Apigenin Reduces NF-κB and Subsequent Cytokine Production as Protective Effect in a Rodent Animal Model of Lung Ischemia-Reperfusion Injury.

PURPOSE: Lung ischemia-reperfusion injury (LIRI) can complicate lung transplantation or cardiac surgery with cardiopulmonary bypass, increasing morbidity and mortality. In LIRI, pro-inflammatory cytokines are activated, reactive oxygen species are generated and nuclear factor-κB (NF-κB) is up-regulated, altering lung mechanics. We tested the effect of the flavonoid apigenin on a rodent model of LIRI. METHODS: Thirty-seven Wistar rats were subjected to LIRI with or without a single or double dose of apigenin. Induction of LIRI involved sternotomy and clamping of either the left lung hilum or the pulmonary artery alone for 30 min, followed by 60 min of reperfusion. Control groups consisted of LIRI plus NaCl, a sham group and a baseline group. At the end of the experiments, both lungs were analyzed by RT-PCR, Western blot, and light microscopy. RESULTS: In placebos, the expression levels of pro-inflammatory markers were increased in both lungs significantly, whereas NF-κB was markedly up-regulated. Administration of apigenin reduced the activation of NF-κB and the expression of TNFα, iNOS, and IL-6. These effects were observed in total lung ischemia. Histology showed greater hemorrhage and exudation in the pulmonary periphery of all groups, whereby damage was practically absent in the central lung regions of the apigenin animals. A second dose of apigenin did not outclass a single one. CONCLUSIONS: We conclude that apigenin given intraperitoneally can reduce activation of NF-κB and also attenuate the expression of TNFα, IL-6, and iNOS in a surgical model of LIRI. The surgical procedure itself can induce significant damage to the lungs.

The effect of amifostine on lung ischaemia-reperfusion injury in rats.

OBJECTIVES: Lung ischaemia-reperfusion injury (LIRI) frequently occurs after lung transplantation or cardiac surgery with cardiopulmonary bypass, thus increasing postoperative morbidity and mortality. As LIRI is associated with the release of reactive oxygen species and a subsequent inflammatory reaction, we tested whether amifostine, a thiol and free radical scavenger, has a beneficial effect on LIRI. METHODS: A total number of 72 Wistar rats were subjected to LIRI with or without a single or double dose of amifostine (100 mg/kg, intraperitoneally). Experimental induction of LIRI was performed by clamping either the left lung hilum or the pulmonary artery alone for 60 min, followed by 90 min of reperfusion. Control groups consisted of LIRI and NaCl, a sham group and a no intervention group (baseline). At the end of the experiments, the left lung was analysed by quantitative RT-PCR of inflammatory marker gene expression, western blot of activated nuclear factor-κB (NF-κB) and light and electron microscopy. RESULTS: In placebo and amifostine groups, the expression levels of pro-inflammatory markers were increased significantly and to a similar extent independent of the type of ischaemia induction. In contrast, amifostine reduced the activation of NF-κB in comparison with placebo. This effect was present independent of the type of ischaemia or the application of a single or double dose of amifostine. However, oedema formation, blood-gas barrier damage and inflammatory reaction were similar in all amifostine or placebo LIRI groups. CONCLUSIONS: Despite a significant reduction in NF-κB activation, amifostine failed to decrease the inflammatory response and structural changes induced by LIRI in this experimental setting.

Hemodynamic effects of peri-operative statin therapy in on-pump cardiac surgery patients.

BACKGROUND: Peri-operative statin therapy in cardiac surgery cases is reported to reduce the rate of mortality, stroke, postoperative atrial fibrillation, and systemic inflammation. Systemic inflammation could affect the hemodynamic parameters and stability. We set out to study the effect of statin therapy on perioperative hemodynamic parameters and its clinical outcome. METHODS: In a single center study from 2006 to 2007, peri-operative hemodynamic parameters of 478 patients, who underwent cardiac surgery with cardiopulmonary bypass, were measured. Patients were divided into those who received perioperative statin therapy (n = 276; statin group) and those who did not receive statin therapy (n = 202; no-statin group). The two groups were compared together using Kolmogorov-Smirnov-Test, Fisher's-Exact-Test, and Student's-T-test. A p value < 0.05 was considered as significant. RESULTS: There was no significant difference in the preoperative risk factors. Onset of postoperative atrial fibrillation was not affected by statin therapy. Extended hemodynamic measurements revealed no significant difference between the two groups, apart from Systemic Vascular Resistance Index (SVRI). The no-statin group had a significantly higher SVRI (882 ± 206 vs. 1050 ± 501 dyn s/cm5/m2, p = 0.022). Inotropic support was the same in both groups and no significant difference in the mortality rate was noticed. Also, hemodynamic parameters were not affected by different types and doses of statins. CONCLUSIONS: Perioperative statin therapy for patients undergoing on-pump coronary bypass grafting or valvular surgery, does not affect the hemodynamic parameters and its clinical outcome.

