Effects of Sildenafil and Tadalafil on Edema and Reactive Oxygen Species Production in an Experimental Model of Lung Ischemia-Reperfusion Injury.

BACKGROUND: Lung ischemia-reperfusion injury is characterized by formation of reactive oxygen species and cellular swelling leading to pulmonary edema and primary graft dysfunction. Phosphodiesterase 5 inhibitors could ameliorate lung ischemia-reperfusion injury by interfering in many molecular pathways. The aim of this work was to evaluate and compare the effects of sildenafil and tadalafil on edema and reactive oxygen species formation in an ex vivo nonhuman animal model of lung ischemia-reperfusion injury. METHODS: Thirty-two Wistar rats were distributed, treated, perfused and the cardiopulmonary blocks were managed as follows: control group: immediate excision and reperfusion without pretreatment; ischemia reperfusion group: treatment with dimethylsulfoxide 0.9% and excision 1 hour later; sildenafil group: treatment with sildenafil (0.7 mg/kg) and excision 1 hour later; and tadalafil group: treatment with tadalafil (0.15 mg/kg) and excision 2 hours later. All cardiopulmonary blocks except control group were preserved for 8 hours and then reperfused. Pulmonary arterial pressure, pulmonary venous pressure, and capillary filtration coefficient were measured. Reactive oxygen species were measured. RESULTS: Edema was similar between control and sildenafil groups, but significantly greater in the ischemia-reperfusion (P ≤ .04) and tadalafil (P ≤ .003) groups compared with the sildenafil group. The malondialdehyde levels were significantly lower in the sildenafil (P ≤ .001) and tadalafil (P ≤ .001) groups than the ischemia-reperfusion group. CONCLUSIONS: Administration of sildenafil, but not tadalafil, decreased edema in lung ischemia-reperfusion injury. Both drugs decreased reactive oxygen species formation in a lung ischemia-reperfusion injury model.

Lyophilized allografts without pre-treatment with glutaraldehyde are more suitable than cryopreserved allografts for pulmonary artery reconstruction.

Various methods are available for preservation of vascular grafts for pulmonary artery (PA) replacement. Lyophilization and cryopreservation reduce antigenicity and prevent thrombosis and calcification in vascular grafts, so both methods can be used to obtain vascular bioprostheses. We evaluated the hemodynamic, gasometric, imaging, and macroscopic and microscopic findings produced by PA reconstruction with lyophilized (LyoPA) grafts and cryopreserved (CryoPA) grafts in dogs. Eighteen healthy crossbred adult dogs of both sexes weighing between 18 and 20 kg were used and divided into three groups of six: group I, PA section and reanastomosis; group II, PA resection and reconstruction with LyoPA allograft; group III, PA resection and reconstruction with CryoPA allograft. Dogs were evaluated 4 weeks after surgery, and the status of the graft and vascular anastomosis were examined macroscopically and microscopically. No clinical, radiologic, or blood-gas abnormalities were observed during the study. The mean pulmonary artery pressure (MPAP) in group III increased significantly at the end of the study compared with baseline (P=0.02) and final [P=0.007, two-way repeat-measures analysis of variance (RM ANOVA)] values. Pulmonary vascular resistance of groups II and III increased immediately after reperfusion and also at the end of the study compared to baseline. The increase shown by group III vs group I was significant only if compared with after surgery and study end (P=0.016 and P=0.005, respectively, two-way RM ANOVA). Microscopically, permeability was reduced by ≤75% in group III. In conclusion, substitution of PAs with LyoPA grafts is technically feasible and clinically promising.

Lyophilized allografts without pre-treatment with glutaraldehyde are more suitable than cryopreserved allografts for pulmonary artery reconstruction

Various methods are available for preservation of vascular grafts for pulmonary artery (PA) replacement. Lyophilization and cryopreservation reduce antigenicity and prevent thrombosis and calcification in vascular grafts, so both methods can be used to obtain vascular bioprostheses. We evaluated the hemodynamic, gasometric, imaging, and macroscopic and microscopic findings produced by PA reconstruction with lyophilized (LyoPA) grafts and cryopreserved (CryoPA) grafts in dogs. Eighteen healthy crossbred adult dogs of both sexes weighing between 18 and 20 kg were used and divided into three groups of six: group I, PA section and reanastomosis; group II, PA resection and reconstruction with LyoPA allograft; group III, PA resection and reconstruction with CryoPA allograft. Dogs were evaluated 4 weeks after surgery, and the status of the graft and vascular anastomosis were examined macroscopically and microscopically. No clinical, radiologic, or blood-gas abnormalities were observed during the study. The mean pulmonary artery pressure (MPAP) in group III increased significantly at the end of the study compared with baseline (P=0.02) and final [P=0.007, two-way repeat-measures analysis of variance (RM ANOVA)] values. Pulmonary vascular resistance of groups II and III increased immediately after reperfusion and also at the end of the study compared to baseline. The increase shown by group III vs group I was significant only if compared with after surgery and study end (P=0.016 and P=0.005, respectively, two-way RM ANOVA). Microscopically, permeability was reduced by ≤75% in group III. In conclusion, substitution of PAs with LyoPA grafts is technically feasible and clinically promising.

