Right heart function interacts with left ventricular remodeling after CRT: A pressure volume loop study.

BACKGROUND: Right ventricular (RV) dysfunction is recognized as a cardinal prognostic marker in systolic heart failure patients. Conflicting data exist on the interaction of RV function and left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT). This prospective monocentric trial was set up to assess the predictive value of baseline RV function and corresponding RV-pulmonary artery (PA) coupling on LV reverse remodeling after CRT. METHODS: 110 patients with a CRT indication were prospectively enrolled. RV function and RV-PA interaction were analyzed at baseline using echocardiographic and invasive pressure-volume loop catheter approach. The primary endpoint was reverse LV remodeling (CRT-responder) defined as a reduction in LV end-systolic volume of ≥15% at 6 months. RESULTS: Responders had higher RV-PA coupling ratios (single-beat end-systolic elastance/PA elastance: Ees/Ea) at baseline, which corresponded to smaller RVs with better ejection fraction and lower afterload. After multivariate adjustment, the baseline Ees/Ea remained an independent predictor for LV response (OR 14.0 [1.5-130.8], p = 0.021). Normal coupling (Ees/Ea ≥ 1) was associated with higher responder rates (RR) (86%). Progressive uncoupling was associated with lower LV-RR (Ees/Ea ≤ 1-0.5: 57%, and Ees/Ea < 0.5: 32%, p < 0.001), corresponded with higher degrees of LV impairment and severity of mitral regurgitation, and was independently associated with an adverse outcome. CONCLUSIONS: A higher baseline RV-PA coupling, reflecting a lower degree of LV-induced pulmonary hypertension and secondary RV-dysfunction, is associated with an improved LV-reverse remodeling and is independently associated with better prognosis. The value of RV-PA ratio as potential guide for CRT patient selection warrants further investigation. Clinical Trial Registration - URL: http://www.drks.de. Unique Identifier: DRKS00011133.

Coagulation factor Xa induces an inflammatory signalling by activation of protease-activated receptors in human atrial tissue.

Activated factor X (FXa) is an important player in the coagulation cascade responsible for thrombin generation, which is activated during atrial fibrillation. Increasing evidence suggests that FXa influences cell signalling in various cell types by activating protease-activated receptors (PARs). It is so far not known if molecular effects of FXa affect atrial signal transduction. To study the effects of FXa, human atrial tissue slices were cultivated with FXa up to 24h. Additionally, rapid pacing was applied at 4Hz to resemble atrial fibrillation. The inhibitory impact of FXa antagonist (Rivaroxaban), protease-activated receptor 1 antagonist (SCH79797), and protease-activated receptor 2 antagonist (GB83) were analysed under experimental conditions. The exposure of atrial tissue to FXa resulted in the 1.7 fold upregulation of PAR2-mRNA, activation of MAP kinases (ERK1/2) and NF-κB signalling. Furthermore FXa increased the expression of adhesion molecule ICAM-1 (1.82 ± 0.20), chemokine IL-8 (1.94 ± 0.20), as well as prothrombotic molecule PAI-1 (1.52 ± 0.17). The combination of rapid pacing and FXa caused significant upregulation of PAR1 (2.82 ± 0.22), PAR2 (2.66 ± 0.40), ICAM-1 (2.13 ± 0.25), IL-8 (2.22 ± 0.24), LOX-1 (2.59 ± 0.35), and PAI-1 (2.65 ± 0.52) at the mRNA level. Rivaroxaban and GB83 prevented upregulation of PARs, ICAM-1, LOX-1, IL-8, and activation of MAP kinases. The elevation in the expression of PAI-1 was hindered in the presence of SCH79797, or Rivaroxaban. The present study indicates that FXa mediates inflammatory signalling in atrial tissue. Importantly, FXa and tachyarrhythmia act synergistically to increase expression of protease-activated receptors and inflammatory mediators. Rivaroxaban prevented effectively FXa-induced molecular effects in human atrial tissue particularly during rapid pacing.

