Simvastatin Sodium Salt and Fluvastatin Interact with Human Gap Junction Gamma-3 Protein.

Finding pleiomorphic targets for drugs allows new indications or warnings for treatment to be identified. As test of concept, we applied a new chemical genomics approach to uncover additional targets for the widely prescribed lipid-lowering pro-drug simvastatin. We used mRNA extracted from internal mammary artery from patients undergoing coronary artery surgery to prepare a viral cardiovascular protein library, using T7 bacteriophage. We then studied interactions of clones of the bacteriophage, each expressing a different cardiovascular polypeptide, with surface-bound simvastatin in 96-well plates. To maximise likelihood of identifying meaningful interactions between simvastatin and vascular peptides, we used a validated photo-immobilisation method to apply a series of different chemical linkers to bind simvastatin so as to present multiple orientations of its constituent components to potential targets. Three rounds of biopanning identified consistent interaction with the clone expressing part of the gene GJC3, which maps to Homo sapiens chromosome 7, and codes for gap junction gamma-3 protein, also known as connexin 30.2/31.3 (mouse connexin Cx29). Further analysis indicated the binding site to be for the N-terminal domain putatively 'regulating' connexin hemichannel and gap junction pores. Using immunohistochemistry we found connexin 30.2/31.3 to be present in samples of artery similar to those used to prepare the bacteriophage library. Surface plasmon resonance revealed that a 25 amino acid synthetic peptide representing the discovered N-terminus did not interact with simvastatin lactone, but did bind to the hydrolysed HMG CoA inhibitor, simvastatin acid. This interaction was also seen for fluvastatin. The gap junction blockers carbenoxolone and flufenamic acid also interacted with the same peptide providing insight into potential site of binding. These findings raise key questions about the functional significance of GJC3 transcripts in the vasculature and other tissues, and this connexin's role in therapeutic and adverse effects of statins in a range of disease states.

Bilateral phrenic nerve palsy following aortic valve surgery.

Bilateral phrenic nerve palsy is an extremely rare but serious complication of open cardiac surgery. We report the case of a 78-year-old female who underwent elective aortic valve replacement and coronary artery bypass grafting under hypothermic cardiopulmonary bypass. Despite otherwise unremarkable postoperative recovery, the patient could not be weaned off ventilatory support. A chest radiograph and radiological screening of the diaphragm confirmed the diagnosis of bilateral phrenic nerve palsy. Following bilateral hemi diaphragm placation and extensive respiratory rehabilitation the patient was discharged several months after initial surgery breathing independently. Literature review revealed only two similar cases. Many contributing factors have been described but the etiology of bilateral phrenic nerve palsy following open cardiac surgery still remains unclear. Raised awareness of this condition is essential.

Is routine chest X-ray following mediastinal drain removal after cardiac surgery useful?

OBJECTIVE: Mediastinal and pleural drains are routinely employed following open-heart surgery to prevent accumulation of blood and fluids in the mediastinum or the pleural cavities. Chest radiographs are obtained after removal of these drains to search for a pneumothorax. We hypothesised that clinical signs and symptoms are sensitive indicators of the presence of significant pneumothorax and routine use of radiographs in these patients is unnecessary. METHODS: A prospective study of 151 consecutive patients undergoing various cardiac surgical procedures over a 10-week period was undertaken. Chest X-rays were performed in all patients within 4h of drain removal. Patients were clinically monitored for development of any respiratory difficulties and the X-rays were evaluated for presence of a pneumothorax or any other abnormality necessitating intervention. The cost of a portable chest X-ray was calculated by taking into consideration the radiographer's time and the cost of an X-ray film. RESULTS: There were 113 males and 38 females with a mean age of 67.5 years. Fourteen patients (9%) had obstructive airway disease. The left and right pleurae were opened in 62% and 11% of patients respectively and a chest drain was inserted in all of them intraoperatively. Three patients (2%) developed pneumothorax following drain removal. Two of these patients had clinical signs and symptoms, which would have warranted a chest X-ray. One patient had a moderate pneumothorax but was not clinically compromised. Two patients needed chest drain reinsertion that was subsequently removed after 3 and 4 days. The third patient was monitored clinically and the pneumothorax resolved spontaneously on subsequent chest X-ray. In the remaining 148 patients, postdrain removal chest X-ray did not provide any additional information to alter the management. The cost saving of omitting an additional chest X-ray was calculated to be about pound10,000 per year. CONCLUSIONS: Incidence of pneumothorax following mediastinal drain removal is very low. Clinical signs and symptoms almost always identify those few patients requiring intervention and the decision to obtain an X-ray could be based on clinical judgement alone. In addition, this approach may result in cost savings without compromising patient safety.

Selective embolotherapy as a treatment option for lower gastrointestinal haemorrhage following open-heart surgery.

Lower gastrointestinal haemorrhage following cardiac surgery is a rare but potentially life threatening complication. Conservative or endoscopic management often fails to detect and control the bleeding, with surgery, often in the form of a major colonic resection, being the last resort. Surgical intervention, however, is associated with high morbidity and mortality. Our case describes the successful management of small bowel haemorrhage, following coronary artery bypass surgery, with angiographic embolotherapy of a branch of the ileocolic artery. We suggest that selective arterial embolisation is a safe and effective therapeutic option available to hospitals undertaking cardiothoracic surgery and should always be considered in the above context.

Early and late outcome after off-pump coronary artery bypass graft surgery with coronary endarterectomy: a single-center 10-year experience.

BACKGROUND: We aimed to review the early and late results of off-pump coronary artery bypass graft surgery (OPCABG) with coronary endarterectomy in patients undergoing surgical revascularization at our institution. METHODS: Between 1995 and 2004, of 680 OPCABG patients in a single surgeon's practice (W.R.D.), 70 patients (10.29%) who underwent concomitant coronary endarterectomy were studied. The mean age was 63.6 +/- 9.29 years. Thirty-three patients (55%) were Canadian Cardiovascular Society class III or IV, and 24 patients (40%) were New York Heart Association class III or IV. Eighteen patients (35%) had impaired left ventricular function. The mean EuroSCORE of these patients was 5.9 +/- 1.8. RESULTS: Fifty-seven patients (81%) underwent right coronary artery endarterectomy, and 12 patients (17%) underwent left anterior descending artery endarterectomy (8 left interior mammary arteries used as conduits). Four patients (5.7%) had two vessels endarterectomized. The mean number of grafts were 2.0 +/- 0.4. The 30-day mortality rate was 2.85% (n = 2). Three patients (4.3%) suffered from postoperative myocardial infarction, and 3 patients (4.3%) required postoperative intra-aortic balloon pump counterpulsation. Mean intensive therapy unit stay was 17.6 +/- 8.1 hours. Patients were extubated after a mean of 10.38 +/- 4.9 hours. The mean length of hospital stay was 6.1 +/- 2.0 days. Fourteen patients (20%) had postoperative atrial fibrillation, and only 1 patient (1.42%) had a transient stroke with complete recovery. There were no conversions to cardiopulmonary bypass. A mean of 0.86 +/- 0.17 units of blood were transfused postoperatively. There was one reopening for bleeding, and 1 patient had renal failure requiring hemofiltration. The median follow-up was 4.91 years, 90% of patients were angina free, and the actuarial survival at 10 years was 78.04% +/- 7.6%. CONCLUSIONS: Off-pump coronary artery bypass graft survery with coronary endarterectomy is feasible and achieves surgical revascularization in patients with diffuse coronary artery disease.