Suture-line reinforcement with glutaraldehyde-preserved bovine pericardium for nonanatomic resection of lung tissue.

In this study we assessed the usefulness of glutaraldehyde-preserved bovine pericardium (GPBP), preparated in our laboratory, in nonanatomic resection of lung tissue in dogs. A 30% resection of the right cranial lobe of the lung was performed in 18 mongrel dogs. The suture line was reinforced with GPBP strips. For group I (n = 6), the GPBP strips were fixed on the lung with nonabsorbable suture by thoracotomy. In Group II (n = 6), the resection and fixation of the GPBP strips were performed with an endoscopic linear stapler by thoracotomy. In Group III (n = 6), the resection and fixation of the GPBP strips were performed with a linear stapler by thoracoscopy. The animals were evaluated each day during the first week after surgery and every other day during the study time. At the end of the study all animals were euthanized with an overdose of pentobarbital. Macroscopic and microscopic examinations of the bioprosthesis and lung were evaluated. All animals survived the surgical procedure and study time (8 weeks). In the three groups, macroscopic examination of the bioprosthesis showed good adaptation to the lung tissue. Microscopically, all groups of animals presented good healing, with the presence of fibrotic tissue layer on the GPBP and its periphery as well as in the lung. However, in group I we observed the presence of giant cells in the suture line. GPBP proved to be a useful material for reinforcement of the nonanatomic resection suture line of lung tissue in dogs.

Association between heroin use, needle sharing and tattoos received in prison with hepatitis B and C positivity among street-recruited injecting drug users in New Mexico, USA.

This study aimed to assess the seroprevalence and risk factors for hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV-1 infections among injecting drug users (IDU) in New Mexico. Serological and behavioural surveys were conducted in conjunction with street-based outreach, education and HIV counselling and testing. High rates of antibody positivity for HCV (82.2%) and HBV (61.1%), and a low rate for HIV (0.5%) were found. In multivariate analyses, both HBV and HCV infection were positively associated with increasing age, increasing years of injection and heroin use. Receipt of a tattoo in prison/jail was associated with HBV (odds ratio = 2.3, 95% confidence interval 1.4, 3.8) and HCV (OR = 3.4, 95% CI = 1.6, 7.5) infections. Prevention of bloodborne pathogens among IDUs should focus on young users, early in their drug use experience. Studies examining the relationship between tattooing and HBV and HCV infection are needed as are efforts to promote sterile tattooing, in prisons and elsewhere.

Thoracoabdominal wall repair with glutaraldehyde-preserved bovine pericardium.

Glutaraldehyde-preserved bovine pericardium (GPBP) is evaluated as a bioprosthesis for the reconstruction of surgical defects in the thoracoabdominal wall. The mechanical properties of bovine pericardium preserved at different concentrations of glutaraldehyde were studied. Samples preserved in 0.5% glutaraldehyde showed a significantly higher tensile strength (11.7 +/- 0.8 N/mm2) than samples preserved in 2.5, 5, or 10% (similar to pericardium preserved in normal saline). The percentage of elongation was significantly lower than samples preserved in 1, 2.5, and 5% glutaraldehyde. GPBP at 0.5% was used to repair experimentally induced defects of the abdominal wall (n = 9), chest wall (n = 6), diaphragm (n = 6), and sternum (n = 7). All animals presented adequate tolerance to the material used and no case of infection or rejection of the material was seen in any of the animals. Finally, 0.5% GPBP was used clinically in a series of 40 patients: postincisional abdominal hernia (n = 30), inguinal hernia (n = 8), diaphragmatic hernia (n = 1), and congenital pelvic defect with prolapse of abdominal organs (n = 1). Surgical use showed that GPBP was a very manageable material and long-term results were good in 37 patients with a mean follow up of 18 months (range 5-35 months). Six patients presented seroma formation (all abdominal hernia patients), three of which eventually developed infection and had the GPBP patch removed at 3, 5, and 7 months postoperatively. The rest of the patients presented good scar formation with adequate resistance at the area of implantation. GPBP is a biological material with sufficient resistance to be used surgically in the repair of thoracoabdominal defects. Ideal concentration of glutaraldehyde to be used in the preparation-preservation of the material is 0.5% since higher concentration negatively affect its tensile rupture strength and elongation.

