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Biomedical subjects

H Shennib

Publications and source records attributed to H Shennib.

At least 55 records · Page 3Linked to original sources

Alterations in bronchoalveolar lavage and plasma endothelin-1 levels early after lung transplantation.

A temporary increase in pulmonary vascular resistance is observed during the first 24 hr following lung allotransplantation. We hypothesized that such early vascular changes are secondary to endothelial injury by ischemia-reperfusion, and that this may be mediated by an increased pulmonary endothelin-1 production/release. To test this hypothesis, radioimmunoassay was used to analyze endothelin-1 levels in bronchoalveolar lavage and plasma taken before surgery and at 1 hr, 4 hr, 24 hr, and 1 week after transplantation. The study was carried out on 2 groups of mongrel dogs. One group was subjected to left single-lung allotransplantation and the other to autotransplantation. Endothelin-1 levels in the bronchoalveolar lavage samples from the lung allografts were significantly increased at 1 (0.70 +/- 0.18 pg/ml) and 4 (1.84 +/- 0.65 pg/ml) hr after transplantation compared with the preoperative value (0.14 +/- 0.05 pg/ml), and declined at 24 (0.85 +/- 0.84 pg/ml) hr after transplantation. Similarly, plasma endothelin-1 levels in the allografts were significantly increased at 1 (2.0 +/- 0.80 pg/ml) and 4 (2.0 +/- 0.71 pg/ml) hr after transplant when compared with preoperative levels (0.54 +/- 0.09 pg/ml). Plasma endothelin-1 levels, however, remained significantly high after 24 hr (1.4 +/- 0.4 pg/ml; P < 0.007) and decreased after 1 week after transplant (0.89 +/- 0.32 pg/ml). On the other hand, endothelin-1 levels in bronchoalveolar lavage from the autograft group remained relatively unchanged; however, plasma levels showed a significant increase at 4 hr (6.6 +/- 1.8 pg/ml) after transplantation compared with preoperative levels (2.8 +/- 0.38 pg/ml). Elevation of endothelin-1 levels early after lung transplantation may play an important role in early high pulmonary vascular resistance and temporary graft dysfunction.

Airway Resistance↗

Postthoracotomy pulmonary function: a comparison of epidural versus intravenous meperidine infusions.

It has remained unclear whether epidural opioid analgesia permits better recovery of postthoracotomy pulmonary function than an optimal method of systemic opioid administration. Lumbar epidural meperidine infusions were compared with intravenous patient-controlled analgesic (PCA) meperidine infusions in a prospective randomized unblinded study for 72 hours postthoracotomy. Before induction of general anesthesia, patients received a bolus of meperidine, 1 mg/kg, and an infusion of meperidine, 0.33 mg/kg/hr, was started via either a lumbar epidural or intravenous catheter. Postoperatively, the meperidine infusion rates were titrated as needed for analgesia. In addition, the intravenous group received meperidine, 10 mg per dose, as required, from a patient-controlled analgesia pump. No other opioid was administered during the study period. Patients were studied for recovery of spirometric tests of pulmonary function, visual analog pain scores, sedation, arterial blood gases, meperidine dose requirements, radiographic pulmonary complications, and neurologic signs and symptoms. A subgroup of 10 patients (5 from each group) had venous blood samples drawn every 24 hours for 96 hours and assayed for serum meperidine and normeperidine concentrations. Epidural meperidine analgesia was associated with improved postthoracotomy pulmonary function, better analgesia scores, and lower meperidine dose requirements than intravenous PCA meperidine. There were no differences between the epidural versus intravenous PCA subgroups with respect to serum meperidine or normeperidine levels. Normeperidine levels greater than 300 ng/mL were associated with an increased incidence of shakiness and/or tremors. Meperidine provides satisfactory postthoracotomy analgesia via a lumbar epidural infusion. This analgesia is associated with improved recovery of postoperative pulmonary function when compared with an intravenous PCA meperidine infusion.

Aged↗

Cytokine interleukin-2, tumor necrosis factor-alpha, and interferon-gamma release after ischemia/reperfusion injury in a novel lung autograft animal model.

