Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury.

Glucagon-like peptide 1 (GLP-1), a gut incretin hormone that stimulates insulin secretion, also activates antiapoptotic signaling pathways such as phosphoinositide 3-kinase and mitogen-activated protein kinase in pancreatic and insulinoma cells. Since these kinases have been shown to protect against myocardial injury, we hypothesized that GLP-1 could directly protect the heart against such injury via these prosurvival signaling pathways. Both isolated perfused rat heart and whole animal models of ischemia/reperfusion were used, with infarct size measured as the end point of injury. In both studies, GLP-1 added before ischemia demonstrated a significant reduction in infarction compared with the valine pyrrolidide (an inhibitor of its breakdown) or saline groups. This protection was abolished in the in vitro hearts by the GLP-1 receptor antagonist exendin (9-39), the cAMP inhibitor Rp-cAMP, the PI3kinase inhibitor LY294002, and the p42/44 mitogen-activated protein kinase inhibitor UO126. Western blot analysis demonstrated the phosphorylation of the proapoptotic peptide BAD in the GLP-1-treated groups. We show for the first time that GLP-1 protects against myocardial infarction in the isolated and intact rat heart. This protection appears to involve activating multiple prosurvival kinases. This finding may represent a new therapeutic potential for this class of drug currently undergoing clinical trials in the treatment of type 2 diabetes.

Malignant triton tumor of the right vagus.

We report on the successful surgical resection of a mediastinal malignant triton tumor of the vagus, an exceedingly rare tumor in this location. Malignant triton tumor is a subtype of malignant peripheral nerve sheath tumors, in which the characteristic histologic finding is of rhabdomyoblastic differentiation among schwannoma cells. A 35-year-old man with associated neurofibromatosis type-1 underwent surgical resection and has been followed up for 18 months.

Vascular anastomotic complications in lung transplantation: a single institution's experience.

OBJECTIVES: Lung transplant recipients were reviewed to compare our early and current experience of vascular complications. Since 1995, we have had a policy of early identification and intervention. METHODS: We undertook a retrospective review of all adult lung transplants performed at our centre. Patients with pulmonary vascular complications before and after 1995 were identified and reviewed to determine changes in management and outcome. RESULTS: We identified a total of 13 patients with either pulmonary artery or venous obstruction out of a total of 720 adult lung transplants (1.8%). There were 9 females and 4 males with an age range of 25-64 years. Complications were more common in patients with fibrotic lung disease and involved 15 vascular anastomoses, most commonly the pulmonary arterial anastomosis. Prior to 1995, 5 cases were identified, all postoperatively. In this group, the mean time for identification of the complication was 9.4 (range 4-14) days. Only 1 patient survived to discharge. After 1995, vascular complications were identified intraoperatively in 4 cases and corrected immediately. Four cases were identified postoperatively (at <1-17 days) by a computed tomography pulmonary angiogram. Three were treated surgically within 24 h of diagnosis (using cardiopulmonary bypass with cold preservation). One patient was managed conservatively. Among patients identified after 1995, 5 survived to discharge. CONCLUSIONS: Though rare, pulmonary vascular complications after lung transplantation carry high mortality. In our opinion, early identification and intervention improves outcome. Intraoperative assessment by pressure gradient measurement and transoesophageal echocardiography is recommended. Despite this, mortality remains high and prevention is better than cure.

Giant cell myocarditis of the left atrium.

Here we describe an unusual case of giant cell myocarditis (GCM) found in the left atrial appendage. Giant cell myocarditis is a rare entity in itself, while isolated left atrial GCM has only been reported on a few occasions. We describe a patient who underwent mitral valve replacement for rheumatic mitral stenosis and excision of a grossly abnormal, thickened, and enlarged left atrial appendage. Histological examination confirmed the presence of GCM.

Stake through the chest.

We present a fascinating case of major penetrating trauma to the chest which resulted in a successful outcome. Often such trauma is associated with a poor outcome due to injury to the heart, lungs or major blood vessels with subsequent massive blood loss, pnuemothorax or haemo-pneumothorax. Late complications include infection rarely mediastinitis, empyema and occasionally chylothorax from damage to the thoracic duct.