Penetrating abdomino-thoracic injuries: report of four impressive, spectacular and representative cases as well as their challenging surgical management.

UNLABELLED: Gunshot wounds are rare events in European countries, but stab and impalement injuries occur more frequently and are often spectacular. The aim of the study was to describe several types of penetrating abdomino-thoracic injuries as well as the appropriate surgical interventions, including complex wound management. MATERIAL AND METHODS: The representative case series includes four patients with abdomino-thoracic penetrating trauma (two impalements and two stabbings), who were treated in a surgical university hospital (tertiary) centre during a 12-month period. RESULTS: 1. A man was impaled on a steel pipe, which entered the body above the right kidney and behind the liver through the mediastinum via the right thorax, passing the heart and aortic arch up to the left clavicle. The rod was removed via sternotomy and median laparotomy. Only the left subclavian vein required repair. Postoperatively, a residual lesion of the left brachial plexus caused temporary pneumonia. 2. A leg of a collapsing chair drilled into a woman's left foramen obturatorium and exited the body at the right anterior iliac spine. At a regional hospital, the chair leg was removed and the canal caused by gluteal penetration was excised. Exploratory laparotomy revealed peritonitis resulting from a perforated ileum. The injury was repaired with segmental resection and anastomosis. Postoperative right inguinal wound necrosis necessitated excision and vacuum-assisted closure sealing. The patient has residual paresthesia in her left leg resulting from a sacral plexus lesion. 3. During an altercation, a man was stabbed twice in the right thorax. The right pulmonary lobe, the diaphragm, and the liver dome between segment VIII and V were injured. The patient also had a large scalp avulsion at the left and right parietooccipital site and transection of the biceps muscle at the middle third of the right humerus. The chest injuries, approached via right subcostal incision and right anterior thoracotomy were managed with liver packing (two towels, removed after 2 days), suture of the diaphragm, and pleural drainage. 4. A man was stabbed in the left thorax, resulting in pneumothorax and lesions of the diaphragm and left third of the transversal colon, and the neck, resulting in lesions of the pharynx and internal jugular vein. These injuries were approached with left thoracic drainage and suture of the colon and diaphragm lesions. Subsequent right thoracotomy was required to treat right pleural empyema caused by bronchopneumonia as a consequence of blunt thoracic trauma. In addition, the patient required relaparotomy to drain an abscess within the Douglas space and Billroth II gastric resection to control recurrent Forrest-Ia bleeding. CONCLUSIONS: Penetrating abdomino-thoracic injuries demand immediate life-saving measures, transfer to a trauma centre, appropriate resuscitative care, prompt diagnosis, and surgical intervention by an interdisciplinary team of abdominal, vascular, and cardiac surgeons. If these measures are provided, outcomes are maximized, mortality is minimized, and permanent damage can be avoided.

Effects of volatile and intravenous anesthesia on the alveolar and systemic inflammatory response in thoracic surgical patients.

