Galectin-3 as a novel biotarget in cardiovascular alterations associated to development of severe aortic stenosis.

Aortic stenosis is one of the most common heart valve diseases, as well as one of the most common causes of heart failure in the elderly. Currently, there are no medical therapies to prevent or slow the progression of the disease. When symptoms develop alongside severe aortic stenosis, there is a poor prognosis unless aortic valve replacement is performed. Aortic stenosis is a heterogeneous disease with a complex pathophysiology involving structural and biological changes of the valve, as well as adaptive and maladaptive compensatory changes in the myocardium and vasculature in response to chronic pressure overload. Galectin-3 serves important functions in numerous biological activities including cell growth, apoptosis, differentiation, inflammation and fibrosis. With evidence emerging to support the function of Galectin-3, the current review aims to summarize the latest literature regarding the potential of Galectin-3 as therapeutic target in aortic valve and cardiovascular alterations associated with aortic stenosis.

Rho-kinase inhibitors prevent agonist-induced vasospasm in human internal mammary artery.

1. Vasospasm of arterial conduits used for coronary artery surgery is an important cause of graft failure and is likely to result partly from raised levels of vasoconstrictor substances such as thromboxane A(2) and endothelin-1. Our aim was to find pharmacological agents that could prevent agonist-induced vasospasm. 2. Isometric tension was recorded from discarded segments of human left internal mammary artery (LIMA). Submaximal contraction evoked by the thromboxane A(2) mimetic U46619 (10 nM) was not inhibited by a blocker of store- and receptor-operated Ca(2+) channels (30 microM SKF96365) in the presence of diltiazem. Furthermore, contractions to < or =1 nM U46619 were preserved when extracellular Ca(2+) was reduced from 2.5 mM to 60 nM. Thus, sustained U46619-evoked contraction occurred without Ca(2+) influx. 3., We hypothesized that contraction might occur via Rho-kinase-mediated Ca(2+)-sensitization of myofilaments. Inhibitors of Rho-kinase (Y27632 and HA1077) were profound relaxants. If contraction was pre-evoked by 10 nM U46619, Y27632 and HA1077 caused full relaxation with EC(50)s of 1.67+/-0.22 microM and 3.58+/-0.35 microM respectively. Y27632 was also effective if applied before U46619, but was less potent. 4. Y27632 abolished contraction evoked by endothelin-1 and significantly reduced resting tone in the absence of a vasoconstrictor. 5. Rho-kinase-mediated Ca(2+)-sensitization appears to be a major mechanism of vasoconstriction in human LIMA. Rho-kinase inhibitors may have an important role in preventing vasospasm in arterial grafts used for coronary artery surgery.

Vasorelaxant properties of nicorandil on human radial artery.

OBJECTIVE: The radial artery is becoming popular as a conduit for coronary artery surgery but there is concern about its tendency to vasospasm. Diltiazem is used clinically in an effort to prevent vasospasm but there are suggestions that it is relatively ineffective. The first aim of the study was to test the effectiveness of Ca(2+) antagonists against vasospasm evoked by vasoconstrictor agonists. Because a large component of vasospasm was resistant to Ca(2+) antagonists, the second aim was to test if a different class of vasodilator, nicorandil, might relax the residual tone. METHODS: Isometric tension was recorded in human radial artery segments harvested from patients undergoing myocardial revascularization surgery. RESULTS: Diltiazem at 10 microM, which strongly inhibits L-type voltage-gated Ca(2+) channels, induced partial relaxation (mean+/-SEM, 44.6+/-3.5%, n=31) of phenylephrine-evoked contraction, but only 14.0+/-4.1% (n=10) and 12. 2+/-4.2% (n=10) relaxation of U46619- (a thromboxane A(2) analogue) or endothelin-1-evoked contraction. Strikingly, nicorandil relaxed agonist-evoked contractions that were resistant to diltiazem or nicardipine. In the absence of a Ca(2+) antagonist, nicorandil (30 microM) evoked 74.1+/-5.6% (n=24), 36.8+/-9.3% (n=10) and 64.5+/-7. 9% (n=14) relaxation of phenylephrine-, U46619- and endothelin-1-evoked contractions. CONCLUSIONS: Nicorandil has a marked relaxant effect on contractions evoked by three different vasoconstrictor agonists, and relaxes vasospasm that is resistant to conventional Ca(2+) antagonists. These in vitro data suggest that nicorandil might be a useful drug for the inhibition of radial artery vasospasm in myocardial revascularization surgery.

Management of isolated sternal fractures: determining the risk of blunt cardiac injury.

A review of the management of isolated sternal fractures in a regional cardiothoracic unit reveals that, in a 2 year period, 37 consecutive patients were admitted for observation and further investigation, including echocardiography and cardiac enzyme measurements to exclude blunt cardiac injury. Minor blunt cardiac injury was detected in only one patient, and was associated with an acutely abnormal electrocardiogram (ECG). ECG showed acute changes in 8 further patients, whilst 3 patients had an abnormal chest X-ray (CXR) due to widening of the mediastinum (1 patient had abnormal CXR and ECG), but none had evidence of cardiac injury. CXR and ECG were both normal in 23 patients, and were predictive of the absence of significant complications. A survey of 22 other cardiothoracic units around the UK confirms that the management of patients with isolated sternal fractures varies considerably from hospital to hospital. As suggested by previous reports, we believe that patients, who are otherwise fit and have normal ECG and CXR on presentation, can be safely discharged home on oral analgesics. The routine use of echocardiography and creatinine kinase (CK) assays in the assessment of isolated sternal fractures is not indicated. The introduction of these guidelines has resulted in a dramatic reduction in the number of patients admitted with isolated sternal fractures to our unit.

Cystic tumour of the atrioventricular nodal region: report of a case successfully treated with surgery.

A case is reported of a 59 year old woman who presented with palpitations. Electrocardiographic studies revealed atrial fibrillation and atrioventricular block. Echocardiography and magnetic resonance imaging showed a right atrial cystic mass attached to the interatrial septum. The patient underwent surgical excision of the mass. Histopathological findings were of a cystic tumour of the atrioventricular nodal region. This is the second report of this condition diagnosed antemortem and treated successfully with surgical excision.