Pulmonary Parenchymal Damage Research Articles

Effects of Tempol, a Membrane-Permeable Radical Scavenger, on Local and Remote Organ Injuries Caused by Intestinal Ischemia/Reperfusion in Rats

Tempol is a stable piperidine nitroxide of low molecular weight that permeates biological membranes and scavenges superoxide anions in vitro. In a variety of animal models, deleterious effects of reperfusion injury on both local and remote organs have been demonstrated. In this study, we aimed to investigate the effects of a membrane-permeable radical scavenger, Tempol, on local and remote organ injuries caused by intestinal ischemia/reperfusion (I/R) in rats. Male Wistar-albino rats were randomized into three groups: (I) Sham-operated control group, laparotomy without I/R injury (n = 12); (II) Intestinal I/R group, 60 min of ischemia by superior mesenteric artery occlusion followed by 2-h of reperfusion (n = 12); and (III) I/R + Tempol-treated group, identical to I/R group except for Tempol administration, 30 mg/kg bolus injection 5 min before reperfusion, followed by an infusion of 30 mg/kg/h intravenously (n = 12). Histopathologically, intestinal mucosal lesions were assessed by Chiu's classification, and pulmonary parenchymal damage was appraised by pulmonary neutrophil infiltration and acute lung injury scaling. Biochemically, myeloperoxidase activity, malondialdehyde, glutathione, and nitrite/nitrate (NO(x)) levels were determined in both intestinal mucosa and lung parenchyma. Evans blue dye concentration and organ wet/dry weight ratios were used as a marker of organ edema. Animal survival was observed up to 1 week. Intestinal mucosal lesions and pulmonary parenchymal damage were significantly attenuated with Tempol treatment, histopathologically (P < 0.05). Tempol administration significantly reduced myeloperoxidase activity and malondialdehyde levels, and also significantly increased glutathione and NO(x) levels of both intestinal and lung tissues, biochemically (P < 0.05). Evans blue dye extravasation and wet/dry weight ratios of organs were significantly reduced with Tempol injection (P < 0.05). The survival rates of rats in Tempol-treated group were significantly higher than that of I/R-treated group (P < 0.05). The present study suggests that Tempol administration significantly reduces both local and remote organ injuries caused by intestinal I/R before and throughout the reperfusion period. Further clinical studies are needed to clarify whether Tempol may be a useful therapeutic agent to use in particular operations where the reperfusion injury occurs.

Pyrrolidine Dithiocarbamate Reduces Lung Injury Caused by Mesenteric Ischemia/Reperfusion in a Rat Model

Pyrrolidine dithiocarbamate (PDTC) is a low-molecular thiol antioxidant and potent inhibitor of nuclear factor-kappaB (NF-kappaB) activation. It has been shown to attenuate local harmful effects of ischemia/reperfusion (I/R) injury in many organs. In this study, we aimed to study the effect of PDTC on lung reperfusion injury induced by superior mesenteric occlusion. Male Wistar-albino rats randomized into three groups: (1) sham-operated control group (n = 12), laparotomy without I/R injury; (2) intestinal ischemia/reperfusion (I/R) group (n = 12), 60 min of ischemia by superior mesenteric occlusion followed by 2 h of reperfusion; and (3) I/R+PDTC-treated group (n = 12), 100 mg/kg injection of PDTC intravenously, 30 min after the commencement of reperfusion. Evans blue dye was injected to half of rats in all groups before the induction of I/R. We assessed the degree of pulmonary tissue injury biochemically by measuring malondialdehyde (MDA), glutathione (GSH), and nitric oxide (NO) levels, and histopathologically by establishing pulmonary neutrophil sequestration and acute lung injury scoring. Pulmonary edema was evaluated by Evans blue dye extravasation, as well as lung tissue wet/dry weight ratios. Pyrrolidine dithiocarbamate treatment significantly reduced the MDA and NO levels, and increased the GSH levels in the lung parenchyma, biochemically (p < 0.05), and atteneuated the pulmonary parenchymal damage, histopathologically (p < 0.05). However, pulmonary neutrophil sequestration was not affected by postischemic treatment with PDTC (p > 0.05). Pyrrolidine dithiocarbamate administration also significantly alleviated the formation of pulmonary edema, as evidenced by the decreased Evans blue dye extravasation and organ wet/dry weight ratios (p < 0.05). This study showed that postischemic treatment with PDTC significantly attenuated the lung reperfusion injury. Further clinical studies are needed for better understanding of the specific mechanisms of PDTC protection against I/R-related organ injury and to clarify whether PDTC may be a useful therapeutic agent during particular operations where remote organ I/R injury occurs.