Previously, we have reported an increase in the cytokines interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) early after left lung allotransplantation in dogs. The purpose of this study was to develop a novel model of canine lung autotransplantation and to observe whether ischemia/reperfusion injury alone (in the absence of an allogenic stimulus) would result in this cytokine release as seen in the allograft. Thus, using this model, early changes in cellular and cytokine composition in the lung autograft were monitored through the use of bronchoalveolar lavage (BAL) and plasma. The effects of ischemia/reperfusion injury on lung histology and major histocompatibility class II (MHC II) antigen expression were also observed. Ten mongrel dogs were subjected to left lung autotransplantation. Lungs were stored cold for 4 h, with a warm ischemic time of 1 h. BAL, blood, and biopsy specimens were taken preoperatively and 1 h, 4 h, 24 h, and 1 wk postoperatively. The mean BAL IL-2 levels significantly rose from a preoperative value of 150 +/- 19 pg/ml to 246 +/- 67 pg/ml 4 h after transplantation (p < 0.05), decreasing to preoperative levels after 24 h (128 +/- 54 pg/ml). Plasma levels of IL-2 did not change from preoperative values. In contrast to IL-2, TNF-alpha and IFN-gamma did not change in either BAL or plasma of the autograft.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Airway mucus and epithelial function in a canine model of single lung autotransplantation.

Impaired mucociliary function following lung transplantation has been reported in several human and animal studies. This could be a result of altered ciliary function or mucus properties or both. We assessed airway epithelial function by means of transepithelial potential difference (PD) measurements and physical analysis of mucus. Six mongrel dogs underwent single lung autologous transplantation. Measurements were performed preoperatively and 1, 2, 4, and 10 months postoperatively. At 1 and 2 months postoperatively, there was a significant fall in PD for the transplanted, left mainstem bronchus only (-13.5 +/- 1.7 mV at 1 month and -14.6 +/- 1.7 mV at 2 months postoperatively vs -18.6 +/- 2.3 mV preoperatively, baseline; p < 0.001 for both). The PD values in the small airways, right mainstem bronchus, and the trachea remained unchanged. At 2 months postoperation, the mucus collection rate on the left side was increased (p = 0.03), while the mucus viscoelasticity was decreased (p = 0.04). By 4 months postoperation, all epithelial parameters had returned to baseline, and there was no difference in radioaerosol clearance between the two lungs. The PD decrease and alterations in secretion rate and viscoelasticity reflect disturbed epithelial functional integrity at the site of anastomosis still present at 2 months postoperation. Recovery of bronchial epithelial function and clearance in canine studies of lung autotransplantation after healing of the anastomosis area suggest that persistent impairment of lung clearance observed in some long-term human lung transplantation survivors may be due to other mechanisms such as impaired healing or epithelial function or both, during immunosuppressive therapy. Mucociliary function in the anastomosis area is compromised until complete healing ensues; we speculate that chest physiotherapy may aid in overcoming this obstacle.

Animals↗

Coronary artery revascularization followed by single-lung transplantation in a patient with combined end-stage idiopathic pulmonary fibrosis and left main coronary artery stenosis.

Single-lung transplantation has been used successfully in patients who have idiopathic pulmonary fibrosis; however, coronary artery disease is often considered a contraindication for lung transplantation in such patients. We report the case of a 53-year-old man with idiopathic pulmonary fibrosis in whom left main coronary artery stenosis was found incidentally during pretransplant evaluation. The patient was treated successfully with elective coronary artery bypass grafting, followed by left single-lung transplantation 35 days later.