Prognostic value of chromosomal imbalances in squamous cell carcinoma and adenocarcinoma of the lung.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most aggressive tumors, with a very low overall survival rate. We investigated surgically resected squamous cell carcinoma (SCC) and adenocarcinoma (AC) to identify chromosomal imbalances and their value for individual prognostication. METHODS: A total of 80 cases, including 55 SCC and 25 AC, were retrospectively analyzed by comparative genomic hybridization. To model the sequential cytogenetic events, an oncogenetic tree model was applied based on maximum likelihood estimation. Clinicopathologic data and follow-up data were correlated with chromosomal imbalances. RESULTS: Fifty-one percent of patients were in stage I, 32% in stage II, and 17% in stage III, without statistically significant differences in staging distribution between SCC and AC. The average number of copy number imbalances was higher in SCC than in AC (9.4±1.2 vs 5.4±1.1; p=0.11). Frequency of chromosomal imbalances at -3p, +3q, -4q, +5q, -5q, +7q, and -13q were significantly different between SCC and AC. Subsequently, oncogenetic tree modeling identified different clusters of chromosomal imbalances for SCC and AC. Appearance of the -3p-cluster in SCC was associated with decreased overall survival independent of clinicopathologic parameters (mean, 42.8±7.5 months vs 80.1±9.1 months, log rank p=0.019), whereas in AC no prognostic value could be identified for specific clusters of chromosomal imbalances. CONCLUSIONS: Although, the limited number of analyzed cases allows a cautious statement on chromosomal imbalances, the oncogenetic tree modeling suggests distinct patterns of cytogenetic evolution for SCC and AC with implications for clinical outcome in SCC.

Morphological investigations of type A aortic dissection.

PURPOSE: The aim of this study was to analyze systematically the morphology of aortal segments of Type A dissection. METHODS: Nineteen patients were operated on for Type A dissection in the Department of Thoracic, Cardiac, and Vascular Surgery in Goettingen, Germany, from January 2002 to January 2005. All diagnoses were confirmed by transesophageal echocardiography and computed tomography of the chest. All taken aortic segments were examined by the conventional histological and electron microscopical method. RESULTS: Besides subadventitial hyperplasia of collagen filaments, the preparations showed hyperplasia of endothelial cells with loose cellular junctions, desquamation of endothelial cells, and morphological changes of endothelial cells with villius development, as well as signs of aortitis. CONCLUSION: The present results arouse suspicion of local inflammation of the aortic wall, but with moderate progress under strong hyperplasia. Because of rupture of the intima, the inflammation appears as an acute disease.

Coronary artery bypass surgery in a patient with Kartagener syndrome: a case report and literature review.

Kartagener syndrome consists of congenital bronchiectasis, sinusitis, and total situs inversus in half of the patients. A patient diagnosed with Kartagener syndrome was referred to our department due to 3-vessel coronary disease. An off-pump coronary artery bypass operation was performed using both internal thoracic arteries and a saphenous vein graft. We performed a literature review for cases with Kartagener syndrome, coronary surgery and dextrocardia. Although a few cases of dextrocardia were found in the literature, no case of Kartagener syndrome was mentioned.

Long-term survival is linked to serum LDH and partly to tumour LDH-5 in NSCLC.

BACKGROUND: Lactate formation is up-regulated in tumorous cells by lactate dehydrogenase (LDH). High serum LDH level is linked to many malignancies with poorer survival, but tumour LDH-5 has not been well investigated in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: In 89 patients operated on for NSCLC stage I-III, the serum LDH level was assayed and immunohistochemistry for tumour LDH-5 was performed. Impact on long-term survival and correlation was analysed. RESULTS: High serum LDH was associated with poorer survival (p<0.001). No correlation was revealed between serum LDH and the tumour LDH-5. Only in tumours greater than 3 cm were high tumour LDH-5 values associated with higher serum LDH values (p=0.04) and in this subgroup, high tumor LDH-5 was associated with poorer long-term survival (p=0.024). CONCLUSION: High serum LDH has a negative impact on long-term survival in NSCLC, whereas for tumour LDH-5, this was seen only in a subgroup of patients with larger tumours.