BACKGROUND: One-lung ventilation (OLV) results in alveolar proinflammatory effects, whereas their extent may depend on administration of anesthetic drugs. The current study evaluates the effects of different volatile anesthetics compared with an intravenous anesthetic and the relationship between pulmonary and systemic inflammation in patients undergoing open thoracic surgery. METHODS: Sixty-three patients scheduled for elective open thoracic surgery were randomized to receive anesthesia with 4 mg · kg⁻¹ · h⁻¹ propofol (n = 21), 1 minimum alveolar concentration desflurane (n = 21), or 1 minimum alveolar concentration sevoflurane (n = 21). Analgesia was provided by remifentanil (0.25 µg · kg⁻¹ · min⁻¹). After intubation, all patients received pressure-controlled mechanical ventilation with a tidal volume of approximately 7 ml · kg ideal body weight, a peak airway pressure lower than 30 cm H2O, a respiratory rate adjusted to a Paco2 of 40 mmHg, and a fraction of inspired oxygen lower than 0.8 during OLV. Fiberoptic bronchoalveolar lavage of the ventilated lung was performed immediately after intubation and after surgery. The expression of inflammatory cytokines was determined in the lavage fluids and serum samples by multiplexed bead-based immunoassays. RESULTS: Proinflammatory cytokines increased in the ventilated lung after OLV. Mediator release was more enhanced during propofol anesthesia compared with desflurane or sevoflurane administration. For tumor necrosis factor-α, the values were as follows: propofol, 5.7 (8.6); desflurane, 1.6 (0.6); and sevoflurane, 1.6 (0.7). For interleukin-8, the values were as follows: propofol, 924 (1680); desflurane, 390 (813); and sevoflurane, 412 (410). (Values are given as median [interquartile range] pg · ml⁻¹). Interleukin-1ß was similarly reduced during volatile anesthesia. The postoperative serum interleukin-6 concentration was increased in all patients, whereas the systemic proinflammatory response was negligible. CONCLUSIONS: OLV increases the alveolar concentrations of proinflammatory mediators in the ventilated lung. Both desflurane and sevoflurane suppress the local alveolar, but not the systemic, inflammatory responses to OLV and thoracic surgery.

Gender and age-dependent differences in the bradykinin-degradation within the pericardial fluid of patients with coronary artery disease.

Cardiovascular diseases (CVD) and, in particular, coronary artery disease (CAD) are the leading causes of death in developed countries, especially in the elderly population. Males exhibit a higher risk for cardiovascular events than women. The pericardial fluid (PF) is in direct contact with the epicardial sections of the coronary arteries and the perimyocardium. A systematic analysis of gender-specific or age-related differences in angiotensin-related pathways like bradykinin metabolism however, has not been performed in the PF so far. Therefore, the amounts of angiotensin-converting enzyme (ACE) and the rate of the degradation of bradykinin (BK) and the amounts/activity of major BK-degrading enzymes, aminopeptidase N (APN) and dipeptidyl-aminopeptidase IV (DPIV), were assessed in the pericardial fluid (PF) of 44 patients undergoing coronary artery bypass grafting. We found BK being degraded within the PF. Interestingly, there was an age-dependent decrease in the amounts of ACE protein in women. In elderly women, ACE/APN and ACE/DPIV ratios were substantially reduced to 41.4% or 29.4% respectively (p<0.05). In contrast, an age-dependent decline of ACE protein and ACE/protease ratios were not found in men. In men and women, total BK degradation correlated with age (r=0.5; p=0.021) further supporting a switch in BK metabolising enzymes in elderly women. Thus, we can show age- and gender-dependent differences in BK metabolism within the PF in patients with coronary artery disease. The present finding that the expression of ACE is lowest in elderly women, despite the presence of similar BK degradation, might help to explain the potentially reduced therapeutic effects of ACE inhibitors in elderly women.

Efficacy and safety of very low-dose self-management of oral anticoagulation in patients with mechanical heart valve replacement.

BACKGROUND: Self-management improves oral anticoagulation control. Here we provide data of a preplanned interim analysis of very low-dose early self-controlled anticoagulation. METHODS: In a prospective, randomized, multicenter trial, 1,137 patients performed low-dose international normalized ratio (INR) self-management with a target INR range of 1.8. to 2.8 for aortic valve replacement recipients and 2.5 to 3.5 for mitral or double valve replacement recipients for the first six postoperative months. Thereafter, 379 patients continued to achieve the aforementioned INR target range (LOW group), whereas the INR target value was set at 2.0 (range, 1.6 to 2.1) for the remaining patients with aortic valve replacement and 2.3 (range, 2.0 to 2.5) for the remaining patients with mitral valve or double valve replacement. One half of this latter group had to check their INR values once a week (VL1 group) the other half twice a week (VL2 group). Patients were followed up for 24 months. RESULTS: Beyond study month six, the incidence of thromboembolic events that required hospital admission was 0.58%, 0.0%, and 0.58% in the LOW, VL1, and VL2 groups, respectively (p = 0.368). The incidence of bleeding events per patient-year was 1.16%, 1.07%, and 0.58% in the LOW, VL1, and VL2 groups, respectively (p = 0.665). Mortality rate did not differ among study groups. CONCLUSIONS: Data demonstrate the efficacy and safety of very low-dose INR self-management.

