced lung myeloperoxidase as compared with the group that received nitric oxide only. Preservation solution flush time was significantly decreased in both groups receiving nitric oxide, suggesting that inhaled nitric oxide used during cadaver ventilation allows for a more even distribution of the preservation solution. We conclude that treatment with inhaled nitric oxide + pentoxifylline results in a synergistic protection from ischemia-reperfusion injury after non-heart-beating donor lung transplantation. This is likely the result of a dual action on the graft vasculature and neutrophil sequestration.
    Journal of Thoracic and Cardiovascular Surgery 06/1997; 113(5):821-9. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. Non-heartbeating-donor (NHBD) lung transplantation could help reduce the current organ shortage. Polymorphonuclear neutrophil (PMN) activation plays a pivotal role in ischemia-reperfusion injury (I-R), and can be inhibited by nitric oxide (NO). We hypothesized that inhaled NO might be beneficial in NHBD lung transplantation. Methods. The effect of inhaled NO on PMNs was studied by measuring in vivo PMN lung sequestration (myeloperoxidase activity) and adhesion of recipient circulating PMNs to cultured pulmonary artery endothelial cells (PAECs) in vitro. Pigs were randomly assigned to an NO or a control group (n=9 each). In the NO group, cadavers and recipients were ventilated with oxygen and 30 parts per million of NO. After 3 hr of postmortem in situ warm ischemia and 2 hr of cold ischemia, left allotransplantation was performed. The right pulmonary artery was ligated, and hemodynamic and gas exchange data were recorded hourly for 9 hr. Recipient PMN adherence to tumor necrosis factor-α- and calcium ionophore-stimulated PAECs was measured before and after reperfusion, and lung PMN sequestration was determined after death. Results. NO-treated animals exhibited lowered pulmonary vascular resistance (P<0.01), as well as improved oxygenation (P<0.01) and survival (P<0.05). Adhesion of PMNs to PAECs was inhibited in the NO group before (P<0.001) and after reperfusion (P<0.0001). Lung PMN sequestration was reduced by NO (P<0.05). Conclusions. Inhaled NO attenuates I-R injury after NHBD lung transplantation. This is likely due to the prevention of I-R-induced pulmonary vasoconstriction and to the direct effect on peripheral blood PMN adhesion to endothelium, which results in reduced sequestration and tissue injury.
    Transplantation 05/1997; 63(10):1380-1386. · 3.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. Surgical management of radiation-induced sarcoma of the chest wall remains difficult because of its impressive local aggressiveness.Methods. Between 1987 and 1995, 15 patients (median age, 58 years) underwent radical resection of radiation-induced sarcoma of the chest wall. This type of tumor was defined as a metachronous, histologically different neoplasm in the irradiated field of the original tumor. Ten patients had a history of primary breast cancer and 5 patients, Hodgkin’s disease. The median delivered radiation dose to the primary tumor area was 45 Gy, and the median interval between radiotherapy and diagnosis of sarcoma was 14 years. Seven tumors were located on the sternum, three on the lateral chest wall, and five in the thoracic outlet. Four total and three partial sternectomies, three lateral chest wall resections and five resections of tumors in the thoracic outlet (three first-rib resections) were performed. Seven patients required stabilization of the chest wall with prosthetic material. Soft tissue reconstruction was carried out with either muscle flaps and skin advancement in 9, musculocutaneous flaps in 4, or skin flaps alone in 2 patients.Results. One patient died 3 months after total sternectomy of respiratory failure. Two patients (13.3%) had a local complication: sepsis after sternectomy in 1 and cutaneous necrosis in 1. Local recurrence occurred in 7 patients after a median interval of 10 months. Two of them died, and 4 underwent a repeat resection, 3 of whom are still alive. Four patients died of systemic recurrence. With a median follow-up of 30 months, overall 5-year survival and 5-year disease-free survival rates were 48% and 27%, respectively.Conclusion. Despite poor long-term disease-free survival, radical resection of radiation-induced sarcoma of the chest wall is justified on the basis of low postoperative morbidity and the lack of other available therapies.(Ann Thorac Surg 1997;63:214–9)
