Effect of glutaraldehyde based cross-linking on the viscoelasticity of mitral valve basal chordae tendineae.

BACKGROUND: Mitral valve failure can require repair or replacement. Replacement bioprosthetic valves are treated with glutaraldehyde prior to implantation. The aim of this study was to determine the changes in mechanical properties following glutaraldehyde fixation of mitral valve chordae. METHODS: To investigate the impact of glutaraldehyde on mitral valve chordae, 24 basal chordae were dissected from four porcine hearts. Anterior and posterior basal (including strut) chordae were used. All 24 chordae were subjected to a sinusoidally varying load (mean level 2N, dynamic amplitude 2N) over a frequency range of 0.5-10 Hz before and after glutaraldehyde treatment. RESULTS: The storage and loss modulus of all chordal types decreased following glutaraldehyde fixation. The storage modulus ranged from: 108 to 119 MPa before fixation and 67.3-87.4 MPa following fixation for basal chordae; 52.3-58.4 MPa before fixation and 47.9-53.5 MPa following fixation for strut chordae. Similarly, the loss modulus ranged from: 5.47 to 6.25 MPa before fixation and 3.63-4.94 MPa following fixation for basal chordae; 2.60-2.97 MPa before fixation and 2.31-2.93 MPa following fixation for strut chordae. CONCLUSION: The viscoelastic properties of mitral valve chordae are affected by glutaraldehyde fixation; in particular, the reduction in storage moduli decreased with an increase in chordal diameter.

Preserving lung after traumatic transection of left lower lobe bronchus from bullet injury.

A 22-year-old soldier was shot in the left chest by a bullet from close range. He was found to have a left haemothorax and remained shocked despite aggressive resuscitation. Due to difficult terrain and night time movement restrictions, there were limitations to the transfer of patient. So he was attended at a peripheral hospital. At emergency thoracotomy, three segmental arteries to left upper lobe were ligated and haemostasis was secured. The level of transection of left lower lobe bronchus was identified to be below the origin of the apical segmental bronchus. The lower lobe bronchus was successfully re-attached and followed up with a daily bronchoscopic clearance of distal airway. The patient made a full recovery. Anastomosis of left lower lobe bronchus after traumatic transection is a viable option for preserving an amputated lobe, in trauma settings, provided haemostatic control has been adequately achieved.

Frequency and diameter dependent viscoelastic properties of mitral valve chordae tendineae.

This study aimed to characterise viscoelastic properties of different categories of chordae tendineae over a range of frequencies. Dynamic Mechanical Analysis (DMA) was performed using a materials testing machine. Chordae (n=51) were dissected from seven porcine hearts and categorised as basal, marginal, strut or commissural. Chordae were loaded under a sinusoidally varying tensile load at a range of frequencies between 0.5 and 5Hz, both at a standardised load (i.e. same mean load of 4N for all chordae) and under chordal specific loading (i.e. based on in vivo loads for different chordae). Storage modulus and stiffness were frequency-dependent. Loss modulus and stiffness were frequency-independent. Storage and loss moduli, but not stiffness, decreased with chordal diameter. Therefore, strut chordae have the lowest moduli and marginal chordae the highest moduli. The hierarchy of dynamic storage and loss moduli is: marginal, commissural, basal and strut. In conclusion, viscoelastic properties of chordae are dependent on both frequency and chordal type. Future/novel replacement chordal materials should account for frequency and diameter dependent viscoelastic properties of chordae tendineae.