[Repair of thoracoabdominal wall defects in dogs using a bovine pericardium bioprosthesis]. / Reparación de defectos de pared tóracoabdominal de perros con bioprótesis de pericardio bovino.

OBJECTIVES: To evaluate the in-vitro resistance of a pericardial tissue bioprothesis as well as its use for the reconstruction of surgical defects in the thoracoabdominal wall. MATERIALS AND METHODS: The prosthesis were preserved for 15 days in different concentrations of glutaraldehyde (0.5% to 10%). Normal saline and Hanks solution were used as controls. Tensile strength and percent elongation were measured using an Instrom 1011 automatic equipment; polypropilene (Marlex) and polyester (Mersilene) mesh samples were included. Also, the 0.5% glutaraldehyde-preserved pericardium was used to repair defects experimentally produced in the abdominal wall (n = 12), chest wall (n = 6), diaphragm (n = 6), and sternum (n = 7) of mongrel dogs. RESULTS: The samples preserved in 0.5% glutaraldehyde showed a significantly higher tensile strength (11.7 N/mm2, SEM = 0.8) than samples preserved in other concentrations as well as in the mesh samples. Percent elongation in 0.5% glutaraldehyde was 56% (SEM = 5.8) which was similar to the meshes' elongation but significantly lower than that seen for the 1%, 2.5% and 5% glutaraldehyde-preserved samples. The dogs showed good tolerance to the 0.5% preparation and the histopathology showed formation of a fibroblast layer with collagen deposits and development of scar tissue. There was no case of infection or rejection in the animals, and all the microbiological cultures of the preparations were negative. CONCLUSION: Pericardial bioprothesis is a resistant material which can be used surgically in the repair of thoracoabdominal defects.

Pulmonary arterial contribution to airway blood flow after lung transplantation in dogs.

Despite the improved success of lung transplantation, ischemia of the donor bronchus continues to be the most important factor influencing airway healing. Recent studies have shown that at the level of the mainstem bronchi the pulmonary contribution to the airway blood flow may be equivalent to or greater than the systemic contribution and could therefore assist early healing of the newly anastomosed bronchus and, in addition, might facilitate the improved healing associated with omentopexy. The aim of this study was to measure the pulmonary contribution to airway blood flow in dogs after allotransplantation of the left lung and to determine whether omentopexy might improve the healing process. Using the radioactive microsphere technique, we measured the pulmonary contribution to airway blood flow in 25 dogs 1 week after allotransplantation of the left lung. Half the dogs had an omental wrap around the anastomotic site. Results showed that pulmonary blood flow increased progressively from lower trachea to distal mainstem bronchus and supplied the left mainstem bronchus above as well as below the anastomotic site. Omentopexy did not increase flow or enhance healing.

[Video-assisted surgery in the management of thoracic problems]. / Cirugía videoasistida en el manejo de problemas torácicos.

OBJECTIVE: To review the experience in minimally invasive videoassisted surgery for the diagnosis and treatment of thoracopulmonary problems. METHOD: Retrospective review of the clinical charts of patients submitted to thoracic videoassisted surgical procedures at the Instituto Nacional de Nutrición Salvador Zubiran from February 1993 to March 1995. RESULTS: A total of 102 patients were submitted to videoassisted thoracic surgery. There were three main indications for the procedure: 1) pleural disease (n = 30); 2) pulmonary disease (n = 66); and 3) various (n = 6). A total of 129 procedures were performed: 38 pleural procedures (biopsy 15, decortication 8, talc poudrage 7, revision/lavage 6, section of adhesions 1, and pleural abrasion 1), 75 pulmonary procedures (lung biopsy 32, pulmonary nodule wedge resection 30, large core needle biopsy 8, bullae resection 3, videoassisted lobectomy with minithoracotomy 2), and 16 various procedures (biopsy of mediastinal adenopathy 6, pericardial window 4, pericardial biopsy 4, subphrenic abscess 1, intercostal artery clippage 1). Morbidity appeared in three patients (two prolonged air leaks and one empiema) and two patients died (one cirrhotic patient who developed postoperative acute hepatic failure and a patient with lupus erythematosus who developed sepsis). All other patients had an uneventfull postoperative course with a mean pleural drainage of 1.76 days for pulmonary procedures (range 0.5-3 days) and 4.6 days for pleural procedures (range 2-15 days). CONCLUSIONS: The use of the videothorascope as an adjuvant in thoracic surgery allows the surgeon to perform different procedures using minimally invasive techniques. Indications are the same as for any thoracic surgical procedure and the general philosophy must be to establish a compromise between minimal invasion of the patient and the correct solution for the particular problem being treated.

Spontaneous vaginal deliveries and perineal trauma in Lucea, Jamaica.