Acute fibrin deposition causing acute failure of two tissue pericardial valves.

We report the early failure of two tissue valves within hours of surgery due to the accumulation of cellular debris in two different institutions in the United Kingdom. The valves were both found at explant to be covered in a cellular material - possibly fibrin. From clinical experience and careful review of the literature we have found no other reports of such early valve failure due to the build up of material on the structure of the valve. This rare occurrence needs to be reported in the literature to forewarn clinicians of an early complication that may not be recognized yet.

Aortic valve replacement in octogenarians.

BACKGROUND AND AIMS: As our population ages and life expectancy increases the number of people aged over 80 and more referred for cardiac surgery is growing. This study sought to identify the outcome of aortic valve replacement (AVR) in octogenarians. METHODS: 68 patients aged 80 years or more underwent AVR at the Freeman Hospital, between April 2001 and April 2004. A retrospective review of the notes and outcomes from the patients' GP and the NHS strategic tracking service was performed. 54% (37) underwent isolated AVR whilst 46% (31) underwent combined AVR and CABG. RESULTS: Follow up was 100% complete. The mean age was 83.1 +/- s.d. 2.9 years, a mean gradient of 83 +/- s.d. 31 mmHg and mean AVA of 0.56 cm2. The mean additive EuroSCORE was 8.6 +/- s.d. 1.2, the logistic EuroSCORE mean 12.0 +/- s.d. 5.9. In hospital 30 day mortality was 13 %. Survival was 80% at 1 year and 78% at 2 years. Median follow up was for 712 days. Stepwise logistic regression identified chronic obstructive airways disease as an independent predictor of mortality (p < 0.05). Survival was not adversely affected by the addition of coronary artery bypass grafts to aortic valve replacement, the presence of peripheral vascular disease, hypertension or diabetes. In this study duration of cross clamp or bypass time were not found to reach significance as independent predictors of mortality. CONCLUSION: Our study demonstrates that the operative mortality for AVR in the over eighties is good, whilst the mid to long term outcome is excellent There is a very low attrition rate with those undergoing the procedure living as long than their age matched population. This study confirms AVR is a safe, acceptable treatment for octogenarians with excellent mid term outcomes.

Myocardial ischaemia-reperfusion injury is attenuated by intact glucagon like peptide-1 (GLP-1) in the in vitro rat heart and may involve the p70s6K pathway.

BACKGROUND AND METHODS: Glucagon Like Peptide-1 (GLP-1), one of the most potent incretin hormones, has potential beneficial actions on the ischaemic and failing heart. This study sought to further identify the mechanisms of action of GLP-1 on the ischaemic heart using an in vitro isolated perfused rat heart model of ischaemic-reperfusion injury (measuring infarct size to area of risk (%)) subjected to 35 min regional ischaemia and 2 h reperfusion. To examine the effect of intact GLP-1 we used an inhibitor of GLP-1 breakdown, Valine pyrrolidide (VP). The downstream target of phosphatidylinositol 3-kinase includes the mTOR/p70s6 kinase pathway which was pharmacologically inhibited by rapamycin. RESULTS AND CONCLUSION: GLP-1 alone did not decrease myocardial infarction (54.4 +/- 3.1%). VP alone did not decrease myocardial infarction (52.5 +/- 4%). GLP-1 in the presence of VP produced significant reduction in myocardial infarction compared to control hearts (28.4 +/- 2.7% vs. 56.4 +/- 3.9% vs. P < 0.05). Inhibiting p70s6 Kinase with rapamycin completely abolished GLP-1 induced protection (57.1 +/- 4.9% vs. 28.4 +/- 2.7% P < 0.05). There was no detectable increase in the phosphorylated p70s6k after either 5 or 10 min of treatment with GLP-1/VP or with VP alone in comparison to control blots. In conclusion we show for the first time that the protective effects of GLP-1 are mediated by intact GLP-1 and can be inhibited by blocking the p70s6 kinase.