N-terminal pro-B-type natriuretic peptide levels and early outcome after cardiac surgery: a prospective cohort study.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a powerful predictor of cardiovascular outcome in many circumstances. There are, however, limited data regarding the utility of NT-proBNP or BNP levels in patients undergoing cardiac surgery. The current study assesses the ability of NT-proBNP to predict early outcome in this setting. METHODS: One thousand and ten patients undergoing non-emergent cardiac surgery were recruited prospectively. Baseline clinical details were obtained and the European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Parsonnet score were calculated. Preoperative NT-proBNP levels were measured using the Roche Elecsys assay. The primary endpoint was 30 day mortality. RESULTS: Median NT-proBNP levels were 624 ng litre(-1) among patients who died within 30 days of surgery (n=29), compared with 279 ng litre(-1) in survivors [odds ratio (OR) 1.03 per 250 ng litre(-1), 95% confidence interval 1.01-1.05, P=0.001). NT-proBNP levels remained predictors of 30 day mortality in models including either the additive EuroSCORE (OR 1.03 per 250 ng litre(-1), P=0.01), the logistic EuroSCORE (OR 1.03 per 250 ng litre(-1), P=0.004), or the Parsonnet score (OR 1.02 per 250 ng litre(-1), P=0.04). Levels of NT-proBNP were also predictors of prolonged (>1 day) stay in the intensive care unit (OR 1.03 per 250 ng litre(-1), P<0.001) and of a hospital stay >1 week (OR 1.07 per 250 ng litre(-1), P<0.001). They remained predictive of these outcomes in regression models that included either the EuroSCORE or the Parsonnet score and in a model that included all study variables. CONCLUSIONS: NT-proBNP levels predict early outcome after cardiac surgery. Their prognostic utility is modest-but is independent of traditional indicators and conventional risk prediction scores.

Socio-economic status and early outcome from coronary artery bypass grafting.

OBJECTIVE: To determine the effects of socio-economic status (SES) on the outcome of coronary artery bypass grafting (CABG). DESIGN: Prospective cohort study. SETTING: Regional cardiac surgical unit. PATIENTS: 1994 consecutive patients undergoing non-emergency CABG. MEASURES: SES was determined from the patient's postcode using Carstairs tables. The primary end-point was all-cause mortality at 30 days. RESULTS: There were 50 deaths (2.5%) within 30 days of surgery. A higher Carstairs score demonstrated a trend towards increased 30-day mortality (odds ratio (OR) 1.09 per unit, 95% CI 1.00 to 1.20, p = 0.06). In a backward conditional model, including other predictors of early mortality, Carstairs scores were independently predictive (OR 1.12 per unit, 95% CI 1.01 to 1.24, p = 0.02). In a model including only Carstairs scores and the EuroSCORE, both were independent predictors of this outcome (OR for Carstairs score 1.11 per unit, 95% CI 1.00 to 1.22, p = 0.04). The 30-day mortality increases in each quartile of Carstairs scores, with patients in quartile 4 (most deprived) at significantly higher risk compared with quartile 1 (uncorrected OR 2.53 per unit, 95% CI 1.04 to 6.15; OR corrected for EuroSCORE, 2.56 per unit, 95% CI 1.03 to 6.34, p = 0.04 for both). Similarly, patients in the least affluent quartile were twice as likely to suffer a serious complication as those in the most affluent quartile (OR 2.14 per unit, 95% CI 1.32 to 3.46, p = 0.002). This increased risk was also independent of the EuroSCORE. CONCLUSIONS: Lower SES is associated with a poorer early outcome following CABG and is independent of other recognised risk factors.

Determination of the pressure required to cause mitral valve failure.

A method has been developed for applying water pressure to a closed mitral valve on the side corresponding to the heart's left ventricle. The pressure is increased until fluid flows through the valve, i.e. until it fails. A specific dissection technique has been developed to produce a specimen with two annular rings, mitral annulus and papillary muscle annulus. Since the valve is maintained intact, with its leaflets attached to papillary muscles by the chordae tendineae, this method allows the effects of ruptured chordae and their surgical repair or replacement to be assessed in vitro. The chamber that holds the valve supports both the mitral annulus and papillary muscle annulus of the specimen. The mitral annulus is sutured onto rubber sheeting held in the chamber. The papillary muscle annulus is held in place by a Perspex support. The main part of the apparatus consists of a water pump connected through flexible tubing to the chamber that holds the valve in place. The pressure at failure is measured using a pressure transducer. Preliminary experiments demonstrate that anterior leaflet marginal chordae, but not strut chordae, are vital to valve function. Posterior leaflet chordae have been found to be important for valve competence.