Coronary Angiography↗

Plasma endothelin-1 levels in human lung transplant recipients.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by vascular endothelial cells and is believed to play an important role in the pathophysiology of the pulmonary vasculature. We have investigated the early changes in ET-1 plasma levels in lung transplant recipients at various intervals before and after isolated lung transplantation. The mean plasma ET-1 level immediately before transplantation was 0.8 +/- 0.1 pg/ml. This was significantly increased to 2.6 +/- 0.5 pg/ml shortly after unclamping and vascular reperfusion of the allograft, and remained high 4 h (2.3 +/- 0.5 pg/ml), 6 h (2.4 +/- 0.6 pg/ml), and 12 h (1.7 +/- 0.3 pg/ml) after transplantation. Thereafter, the level of ET-1 started to decline, reaching 1.3 +/- 0.3 pg/ml 24 h and 0.9 +/- 0.3 pg/ml 1 week after transplantation. This early increase in ET-1 plasma level is consistent with our observation of alterations in pulmonary vascular resistance, pulmonary artery pressure and cardiac output early after transplantation. These findings demonstrate that an increase in plasma ET-1 levels shortly after lung transplantation may have a detrimental effect during the postoperative course early after transplantation.

Blood Pressure↗

The early release of interleukin-2, tumor necrosis factor-alpha and interferon-gamma after ischemia reperfusion injury in the lung allograft.

A period of cold and warm ischemia is obligatory when performing lung transplantation. Subtle ischemia-reperfusion injury induced in the course of transplantation can pass undetected or cause a short phase of reversible lung dysfunction. We hypothesized that ischemia-reperfusion injury may result in the local release of cytokines that have the capability to mediate acute lung injury early following transplantation. To test this hypothesis, 10 mongrel dogs were subjected to left lung allotransplantation. As performed in the clinical setting, donor lungs were preserved with Eurocollins solution and stored at 4 degrees C for 4 hr, which was followed by 1 hr of warm ischemia. Recipients received standard immunosuppression of cyclosporine, azathioprine, and low dose steroids. Bronchoalveolar lavage (BAL) and open lung biopsies were performed before operation and at approximately 1 hr, 4 hr, 24 hr, and 1 week after transplantation. A significant increase in BAL IL-2 levels was observed 4 hr after surgery (0 hr: 349 +/- 138 pg/ml; 4 hr: 757 +/- 284 pg/ml) (mean +/- SEM) (P < 0.05) which subsequently decreased 24 hr (320 +/- 168 pg/ml) after transplantation. BAL TNF-alpha levels were significantly increased 1 hr after transplantation (P < 0.05) (0 hr: 3.4 +/- 0.65 pg/ml; 1 hr: 13.3 +/- 8.0 pg/ml) returning to baseline after 24 hr (5.8 +/- 2.8 pg/ml). BAL IFN-gamma levels also significantly increased 1 and 4 hr after transplantation (0 hr: 7.2 +/- 2.1 pg/ml; 1 hr: 68.2 +/- 49.2 pg/ml; 4 hr: 301 +/- 131 pg/ml) (P < 0.05). This decreased back to baseline after 24 hr and 1 week (5.2 +/- 1.2 pg/ml and 9.7 +/- 7.9 pg/ml, respectively). There were no changes detected in plasma levels of cytokines. Histology showed evidence of grade 1-2 rejection after 1 week. We conclude that subjection of a lung allograft to standard periods of cold-warm ischemia will result in a temporary early elevation of IL-2, TNF-alpha, and IFN-gamma detectable only in the bronchoalveolar compartment. Such local increase in cytokines in the lung allograft may play an important role in the development of early allograft dysfunction.

Animals↗

Video-assisted minithoracotomy versus muscle-sparing thoracotomy for performing lobectomy.

We prospectively analyzed the outcome of lobectomy in a cohort of 67 patients. Operative time, postoperative pain, pulmonary function, and early outcome were compared between the patients undergoing video-assisted techniques (n = 44) and those undergoing standard muscle-sparing procedures (n = 23). Pain was quantified daily throughout the first week using the visual analog scale. The forced expiratory volume in 1 second and the forced vital capacity were measured at days 2, 4, and 8 postoperatively. The operative time was significantly longer (p < 0.02) and the postoperative pain was significantly less (p < 0.006) in the group undergoing video-assisted procedures. Pain-related morbidity, the mean duration of air leaks, the duration of chest tube placement, and the hospital stay were all less in the video-assisted group, but the differences did not reach statistical significance. However, the impairment in pulmonary function and the overall morbidity were identical for the two groups. Based on our findings, we conclude that video-assisted minithoracotomy is a safe and reliable approach for performing lobectomies, and that the decreased postoperative pain associated with this minimally invasive approach does not result in preserved pulmonary function and significantly reduced morbidity when compared with a muscle-sparing thoracotomy.