Implementation and efficacy of selective sonographic screening for carotid disease before cardiac surgery.

BACKGROUND: Preoperative carotid sonography with consecutive preventive strategies might reduce stroke risk during cardiac surgery. Since routine sonography in all patients may be unfeasible, an approach to examine preselected patients was investigated. METHODS: A prognostic model predicting carotid disease was developed using the clinical data of 1,768 routinely examined patients. It recommended 1,018 of 4,814 patients of a following collective for selective sonography. Patients recommended for preoperative sonography were compared to those selected in clinical practice. RESULTS: Besides the evaluated predictor variables, a history of syncope/cardiogenic shock and of pulmonary disease was associated with patient selection for sonography in clinical practice, even though both variables were not associated with severe carotid disease. In patients who underwent sonography, although this was not recommended by the prognostic model, severe carotid disease was estimated lower than what was actually detected, suggesting a change in relative relevance of predicting variables along with the change in frequencies of patients' cardiovascular characteristics. CONCLUSION: Prognostic models for selective screening before cardiac surgery may require reevaluation over time, especially when baseline characteristics used for prediction have changed. Criteria used in clinical practice to select patients for screening may differ from those recommended by investigational studies.

Outcome after implantation of cardiac resynchronization/defibrillation systems in patients with congestive heart failure and left bundle-branch block.

OBJECTIVE: The implantation of cardiac resynchronization/defibrillation devices (CRT-Ds) increasingly is used in patients with congestive heart failure and left bundle-branch block. There are no data on the effects of anesthesia and surgery on outcome after implantation. DESIGN: A retrospective, observational study; postoperative survey. SETTING: University hospital. PARTICIPANTS: Three hundred forty-one patients (258 men/83 women, 63 +/- 9 years) with congestive heart failure and left bundle-branch block who underwent CRT-D implantation in 1996 to 2005. MEASUREMENTS AND MAIN RESULTS: Perioperative data were retrieved from the patients' records. Cardiologists caring for the patients were contacted to obtain information on current New York Heart Association (NYHA) status and mortality after CRT-D implantation. Preoperatively, 45 patients were classified as NYHA II, 246 as NYHA III, and 50 as NYHA IV. CRT was performed via thoracotomy in 100 and transvenously in 241 cases. General anesthesia (propofol or sevoflurane and remifentanil) was performed in 273 and local anesthesia (lidocaine) in 68 patients. Hypotension occurred mainly during general anesthesia (43% v 4%). The 30-day mortality was 0%. The postoperative survey started in 2006 and was completed by 215 patients. The mean survival time was 77 months; 151 patients survived the study period. Outcome was not influenced by local and general anesthesia. Presence of preoperative NYHA class >II (odds ratio [OR] = 1.6, confidence interval [CI] = 0.5-5.1), mitral regurgitation (OR = 2.5, CI = 1.2-5.5), and serum creatinine >1.1 mg/dL (OR = 3.0, CI = 1.5-6.2) resulted in an inferior prognosis. CONCLUSIONS: In patients with severely impaired cardiac function, general anesthesia for the implantation of a biventricular pacing device can be used with justifiable risk. The method of anesthesia did not influence outcome.

