Pierre Corbi

Human cardiomyocyte hypertrophy induced in vitro by gp130 stimulation

OBJECTIVES Recent in vivo and in vitro studies in animals have demonstrated that cytokines of the IL-6 family are involved in cardiac hypertrophy and in protection of cardiomyocytes against apoptosis. The present study aims to analyse the capacity of human atrial cardiac cells (i.e., cardiomyocytes and fibroblasts) to display the gp130 receptor subunit, and to evaluate its functionality. METHODS Twenty human atrial biopsies were used for immunohistochemistry, in situ hybridisation, and western blot analysis or dissociated for isolation and primary culture of cardiac cells. RESULTS Fibroblasts present in tissue or maintained in primary culture clearly express gp130 whereas the signal in cardiomyocytes is weaker. Culture of cardiac cells with a gp130 agonist antibody enhances atrial natriuretic peptide (ANP), beta myosin heavy chain (beta-MHC) expression in cardiomyocytes, and significantly increases the cell surface area microm(2)). This process could involve STAT3 (signal transducer and activator of transcription 3) phosphorylation. CONCLUSIONS These results demonstrate that gp130 activation in human cardiac cells leads to cardiomyocyte hypertrophy. We discuss several hypotheses on the role of IL-6-type cytokines on cardiomyocyte functions.

Circulating soluble gp130, soluble IL-6R, and IL-6 in patients undergoing cardiac surgery, with or without extracorporeal circulation

OBJECTIVE Soluble forms of interleukin-6 (IL-6) receptors are known to modulate biological activities of IL-6. The purpose of the study was to measure circulating levels of IL-6, sIL-6R and sgp130 in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB group) or without CPB (non-CPB group). METHODS The CPB group included 19 patients and the non-CPB group 12 patients. Sera levels of IL-6, sIL-6R and sgp130 were measured by specific ELISA at the beginning of the operation (T0, 15 min before skin incision) and 6 h later (T1). RESULTS IL-6 sera levels were respectively 9+/-20 pg/ml (mean+/-SD) and 13+/-19 pg/ml at T0 and reached 340+/-250 pg/ml and 965+/-1060 pg/ml at T1 in CPB and non-CPB groups, indicating a significant increase from T0 to T1, but no differences between the two groups. When compared to T0 values, sgp130 levels decreased in both groups (respectively 105+/-37 and 115+/-35 ng/ml at T0 for CPB and non-CPB groups, and 72+/-25 and 84+/-29 ng/ml at T1) while we are not able to detect differences between the groups. Whatever the group or the time, sIL-6R concentrations remained unchanged. CONCLUSIONS We showed that the increase of IL-6 after artery bypass grafting was similar between patients operated with CPB or without CPB. We conclude that the main inductor of IL-6 release is linked to surgical trauma rather than a reaction to CPB. Since it is known that gp130 inhibits IL-6-biological activities, we suggest that the decrease of sgp130 sera levels could further enhance the inflammatory effects of IL-6 in cardiac surgery.

Prospective comparison of minimally invasive and standard techniques for aortic valve replacement: initial experience in the first hundred patients.

Abstract Background:Aortic valve replacement (AVR) can be performed through a partial upper sternotomy. In this study we compared the early postoperative outcome in two groups of patients who underwent AVR with a minimally invasive procedure(n = 30)or with a conventional approach(n = 70). The predicted operative mortality (Parsonnet Index) was slightly higher in the conventional group(17.69 ± 0.85 versus 12.7 ± 1.02), reflecting the greater mean age of the patients(70.96 ± 1.17 versus 64.20 ± 2.57). Results: The distribution of the different etiologies of aortic valve pathology did not differ between groups. There was no postoperative death in the mini‐invasive group. Cardiopulmonary bypass time was longer in the mini‐invasive group, but the other operative parameters did not differ between groups. Postoperative morbidity regarding the need for blood transfusion, the duration of assisted ventilation, length of stay in the intensive care unit, and abnormalities of cardiac rhythm and conduction was slightly but not significantly reduced in the mini‐invasive group. Conclusions: Our data demonstrate that a partial upper sternotomy is a safe and effective technique for AVR. Postoperative morbidity is not significantly reduced in patients undergoing AVR by this approach. Further studies in a larger patient population are necessary to assess whether postoperative morbidity is significantly reduced.(J Card Surg 2003;18:133‐139)

