The effect of elevated dietary cholesterol on pulmonary surfactant function in adolescent mice.

It has been established that phospholipids and cholesterol interact in films of pulmonary surfactant (PS). Generally it is thought that phospholipids increase film stability whereas cholesterol increases film fluidity. To study this further, we modified dietary cholesterol in mice which received either standard rodent lacking cholesterol (sd), or high cholesterol (2%) diet (hc) for 1 month. Phospholipid stability was investigated by a capillary surfactometer (CS), which measures airflow resistance and patency. PS was collected by bronchiolar lavage and centrifuged to obtain the surface-active film (SAF). Results showed that the hc-SAF had significantly more cholesterol than sd-SAF. CS analyses at 37 degrees C showed no significance differences in airflow resistance between hc-SAF and sd-SAF. However, at 37 degrees C, sd-SAF showed greater ability to maintain patency compared to hc-SAF, whereas at 42 degrees C hc-SAF showed patency ability similar to sd-SAF. The results suggested that increased cholesterol in hc-SAF induced less stability in the SAF possibly due to cholesterol's fluidizing effect on phospholipids at physiological temperatures.

Lung volume reduction surgery for the treatment of severe emphysema: a study in a single Canadian institution.

OBJECTIVE: To evaluate lung volume reduction surgery (LVRS) and its effectiveness in improving pulmonary function, exercise capacity and quality of life in a population of emphysema patients referred to and screened in a single centre. DESIGN: A prospective case series. SETTING: A Canadian tertiary care hospital. PATIENTS: Patients with severe emphysema, significant dyspnea and impaired exercise capacity interfering with quality of life. INTERVENTIONS: Bilateral LVRS was performed through a median sternotomy. MAIN OUTCOME MEASURES: Pulmonary function tests (preoperative forced expiratory volume in the first second [FEV1], residual volume [RV]), 6-minute walk (6 MW) distance, quality of life (Medical Outcomes Study 36-item short-form health survey) and degree of dyspnea (Medical Research Council of Great Britain dyspnea scale and the baseline and transitional dyspnea indices) were assessed before LVRS and at 6 and 12 months after. RESULTS: Fifty-seven patients were assessed for LVRS, of whom 10 were selected for surgery. Homogeneous distribution of disease was the most common reason for exclusion. Of the 10 patients operated upon, 1 died of acute cor pulmonale on the fourth postoperative day and 1 died of recurrent exacerbations of chronic obstructive pulmonary disease and chronic respiratory failure at 315 days postoperatively. In the surviving patients, the mean preoperative FEV1 increased from 0.70 L before surgery to 0.90 L at 1 year, with a mean relative increase of 33.4%. The mean RV decreased from 5.57 L to 4.10 L, with a mean relative decrease of 27.6%. The 6 MW distance increased from 302.7 m to 356.9 m at 1 year, with a mean relative increase of 21.6%. Quality of life and degree of dyspnea were improved significantly at 1 year after LVRS. Of the 5 patients on oxygen at home before surgery, 4 were able to reduce their requirements but not to discontinue oxygen. CONCLUSIONS: LVRS is an effective palliative treatment for dyspnea and poor exercise tolerance in highly selected patients. Although the duration of palliation is unknown, our results show that improvements in pulmonary function, exercise, quality of life and degree of dyspnea are preserved over the first year. Only a minority of the patients screened were eligible for surgery. The 2 deaths in our series emphasize the need for even further delineation of selection criteria.

Antiestrogens sensitize human ovarian and lung carcinomas for lysis by autologous killer cells.

BACKGROUND: The antiestrogens tamoxifen (TX) and toremifene (TO) were shown previously to enhance the lysis of target cells by natural killer cells (NK), lymphokine activated killer (LAK) cells, and by cytotoxic T lymphocytes (CTL). MATERIALS AND METHODS: CTL were cultured from lung cancer tissue and from ascites fluid of ovarian carcinoma patients with the aid of human recombinant interleukin-2 (hrIL-2). The target, effector or both cell populations were pretreated by TX, TO and/or with human recombinant interferon-alpha (IFN-alpha). RESULTS: Significant enhancement of cytotoxicity occurred when the tumor targets or both the target and effector cells were treated with TX, TO or when these drugs were used in combination with IFN-alpha. The lytic activity of CTL cultured from draining lymph nodes of lung cancer patients, was also observed after similar treatment. The lytic effect of autologous LAK cells derived from peripheral blood was increased to a lesser extent, which could be amplified by additional treatment with IFN-alpha. CONCLUSIONS: The antiestrogens TX and TO and IFN-alpha enhance the lysis of autologous tumor cells by CTL and LAK effectors.