Atrial expression of endothelial nitric oxide synthase in patients with and without atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with oxidative stress within the fibrillating atrial myocardium. Experimental studies suggest that reduced levels of nitric oxide (NO) caused by down-regulation of the NO synthase (eNOS) contribute to the development of prothrombotic endocardial remodeling in AF. This study was designed to determine the endocardial expression of eNOS in atrial tissue samples from patients with and without AF. METHODS: Tissue microarrays were used to analyze right atrial tissue specimens obtained from 234 patients (38 with AF; 196 with sinus rhythm) for differences in atrial eNOS expression. In selected patients, immunohistological results were confirmed by Western blotting. RESULTS: Immunohistochemical analyses showed that eNOS is expressed by endocardial cells and myocytes. However, endocardial expression of eNOS was not independently related to AF per se. There was no difference between paroxysmal and persistent AF. Clinical factors like gender (P=.05) and coronary artery disease (P=.06) were associated with down-regulation of eNOS. Interestingly, diabetes mellitus (P=.02) was associated with an up-regulation of endocardial eNOS, whereas other risk factors for thromboembolic events did not influence eNOS levels. Multivariable analysis showed that eNOS expression is influenced by interactions between diabetes mellitus and AF (P=.09) as well as by interactions between gender and AF (P=.04). Lowest levels of eNOS were found in women with AF. CONCLUSION: AF does not independently effect atrial eNOS expression in humans. Due to the nonuniform regulation of endocardial eNOS expression, it appears unlikely that down-regulation of eNOS is a final common pathway for the development of prothrombotic endocardial remodeling, since classical risk factors for thromboembolic events do not reduce endocardial eNOS protein.

Successful surgical treatment of a giant coronary artery aneurysm presenting with recurrent profuse haemoptysis.

We present the case of successful resection of a giant aneurysm of the LAD presenting with recurrent severe haemoptysis in a 72-year old man. He was admitted to a regional hospital with fever, recurrent bloody sputum, weight loss and left sided chest pain, and developed respiratory failure requiring ventilation. Investigations are summarised and reviewed and the diagnosis was eventually reached by TTE, CT and MRI scans, confirmed by coronary angiography. Successful emergency surgery to resect the aneurysm and put a vein graft to the LAD is described. The presentation and management of coronary giant aneurysm is reviewed.

Mitochondrial dysfunction and redox signaling in atrial tachyarrhythmia.

Accumulating evidence links calcium-overload and oxidative stress to atrial remodeling during atrial fibrillation (AF). Furthermore, atrial remodeling appears to increase atrial thrombogeneity, characterized by increased expression of adhesion molecules. The aim of this study was to assess mitochondrial dysfunction and oxidative stress-activated signal transduction (nuclear factor-kappaB [NF-kappa B], lectin-like oxidized low-density lipoprotein receptor [LOX-1], intercellular adhesion molecule-1 [ICAM-1], and hemeoxgenase-1 [HO-1]) in atrial tissue during AF. Ex vivo atrial tissue from patients with and without AF and, additionally, rapid pacing of human atrial tissue slices were used to study mitochondrial structure by electron microscopy and mitochondrial respiration. Furthermore, quantitative reverse transcription polymerase chain reaction (RT-PCR), immunoblot analyses, gel-shift assays, and enzyme-linked immunosorbent assay (ELISA) were applied to measure nuclear amounts of NF-kappa B target gene expression. Using ex vivo atrial tissue samples from patients with AF we demonstrated oxidative stress and impaired mitochondrial structure and respiration, which was accompanied by nuclear accumulation of NF-kappa B and elevated expression levels of the adhesion molecule ICAM-1 and the oxidative stress-induced markers HO-1 and LOX-1. All these changes were reproduced by rapid pacing for 24 hours of human atrial tissue slices. Furthermore, the blockade of calcium inward current with verapamil effectively prevented both the mitochondrial changes and the activation of NF-kappa B signaling and target gene expression. The latter appeared also diminished by the antioxidants apocynin and resveratrol (an inhibitor of NF-kappa B), or the angiotensin II receptor type 1 antagonist, olmesartan. This study demonstrates that calcium inward current via L-type calcium channels contributes to oxidative stress and increased expression of oxidative stress markers and adhesion molecules during cardiac tachyarrhythmia.