Transient Receptor Potential Canonical Channel 6 Links Ca2+ Mishandling to Cystic Fibrosis Transmembrane Conductance Regulator Channel Dysfunction in Cystic Fibrosis

In cystic fibrosis (CF), abnormal control of cellular Ca(2+) homeostasis is observed. We hypothesized that transient receptor potential canonical (TRPC) channels could be a link between the abnormal Ca(2+) concentrations in CF cells and cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. We measured the TRPC and CFTR activities (using patch clamp and fluorescent probes) and interactions (using Western blotting and co-immunoprecipitation) in CF and non-CF human epithelial cells treated with specific and scrambled small interfering RNA (siRNA). The TRPC6-mediated Ca(2+) influx was abnormally increased in CF compared with non-CF cells. After correction of abnormal F508 deletion (del)-CFTR trafficking in CF cells, the level of TRPC6-dependent Ca(2+) influx was also normalized. In CF cells, siRNA-TRPC6 reduced this abnormal Ca(2+) influx. In non-CF cells, siRNA-TRPC6 reduced the Ca(2+) influx and activity wild-type (wt)-CFTR. Co-immunoprecipitation experiments revealed TRPC6/CFTR and TRPC6/F508 del-CFTR interactions in CF or non-CF epithelial cells. Although siRNA-CFTR reduced the activity of wt-CFTR in non-CF cells and of F508 del-CFTR in corrected CF cells, it also enhanced TRPC6-dependent Ca(2+) influx in non-CF cells, mimicking the results obtained in CF cells. Finally, this functional and reciprocal coupling between CFTR and TRPC6 was also detected in non-CF ciliated human epithelial cells freshly isolated from lung samples. These data indicate that TRPC6 and CFTR are functionally and reciprocally coupled within a molecular complex in airway epithelial human cells. Because this functional coupling is lost in CF cells, the TRPC6-dependent Ca(2+) influx is abnormal.

Flail Chest in Polytraumatized Patients: Surgical Fixation Using Stracos Reduces Ventilator Time and Hospital Stay

Objectives. Conservative management of patients with flail chest is the treatment of choice. Rib fracture repair is technically challenging; however, with the advent of specially designed molding titanium clips, surgical management has been simplified. Surgical stabilization has been used with good outcomes. We are reporting on our institutional matched-case-control study. Methods. Between April 2010 and April 2011, ten polytraumatized patients undergoing rib stabilization for flail chest were matched 1 : 1 to 10 control patients by age ±10 years, sex, neurological or vertebral trauma, abdominal injury, and arm and leg fractures. Surgery was realized in the first 48 hours. Results. There were no significant differences between groups for matched data and prognostic scores: injury severity score, revised trauma score, and trauma injury severity score. Ventilator time (142 ± 224 versus 74 ± 125 hours, P = 0.026) and overall hospital stay (142 ± 224 versus 74 ± 125 hours, P = 0.026) were significantly lower for the surgical group after adjustment on prognostic scores. There was a trend towards shorter ICU stay for operative patients (12.3 ± 8.5 versus 9.0 ± 4.3 days, P = 0.076). Conclusions. Rib fixation with Stracos is feasible and decreases the length of ventilation and hospital stay. A multicenter randomized study is warranted so as to confirm these results and to evaluate impact on pulmonary function status, pain, and quality of life.

Beneficial effect of polyethylene glycol in lung preservation: early evaluation by proton nuclear magnetic resonance spectroscopy