Extensive pneumothorax, pneumomediastinum and surgical emphysema as a complication of bleomycin therapy

Bleomycin is a commonly used chemotherapeutic agent and one of the commonest cytotoxic drugs leading to pulmonary parenchymal damage. It generally leads to interstitial pneumonitis and fibrosis, hypersensitivity reactions and acute respiratory distress syndrome. We describe an 8-year-old boy who, following prolonged bleomycin therapy, demonstrated extensive air dissection and extrapulmonary air, an unusual and fatal complication.

Pre-treatment of donor with 1-deamino-8-d-arginine vasopressin could alleviate early failure of porcine xenograft in a cobra venom factor treated canine recipient☆

Unlike cardiac or renal xenotransplants, the depletion of complement using cobra venom factor (CVF) does not improve pulmonary xenograft survival. Several cases suggest that the swine von Willebrand factor (vWF) may play a major role in presenting a different pathogenesis of pulmonary xenograft dysfunction from other organs. To evaluate the role of vWF and the complement system in mediating hyperacute vascular injury of pulmonary xenografts and elucidate pathogenesis of the injury, we performed swine-to-canine orthotropic single lung xenotransplantation after pre-treatment of 1-deamino-8-d-arginine vasopressin (DDAVP) and CVF. We set up three groups for lung xenotransplantation: group I served as the control group; group II, recipients pre-treated with CVF; group III, donors pre-treated with DDAVP (9 mg/kg, 3 days)/recipients pre-treated with CVF (60 u/kg). Hemodynamic data, coagulation and complement system parameters, and grafted lung pathologies were examined serially for 3h after transplantation. DDAVP infusion reduced the vWF content in swine lung tissue in vivo (7.7+/-2.4 AU/mg vs 16.0+/-5.6 AU/mg, P < 0.0001). Infusion of CVF 24 h prior to transplantation effectively depleted the recipient's serum C3 and complement hemolytic activity below the detectable range. Regardless of the use of CVF, both groups I and II transplanted with unmodified grafts showed an immediate drop in leukocytes and platelet counts after transplantation. However, in group III, in recipients transplanted with DDAVP pre-treated swine lung, the platelet count did not decrease after transplantation (P = 0.0295). The decrease of plasma antithrombin and fibrinogen tended to be attenuated in group III. Light microscopic examination revealed extensive vascular thromboses in both capillary and larger vessels, as well as early pulmonary parenchymal damage in groups I and II, but were rarely observed in group III. Complement inhibition alone was not enough to alleviate intravascular thrombosis, the main pathology in pulmonary xenotransplantation. Pre-infusion of DDAVP to the donor animal was effective in preventing platelet sequestration and attenuated intravascular thrombosis. It is suggested that the strategies targeting vWF would be promising for successful pulmonary xenotransplantation.

Combined Approach for a Case of Aortic Arch Aneurysm: Cervical Vessel Reconstruction and Aortic Endoprosthesis Placement

Endovascular treatment for aortic aneurysms carries a lower mortality than open surgery, especially for thoracic aortic aneurysms (TAA) which usually affect a high-risk patient population. Furthermore when the aneurysm is located in the aortic arch, the surgical approach presents additional problems such as recurrent laryngeal nerve and phrenic nerve lesions, cerebrovascular complications and pulmonary parenchymal damage. Nevertheless the endovascular approach, even if less invasive, can be difficult because of the curvature of the aortic arch and because of the need to keep the cerebral vessels open. This paper describes a combined approach, surgical and endovascular, where cerebral vessel reconstruction was carried out before endovascular surgery.