Adult↗

Airway complications in lung transplantation.

This article reviews the literature on airway healing after lung transplantation. From a historical point of view, this has been the Achilles' heel of lung transplantation through two decades, from the first attempt at single-lung transplantation in 1963 to the clinical successes in the early 1980s. The overall incidence of lethal airway complications is estimated to be 2% to 3%, whereas that of late stricture is 7% to 14%. Comparison of experiences has been difficult without a universal classification; a new classification for airway and anastomotic complications and healing is proposed. Ischemia appears to be the most important factor influencing airway healing. Low-pressure collateral bronchial blood flow from the pulmonary artery may be affected by low cardiac output, reperfusion edema, or rejection; mucosal injury may be further increased by prolonged positive-pressure ventilation. Good bronchial healing appears to be possible without a protective wrap and with early use of steroids. The management of bronchial complications is challenging and requires endoscopic skills including knowledge of endobronchial laser photocoagulation and stent insertion techniques.

Anastomosis, Surgical↗

Bronchoalveolar lavage: results of sequential, selective techniques in viable murines.

The purpose of this study was to develop an optimal technique for performing sequential bronchoalveolar lavage (BAL) in a murine animal model. Two general anesthetic regimens and four operative techniques of BAL were tested. Anesthesia by intraperitoneal injection of ketamine hydrochloride (100 mg/kg body wt) resulted in death for four of ten subjects, whereas inhalation of diethyl ether led to death for one of ten subjects. BAL using a balloon catheter under bronchoscopic guidance was comparable with postmortal lavage, tolerated better, and resulted in superior cell retrieval with respect to cell differential (macrophages: 95 +/- 2.3; lymphocytes: 3 +/- 1.2; polymorphonuclear lymphocytes [PNL]: 1.2 +/- 1.4) compared with two other techniques using a bent metal tube/polyethylene tubing combination (macrophages: 19.3 +/- 27.4; lymphocytes: 3.8 +/- 4.3; PNL: 35.5 +/- 35.5) and a bronchoscope/polyethylene tubing combination (macrophages: 11.1 +/- 25.5; lymphocytes: 0.7 +/- 1.0; PNL: 55.8 +/- 41.0). The BAL fluid contained significantly more alveolar macrophages and fewer PNL and epithelial cells (p = 0.0001, p = 0.0025, p = 0.02, respectively). We conclude that the technique using a balloon catheter under bronchoscopic guidance during inhalation of diethyl ether is the procedure of choice and results in a representative sample of BAL.

Anesthesia↗

Expression of endothelin-1 in the lungs of patients with pulmonary hypertension.

BACKGROUND: Pulmonary hypertension is characterized by an increase in vascular tone or an abnormal proliferation of muscle cells in the walls of small pulmonary arteries. Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide with important mitogenic properties. It has therefore been suggested that endothelin-1 may contribute to increases in pulmonary arterial tone or smooth-muscle proliferation in patients with pulmonary hypertension. We studied the sites and magnitude of endothelin-1 production in the lungs of patients with various causes of pulmonary hypertension. METHODS: We studied the distribution of endothelin-1-like immunoreactivity (by immunocytochemical analysis) and endothelin-1 messenger RNA (by in situ hybridization) in lung specimens from 15 control subjects, 11 patients with plexogenic pulmonary arteriopathy (grades 4 through 6), and 17 patients with secondary pulmonary hypertension and pulmonary arteriopathy of grades 1 through 3. RESULTS: In the controls, endothelin-1-like immunoreactivity was rarely seen in vascular endothelial cells. In the patients with pulmonary hypertension, endothelin-1-like immunoreactivity was abundant, predominantly in endothelial cells of pulmonary arteries with medial thickening and intimal fibrosis. Likewise, endothelin-1 messenger RNA was increased in the patients with pulmonary hypertension and was expressed primarily at sites of endothelin-1-like immunoreactivity. There was a strong correlation between the intensity of endothelin-1-like immunoreactivity and pulmonary vascular resistance in the patients with plexogenic pulmonary arteriopathy, but not in those with secondary pulmonary hypertension. CONCLUSIONS: Pulmonary hypertension is associated with the increased expression of endothelin-1 in vascular endothelial cells, suggesting that the local production of endothelin-1 may contribute to the vascular abnormalities associated with this disorder.