    The Annals of Thoracic Surgery 02/1997; · 3.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: In non-heart-beating donor lung transplantation, postmortem warm ischemia poses a special challenge. Inhaled nitric oxide and pentoxifylline have been shown to attenuate ischemia-reperfusion injury after lung transplantation. We hypothesized that concomitant administration of inhaled nitric oxide and pentoxifylline would result in a synergistic effect on ischemia-reperfusion lung injury. Methods: Lungs were harvested from non-heart-beating donors after 30 minutes of in situ warm ischemia, flushed, and stored for 2 hours at 4° C before left lung transplantation in rats. Inhaled nitric oxide (30 ppm) was added during cadaver ventilation and reperfusion; pentoxifylline was given intravenously throughout reperfrsion. The following groups were studied (n = 8 each): control, pentoxifylline, nitric oxide, and nitric oxide + pentoxifylline. Hemodynamic indices and arterial blood gases were obtained after ligation of the right pulmonary artery. Lung myeloperoxidase and wet/dry ratio were measured after death. Results: All rats that did not receive nitric oxide died within 10 minutes after ligation. Inhaled nitric oxide significantly decreased pulmonary vascular resistance and improved recipient survival. Nitric oxide + pentoxifylline improved pulmonary vascular resistance, arterial oxygen tension, and survival even further and reduced lung myeloperoxidase as compared with the group that received nitric oxide only. Preservation solution flush time was significantly decreased in both groups receiving nitric oxide, suggesting that inhaled nitric oxide used during cadaver ventilation allows for a more even distribution of the preservation solution. Conclusion: We conclude that treatment with inhaled nitric oxide + pentoxifylline results in a synergistic protection from ischemia-reperfusion injury after non-heart-beating donor lung transplantation. This is likely the result of a dual action on the graft vasculature and neutrophil sequestration. (J Thorac Cardiovasc Surg 1997;113:821-9)
    Journal of Thoracic and Cardiovascular Surgery - J THORAC CARDIOVASC SURG. 01/1997; 113(5):821-829.
  • Transplantation 01/1997; 63(10):1380-1386. · 3.78 Impact Factor
  • Cardiovascular Surgery 01/1997; 5:43-43.
  • [Show abstract] [Hide abstract]
    ABSTRACT: In lung transplantation using non-heart-beating donors (NHBD), the postmortem period of warm ischemia exacerbates lung ischemia-reperfusion injury. We hypothesized that inhaled nitric oxide (NO) would reduce ischemia-reperfusion injury, and thus ameliorate the viability of the lung graft. A blood-perfused, isolated rat lung model was used. Lungs were flushed and harvested from non-heart-beating donors after 30 minutes of in situ warm ischemia. The lung was then stored for 2 hours at 4 degrees C. Inhaled NO at 30 ppm was given either during the period of warm ischemia, during reperfusion, or during both periods. Lung ischemia-reperfusion injury was assessed after 1 hour of reperfusion by measuring pulmonary vascular resistance, coefficient of filtration, wet-to-dry lung weight ratio, and myeloperoxidase activity. A severe IR injury occurred in lungs undergoing ischemia and reperfusion without NO as evidenced by high values of pulmonary vascular resistance (6.83 +/- 0.36 mm Hg. mL-1.min-1), coefficient of filtration (3.02 +/- 0.35 mL.min-1.cm H2O-1 x 100 g-1), and wet-to-dry lung weight ratio (8.07 +/- 0.45). Lower values (respectively, 3.31 +/- 0.44 mm Hg.mL-1.min-1, 1.49 +/- 0.34 mL.min-1.cm H2O-1 x 100 g-1, and 7.44 +/- 0.43) were observed when lungs were ventilated with NO during ischemia. Lung function was further improved when NO was given during reperfusion only. All measured variables, including myeloperoxidase activity were significantly improved when NO was given during both ischemia and reperfusion. Myeloperoxidase activity was significantly correlated with coefficient of filtration (r = 0.465; p < 0.05). These data suggest that inhaled NO significantly reduces ischemia-reperfusion injury in lungs harvested from non-heart-beating donors. This effect might be mediated by inhibition of neutrophil sequestration in the reperfused lung.