Nosocomial pneumonias in haematological malignancies in the medical intensive care unit

30 patients with malignant haematological disorders and nosocomial pneumonia, treated during a three-year period in the medical intensive care unit (ICU) of a university hospital, were studied in retrospect. Twelve patients had received bone marrow or peripheral stem cell transplantations 90 +/- 143 (10 - 546) days prior to ICU admission. Six of these received cyclosporin A. 19 of 30 patients were on corticosteroids and 20 had received courses of chemotherapy within a period of one month prior to ICU admission. Patients presented with signs of pulmonary infection and respiratory failure. In 24 patients the likely causative pathogen for pneumonia could be identified. Gram-negative bacteria (n = 17) were in the majority, lead by Pseudomonas, Enterobacter, and Klebsiella species. Gram-positive bacteria (n = 5) were Streptococcus and Staphylococcus species. Infections with Chlamydiae species were diagnosed in two cases. Fungal infections were caused by Candida (n = 8) or Aspergillus species (n = 3) and viral infections by Cytomegalovirus (n = 6). Infections with more than one pathogen were common. Ten patients had pneumonia associated with signs of diffuse pulmonary parenchymal damage of varying degree. 26 patients received mechanical ventilation for 7 +/- 9 (1 - 32) days. The duration of stay in the ICU was 11 +/- 10 (1 - 43) days. 26 of the 30 patients (87 %) died. Patients with haematological malignancies and nosocomial pneumonias have despite medical intensive care treatment a poor prognosis with substantial mortality.

Smoke Inhalation Injury

Smoke inhalation injuries are the leading cause of fatalities from burn injury. The major forms of inhalation injuries are carbon monoxide toxicity, injury to the upper airway, and pulmonary parenchymal damage. The compromised airway is protected by tracheal intubation, and respiratory failure is treated with assisted ventilation. Maintenance of good pulmonary hygiene, optomized fluid resuscitation, and routine invasive hemodynamic monitoring are the mainstays of therapy. The development of acute pulmonary insufficiency, pulmonary edema, or bronchopneumonia requires a comprehensive approach to all aspects of the illness. Acute pathophysiologic responses to inhalation injury are complex. Future therapies will target improved ventilatory strategies and the redundant host inflammatory response.

Massive haemothorax following thoracic vertebral fracture

Haemothorax is common in major trauma. Most frequently this results from pulmonary parenchymal laceration or damage to the chest wall vessels and occasionally from a ruptured aorta or pulmonary artery. We present a rare cause due solely to a fractured thoracic vertebra [ [1] Parry G.W. Morgan W.E. Salama F.D. Management of haemothorax. Ann. R. Coll. Surg. Engl. 1996; 78: 325-326 PubMed Google Scholar ].

Histopathologic alterations induced in the lungs of sheep by use of α2-adrenergic receptor agonists

Abstract Objective To study effects of central- and peripheral-acting α2-adrenergic receptor agonists on lung parenchyma, platelets, and pulmonary intravascular macrophages (PIM) of sheep. Animals 12 healthy mature female sheep. Procedure Group-1 (control, n = 2) sheep received 5 ml of physiologic saline solution IV and were euthanatized 3 minutes later. Sheep of group 2 (n = 8) received xylazine (150 µg/kg of body weight, IV), then 2 sheep each were euthanatized 3, 10, or 60 minutes, or 12 hours later. Sheep (n = 2) of group 3 were given ST-91 (30 µg/kg, IV), then were euthanatized 3 minutes later. Immediately after euthanasia, the lungs were fixed intratracheally and tissue was obtained for light and electron microscopy after 1 hour. Results Pulmonary parenchymal damage or morphologic alterations in PIM and platelets were not evident in control sheep. Three minutes after xylazine administration, morphologic changes in PIM were appreciable. After 10 minutes, extensive damage to the capillary endothelium and alveolar type-I cells, intra-alveolar hemorrhage, and interstitial and alveolar edema were evident. Most PIM had complete internalization of the surface coat. Similar changes were seen 60 minutes after xylazine administration; however, by 12 hours, morphologic features of PIM and lung parenchyma were almost completely restored. Evidence of PIM activation, obvious damage to capillary endothelium, and extensive pulmonary edema also were evident 3 minutes after ST-91 administration. Conclusions Xylazine induces severe pulmonary parenchymal damage when administered at clinical sedative doses in sheep; morphologic changes in PIM within 3 minutes after administration of these drugs are substantial; and platelet aggregation is not apparent. (Am J Vet Res 1999;60:154-161)