Epinephrine decreases postoperative requirements for continuous thoracic epidural fentanyl infusions.

Epidural thoracic fentanyl infusions provide effective preoperative analgesia after thoracotomy; however, side effects can limit the effectiveness of this technique. This study evaluates epinephrine as an adjunct to continuous thoracic epidural fentanyl infusions after thoracotomy. Thirty-eight patients were studied in a prospective, randomized, double-blind trial comparing fentanyl alone to fentanyl with epinephrine 1:300,000. Epidural infusion rates were titrated to equivalent pain relief using a visual analog scale. With the addition of epinephrine, there was a significant reduction in fentanyl requirements (0.82 +/- 0.07 vs 1.19 +/- 0.11 micrograms.kg-1.h-1, P = 0.005, repeated-measures analysis of variance) and in plasma fentanyl concentrations (steady state: 0.91 +/- 0.13 vs 1.65 +/- 0.23 ng/mL, P = 0.007, repeated-measures analysis of variance). There were no differences in pain scores, side effects, spirometry, patient satisfaction scores, or hemodynamic variables. This study demonstrates that adding epinephrine 1:300,000 to continuous thoracic epidural infusions decreases fentanyl requirements titrated for effective analgesia. The reduction in fentanyl requirements was associated with reduced fentanyl plasma concentrations.

Lung preservation and lung injury.

Lung preservation and its attendant ischemia-reperfusion injury is a complex phenomenon that begins with lung injury that may be present in the donor before any preservation intervention. Acute preservation interventions in common use include single-flush perfusion and donor core-cooling on cardiopulmonary bypass. From this moment forward the ischemia injury begins, and increases during the phase of organ storage. The lung continues to metabolize glucose even at these low temperatures, and future improvements may well lie in recognizing this requirement. With reperfusion, another phase of lung injury begins as the ischemic lung is overloaded with oxygen and oxygen free radicals are generated. Research efforts have focused on minimizing the effect of free-radicals at various steps along their formation and diminishing their interaction with cell membranes.

Cardiopulmonary bypass resuscitation for accidental hypothermia.

Many victims of accidental hypothermia have been successfully resuscitated with cardiopulmonary bypass, but questions remain regarding treatment indications and efficacy. To assess the role of cardiopulmonary bypass in resuscitation from hypothermia, a collective literature review was performed. Data on 68 hypothermic patients resuscitated with cardiopulmonary bypass were analyzed. Impairment from alcohol, drug abuse, or mental illness was the most common predisposing factor for accidental hypothermia. Mean initial core temperature was 21 degrees C. Sixty-one patients (90%) were in cardiac arrest. Femoral-femoral bypass was used in 72% of patients. Overall survival was 60%. Eighty percent of survivors returned to their previous level of function. Sixty-seven percent of nonsurvivors died because of inability to establish a cardiac rhythm or wean from bypass. Patient age, type of cardiopulmonary bypass (femoral-femoral or atrial-aortic), and initial core temperature were not significant prognostic indicators. There were no survivors among the 6 patients with a core temperature less than 15 degrees C. Patients in cardiac arrest had a higher mortality than patients who were not (p = 0.02). Climbing and avalanche victims had a higher mortality than other hypothermic patients (p = 0.003). The possibility of publication bias must be considered before firm conclusions can be drawn from this collective literature review. Controlled studies comparing the efficacy of cardiopulmonary bypass and alternative warming techniques have not been done. Nevertheless, cardiopulmonary bypass has several advantages over other warming methods for profoundly hypothermic patients. Tissue perfusion and oxygenation are maintained while rapid warming occurs. Cardiopulmonary bypass resuscitation is recommended for hypothermic patients in arrest and for patients with core temperatures lower than 25 degrees C, irrespective of rhythm. Patients in stable condition with temperatures between 25 degrees and 28 degrees C can be treated with cardiopulmonary bypass or conventional warming methods.

Thoracic versus lumbar epidural fentanyl for postthoracotomy pain.