    The Annals of Thoracic Surgery 12/1996; 62(6):1632-8. · 3.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lung transplantation is associated with complications such as reperfusion injury and graft rejection. Gene therapy targeted to the graft offers a promising approach to the prevention of these complications. Because adenovirus vectors can transfer genes in vivo to the lung vasculature, we evaluated the feasibility of adenovirus-mediated gene transfer to the lung graft in a porcine model of left lung allotransplantation. Following removal of the donor lung, an adenovirus vector encoding the beta-galactosidase (beta-Gal) gene was injected ex vivo into the lumen of the upper lobe pulmonary artery of the graft. After 2 hr of incubation at 10 degrees C, the lung graft was implanted into the recipient animal. Three days later, the animals were sacrificed and the lung graft was evaluated for beta-Gal activity. No beta-Gal activity was detected in the left lower lobe used as a control. In contrast, beta-Gal activity was detected in endothelial cells of the left upper lobe pulmonary circulation, and was also observed in airway and alveoli epithelial cells. However, less than 1% of cells of the graft expressed beta-Gal. In vitro experiments showed that this may be explained in part by the low temperature and the short duration of adenovirus incubation within the graft, and by the low susceptibility of porcine cells to human adenovirus. Furthermore, expression of the exogenous gene occurred in several organs of recipient animals. Thus, adenovirus-mediated gene transfer to the lung graft is feasible ex vivo, but several parameters limit gene transfer efficiency and need to be improved before clinical application is attempted.
    Human Gene Therapy 11/1996; 7(15):1837-45. · 4.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The combination of ischemia and reperfusion after lung transplantation is characterized by endothelial damage, neutrophil sequestration, and decreased release of endothelial nitric oxide. Because nitric oxide has been shown to selectively dilate the pulmonary vasculature, abrogate neutrophil adherence, and restore endothelial dysfunction, we hypothesized that inhaled nitric oxide given for 4 hours during initial reperfusion might attenuate reperfusion injury in a porcine model of left single-lung transplantation. We tested hemodynamic and gas exchange data, lung neutrophil sequestration, and pulmonary artery endothelial dysfunction after 4 and 24 hours of reperfusion in 12 pigs randomly assigned to nitric oxide and control groups. Harvested lungs were preserved in normal saline solution for 24 hours at 4 degrees C. During transplantation, inflatable cuffs were placed around each pulmonary artery to allow separate evaluation of each lung by occluding flow. Compared with the transplanted lungs in the control group, transplanted lungs in pigs treated with inhaled nitric oxide significantly improved gas exchange, pulmonary vascular resistance, shunt fraction, and oxygen delivery at 4 and 24 hours after reperfusion. Neutrophil sequestration, as measured by the neutrophil-specific enzyme myeloperoxidase and the alveolar leukocyte count per light microscopic field, was significantly lower at 24 hours after reperfusion in the transplanted lungs of the nitric oxide group. The nitric oxide-treated native right lungs exhibited significantly reduced increase in neutrophil accumulation compared with that in control native right lungs. After 24 hours of reperfusion, endothelium-dependent relaxation to acetylcholine was similarly and severely altered in both groups. We conclude that short-term inhaled nitric oxide given during the first 4 hours of reperfusion after lung transplantation significantly attenuates reperfusion injury, improving graft function as long as 24 hours after operation. This effect is probably mediated by a decrease in neutrophil sequestration. A protective effect on the contralateral lung was also observed. Inhaled nitric oxide may be a suitable agent when an acute reperfusion phenomenon is anticipated.
    Journal of Thoracic and Cardiovascular Surgery 10/1996; 112(3):590-8. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The combination of ischemia and reperfusion after lung transplantation is characterized by endothelial damage, neutrophil sequestration, and decreased release of endothelial nitric oxide. Because nitric oxide has been shown to selectively dilate the pulmonary vasculature, abrogate neutrophil adherence, and restore endothelial dysfunction, we hypothesized that inhaled nitric oxide given for 4 hours during initial reperfusion might attenuate reperfusion injury in a porcine model of left single-lung transplantation. We tested hemodynamic and gas exchange data, lung neutrophil sequestration, and pulmonary artery endothelial dysfunction after 4 and 24 hours of reperfusion in 12 pigs randomly assigned to nitric oxide and control groups. Harvested lungs were preserved in normal saline solution for 24 hours at 4º C. During transplantation, inflatable cuffs were placed around each pulmonary