A Case of Bronchial Lipoma with Extrabronchial Growth causing Middle Lobe Syndrome and Pneumonia

Benign pulmonary tumors are rare entities, and among them bronchial lipomas are the most uncommon. Up to date, about 80 cases have been reported in the English literature. But, the bronchial lipoma with extrabronchial growth causing middle lobe syndrome and pneumonia is extremely rare. Bronchial lipomas, mainly arising from normal fatty tissue of the proximal portion of the lobar or segmental bronchi, are histologically benign. But if diagnosis and treatments are delayed, they can produce extensive pulmonary parenchymal damage and irreversible brochiectasis distally. So whenever possible, the treatment of choice is resection by means of bronchoscopy via early diagnosis. But if endoscopic removal is not possible because the distal end of the tumor could not be visualized by fiberoptic bronchoscopy or if the nature of the tumor is unclear, surgery is necessary, with lobectomy or pneumonectomy being required in most cases due to the extensively damaged pulmonary parenchyma. We present a case of bronchial lipoma with extrabronchial growth, with a review of the literature and report of an unusual case.

Methylene blue prevents pulmonary injury after intestinal ischemia-reperfusion.

To investigate the effect of methylene blue, an inhibitor of oxygen radicals, on lung injury caused by reperfusion of ischemic tissue. Intestinal ischemia-reperfusion injury was induced in rats by clamping the superior mesenteric artery for 1 hour. Thereafter, the experimental group was administered 1% methylene blue intraperitoneally and the control group received saline. After 4 hours, pulmonary histopathologic features were assessed, and lung wet-weight to dry-weight ratios and tissue xanthine oxidase were determined. The control group suffered from severe pulmonary parenchymal damage, compared with slight damage in the experimental group. The number of sequestered neutrophils was significantly higher in the control group (319 +/- 60 polymorphonuclear cells per 10 high-power fields) than in the methylene blue-treated group (91 +/- 8 polymorphonuclear cells per 10 high-power fields; p < 0.001). The wet-weight to dry-weight ratio was significantly increased in the saline-treated rats compared with the methylene blue-treated group (6.19 +/- 0.28 vs. 5.07 +/- 0.21; p < 0.001). Xanthine oxidase activity was similar in both groups. Methylene blue attenuated lung injury after intestinal ischemia-reperfusion. Inhibition of oxygen free radicals may be the protective mechanism.

Inhalation injury increases the anastomotic bronchial blood flow in the pouch model of the left ovine lung.

Pulmonary parenchymal damage often occurs after airway injury. Bronchial venous drainage empties into the pulmonary microvasculature. We developed an in vivo model to study the bronchopulmonary portal system after smoke inhalation injury. Eight ewes were instrumented with hydraulic occluders on the left pulmonary artery (LPA), the left pulmonary vein, and the bronchoesophageal artery (BEA); a catheter in the LPA; and Swan-Ganz and femoral artery catheters. The vasculature between the occluders was defined as pouch. At stable mean arterial and right pulmonary arterial pressures, LPA occlusion reduced the left pulmonary artery pressure (LPAP) from 17 +/- 1 mmHg to 8 +/- 1 mmHg (p < .05). After left pulmonary vein occlusion, LPAP rose to 28 +/- 4 mmHg (p < .05 vs. baseline), indicating that systemic blood had entered the pouch. Opening the pouch to atmospheric pressure revealed an anastomotic bronchial blood flow (anastomotic Qbr) of .76 +/- .11% of cardiac output (CO). BEA occlusion reduced the anastomotic Qbr to .32 +/- .06% of CO (p < .05). Smoke inhalation injury resulted in a further increase in the maximal LPAP to 38 +/- 5 mmHg (p < .05 vs. right pulmonary artery pressure). The anastomotic Qbr rose to 1.29 +/- .13% of CO (p < .05) and was reduced to .40 +/- .09% of CO (p < .05) by BEA occlusion. Inhalation injury increased the anastomotic Qbr mainly due to BEA vasodilatation. Because the BEA supplies the injured airway, it may deliver deleterious material to the lung parenchyma.