Thirty patients were prospectively randomized to receive either thoracic or lumbar epidural fentanyl infusion for postthoracotomy pain. Epidural catheters were inserted, and placement was confirmed with local anesthetic testing before operation. General anesthesia consisted of nitrous oxide, oxygen, isoflurane, intravenous fentanyl citrate (5 micrograms/kg), and vecuronium bromide. Pain was measured by a visual analogue scale (0 = no pain to 10 = worst pain ever). Postoperatively, patients received epidural fentanyl in titrated doses every 15 minutes until the visual analogue scale score was less than 4 or until a maximum fentanyl dose of 150 micrograms by bolus and an infusion rate of 150 micrograms/h was reached. The visual analogue scale score of patients who received thoracic infusion decreased from 8.8 +/- 0.5 to 5.5 +/- 0.7 (p < or = 0.05) by 15 minutes and to 3.5 +/- 0.4 (p < or = 0.05) by 45 minutes. The corresponding values in the lumbar group were 8.8 +/- 0.6 to 7.8 +/- 0.7 at 15 minutes and 5.3 +/- 0.9 at 45 minutes (p < or = 0.05). The infusion rate needed to maintain a visual analogue scale score of less than 4 was lower in the thoracic group (1.55 +/- 0.13 micrograms.kg-1 x h-1) than in the lumbar group (2.06 +/- 0.19 microgram.kg-1 x h-1) during the first 4 hours after operation (p < or = 0.05). The epidural fentanyl infusion rates could be reduced at 4, 24, and 48 hours after operation without compromising pain relief. Four patients in the lumbar group required naloxone hydrochloride intravenously.(ABSTRACT TRUNCATED AT 250 WORDS)

Vascular and interstitial effect of University of Wisconsin solution on canine lung.

Belzer's University of Wisconsin cold storage solution (UWCSS) has proved useful in extending the shelf life of organs in extrathoracic transplantation and more recently has also been shown to be useful in heart transplantation. I investigated the effect of 4 degrees C UWCSS on the vascular and interstitial properties of the lung to see whether it affected the pulmonary microcirculation or caused pulmonary edema. Infusion of UWCSS was associated with a slight decrease in oxygen tension, but the final oxygen tension was no different from that previously demonstrated with Euro-Collins solution. Vascular conductance was not affected by UWCSS, but average vascular closure increased slightly, indicating that increased vascular tone occurs. This effect is similar to but less than that previously observed with Euro-Collins solution. Based on comparisons of wet to dry weight ratios, estimates of interstitial compliance, transvascular fluid flux, and microvascular filtration coefficient, it does not appear that UWCSS causes pulmonary edema. Further investigation into the usefulness of UWCSS in lung transplantation is therefore warranted.

Plasma cell granuloma of the lung.

Plasma cell granuloma is an uncommon, nonneoplastic pulmonary lesion. An 11-year retrospective review of resected pulmonary tumors yielded six patients with plasma cell granulomas. Fine needle aspiration biopsy results were falsely positive for carcinoma in one patient. Adherence or invasion of the mediastinum was present in three patients. Granuloma in one patient, who underwent two operative procedures, was deemed unresectable at the initial thoracotomy. For both diagnostic and therapeutic reasons, early surgical excision is recommended for plasma cell granulomas of the lung.

Pneumothorax complicating cardiac surgery.

Pneumothorax is an infrequent complication of cardiac surgery. In order to evaluate potential causative or associated factors and to formulate guidelines for prevention and management of this complication, we undertook a retrospective nine-year analysis of our adult cardiac surgical procedures. Twenty-one of 1463 patients suffered a postoperative pneumothorax for an overall incidence of 1.4%. Life threatening pneumothoraces occurred in four patients. Seven of 21 had chronic obstructive pulmonary disease. Eighteen required chest tube insertion. Four patients, including three with chronic obstructive pulmonary disease, required further interventions. These included additional chest tube insertion in three, high constant chest tube suction in three, tetracycline pleurodesis in three, and thoracotomy in one patient. Pneumothoraces following cardiac surgery are often preventable, may be associated with prolonged morbidity, and are potentially life threatening. Conservative management with chest tube drainage is usually successful. Patients with chronic obstructive lung disease are more likely to suffer prolonged morbidity and require thoracotomy.

Does pentobarbital anesthesia depress left ventricular contractility in dogs?

Although pentobarbital sodium (NP) anesthesia has been shown to depress left ventricular (LV) contractility in dogs, measurements of LV contractility in previous studies have been made soon after a bolus of NP was given when serum concentrations would be extremely high. In this study, we compared indexes of LV contractility during awake and anesthetized conditions. During anesthesia, measurements were obtained 1 h after an intravenous bolus of NP was given when serum concentrations were approximately 25 mg/l and above that reported to abolish pain. In 13 dogs, subendocardial ultrasonic crystal transducers and a high-fidelity pressure transducer were implanted into the LV. Measurements were obtained with and without prior treatment with propranolol to produce beta-adrenergic blockade. LV contractility was assessed by ejection fraction and the end-systolic pressure-volume relationship. The effect of NP on ventricular myocardium was also examined in an in vitro canine right trabecular preparation to compare in vivo and in vitro effects. In the in vivo study, the results showed no decrease in LV contractility during anesthesia regardless of whether propranolol was administered. The in vitro preparation showed only a minimal decrease in isometric tension at the concentrations used in the in vivo study. We conclude that NP anesthesia does not depress LV contractility when concentrations are maintained at approximately 25 mg/l.