BACKGROUND Proton nuclear magnetic resonance spectroscopy can be used to measure organic molecules in biological fluids. In this study, proton nuclear magnetic resonance spectroscopy of bronchoalveolar lavage was assessed to detect cellular damage in lung transplants. Also we evaluated a polyethylene glycol solution in lung preservation. METHODS An isolated perfused and working pig lung was used to assess initial pulmonary function after in situ cold flush and cold storage for 6 hours in three preservation solutions: (1) Euro-Collins solution, (2) University of Wisconsin solution, and (3) low potassium solution with polyethylene glycol (PEG). Pulmonary vascular resistance and partial pressure of arterial oxygen were measured during reperfusion. Bronchoalveolar lavage was studied by proton nuclear magnetic resonance spectroscopy and a histologic study of the lungs was done at the harvest after ischemia and after reperfusion. RESULTS Partial pressure of arterial oxygen and pulmonary vascular resistance were significantly better in PEG compared with Euro-Collins solution (p = 0.011). Interstitial edema was significantly higher in Euro-Collins solution (2.4 +/- 0.24; p = 0.02) and University of Wisconsin solution (2.7 +/- 0.20; p = 0.0003) than PEG (2 +/- 0.16). Mitochondria scale was better in PEG (8.1 +/- 0.46) than in Euro-Collins solution (6.2 +/- 0.37; p = 0.0001) or University of Wisconsin solution (5.6 +/- 1.36; p = 0.0046). In bronchoalveolar lavage proton nuclear magnetic resonance spectroscopy spectra, lactate, pyruvate, citrate, and acetate were only detected after reperfusion, with a significantly reduced production of acetate in PEG. Pyruvate was reduced at the limit of significance in PEG versus University of Wisconsin solution. CONCLUSIONS Proton nuclear magnetic resonance spectroscopy seems to be a simple and suitable method for assessment of early injury to the lung transplant. In this experimental study, PEG preserved the lung better than University of Wisconsin solution and Euro-Collins solution in both the proton nuclear magnetic resonance spectroscopy study as well as the physiologic study.

Five‐Year Experience with the Medtronic Hall Prosthesis in Isolated Aortic Valve Replacement

We reviewed clinical data in 216 patients who underwent isolated aortic valve replacement with the Medtronic Hall prosthesis. Between January 1983 and December 1990, a total of 216 prosthetic valves were implanted in 180 males and 36 females. Preoperatively, 45.5% of patients were in New York Heart Association (NYHA) Class III to IV. Cumulative follow‐up was 682 years, and 3.2% of patients were lost to follow‐up. The actuarial 5‐year survival rate was 90% for the whole group. All the patients were anticoagulated with aceno‐coumarol (SintromR). There were no cases of structural dysfunction and one patient presented with valve thrombosis. The Medtronic Hall valve has a low rate of thromboembolic events without structural failure. It is an excellent device for aortic valve replacement.

Acute aortic valve thrombosis secondary to recombinant factor VIIa.

A60-year-old male patient was admitted on an elective basis for coronary artery bypass grafting. His past medical history included hypertension and multiple sclerosis. He had experienced an acute inferior myocardial infarction 1 month earlier. Coronary angiography revealed severe triple-vessel disease. Transthoracic echocardiography disclosed a normal aortic valve and an ejection fraction of 45%. The patient had normal hepatic and renal function and a normal coagulation profile before the operation. Cardiopulmonary bypass was established through a median sternotomy. A saphenous vein was grafted onto the right coronary artery, and the left internal thoracic artery was anastomosed to the left anterior descending artery. The obtuse marginal artery was not identified during the operation and was therefore left ungrafted. Attempts to wean the patient from cardiopulmonary bypass were unsuccessful, and femorofemoral extracorporeal membrane oxygenation (ECMO) was instituted. Electrocardiography revealed ST segment elevation in lateral chest derivations. The patient was

Aortic Root Replacement in a Patient With Left Ventricular Noncompaction

We describe the case of a 57-year-old woman with noncompaction of the left ventricle and regurgitant bicuspid aortic valve who presented with progressive congestive heart failure and was successfully treated with aortic root replacement. The long-term outcome for these patients is poor because of progressive left ventricular impairment, increased rates of life-threatening arrhythmias, and intraventricular thrombi. To our knowledge, only 3 patient with noncompaction of the left ventricle has been reported to have undergone aortic valve replacement for severely regurgitant bicuspid aortic valve. Herein, we describe a patient with noncompaction of the left ventricle who underwent successful mechanical aortic root replacement.

Post‐Myocardial Infarction Ventricular Septal Defect

A 74-year-old patient presented with shortness of breath one week after untreated anterior myocardial infarction (MI). Coronary angiography showed an occluded left anterior descending artery and a severe stenosis of the circumflex artery and the diagonal branch. An echocardiogram revealed an antero-apical large aneurysm with a left-to-right shunt flow (Fig. 1A) and a depressed left ventricle ejection fraction (EF 1⁄4 40%). A cardiac-enhanced CT scan depicted clearly aneurysm location and small septal perforation site (Fig. 1 B). Prompt surgical treatment was undertaken (Fig. 2). The small septal channel was identified after