Angiotensin II receptor blockade reduces tachycardia-induced atrial adhesion molecule expression.

BACKGROUND: Increased levels of inflammatory markers are predictors of thromboembolic events during atrial fibrillation (AF). Increased endocardial expression of adhesion molecules (ie, vascular cell adhesion molecule [VCAM] and intercellular adhesion molecule [ICAM]) could be an important link between initiation of inflammatory and prothrombogenic mechanisms responsible for thrombus development at the atrial endocardium (endocardial remodeling). METHODS AND RESULTS: Tissue microarrays were used to screen right atrial tissue specimens obtained from 320 consecutive patients for differences in atrial expression of the prothrombogenic proteins VCAM-1, ICAM-1, thrombomodulin, plasminogen activator inhibitor-1, and von Willebrand factor. An in vitro organotypic human atrial tissue model and a pig model of rapid atrial pacing were used to determine the therapeutic impact of angiotensin II receptor blockade. Immunohistochemical analyses showed that all prothrombogenic proteins are expressed by endocardial cells. Using multivariable analysis, only the intensity of VCAM-1 expression was increased in patients with AF (P=0.03). Increased atrial VCAM-1 expression was confirmed by Western blotting in patients with persistent and paroxysmal AF (persistent AF 207+/-42% versus sinus rhythm 100+/-16%, P=0.028; paroxysmal AF 193+/-42%, P=0.024 versus sinus rhythm). In vitro pacing of ex vivo human atrial tissue slices confirmed that rapid activation causes VCAM-1 upregulation (mRNA and protein levels). Pacing-induced VCAM-1 expression was abolished by olmesartan. To confirm this finding in vivo, VCAM-1 expression was determined in 14 pigs after rapid atrial pacing (600 bpm). Atrial tachycardia caused an upregulation of VCAM-1 expression, which was prevented by irbesartan, consistent with the observed increase in plasma levels of angiotensin II. Alterations in the in vivo VCAM-1 expression were more pronounced in the left atrium (>5-fold compared with sham) than in the right atrium (3.5-fold compared with sham). CONCLUSIONS: AF and rapid atrial pacing both increase endocardial VCAM-1 expression, which can be attenuated by angiotensin II receptor blockade. This provides evidence that angiotensin II plays a pathophysiological role in prothrombotic endocardial remodeling.

Worldwide surgical experience with the Paracor HeartNet cardiac restraint device.

OBJECTIVE: An elastic ventricular restraint device has been developed for patients with heart failure who remain symptomatic despite treatment with standard therapies. The safety and efficacy of this device are under clinical investigation. Six-month data for the first 51 patients treated worldwide are reported. We hypothesize that the Paracor HeartNet device (Paracor Medical, Sunnyvale, Calif), placed through a minithoracotomy in patients with severe dilated cardiomyopathy, improves clinical and functional status. METHODS: Fifty-one patients with an ejection fraction of 35% or less, with a New York Heart Association class II or III, and receiving optimal medical therapy for at least 3 months, were selected at 15 sites (3 in Europe, 12 in the United States) to undergo implantation of the HeartNet device through a minithoracotomy. Patients were evaluated at baseline and at 6-month follow-up by echocardiography, the 6-minute walk test, cardiopulmonary exercise testing (partial oxygen pressure in mixed venous blood), New York Heart Association class, and (in the United States) the Minnesota Living with Heart Failure questionnaire. RESULTS: The average age was 52 years (30-73 years), with a preponderance of men and nonischemic cause of heart failure. Implantation was accomplished in 50 of 51 patients (98%). Adverse events included 2 in-hospital deaths secondary to pulmonary complications (4%), additional pulmonary complications in 7 patients (14%), arrhythmia in 14 patients (27%), epicardial laceration in 2 patients (4%), and empyema in 1 patient (2%). Six-month data demonstrated significant improvement in the 6-minute walk test (+65.7, P = .002) and Minnesota Living with Heart Failure scores (-15.7, P = .002) and improvement in echocardiographic findings. CONCLUSION: The Paracor HeartNet device can be reliably implanted in patients with heart failure and marked reduction of left ventricular function. These data suggest a functional and clinical benefit, with a trend toward reverse remodeling, and support the conduct of a randomized controlled pivotal trial.