Increased production and immunohistochemical localization of transforming growth factor-beta in idiopathic pulmonary fibrosis.

Transforming growth factor-beta (TGF-beta) can regulate cell growth and differentiation as well as production of extracellular matrix proteins. Elevated production of TGF-beta has been associated with human and rodent chronic inflammatory and fibrotic diseases. Using immunohistochemical staining, we have examined lung sections of patients with advanced idiopathic pulmonary fibrosis (IPF), a disease characterized by chronic inflammation and fibrosis and demonstrated a marked and consistent increase in TGF-beta production in epithelial cells and macrophages when compared to patients with nonspecific inflammation and those with no inflammation or fibrosis. In patients with advanced IPF, intracellular staining with anti-LC (1-30) TGF-beta antibody was seen prominently in bronchiolar epithelial cells. In addition, epithelial cells of honeycomb cysts and hyperplastic type II pneumocytes stained intensely. Anti-CC (1-30) TGF-beta antibody, which reacts with extracellular TGF-beta, was localized in the lamina propria of bronchioles and in subepithelial regions of honeycomb cysts in areas of dense fibroconnective tissue deposition. The close association of subepithelial TGF-beta to the intracellular form in advanced IPF suggests that TGF-beta was produced and secreted primarily by epithelial cells. Because of the well-known effects of TGF-beta on extracellular matrix formation and on epithelial cell differentiation, the increased production of TGF-beta in advanced IPF may be pathogenic to the pulmonary fibrotic and regenerative responses seen in this disease.

Fistulas between the aorta and tracheobronchial tree.

Aortobronchial fistula is a rare condition that is invariably fatal if not diagnosed and surgically treated. With appropriate surgical intervention, survival rates greater than 70% can be achieved. A review of the literature and an illustrative case report are presented. A total of 63 fistulas in 62 patients have been described. The case we present is unusual in the use of serratus anterior muscle for repair of the fistula. Eighty-seven percent of the cases documented in the literature were associated with an aneurysm of the thoracic aorta. Eighty-six percent of the fistulas were between the descending aorta and left bronchopulmonary tree. More than 95% of patients experienced at least a single episode of hemoptysis, and massive hemoptysis occurred in more than half of the reported cases. A correct preoperative diagnosis was made in only 54% of cases. Plain chest radiographs definitively demonstrated an aneurysm in only 16%. The computed tomographic scan was the most rewarding test, identifying an aneurysm in 11 of 12 patients and the fistula in 50% of them. Surgical repair resulted in a 76% survival rate.

Primary malignant melanoma of the esophagus with diffuse melanocytic atypia and melanoma in situ.

Primary malignant melanoma is an unusual lesion in the esophagus that is not infrequently seen in association with melanosis. A case of esophageal invasive malignant melanoma with melanosis is described in which the melanosis exhibited melanocytic atypia extending through to melanoma in situ. The authors know of no previously reported such finding.

Closure of a post-pneumonectomy bronchopleural fistula with fibrin sealant (Tisseel).

A persistent post-pneumonectomy bronchopleural fistula and empyema were successfully treated by draining and cleansing the empyema cavity and then occluding the fistula with fibrin sealant.

Vascular and interstitial mechanics in canine pulmonary emphysema.

We examined the changes in vascular and interstitial mechanics in pulmonary emphysema (PE) using a canine lobar model. PE was produced in the left lower lobe (LLL) of five dogs (group E) by six weekly intrabronchial instillations of the enzyme papain. In five control dogs (group C), a normal saline solution was used. In our in vivo preparation, vascular flow (Q) to the LLL was measured. Inflow (Ppa) and outlow (Pv) pressures to the LLL could be varied independently. The relationship of Ppa to Q was examined in zones 2 and 3 of West. The slope of the Ppa-Q relationship was used to determine vascular conductance, whereas the extrapolation to zero flow in zone 2 conditions represented the mean pressure required for vascular recruitment (Pi). Lobar weight gain was measured continuously. Following step increases in Ppa, the rapid increase in wet weight measured when Q to the LLL was zero was used to obtain vascular compliance (C). Subsequent slow increases in wet weight were used to determine the rate of fluid exchange with the interstitium (Qf). The slope of the Qf-Ppa relationship represented fluid conductance (Kf). The extrapolation to zero Qf gave the minimal pressure required for continuous edema formation (Pm). Compared with group C, vascular conductance (G) decreased and Pi increased in group E, whereas fluid conductance (Kf) and Pm increased. The decrease in G most likely resulted from the loss of vascular cross-sectional area in emphysematous lungs, whereas the increase in Pi was possibly due to mechanical changes in the lung interstitium which increased vessel closure. We propose that the increase in Kf in group E reflected an increase in interstitial conductance, such that due to structural changes in the interstitium in emphysematous lungs, tissue resistance to fluid flux decreased.