In 1991, there were 995 uncomplicated vaginal deliveries at Noel Holmes Hospital (NHH) in Lucea, Jamaica. Seven hundred and forty-two women were discharged with intact perineums. Only 3 episiotomies were performed. These data raise a concern that episiotomy may be overused in the United States.

Spontaneous vaginal deliveries and perineal trauma in Lucea, Jamaica

In 1991 there were 995 uncomplicated vaginal deliveries at Noel Holmes Hospital (NHH) in Lucea, Jamaica. Seven hundred and forty-two women were discharged with intact perineums. Only 3 episiotomies were performed. These data raise a concern that episiotomy may be overused in the United States. (AU)

[Unilateral lung transplant in a case of terminal pulmonary fibrosis]. / Trasplante unilateral de pulmón en un caso de fibrosis pulmonar terminal.

Up to 1980, less than 40 lung transplants had been reported worldwide without any success. The factors influencing these poor results were related to complications at the bronchial anastomosis and ineffective immunosuppressive regimens. The development of new immunosuppressive drugs has permitted the reevaluation of lung transplantation as a therapeutic option. The success with heart-lung transplantation stimulated the development of clinical human single-lung and double-lung transplantation. However the world experience is still scarce. In our institution we have developed experimental work leading to the establishment of a lung transplant program. This paper describes our first single lung transplant patient. The patient, a 33 year old man with end-stage pulmonary fibrosis, was totally oxygen dependant, maintaining arterial blood oxygen levels below 40 mmHg without oxygen supplementation and confined to a wheelchair. A single left lung transplant was performed from a young brain-dead donor. The bronchial anastomosis was protected with an omental flap. The immunosuppressive regimen was based on cyclosporin A and azathioprine from the beginning, adding prednisone on the third postoperative week. There has been only one episode suggestive of acute rejection which was managed with methylprednisolone. On the 9th postoperative week the patient developed a bronchial stenoses at the anastomotic site which required dilation and stenting with an endobronchial silastic stent. His clinical course has been uneventful since then. His ventilatory parameters showed an increase of vital capacity from 900 to 2100 mL and his FEV1 from 700 to 1500 mL. His gas exchange has been normal with arterial blood gas oxygen above 60 mmHg and oxygen saturation above 94%.(ABSTRACT TRUNCATED AT 250 WORDS)

[Protection of the bronchial anastomosis with omental pedicle in unilateral lung transplant]. / Protección de la anastomosis bronquial con colgajo de omento en el trasplante pulmonar unilateral.

Lung transplantation has been slow to develop due mainly to the association of complications at the bronchial anastomosis secondary to the devascularization incurred during procurement. In the present study we evaluate the importance of the protection of the bronchial anastomoses with an omental pedicle. Mongrel dogs were operated upon forming four study groups: lung allotransplantation with bronchial protection (group T1, n = 9), lung allotransplantation without protection (group T2, n = 6); the two remaining groups did not receive a transplant but instead underwent surgery with extensive dissection and transection with reanastomoses of the left main bronchus with (group B1, n = 5) and without (group B2, n = 5) bronchial protection. All animals survived the surgical procedure. There were 8 complications at the bronchial anastomosis, six of which appeared in group T2 and were directly responsible for the animals death (p less than 0.05 when comparing lethal complications with group T1). Angiographic and dye perfusion studies were performed through the right gastroepiploic artery of the omentum. Bronchial neovascularization was demonstrated macroscopically as well as with light microscopy in all animals receiving protection with omentum (groups T1 and B1). We conclude that adequate bronchial protection is achieved with an omental pedicle flap brought up to the thorax during lung transplantation. It diminishes significantly the incidence of lethal complications at the bronchial anastomosis due to the revascularization that occurs through the omentum.

Urinary thromboxane B2 as an indicator of acute rejection in lung allotransplantation.

The behavior of urinary thromboxane B2 (TXB2) during acute rejection of lung allotransplants was evaluated. Unmatched mongrel dogs were submitted to a left lung orthotopic allotransplantation (groups I and II), or a sham operation (group III). All animals had an initial significant elevation of TXB2 excretion due to surgical trauma; however, in sham-operated animals (group III) this elevation returned to basal levels after 3 days. All transplanted animals (groups I and II) had persistent TXB2 elevation with 2 important peaks on postop days 5 and 9. The elevated TXB2 excretion persisted in spite of immunosuppressive treatment with azathioprine and prednisone (group II). Rejection was followed by means of an objective grading system applied to chest roentgenograms taken on all animals. It was found that TXB2 levels correlated directly with the grade of radiographic changes seen, thus indicating degree of rejection. TXB2 can be useful as a noninvasive indicator for surveillance of lung allograft rejection.