Bentall procedure 39 years after implantation of a Starr-Edwards aortic caged-ball-valve prosthesis.

We report a case of a male patient who received an implantation of a Starr-Edwards-caged-ball-valve-prosthesis in 1967. The surgery and postoperative course were without complications and the patient recovered well after the operation. For the next four decades, the patient remained asymptomatic--no restrictions on his lifestyle and without any complications. In 2006, 39 years after the initial operation, we performed a Bentall-Procedure to treat an aortic ascendens aneurysm with diameters of 6.0 x 6.5 cm: we explanted the old Starr-Edwards-aortic-caged-ball-valve-prosthesis and replaced the ascending aorta with a 29 mm St.Jude Medical aortic-valve-composite-graft and re-implanted the coronary arteries.This case represents the longest time period between Starr-Edwards-caged-ball-valve-prosthesis-implantation and Bentall-reoperation, thereby confirming the excellent durability of this valve.

A three-group model to predict mortality in emergent coronary artery bypass graft surgery.

BACKGROUND: Emergent coronary artery bypass graft surgery (CABG) for acute myocardial infarction is associated with an increased operative risk. For estimation of mortality risk, the European System for Cardiac Operative Risk Evaluation (EuroSCORE) is appropriate up to a medium risk score (<6 points). To predict mortality risk more accurately in cases of higher EuroSCORE, additional cardiac data can be helpful. METHODS: Over a 3-year period, patient data including acute myocardial infarction and emergent CABG were retrospectively reviewed. Univariate and multivariate analysis for in-hospital mortality was performed. The EuroSCORE analysis and follow-up was investigated. RESULTS: Overall in-hospital mortality was 18.3%. Preoperative cardiac related predictors for in-hospital mortality were cardiogenic shock (p < 0.001), very poor left ventricular function (p = 0.001), and ST-segment elevation (p = 0.012). In multivariate regression analysis, age, cardiogenic shock, and pulmonary hypertension were independent preoperative risk factors. According to the EuroSCORE, we could define three statistically different groups: intermediate-risk, high-risk, and very high risk, with an observed mortality of 3.3%, 20.0%, and 63.2%, respectively. The EuroSCORE correlates with but overestimates the mortality risk. In subgroup analysis, the creatine kinase-myocardial band/hour ratio for the intermediate-risk group and ST-segment elevation for the high-risk group were additional cardiac risk factors. CONCLUSIONS: Patients with an acute myocardial infarction and emergency aortocoronary CABG have an elevated operative risk. Logistic EuroSCORE overestimates the mortality rate. Three different risk groups can be defined, in which creatine kinase-MB/h-ratio and ST-segment elevation can more accurately predict operative risk.

Factors affecting post minimally invasive direct coronary artery bypass grafting incidence of myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting and mortality of cardiac origin.

In the present study we identify parameters which influence the incidence of myocardial infarction (MI), need for percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and cardiac mortality after minimal invasive coronary artery bypass grafting (MIDCABG). With a mean follow-up of 30+/-11.2 months, 390 patients were assessed with Wald test-corrected chi(2) analysis to identify preoperative factors which correlate with a higher incidence of post-MIDCABG MI, PCI, CABG and mortality from cardiac causes. We found an increased incidence of postoperative MI in patients with 2-vessel (8.7%) and 3-vessel (7.7%) vs. 1.3% 1-vessel coronary artery disease (CAD) (P=0.023), and in patients with preceding cardiac procedure (CABG and PCI: 8.4% vs. 2.0% without, P=0.023). Also diabetes was associated with higher post-MIDCABG frequency of MI (P=0.035). Severity of angina was associated with lesser post-MIDCAB-PCI (P=0.011) while preceding CABG predicted a higher incidence (P=0.012). Preoperative low ejection fraction (EF) (multivariate, P<0.001), preoperative MI (P=0.007) and extent of CAD (P=0.001) were associated with a higher post-MIDCABG mortality. None of the parameters correlated with subsequent CABG MIDCABG. The extent and history of CAD, history of cardiac interventions and low EF seem to influence the outcome adversely and should be considered deciding pro or against the MIDCAB-option.