Pulsion intubation versus traction intubation for obstructing carcinomas of the esophagus.

Eighty-eight patients were intubated to relieve the dysphagia of malignant esophageal obstruction. Because of advanced metastatic disease or poor general condition, 49 patients could not be operated on and were intubated endoscopically. Under radiographic control, the Nottingham Introducer was used to position Atkinson or modified Celestin tubes. In 39 other patients, palliative resection could not be done or liver metastasis was found at preliminary exploration with a view to esophagectomy. In these patients, Celestin tubes were inserted by the traction technique. The pulsion intubation group was older than the traction intubation group but comparable in other respects. Hospital stay was significantly shorter for the pulsion intubation group (8.4 versus 18.6 days). Hospital mortality rates were comparable (14.3% in the pulsion intubation group versus 23.1% in the traction intubation group), and survival did not differ (93 days in the pulsion intubation group versus 137 days in the traction intubation group). Overall complication rates were similar, but there were two significant differences: (1) wound infection or dehiscence was a major problem in the traction intubation group, occurring in 23% of the patients; and (2) tube obstruction or displacement occurred more frequently in the pulsion intubation group (18.3% versus 5.1%) but did not constitute a serious problem. Perforation occurred in 4 patients (8.2%) in the pulsion intubation group but was fatal in only 1. Pulsion intubation offers distinct advantages over traction intubation in that hospital stay is decreased and morbidity reduced.

Pulmonary interstitial compartments and tissue resistance to fluid flux.

We have produced interstitial fluid exchange in six isolated plasma-perfused canine lobes by introducing small increases in microvascular hydrostatic pressure. We measured early fast fluid exchange with a colorimetric technique and used weight changes to follow slow exchange. The observed biphasic time course suggested fluid flux across the microvascular membrane into two interstitial compartments in series (perimicrovascular and central). We related the initial rate of fluid flux into each compartment to the applied hydrostatic pressure change to obtain membrane (Kf1) and tissue conductances (Kf2) and to the exchanged volume to determine perimicrovascular (C1) and central (C2) interstitial compliances. C2 (0.25 +/- 0.193) was twice C1 (0.10 +/- 0.031 ml X cmH2O-1 X g DW-1, where DW represents dry weight. C2 increased significantly with hydration (C2 = 0.06 X WW/DW - 0.15) ml X cmH2O-1 X g DW-1 (WW/DW, wet-to-dry weight ratio), whereas C1 did not. Kf1 (0.26 +/- 0.17) was one order of magnitude larger than Kf2 (0.027 +/- 0.014 ml X min-1 X cmH2O-1 X g DW-1). Kf2 increased with hydration (Kf2 = 0.005 X WW/DW - 0.007) ml X min-1 X cmH2O-1 X g DW-1, whereas Kf1 did not. Our data point to the tissues and not the microvascular membranes as the major rate-limiting structure. Our data suggest an interstitium composed of a smaller rigid perimicrovascular space which communicates to a larger looser downstream space by a high-resistance pathway. As hydration increases, fluid accumulation becomes easier because tissue resistance to fluid flux drops and the compliance of the downstream compartment doubles.

Transvascular fluid flux measured from intravascular water concentration changes.

We have measured transvascular water flux in eight canine left lower lobes perfused in a zone 3 of West with indocyanine green-stained plasma. Transvascular flux of water was induced by a step change in the inflow pressure. Assuming the indocyanine green-labeled protein did not significantly cross the capillary membrane in one pass, the rate of transvascular fluid flux could be calculated from the change in outflow-to-inflow concentration of water. The method was validated against gravimetric measurements of water exchange. By comparing our direct measurements of transvascular flux with the time course of lobar weight change, we conclude that following changes in inflow pressure, vascular volume changes occur rapidly and slow changes in lung mass can be accounted for exclusively by water exchange. Our method shows transvascular flux follows a biphasic course, suggesting both a membrane and an interstitial resistance to fluid transudation.