Thoracoscopic thoracic duct ligation for traumatic chylothorax.

Traumatic chylothorax requires surgical intervention when conservative medical management fails to reduce chyle leakage. This usually entails thoracotomy or laparotomy. We report a case in which successful ligation of a torn thoracic duct was achieved using a video-assisted thoracoscopic technique.

Juxtacardiac costal osteochondroma presenting as recurrent haemothorax.

A 21-year-old man presenting with a recurrent spontaneous haemothorax was found to have an osteochondroma arising out of the left 4th rib. This was penetrating the apical part of the heart. Surgical excision was uneventful.

Twenty years' experience with the Medtronic Hall valve.

OBJECTIVE: To assess the performance of the Medtronic Hall valve (Medtronic, Inc, Minneapolis, Minn) in one institution over a 20-year period. METHODS: Since 1979, Medtronic Hall valves have been used in 1766 procedures (736 aortic, 796 mitral, and 234 double). Patients were followed up prospectively at 6- to 12-month intervals for a total of 12,688 follow-up years. Anticoagulation data (international normalized ratio) were recorded for all patients (approximately 95,000 observations). RESULTS: Linearized rates of valve-related late death for aortic, mitral, and double valve replacement were 0.8%/y, 0.9%/y, and 1.1%/y, respectively. Risk factors for late mortality were (relative risk) diabetes (1.9), decade of age (1.6), concomitant coronary artery bypass grafting (1.4), hypertension (1.3), non-sinus rhythm (1.3), large valve size (1.1), valve regurgitation (1.3), and male sex (1.2). For aortic, mitral, and double valve replacement, linearized rates (percent per year) of adverse events were valve thrombosis 0.04, 0.03, and 0.0; all thromboembolism 2.3, 4.0, and 3.4; stroke 0.6, 0.8, and 0.6; major hemorrhage 1.2, 1.4, and 1.6; and prosthetic endocarditis 0.4, 0.4, and 0.7. Risk factors for thromboembolism were (relative risk) mitral valve replacement (1.9), diabetes (1.8), hypertension (1.5), and history of embolism (1.4). CONCLUSION: At 20 years the Medtronic Hall valve demonstrates excellent durability, good hemodynamic performance, and very low thrombogenicity, with a valve thrombosis rate lower than those reported for bileaflet designs. With this prosthesis, both survival and thromboembolic events are predominantly determined by patient risk factors.

PPAR agonists as direct modulators of the vessel wall in cardiovascular disease.

Successful management of cardiovascular (CV) disease and associated metabolic syndromes, such as diabetes, is a major challenge to the clinician. Reducing CV risk factors, such as abnormal lipid profiles, insulin resistance or hypertension is the foundation of such therapy. A relatively new class of therapeutic agent, activators of peroxisome proliferator-activated receptors (PPAR), is poised to make a major impact with regard to several areas of risk factor management. However, there is growing evidence that PPAR agonists may also influence the CV system directly by modulating vessel wall function. These observations suggest that additional benefit, in the treatment of CV disease, may derive not only from the ability of agents to modify risk factors but also to influence directly the cellular mechanisms of disease within the vessel wall. A precedent for this dual action comes from examination of the effects of inhibitors of HMG CoA reductase (statins), where risk factor modulation is accompanied by direct actions on the vessel wall. In this review, we summarize the evidence suggesting that PPAR agonists may directly modulate vessel wall function, and that these may parallel those effects reported recently for the statins.

Thoracic organ transplantation at Papworth Hospital.

More than 1,200 patients have now undergone thoracic transplantation at Papworth Hospital and about 90 transplants are performed annually. Papworth remains one of the largest transplant units in the UK. Unique activities include a very large heart-lung transplant program: 247 patients have now undergone heart-lung transplants and 73 domino heart transplants have been performed. The 5-year survival rates are 71% for heart transplants, 48% for heart-lung and 41% for lung transplants, respectively. Chronic obliterative bronchiolitis remains an important limitation for heart-lung and lung transplant survival.

pPV: a novel IRES-containing vector to facilitate plasmid immunization and antibody response characterization.