Impaired cerebral autoregulation distal to carotid stenosis/occlusion is associated with increased risk of stroke at cardiac surgery with cardiopulmonary bypass.

OBJECTIVES: Severe carotid stenosis and occlusion are associated with an increased risk of stroke during and after cardiac surgery with cardiopulmonary bypass. Relevance of an impaired cerebral autoregulation caused by stenosis/occlusion is unknown. METHODS: We prospectively assessed the incidence of stroke in relation to severity of carotid disease and corresponding autoregulatory reserve in 2797 patients who had coronary artery bypass graft and/or valve surgery with cardiopulmonary bypass. Patients underwent preoperative carotid sonography and, in case of severe extracranial disease, transcranial Doppler sonography with carbon dioxide stimulation to assess cerebrovascular reserve capacity. RESULTS: Sixty-seven (2.4%) patients had an ischemic stroke, which was fatal in 5. Anterior hemispheric stroke occurred in 42 (1.9%) patients with no/low-grade stenosis, 6 (1.8%) with medium-grade stenosis, 1 (0.6%) with high-grade stenosis/occlusion and normal autoregulation, and 3 (27.3%) with high-grade stenosis/occlusion and exhausted autoregulatory reserve. Increased risk was observed in patients with high-grade stenosis/occlusion and exhausted autoregulatory reserve also after adjustment for potential confounders (adjusted odds ratio [OR] 28.3, 95% confidence interval [CI] 5.8-139.1). Stroke risk was not increased in patients with stenosis/occlusion and normal autoregulation (1.5%, adjusted OR 0.6, 95% CI 0.2-1.6). CONCLUSIONS: Cerebrovascular reserve capacity evaluated by preoperative transcranial Doppler carbon dioxide testing is a major determinant of stroke risk in patients with carotid artery stenosis/occlusion undergoing cardiac surgery with cardiopulmonary bypass. Its assessment facilitates identification of patients with an excess perioperative stroke risk.

Cigarette smoking induces atrial fibrosis in humans via nicotine.

BACKGROUND: Cigarette smoking (CS) promotes endothelial dysfunction and atherosclerosis in the vascular bed. The impact of smoking on atrial myocardium is not defined in humans. OBJECTIVE: To determine the effect of CS on the development of interstitial fibrosis in atrial myocardium. DESIGN: Case-control study. PATIENTS: 95 patients (46 smokers and 49 non-smokers) undergoing coronary artery bypass grafting (CABG). MAIN OUTCOME MEASURES: Amount of atrial fibrosis, collagen I, III and IV expression pattern, and quantitative reverse transcriptase-PCR. Occurrence of postoperative atrial fibrillation (AF). RESULTS: In the study population, patient age correlated significantly with the amount of atrial fibrosis (r = 0.18; p<0.05). Nicotine misuse (pack years) was identified as the only factor related to atrial fibrosis in smokers (r = 0.311; p<0.05). The amount of fibrosis was higher in patients with postoperative AF (22.9% (6.2%) vs. 27.0% (8.2%); p<0.05). To show a causal relationship between CS and atrial fibrosis, atrial tissue slices from non-smokers (n = 8) were cultured in the presence of nicotine base (185 and 740 nmol/l). Nicotine base induced mRNA expression of collagen III (up to 10-fold) in a concentration-dependent manner resembling the immunohistological collagen expression pattern observed in CS. CONCLUSION: CS contributes to the development of atrial fibrosis via nicotine. Atrial fibrosis by itself has been shown to provide an arrhythmogenic substrate, which may increase the likelihood of the occurrence of atrial arrhythmias, including postoperative AF.

