Song Wan

Quantitative Analysis of Mitral Valve Morphology in Mitral Valve Prolapse With Real-Time 3-Dimensional Echocardiography Importance of Annular Saddle Shape in the Pathogenesis of Mitral Regurgitation

Background— Few data exist on the relation of the 3-dimensional morphology of mitral valve and degree of mitral regurgitation (MR) in mitral valve prolapse. Methods and Results— Real-time 3-dimensional transesophageal echocardiography of the mitral valve was acquired in 112 subjects, including 36 patients with mitral valve prolapse and significant MR (≥3+; MR+ group), 32 patients with mitral valve prolapse but no or mild MR (⩽2+; MR− group), 12 patients with significant MR resulting from nonprolapse pathologies (nonprolapse group), and 32 control subjects. The 3-dimensional geometry of mitral valve apparatus was measured with dedicated quantification software. Compared with the normal and MR− groups, the MR+ group had more dilated mitral annulus (P<0.0001), a reduced annular height to commissural width ratio (AHCWR) (P<0.0001) indicating flattening of annular saddle shape, redundant leaflet surfaces (P<0.0001), greater leaflet billow volume (P<0.0001) and billow height (P<0.0001), longer lengths from papillary muscles to coaptation (P<0.0001), and more frequent chordal rupture (P<0.0001). Prevalence of chordal rupture increased progressively with annulus flattening (7% versus 24% versus 42% for AHCWR >20%, 15%–20%, and <15%, respectively; P=0.004). Leaflet billow volume increased exponentially with decreasing AHCWR in patients without chordal rupture (r2=0.66, P<0.0001). MR severity correlated strongly with leaflet billow volume (r2=0.74, P<0.0001) and inversely with AHCWR (r2=0.44, P<0.0001). In contrast, annulus dilatation but not flattening occurred in nonprolapse MR patients. An AHCWR <15% (odds ratio=7.1; P=0.0004) was strongly associated with significant MR in mitral valve prolapse. Conclusion— Flattening of the annular saddle shape is associated with progressive leaflet billowing and increased frequencies of chordal rupture and may be important in the pathogenesis of MR in mitral valve prolapse.Background— Few data exist on the relation of the 3-dimensional morphology of mitral valve and degree of mitral regurgitation (MR) in mitral valve prolapse.nnMethods and Results— Real-time 3-dimensional transesophageal echocardiography of the mitral valve was acquired in 112 subjects, including 36 patients with mitral valve prolapse and significant MR (≥3+; MR+ group), 32 patients with mitral valve prolapse but no or mild MR (≤2+; MR− group), 12 patients with significant MR resulting from nonprolapse pathologies (nonprolapse group), and 32 control subjects. The 3-dimensional geometry of mitral valve apparatus was measured with dedicated quantification software. Compared with the normal and MR− groups, the MR+ group had more dilated mitral annulus ( P 20%, 15%–20%, and <15%, respectively; P =0.004). Leaflet billow volume increased exponentially with decreasing AHCWR in patients without chordal rupture ( r 2=0.66, P <0.0001). MR severity correlated strongly with leaflet billow volume ( r 2=0.74, P <0.0001) and inversely with AHCWR ( r 2=0.44, P <0.0001). In contrast, annulus dilatation but not flattening occurred in nonprolapse MR patients. An AHCWR <15% (odds ratio=7.1; P =0.0004) was strongly associated with significant MR in mitral valve prolapse.nnConclusion— Flattening of the annular saddle shape is associated with progressive leaflet billowing and increased frequencies of chordal rupture and may be important in the pathogenesis of MR in mitral valve prolapse.nn# Clinical Perspective {#article-title-34}

Sustained Reduction of Vein Graft Neointima Formation by Ex Vivo TIMP-3 Gene Therapy

Background— Coronary artery vein graft failure, resulting from thrombosis, intimal thickening, and atherosclerosis, is a significant clinical problem, with approximately 50% of vein grafts failing within 10 years. Intimal thickening is caused by migration of vascular smooth muscle cells from the media to the intima, where they proliferate. Interventions using gene transfer to inhibit vascular smooth muscle cells proliferation and migration are attractive because ex vivo access to the graft is possible. The involvement of matrix-degrading metalloproteinases in intimal thickening is well established, and we previously showed that adenoviral-delivered overexpression of an endogenous inhibitor, the tissue inhibitor of metalloproteinases-3 (TIMP-3), significantly retarded intimal thickening in short-term autologous porcine arteriovenous interposition grafts (28 days). However, it is essential to determine whether this approach will provide longer-term benefits. Methods and Results— We assessed whether a recombinant adenovirus that overexpresses TIMP-3 (RAdTIMP-3) affects vein graft intimal thickening in the longer term (at 3 months). Porcine saphenous veins were subjected to luminal infection with 2.5×1010 pfu/mL RAdTIMP-3 or RAd60 (control virus) or vehicle control, for 30 minutes before implantation into the carotid artery. Analysis of grafts harvested 3 months after delivery revealed that RAdTIMP-3–infected grafts had significantly reduced intimal areas compared with both controls (3.2±0.4 mm2 versus 5.6±0.7 mm2 and 5.9±0.5 mm2, RAdTIMP-3, RAd60, and vehicle, respectively). Medial areas were also significantly decreased by TIMP-3 (3.8±0.3 mm2 versus 6.7±1.0 mm2 and 5.2±0.4 mm2, RAdTIMP-3, RAd60, and vehicle, respectively). Conclusions— Overexpression of TIMP-3 provides a sustained retardation of vein graft intimal thickening and highlights the translational potential for ex vivo TIMP-3 gene therapy.