Increased pulmonary clearance of aerosolized 99Tcm-DTPA in patients with a subset of stage I sarcoidosis

Measurement of the pulmonary clearance of aerosolized 99Tcm-diethylenetriamine pentaacetate (99Tcm-DTPA) as a marker of pulmonary parenchymal damage was performed in 10 non-smokers with sarcoidosis, none of whom was on medication, and the results compared with 12 normal controls. Posterior images were obtained using a single-headed gamma camera, with the subjects in a supine position, for 30 min after inhalation of aerosolized 99Tcm-DTPA had ceased. The pulmonary clearance of 99Tcm-DTPA was significantly increased in the sarcoidosis patients (57.6 +/- 22.1 min in the right lung, 62.2 +/- 22.7 min in the left lung) compared with the controls (79.3 +/- 10.2 and 78.4 +/- 7.7 min in the right and left lungs, respectively) (P < 0.05). Six of the 10 patients with sarcoidosis showed levels of pulmonary clearance, in both the right and left lungs, below the 95.5% confidence limit (mean +/- 2 S.D.) for the controls. Increased pulmonary clearance of 99Tcm-DTPA was also found in 2 of 4 patients with stage I sarcoidosis. No relationship was found between the pulmonary clearance of 99Tcm-DPTA and inflammatory markers (ACE, lysozyme) in the serum.

Pulmonary sequelae of prolonged total venoarterial bypass: Evaluation with a new experimental model

Total normothermic venoarterial bypass was established in 6 healthy pigs over a period of 18 hours. A heparincoated closed extracorporeal system was used and no heparin was administered systemically. During the bypass period the main pulmonary artery was occluded and the heart was maintained in a beating state. All the animals maintained stable hemodynamics and normal blood gases during the entire period of bypass. In the postbypass period, the central hemodynamics continued to be stable while the arterial oxygen tension (inspired oxygen fraction = 0.21) decreased significantly (p ≤ 0.05). The total body oxygen uptake, on the other hand, remained unaltered. All the animals died within 4 hours after weaning off the venoarterial bypass circuit on account of pulmonary edema in 2 and cardiac arrest in 4. Death was preceded by progressive pulmonary hypertension and lactacidosis in all the animals. Histological examination of the lungs showed pulmonary parenchymal damage ranging from interstitial edema to intraalveolar hemorrhage and parenchymal necrosis involving more than 80% of the pulmonary parenchyma. A normothermic total venoarterial bypass of 18 hours duration or more produces pulmonary edema of varying severity, pulmonary hypertension, pulmonary parenchymal necrosis, and lactacidosis in healthy juvenile pigs, resulting uniformly in their death. Despite these sequelae the systemic arterial hypoxemia may only be mild to moderate.

Scintigraphic determination of severity in pulmonary parenchymal damage in patients with atrial septal defect

According to the pattern observed on a lung perfusion scan, patients with atrial septal defect (ASD) were classified into three stages: stage I, normal perfusion (n = 15); stage II, apical prone perfusion (n = 22); and stage III, mottled perfusion (n = 23). These stages were compared with hemodynamic data obtained from cardiac catheterization and with the right ventricular ejection fraction (RVEF). Staging from I to III correlated well with pulmonary arterial pressure, and patients in stage III showed a significant increase in pulmonary arteriolar resistance and a significant decrease in Qp/Qs. There was no significant difference in RVEF between the stages. We concluded that the scintigraphic severity determined by lung perfusion scan could be valid for evaluating the extent of pulmonary parenchymal damage in patients with ASD.

Drug-induced pulmonary disease.