BACKGROUND: The ability to derive immunological reagents for basic and applied research in a timely fashion is a basic requirement of many research projects and is becoming increasingly important as the number of novel gene products of potential interest continues to evolve rapidly. DNA immunization provides a means of facilitating the production of antibody reagents by circumventing the need to derive either purified protein or define peptides before initiating an in vivo immunization protocol. OBJECTIVES: The DNA construct pPV, for plasmid vaccination, has been designed to facilitate the generation and characterization of antibody reagents against either random or defined molecular targets. STUDY DESIGN: pPV incorporates mammalian regulatory and structural features that promote expression of a bifunctional messenger RNA (mRNA) from a single promoter within mammalian cells both in vitro and in vivo. The bifunctional mRNA encodes a control epitope (human IL5), and the 'test' epitope expressed as a tagged recombinant polypeptide in either a random 'shot-gun' mode or a predetermined fashion. In addition, to aid subsequent characterization of antibody responses elicited in vivo, a T7 promoter is included to enable in vitro expression of tagged recombinant polypeptides. RESULTS: The utility and functionality of pPV for the in vitro expression of recombinant protein and the in vivo elicitation of antibody responses is illustrated using a defined 'test' epitope, human proIL1 beta. CONCLUSION: It is anticipated pPV will find particular utility in the future rapid generation and characterization of antibody reagents against the plethora of novel genes emerging from ongoing genomics activity in a directed or genome wide fashion.

Surgical management of penetrating mediastinal arterial trauma.

Fifty-two patients with penetrating injury to the arteries caudal to the thoracic inlet and cephalad to the heart came under the care of the Durban Metropolitan Vascular Service, South Africa, over a 13-year period. The innominate artery was the commonest vessel injured (n = 23). Five patients (11%) had multiple vessel injuries, four of which involved the aortic arch, and 18 (34%) had arteriovenous fistulae. Mortality was greatest with injuries involving the aortic arch (n = 17) and ascending aorta (n = 4) in which intra-operative exsanguination was the leading cause of death (five patients). Injuries involving the inferior and posterior walls of the aortic arch and those located between the innominate and left common carotid origins were the most difficult to control. Seven patients with aortic injuries presented with cardiac tamponade, three of whom had associated injuries involving the atria. Seven of 21 (33%) patients with aortic injuries died compared to 2 of 31 (6%) with aortic arch branch injury (p < 0.05, chi-square) for an overall mortality of 17%.

Characterisation of the endothelin receptor mediating contraction of human pulmonary artery using BQ123 and Ro 46-2005.

We have characterised the endothelin receptor mediating contraction of human isolated pulmonary artery. Endothelin-1 induced a concentration-dependent contraction of human endothelium-denuded pulmonary artery (EC50 5.6 nM). In contrast, endothelin-3 produced only a small contraction (approximately 12% of maximum endothelin-1 response) at the highest concentration tested (1 microM). The ETB receptor-selective agonist, sarafotoxin S6c (0.1 nM to 1 microM) did not cause contraction of human pulmonary artery. Pretreatment of human pulmonary artery with BQ123 (1-10 microM), an ETA receptor-selective blocking drug, resulted in a concentration-dependent, surmountable antagonism of endothelin-1-induced contractions (apparent pKB 6.6-7.0). Schild analyses yielded a shallow slope (0.58), which was significantly less than unity and, consequently, the calculated pA2 (8.1) was greater than the individual pKB values. Pretreatment of human pulmonary artery with Ro 46-2005 (30 microM), a non-peptide. non-selective endothelin receptor-blocking drug, resulted in a surmountable antagonism of endothelin-1-induced contractions (apparent pKB 5.5). In conclusion, endothelin-1-induced contraction of human pulmonary artery appears to be mediated predominantly via ETA receptors, although the shallow Schild slope observed with BQ123 indicates possible receptor heterogeneity.