Modulation by simvastatin of iberiotoxin-sensitive, Ca2+-activated K+ channels of porcine coronary artery smooth muscle cells.

BACKGROUND AND PURPOSE: Statins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase inhibitors) have been demonstrated to reduce cardiovascular mortality. It is unclear how the expression level of HMG CoA reductase in cardiovascular tissues compares with that in cells derived from the liver. We hypothesized that this enzyme exists in different cardiovascular tissues, and simvastatin modulates the vascular iberiotoxin-sensitive Ca2+-activated K(+) (BK(Ca)) channels. EXPERIMENTAL APPROACHES: Expression of HMG CoA reductase in different cardiovascular preparations was measured. Effects of simvastatin on BK(Ca) channel gatings of porcine coronary artery smooth muscle cells were evaluated. KEY RESULTS: Western immunoblots revealed the biochemical existence of HMG CoA reductase in human cardiovascular tissues and porcine coronary artery. In porcine coronary artery smooth muscle cells, extracellular simvastatin (1, 3 and 10 microM) (hydrophobic), but not simvastatin Na+ (hydrophilic), inhibited the BK(Ca) channels with a minimal recovery upon washout. Isopimaric acid (10 microM)-mediated enhancement of the BK(Ca) amplitude was reversed by external simvastatin. Simvastatin Na+ (10 microM, applied internally), markedly attenuated isopimaric acid (10 microM)-induced enhancement of the BK(Ca) amplitude. Reduced glutathione (5 mM; in the pipette solution) abolished simvastatin -elicited inhibition. Mevalonolactone (500 microM) and geranylgeranyl pyrophosphate (20 microM) only prevented simvastatin (1 and 3 microM)-induced responses. simvastatin (10 microM ) caused a rottlerin (1 microM)-sensitive (cycloheximide (10 microM)-insensitive) increase of PKC-delta protein expression. CONCLUSIONS AND IMPLICATIONS: Our results demonstrated the biochemical presence of HMG CoA reductase in different cardiovascular tissues, and that simvastatin inhibited the BK(Ca) channels of the arterial smooth muscle cells through multiple intracellular pathways.

Video assisted thoracic surgery in the management of spontaneous pneumothorax: the current status.

Over the past decade, video assisted thoracic surgery (VATS) has changed the way spontaneous pneumothorax (SP) is managed. Benefits of VATS include less postoperative pain, shorter hospital stay, and attenuated postoperative inflammatory response are evident compared with open thoracic procedures. Furthermore, the increasing acceptance by patients and referring physicians is testament to its success. Recent studies and the authors decade of experience in management of SP by VATS show that it is quick, safe, and effective, with recurrence rates generally comparable to open procedures, with some exceptions. However, selecting the correct procedure and patient, as well as knowing the limitations of the surgeons and techniques are paramount for success. Even to this day, there are considerable variations in the treatment of SP and large scale controlled studies are needed to better define timing of surgery and the role of the different procedures in the treatment and prevention of SP.

Pulmonary ischaemia-reperfusion injury: role of apoptosis.

The central role of lung ischaemia-reperfusion injury in pulmonary dysfunction after cardiac surgery, particularly thoracic organ transplantation, has been well recognised. Lung tissue necrosis after prolonged ischaemia is known to worsen lung function, which was believed to be due largely to adjacent tissue inflammation. Recent studies suggest that lung apoptosis following ischaemia-reperfusion could be equally important in the development of post-operative lung dysfunction. The current literature on the mechanism and pathways involved in pulmonary dysfunction and, in particular, its relationship with apoptosis after lung ischaemia-reperfusion is briefly reviewed here. A better understanding of lung apoptosis, as well as the upstream pathways, may help in the development of therapeutic strategies that could benefit patients undergoing cardiac and lung transplantation.

Current indications and results of VATS in the evaluation and management of hemodynamically stable thoracic injuries.

OBJECTIVE: Thoracic injuries are among the most severe forms of trauma and also a leading cause of morbidity and mortality. Video Assisted Thoracic Surgery (VATS) has recently provided an alternative method to simultaneously diagnose and manage patients sustaining chest injuries. We analyze our experience with VATS in the setting of thoracic trauma detailing indications for exploration, procedures performed and results of surgery. METHODS: A 6-year single institution review of patients undergoing VATS due to injuries sustained from both blunt and penetrating chest trauma at a Level I trauma center and university teaching hospital. Comparisons were made between groups of blunt and penetrating trauma as to Injury Severity Score (ISS), presence of extra-thoracic injuries, initial thoracostomy drainage and length of postoperative stay. RESULTS: VATS was successfully performed in 19 consecutive patients without conversion to thoracotomy. Indications for exploration included acute hemorrhage, retained hemothorax, suspected diaphragmatic injuries (DI), suspected cardiac injury, intra-thoracic foreign body, persistent airleak and chronic empyema. Procedures performed consisted of evacuation of retained hemothorax, hemostasis of intra-thoracic bleeders, repair of DI, wedge lung resections and decortication. Mean postoperative length of stay was 5.86 days. There were no morbidities. One patient with severe intra-abdominal injuries expired on the first postoperative day. CONCLUSION: In hemodynamically stable patients with thoracic injuries, VATS provides an accurate assessment of intra-thoracic organ injury and can be utilized to definitively and effectively manage injuries sustained as a result of blunt or penetrating thoracic trauma. VATS should be used with caution in patients sustaining severe and life threatening intra-abdominal injuries.

Video-assisted thoracic surgery for mediastinal extramedullary haematopoiesis.

Extramedullary haematopoiesis is a rare cause of an intrathoracic mass. We report a case of posterior mediastinal extramedullary haematopoietic mass in a 50-year-old man who presented with non-specific symptoms and a paravertebral mass on chest X-ray. Diagnosis was achieved by using video-assisted thoracic surgery.

Idiopathic localised bladder amyloidosis: rare cause of haematuria.

Idiopathic Localised Bladder Amyloidosis is a rare cause of haematuria and urinary tract symptoms. A review of the literature highlights the varied presentations and the appropriate investigations for this condition, with emphasise on the exclusion of a secondary cause. In addition, the range of treatment options is fully discussed. Our report on a 65-year old gentleman illustrates that a high index of suspicion is required for its diagnosis. Furthermore, conservative management can be an effective strategy in selected patients.