Role of osteopontin in the development of neointimal hyperplasia in vein grafts

OBJECTIVESnNeointimal hyperplasia and superimposed atherosclerosis are central to late vein graft failure following coronary artery bypass grafting. Recent studies on post-injury arterial vessels have suggested a role of osteopontin (OPN) in the process of vascular remodelling. This study was designed to assess the in vivo performance of OPN following vein grafting.nnnMETHODSnBilateral saphenous vein-carotid artery interposition grafting was performed in 16 Large White pigs (35-45 kg). All patent vein grafts were removed and fixed at 1, 2, 4 (n = 8 grafts in each group) and 12 weeks (n = 6 grafts) following surgery. Multiple histological sections from each graft were prepared. The expression of OPN in the vein grafts was determined by immunostaining and western blot assay. Proliferating cell nuclear antigen (PCNA) was detected by immunocytochemistry. Vein graft morphology was assessed using computer-aided planimetry.nnnRESULTSnThe expression of OPN remarkably increased in the intima of the vein grafts at the first week postoperatively and then gradually declined from the second postoperative week, although OPN expression remained significantly higher than the baseline level at the end of the 3-month study period. More importantly, the number of PCNA-positive cells and matrix metalloproteinases (MMPs) expression correlated well with the OPN expression.nnnCONCLUSIONSnEarly induction of OPN in vein grafts may contribute to the subsequent increase in MMPs activities as well as vascular smooth muscle cell proliferation. Therefore, OPN could play an important role in the development of neointimal hyperplasia in venous conduits after coronary artery bypass grafting.

Lung ischaemia-reperfusion induced gene expression.

OBJECTIVESnPulmonary dysfunction following lung ischaemia-reperfusion is a well-known phenomenon, which may contribute to post-cardiac surgical morbidity. The process is associated with pulmonary inflammatory response and cellular apoptosis. Early molecular mechanisms leading to such lung injury remain largely unknown. We examined whether lung ischaemia and reperfusion cause significant expression changes in numerous genes in the lungs involved in pulmonary apoptosis and other cellular processes by using oligonucleotide microarrays in an experimental model of rodent lung ischaemia-reperfusion injury.nnnMETHODSnSprague-Dawley rodents (n=5 in each group) were anaesthetised and underwent controlled ventilation, with varying durations of warm lung ischaemia (60 and 90 min) followed by a short reperfusion period. The right middle lobe of the lung was harvested. Gene expression changes in the lungs were analysed by rodent DNA microarray chips, and reverse transcription polymerase chain reaction (RT-PCR) performed to validate changes in gene expression.nnnRESULTSnSignificant expression changes, with reference to false discovery rate (FDR) controls, were detected in over 80 genes following controlled lung ventilation, and more than 50 were up-regulated more than 2-fold. Lung ischaemia-reperfusion caused expression changes in over 50 additional genes, including many novel genes not previously associated with lung ischaemia-reperfusion. Up-regulated genes identified include those associated with apoptosis, inflammation and cell-cycle control.nnnCONCLUSIONSnLarge numbers of genes relating to cell metabolism, transcription control, inflammation and apoptosis were significantly up- and down-regulated following controlled ventilation and early lung ischaemia-reperfusion, consistent with previous studies. In addition, novel genes related to lung injury were identified. These genetic signatures provide new insights into early molecular mechanisms of ischaemia-reperfusion lung injury and help refine therapeutic strategies to lessen pulmonary dysfunction following cardiac surgery.

Ventilation during cardiopulmonary bypass: impact on neutrophil activation and pulmonary sequestration.

Background: Cardiopulmonary bypass (CPB) is associated with neutrophil activation, pulmonary sequestration, and release of inflammatory mediators leading to pulmonary dysfunction. We investigate the effect of continuous ventilation during cardiopulmonary bypass on neutrophil activation and pulmonary sequestration. Methods: Forty-six patients undergoing coronary artery bypass grafting with cardiopulmonary bypass were prospectively randomized to continuous ventilation and nonventilation groups. Blood samples were collected, and bronchoalveolar lavage (BAL) was performed following induction of anesthesia and at 4 hr after aortic declamping. Differential white cell count was measured, and flow cytometry to determine cell count numbers and quantify CD45 and CD11b leukocyte cell surface adhesion molecule expression was performed on the blood and BAL samples. Results: Twenty-three patients were randomized to standard nonventilated CPB and 23 patients to ventilation throughout CPB. Significant increases in blood and BAL neutrophil numbers were detected at 4 hr following aortic declamping in both groups (Blood: NV p <. 0001, V p <. 0001; BAL: NV p =. 017, V p =. 0007). No significant inter-group differences in BAL and blood neutrophil numbers were found. Significantly higher blood neutrophil CD11b mean fluorescent intensity levels were present 4 hr following declamping compared with baseline in both groups (NV Blood, p =. 021; V Blood p <. 0001). No significant inter- or intragroup differences in BAL neutrophil CD11b mean fluorescent intensity levels were found. There was no death or major complication. Conclusions: Cardiopulmonary bypass during coronary artery bypass grafting is associated with increased neutrophil pulmonary sequestration, and blood neutrophil CD11b activation. Continuous ventilation during cardiopulmonary bypass does not significantly reduce neutrophil pulmonary sequestration or activation.

Spontaneous haemopneumothorax: current management

Spontaneous haemopneumothorax (SHP) can be life threatening and is an important cause for unexplained signs of significant hypovolaemia. There is still some debate relating to patient selection and timing of surgery, particularly in those who become stable following chest tube insertion without further blood loss. Review of the literature over the past decade in the management of SHP are presented and discussed. Surgery should be considered early in the management of SHP to reduce morbidity associated with continued haemorrhage and inadequate drainage. Lower postoperative complications and shorter hospital stay following video assisted thoracic surgery compared with thoracotomy have led to its increased acceptance as an alternative approach for SHP patients who are haemodynamically stable.