Surgical treatment of pulmonary aspergillosis/mycosis in immunocompromised patients.

Invasive pulmonary aspergillosis is a severe complication in immunosuppressed patients. Surgical resection can be curative in certain patients after antifungal treatment. Over a 7-year period, ten patients with suspected invasive pulmonary aspergillosis of two university hospitals were retrospectively reviewed. A literature review was undertaken. Patient's age was 48.1 years (mean); the cause of immunosuppression was a hematological disease with consecutive therapy in seven patients and chronically corticoid therapy in three patients. After an antifungal therapy, surgical resection was performed with lobectomy/segmentectomy in 60% and with wedge-resection in 40%. Postoperative course were uneventful in seven patients, two patients died due to infectional circumstances, and one patient was reoperated because of empyema. The underlying disease marked long-term follow-up. Resection of focal pulmonary invasive aspergillosis can be curative. Clinical circumstances and dissemination must be taken into consideration to indicate surgery. To point out the best pathway randomised prospective studies are necessary.

Accelerated intimal hyperplasia in aortocoronary internal mammary vein grafts in minipigs.

BACKGROUND: More than 50% of aortocoronary saphenous vein grafts are occluded 10 years after surgery. Intimal hyperplasia is the initial critical step in the progression toward occlusion. Internal mammary veins, which are physiologically prone to less hydrostatic pressure, may undergo an accelerated progression to intimal hyperplasia and thus be suitable for investigation of the mechanisms of aortocoronary vein graft disease. METHODS: Six minipigs underwent aortocoronary bypass grafting using standard cardiopulmonary bypass and cardioplegic arrest. Mammary vein were grafted in a reversed manner from ascending aorta to left anterior descending coronary artery (LAD). The proximal LAD was ligated, rendering the anterior left ventricle vein graft-dependent. Minipigs were killed after 4 weeks, and vein grafts were harvested. Histological and immunohistological investigation were performed with respect to morphometric analysis, endothelial damage/dysfunction (v-Willebrand-factor (vWF)), smooth muscle cells (alpha-smooth actin) and proliferation rate (proliferation marker Ki 67). RESULTS: Mean intimal area of vein grafts was increased compared to ungrafted mammary veins. Intimal hyperplasia in vein grafts was characterized by massive accumulation of smooth muscle cells with a high proliferation rate and endothelial perturbation. Significant (p = 0.001) intimal hyperplasia of the grafted mammary vein compared to the ungrafted mammary vein was found. These changes were absent in ungrafted mammary veins. CONCLUSION: The present study demonstrates a pig model of aortocoronary vein graft intimal hyperplasia which is characterized by an accelerated progression within internal mammary veins. The model is suitable to investigate the pathophysiology of aortocoronary vein graft intimal hyperplasia as well as therapeutic approaches.

Investigating the failure to aspirate subglottic secretions with the Evac endotracheal tube.

BACKGROUND: Aspiration of subglottic secretions is a widely used intervention for prevention of ventilator-associated pneumonia. However, using the Hi-Lo Evac endotracheal tube (Hi-Lo Evac; Mallinckrodt; Athlone, Ireland) (Evac ETT), dysfunction of the suction lumen and subsequent failure to aspirate the subglottic secretions are common. Our objective in this study was to determine the causes of suction lumen dysfunction experienced with the Evac ETT. METHODS: We studied 40 adult patients intubated with the Evac ETT. In all cases for which dysfunction of the suction lumen was observed, the subglottic suction port was examined visually using a flexible bronchoscope. RESULTS: Dysfunction of the suction lumen occurred in 19 of 40 patients (48%). In 17 of these (43%), it was attributed to blockage of the subglottic suction port by suctioned tracheal mucosa. CONCLUSION: Evacuation of subglottic secretions using the Evac ETT is often ineffective due to prolapse of tracheal mucosa into the subglottic suction port.

Internal thoracic artery side branch ligation for post coronary surgery ischemia.

Two cases of internal thoracic artery side-branch ligation in patients with recurrent angina after coronary bypass are reported with long-term follow-up. Ligation was performed with clips via a left thoracotomy. Treadmill stress testing after 3 and 4 years did not provoke any myocardial ischemia. These findings suggest that an unligated side-branch can produce a steal phenomenon.