Administration of more than 40 separate pharmacologic agents has been associated with some form of pulmonary toxicity. This problem is becoming more significant every year. Occasionally, effective modes of therapy must be withdrawn because of undesirable pulmonary side effects, putting patients at risk for potentially lethal diseases. Pulmonary parenchymal damage due to drugs is an especially troublesome problem because irreversible pulmonary disease may occur. Mechanisms of pulmonary parenchymal tissue damage by drugs are unclear. It appears that some drugs induce direct tissue injury in addition to indirect tissue damage through amplification of pulmonary inflammation; other drugs cause pulmonary alterations solely through indirect mechanisms. Common clinical syndromes associated with drug-induced pulmonary parenchymal disease include pneumonitis/fibrosis, hypersensitivity lung disease, and noncardiogenic pulmonary edema. Less common patterns of pulmonary parenchymal injury by drugs include bronchiolitis obliterans and a pulmonary renal syndrome. Risk factors for pulmonary injury due to pharmacologic agents are partially defined but not entirely understood. To date, there are no adequate tests for early detection of pulmonary damage by drugs, although research into this area is active. This review discusses mechanisms and clinical features of drug-induced pulmonary parenchymal injury to aid the clinician in recognizing and understanding these syndromes.

Respiratory Care of the Burn Patient

The vast majority of respiratory disorders in thermally injured patients arise from associated inhalation injuries. The major forms of these injuries are carbon monoxide poisoning, injury to the upper airway, and pulmonary parenchymal damage. One hundred per cent oxygen, initiated at the scene of the accident, is the single most effective treatment of carbon monoxide toxicity, which must be assessed by carboxyhemoglobin determinations. Respiratory tract damage is identified by fiberoptic bronchoscopy and xenon ventilation-perfusion scintigrams. The compromised airway is protected by tracheal intubation, and respiratory failure is treated with assisted ventilation and supplemental oxygen. Pulmonary infection requires specific antibiotics based on isolated organisms and their sensitivities to antimicrobials. The upper respiratory tract of patients requiring long-term intubation should be assessed by fiberoptic bronchoscopy and other modalities to prevent fatal late airway occlusion.

Pulmonary Parenchymal Injuries

Pulmonary parenchymal damage is a frequent consequence of major trauma to the chest. Among the injuries considered in this article are traumatic pulmonary pseudocysts, pulmonary hematomas, major pulmonary lacerations, pulmonary contusions, and penetrating pulmonary parenchymal injuries. Also discussed is emergency resuscitation of patients with pulmonary parenchymal injuries.

Nonciliated bronchiolar epithelial (Clara) cell necrosis induced by organometallic carbonyl compounds

The administration of transition metal organometallic compounds such as manganese, chromium, and iron carbonyls by the i.p. route, and nickel by inhalation (mice) or intravenously (rats), resulted in selective necrosis of the noneiliated bronehiolar epithelial (Clara) cells and variable pulmonary parenchymal damage in BALB/c mice and Fischer-derived rats within 24 h of administration. The pulmonary toxicity of methylcyclopentadienyl manganese tricarbonyl (MMT), a representative of this group of compounds, was enhanced by pretreatment with piperonyl butoxide (PB), an inhibitor of the mixed-function oxidase system. This finding suggests that Clara cell necrosis can result from direct toxicity and that the specificity of toxic agents for Clara cells may not be related solely to the presence of the mixed-function oxidase system.

Radiographic detection of mobilizable lung water: the gravitational shift test.

A radiographic method for detecting excessive lung water in patients with pulmonary infiltrates of uncertain cause is described. The gravitational shift test uses bedside frontal films before and after prolonged lateral decubitus positioning. Excess lung water is identified by detecting a shift in infiltrate to the dependent lung while the opposite side clears or remains stable. The test was evaluated in 33 patients with infiltrates of well defined etiology. Twelve patients had heart failure or fluid overload (edema): 14 had pulmonary infection or parenchymal damage (inflammation); and seven had inflammation plus edema. Infiltrates shifted to the dependent lung in 85% of patients with lung edema, but did not shift in 78% of patients with inflammatory disease. The test also detected excess lung water in six of seven patients with underlying inflammatory disease. Each patient with a positive test showed clinical, physiologic, and radiographic improvement after therapy directed at mobilizing excessive lung water. When the differential diagnosis of a diffuse infiltrate is in question, a positive test represents a strong indication for a trial of diuretic therapy.