Adult↗

[Lung transplantation. Contraindications and new indications].

The authors review the recent changes observed in the indications for lung transplantation. Several classical contra-indications have been alleviated or even cancelled. Chronic infection presenting as cystic fibrosis has become one of the first indications for lung replacement. Respirator-dependent patients are at an operative risk comparable to the overall results. Long-term corticosteroid therapy and pleural adhesions are no longer formal contraindications but should be approached with extreme caution. In recent years, single lung transplantation has been extended to diseases, such as emphysema and pulmonary hypertension, which were formerly indications for double-lung or heart-lung transplantation. The reasons for this include donor shortage and the better 1-year survival following single lung transplantation. The most recent development is paediatric lung transplantation. The legitimacy of redo transplantation is controversial.

Adolescent↗

Double-lung transplantation in mechanically ventilated patients with cystic fibrosis.

Many lung transplant programs consider ventilator dependence as a contraindication for transplantation. Among 54 patients in whom bilateral lung transplantations for cystic fibrosis were performed by the Joint Marseille-Montreal Lung Transplant Program, 10 were ventilator dependent. Three of them died in the early postoperative period (30%): 2 as a result of cerebral anoxia and sepsis, 1 of Pseudomonas cepacia pneumonia. Two patients died at 15 and 19 months after transplantation of obliterative bronchiolitis and secondary bacterial pneumonitis. Another 2 patients in whom obliterative bronchiolitis developed underwent retransplantation with a heart-lung block; 1 of those was operated on at 12 months and is well at 29 months after his initial transplantation; the second was operated on at 34 months and died of primary graft failure. Three other patients are alive and well at 3, 11, and 14 months after transplantation. Actuarial survival at 1 year was 70%. The postoperative course and the infectious and rejection complications were no different from those in patients who underwent transplantation while spontaneously breathing. Obliterative bronchiolitis developed in 66% of patients at risk (2 of 6 patients surviving more than 6 months). We conclude that transplantation in mechanically ventilated patients with cystic fibrosis is not associated with an increase in morbidity or mortality after bilateral lung transplantation. Long-term survival, as in patients who undergo transplantation while spontaneously breathing, is limited by the development of obliterative bronchiolitis.

Adolescent↗

Intraoperative localization techniques for pulmonary nodules.

Video-assisted thoracoscopic resection has emerged as a safe procedure for diagnosis and treatment of peripheral pulmonary nodules. Its role alone or with adjuvant radiotherapy in the management of high-risk patients with T1 peripheral lung cancer is currently under evaluation. Most often, inspection of the lung with imaging will reveal surface changes indicative of tumor location (erythema, puckering, scarring), and gentle instrumental probing will allow both visual and tactile discrimination of normal and tumor boundaries. With experience, most lesions can be identified this way. However, when experience is limited, in particular circumstances where lesions are very small, located posteromedially or basomedially, or when there is underlying lung disease (eg, lung fibrosis, radiation changes, adhesions), intraoperative identification of peripheral nodules can be difficult. Computed tomography of the chest helps in planning the operative procedure, the position of the patient, and the ideal ports. Methylene blue injection and insertion of a guidewire into the lung nodule facilitates its identification intraoperatively. We found ultrasound probes to be helpful in defining the tumor's margins and its relation to bronchovascular structures, and thus in planning the strategy of resection whether by stapling devices, cautery, or laser dissection.

Diagnostic Imaging↗