Intramyocardial injection of low-dose basic fibroblast growth factor or vascular endothelial growth factor induces angiogenesis in the infarcted rabbit myocardium.

BACKGROUND: Myocardial angiogenesis after the systemic administration of basic fibroblast growth factor or vascular endothelial growth factor at high therapeutic doses has been implicated in the occurrence of side effects that may undermine their safety. The aim of this study was to investigate the angiogenic effects of the intramyocardial administration of recombinant human basic fibroblast growth factor or vascular endothelial growth factor protein, at low doses, in the infarcted rabbit myocardium. METHODS AND RESULTS: Twenty-five New Zealand White rabbits were divided into five groups (n=5) and subjected to coronary artery ligation after lateral thoracotomy, inducing acute myocardial infarction. Five minutes later, the following substances were injected intramyocardially into the infarcted area: (a) normal saline (controls); (b) 6.25 or 12.5 mug of recombinant human basic fibroblast growth factor protein (basic fibroblast growth factor-1 group or basic fibroblast growth factor-2 group); or (c) 5 or 10 microg of recombinant human vascular endothelial growth factor 165 protein (vascular endothelial growth factor-1 group or vascular endothelial growth factor-2 group). On the 21st postoperative day, the animals were euthanized, and their hearts were subjected to histopathological examination and immunohistochemical assessment of vascular density in the infarcted area. The alkaline phosphatase anti-alkaline phosphatase procedure and the primary monoclonal antibody JC70 were used. Histopathological examination confirmed the induction of myocardial infarction. Vascular density was significantly increased (P<.004) in all treatment groups (in mean+/-S.E. vessels/x 200 optical field: basic fibroblast growth factor-1: 85.8+/-10.9; basic fibroblast growth factor-2: 76.6+/-3.7; vascular endothelial growth factor-1: 73.4+/-3.2; vascular endothelial growth factor-2: 89.5+/-5.2) compared to that in controls (58.9+/-4.9 vessels/x 200 optical field). Vascular density in the vascular endothelial growth factor-2 group was significantly higher than that in the vascular endothelial growth factor-1 group (P<.001). CONCLUSIONS: Low doses of recombinant human basic fibroblast growth factor or vascular endothelial growth factor protein, when administered intramyocardially, stimulate angiogenesis in the infarcted myocardium.

Diltiazem versus amiodarone to prevent atrial fibrillation in coronary surgery.

The prophylactic effect of amiodarone on atrial fibrillation after coronary bypass grafting with extracorporeal circulation was compared with that of diltiazem in two groups of 60 patients each. Patients were monitored continuously for 8 days. The incidence of atrial fibrillation was recorded retrospectively in a control group of 60 patients who received our standard prophylactic regimen of an oral beta blocker. The incidence of postoperative atrial fibrillation was not significantly different in the two test groups: 11.7% for the amiodarone group and 10% for the diltiazem group. The incidence of atrial fibrillation in the control group was 23.3% and the differences were marginally significant when compared to the amiodarone ( p = 0.093) and diltiazem groups ( p = 0.050). The prophylactic use of diltiazem or amiodarone is feasible and safe for patients undergoing coronary bypass, with similar rates of atrial fibrillation.

Air-mattress motion therapy for respiratory failure after cardiothoracic surgery.

PURPOSE: The standard management of respiratory failure after cardiothoracic surgery involves prolonged mechanical ventilation, drug support, and chest physiotherapy. We report the effectiveness of a novel type of respiratory physiotherapy, the air mattress V-CUE unit, which utilizes a computerized automatic combination of three movements: rotation, percussion, and vibration. METHODS: Among 189 patients who underwent various cardiothoracic operations, 6 were eligible for V-CUE application, after the development of respiratory failure caused by early adult respiratory distress syndrome, massive atelectasis, or pulmonary infection. RESULTS: The V-CUE unit was used to treat six postsurgical patients, aged 58-73 years (mean, 65.8 years); four who had undergone coronary artery bypass grafting, one who had undergone mitral valve replacement, and one who had undergone a bilobectomy. The mean duration of supportive V-CUE was 3.9 days (range 2-6 days), and the mean duration of mechanical ventilation was 2.9 days. There was no need for reintubation or tracheotomy, and all six patients recovered uneventfully. CONCLUSION: Our preliminary results indicate that V-CUE dynamic air therapy is effective for managing postoperative respiratory failure, adjuvant to or complementary to standard therapy.