artery to allow separate evaluation of each lung by occluding flow. Compared with the transplanted lungs in the control group, transplanted lungs in pigs treated with inhaled nitric oxide significantly improved gas exchange, pulmonary vascular resistance, shunt fraction, and oxygen delivery at 4 and 24 hours after reperfusion. Neutrophil sequestration, as measured by the neutrophil-specific enzyme myeloperoxidase and the alveolar leukocyte count per light microscopic field, was significantly lower at 24 hours after reperfusion in the transplanted lungs of the nitric oxide group. The nitric oxide–treated native right lungs exhibited significantly reduced increase in neutrophil accumulation compared with that in control native right lungs. After 24 hours of reperfusion, endothelium-dependent relaxation to acetylcholine was similarly and severely altered in both groups. We conclude that short-term inhaled nitric oxide given during the first 4 hours of reperfusion after lung transplantation significantly attenuates reperfusion injury, improving graft function as long as 24 hours after operation. This effect is probably mediated by a decrease in neutrophil sequestration. A protective effect on the contralateral lung was also observed. Inhaled nitric oxide may be a suitable agent when an acute reperfusion phenomenon is anticipated. (J THORAC CARDIOVASC SURG 1996;112:590-8)
    Journal of Thoracic and Cardiovascular Surgery - J THORAC CARDIOVASC SURG. 01/1996; 112(3):590-598.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. In lung transplantation using non-heart-beating donors (NHBD), the postmortem period of warm ischemia exacerbates lung ischemia-reperfusion injury. We hypothesized that inhaled nitric oxide (NO) would reduce ischemia-reperfusion injury, and thus ameliorate the viability of the lung graft.Methods. A blood-perfused, isolated rat lung model was used. Lungs were flushed and harvested from non-heart-beating donors after 30 minutes of in situ warm ischemia. The lung was then stored for 2 hours at 4°C. Inhaled NO at 30 ppm was given either during the period of warm ischemia, during reperfusion, or during both periods. Lung ischemia-reperfusion injury was assessed after 1 hour of reperfusion by measuring pulmonary vascular resistance, coefficient of filtration, wet-to-dry lung weight ratio, and myeloperoxidase activity.Results. A severe IR injury occurred in lungs undergoing ischemia and reperfusion without NO as evidenced by high values of pulmonary vascular resistance (6.83 ± 0.36 mm Hg · mL−1 · min−1), coefficient of filtration (3.02 ± 0.35 mL · min−1 · cm H2O−1 · 100 g−1), and wet-to-dry lung weight ratio (8.07 ± 0.45). Lower values (respectively, 3.31 ± 0.44 mm Hg · mL−1 · min−1, 1.49 ± 0.34 mL · min−1 · cm H2O−1 · 100 g−1, and 7.44 ± 0.43) were observed when lungs were ventilated with NO during ischemia. Lung function was further improved when NO was given during reperfusion only. All measured variables, including myeloperoxidase activity were significantly improved when NO was given during both ischemia and reperfusion. Myeloperoxidase activity was significantly correlated with coefficient of filtration (r = 0.465; p < 0.05).Conclusions. These data suggest that inhaled NO significantly reduces ischemia-reperfusion injury in lungs harvested from non-heart-beating donors. This effect might be mediated by inhibition of neutrophil sequestration in the reperfused lung.
    Annals of Thoracic Surgery - ANN THORAC SURG. 01/1996; 62(6):1632-1638.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Experimental studies reveal that inhaled nitric oxide (NO) can prevent, worsen, or have no effect on lung injury in the setting of ischemia-reperfusion (I-R). We tested the hypothesis that these dispar- ate effects could be related to differences in the timing of administration and/or concentration of in- haled NO during I-R. Isolated rat lungs were subjected to 1-h periods of ischemia followed by 1-h pe- riods of blood reperfusion. We investigated the effects of NO (30 ppm) given during ischemia, NO (30 or 80 ppm) begun immediately at reperfusion, or NO (30 ppm) given 15 min after the beginning of reperfusion, on total pulmonary vascular resistance (PVR), the coefficient of filtration (K fc ), the lung wet/dry weight ratio (W/D) of lung tissue, and lung myeloperoxidase activity (MPO). A control group did not receive NO. NO given during ischemia had no effect on K fc or MPO, but decreased PVR. NO (30 ppm) during reperfusion (early or delayed) decreased PVR, W/D, K fc , and MPO. NO at 80 ppm decreased PVR and MPO but not W/D or K fc . In conclusion, NO at 30 ppm, given immediately or in a delayed fashion during reperfusion, attenuates I-R-induced lung injury. NO at 30 ppm given during ischemia or at 80 ppm during reperfusion is not protective. Murakami S, Bacha EA, Mazma- nian GM, Détruit H, Chapelier A, Darteville P, Hervé P, for the Paris-Sud University Lung Trans- plantation Group. Effects of various timings and concentrations of inhaled nitric oxide in lung ischemia-reperfusion. AM J RESPIR CRIT CARE MED 1997;156:454-458.