The pulmonary immune effects of mechanical ventilation in patients undergoing thoracic surgery.

UNLABELLED: Mechanical ventilation (MV) may induce an inflammatory alveolar response. One-lung ventilation (OLV) with tidal volumes (Vt) as used during two-lung ventilation is a suggested algorithm but may impose mechanical stress of the dependent lung and potentially aggravate alveolar mediator release. We studied whether ventilation with different Vt modifies pulmonary immune function, hemodynamics, and gas exchange. Thirty-two patients undergoing open thoracic surgery were randomized to receive either MV with Vt = 10 mL/kg (n = 16) or Vt = 5 mL/kg (n = 16) adjusted to normal Pa(CO2) during and after OLV. Fiberoptic bronchoalveolar lavage of the ventilated lung was performed, and cells, protein, tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, soluble intercellular adhesion molecule (sICAM)-1, IL-10, and elastase were determined in the bronchoalveolar lavage. Data were analyzed by parametric or nonparametric tests, as indicated. In all patients, an increase of proinflammatory variables was found. The time courses of intra-alveolar cells, protein, albumin, IL-8, elastase, and IL-10 did not differ between the groups after OLV and postoperatively. TNF-alpha (8.4 versus 5.0 microg/mL) and sICAM-1 (52.7 versus 27.5 microg/mL) concentrations were significantly smaller after OLV with Vt = 5 mL/kg. These results indicate that MV may induce epithelial damage and a proinflammatory response in the ventilated lung. Reduction of tidal volume during OLV may reduce alveolar concentrations of TNF-alpha and of sICAM-1. IMPLICATIONS: Reductions of tidal volume, with subsequently decreased peak airway pressures, may reduce some alveolar inflammatory responses seen with mechanical ventilation.

Expression of opioid receptor subtypes and their ligands in fibrillating human atria.

The delta- and kappa-receptor subtypes are both abundantly expressed in the human heart and participate in age- and stress-related alterations of cardiac function. Opioid receptor agonists mediate cardioprotection in response to ischemic preconditioning via increased intracellular Ca(2) (+) levels, opening mitochondrial K(ATP) channels, and PKC activation. We studied the expression of opioid receptor subtypes kappa and delta, and of their ligand precursors, proopiomelanocortin (POMC) and preproenkephalin A (PENKA), in human atrial tissue of patients in sinus rhythm (SR), or persistent atrial fibrillation (AF). The mitochondrial size was also compared between the two groups. The atrial mRNA expression of opioid peptide precursors and receptors was assessed by competitive and real-time RT-PCR in 16 patients in AF and 16 patients in SR. Mitochondria were analyzed in the atrial tissue by electron microscopy in four patients in AF and four patients in SR. Both PENKA (SR: 100 +/- 33% vs AF: 33 +/- 21%; P < 0.05) and kappa-receptor mRNA amounts (AF: 78 +/- 20% vs SR: 100 +/- 11%; P < 0.05) were both decreased in AF in comparison to SR. In addition, POMC mRNA levels were decreased in AF (SR: 100 +/- 54% vs AF: 37 +/- 26%; P < 0.05), whereas the expression of the corresponding delta-opioid receptor was unchanged (AF: 102 +/- 34% vs 100 +/- 44%). Mitochondrial size was increased during persistent AF. Persistent AF is associated with the down-regulation of the opioid receptor/ligand expression. This suggests a loss of protective capacity in the fibrillating atrial tissue, resulting in an ultrastructural remodeling of atrial myocytes.