Research

Clough RE, Vallely MP, Henein MY, Pepper JR

Int. J. Cardiol. 2009 May;134(3):408-9

PMID: 18378019

Abstract

Yan TD, Boyer M, Tin MM, Sim J, Kennedy C, McLean J, Bannon PG, McCaughan BC

Ann. Thorac. Surg. 2009 May;87(5):1552-6

PMID: 19379903

Abstract

BACKGROUND: The primary aim of this study was to evaluate prognostic features of long-term survivors with pleural mesothelioma.

METHODS: Overall survival outcome was analyzed in 456 patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy (EPP), pleurectomy/decortications, or pleurodesis/biopsy with at least 18 months of follow-up. Prospectively collected clinicopathologic and treatment data were assessed for their correlations with actual 18-month survivors in both univariate and multivariate analyses.

RESULTS: The actual 18-month survival was 28%. Epithelial subtype was present in 185 patients (41%) and nonepithelial subtype in 183 (40%). Procedures were EPP in 59 patients (13%), pleurectomy/decortication in 250 (55%), and pleurodesis/biopsy in 147 (32%). Forty-two patients (9%) underwent positron emission tomography (PET) scanning. Forty patients (9%) received adjuvant radiotherapy and 45 (10%) received postoperative pemetrexed combination chemotherapy. In univariate analysis, age 65 years or younger (p < 0.001), malignant pleural effusion (p = 0.041), epithelial subtype (p < 0.001), EPP (p < 0.001), PET scan (p = 0.012), adjuvant radiotherapy (p = 0.042), and postoperative pemetrexed combination chemotherapy (p = 0.035) were strongly associated with 18-month survivors. In multivariate analysis, epithelial histopathologic subtype (p < 0.001) and EPP (p < 0.001) were independently associated with 18-month survivors.

CONCLUSIONS: The actual 18-month survival was 28% in 456 pleural mesothelioma patients who underwent operation. Epithelial histologic subtype and EPP were identified as independent predictors for 18-month survivors.

Vallely MP, Bannon PG, Bayfield MS, Hughes CF, Kritharides L

Heart Lung Circ 2009 Apr;18(2):123-30

PMID: 19081297

Abstract

BACKGROUND: With the increasing use of OPCAB, potentially devastating thromboembolic events, including graft thrombosis may become increasingly evident. We present a study of the quantitative and temporal differences of the coagulation system, fibrinolysis and platelet activation after coronary artery surgery with or without cardiopulmonary bypass.

METHODS: Patients undergoing on-pump CABG (n=10) or OPCAB (n=10) had six blood samples taken before surgery and up to 24h post-operatively. Activation of the coagulation cascade (tissue factor pathway-factor VIIa), endothelial injury (von Willebrand Factor antigen), thrombin generation (prothrombin fragments FI+II), fibrinolysis (decreased plasminogen levels), fibrin degradation (D-Dimer), platelet counts and platelet activation (soluble P-selectin) were quantified.

RESULTS: CABG caused earlier and more significant generation of thrombin, however OPCAB caused a late and sustained generation of thrombin. CABG caused intraoperative activation of fibrinolysis and fibrin degradation, however, at 24h these parameters were equally elevated in both groups. Platelet activation was significant in the CABG group, but did not occur in the OPCAB group.

CONCLUSIONS: Late thrombin generation and reduced fibrinolysis in the presence of intact, functioning platelets may contribute to adverse thromboembolic events after OPCAB surgery. Thromboembolic prophylaxis and anti-platelet therapy may need to be more aggressive after OPCAB surgery.

Yin Y, Wise SG, Nosworthy NJ, Waterhouse A, Bax DV, Youssef H, Byrom MJ, Bilek MM, McKenzie DR, Weiss AS, Ng MK

Biomaterials 2009 Mar;30(9):1675-81

PMID: 19157535

Abstract

Currently available endovascular metallic implants such as stents exhibit suboptimal biocompatibility in that they re-endothelialise poorly leaving them susceptible to thrombosis. To improve the interaction of these implants with endothelial cells we developed a surface coating technology, enabling the covalent attachment of biomolecules to previously inert metal surfaces. Using horseradish peroxidase as a probe, we demonstrate that the polymerised surface can retain the presentation and activity of an immobilised protein. We further demonstrated the attachment of tropoelastin, an extracellular matrix protein critical to the correct arrangement and function of vasculature. Not only it is structurally important, but it plays a major role in supporting endothelial cell growth, while modulating smooth muscle cell infiltration. Tropoelastin was shown to bind to the surface in a covalent monolayer, supplemented with additional physisorbed multilayers on extended incubation. The physisorbed tropoelastin layers can be washed away in buffer or SDS while the first layer of tropoelastin remains tightly bound. The plasma coated stainless steel surface with immobilised tropoelastin was subsequently found to have improved biocompatibility by promoting endothelial cell attachment and proliferation relative to uncoated stainless steel controls. Tropoelastin coatings applied to otherwise inert substrates using this technology could thus have broad applications to a range of non-polymeric vascular devices.

Vallely MP, Semsarian C, Bannon PG

Heart Lung Circ 2008 Oct;17(5):357-63

PMID: 18514024

Abstract

Bicuspid aortic valve (BAV) disease is the most common form of congenital heart disease, affecting 1-2% of the population. Only 20% of patients will maintain normal valve function throughout their life and more than 30% of patients will develop serious morbidity. It is a highly heritable condition, with transmission likely to be autosomal dominant. Patients with BAV have a 10-fold risk of aortic dissection when compared to the normal population. Management of BAV associated aortopathy represents a significant clinical challenge.

Nouri M, Chalian H, Bahman A, Mollahajian H, Ahmadi-Faghih M, Fakheri H, Soroush A

Arch Iran Med 2008 Jul;11(4):392-6

PMID: 18588371

Abstract

BACKGROUND: The objective of our study was to compare the zinc and molybdenum contents of nails in two populations at high and low risk for esophageal cancer in northern Iran.

METHODS: Four groups were studied including a control group in Tehran–a low-risk area (n=20); a group of patients with esophageal cancer from Sari–a moderate- risk region in northern Iran (n=20); a group of patients’ family members (n=20); and a control group in Sari (n=40). Molybdenum and zinc levels were measured in their nail samples using flame atomic absorption spectrometry.

RESULTS: Both molybdenum and Zinc were significantly (P<0.01) lower in the Sari control group (molybdenum: 0.472 ppm, zinc: 173.0 ppm) compared with the Tehran control group (molybdenum: 0.740 ppm, zinc: 251.5 ppm). These elements were lower in content in patients with esophageal cancer (molybdenum: 0.283 ppm, zinc: 126.5 ppm) compared with the Sari control group (P<0.05 for molybdenum and P<0.001 for zinc). Only zinc was significantly (P<0.001) lower in patients compared with their family members (molybdenum: 0.456 ppm, zinc: 175.5 ppm). No differences were found between the Sari control group and the patients' family members in any of the two elements.

CONCLUSION: Zinc and molybdenum levels are much lower in north of Iran–a moderate- risk area for esophageal cancer–compared with Tehran–a low-risk area. Based on these results, more investigations on the relations of trace elements with esophageal cancer in high-risk areas in northern Iran are warranted.

Vallely MP, Potger K, McMillan D, Hemli JM, Brady PW, Brereton RJ, Marshman D, Mathur MN, Ross DE

Heart Lung Circ 2008 Aug;17(4):299-304

PMID: 18294911

Abstract

BACKGROUND: Stroke remains one of the most devastating complications of cardiac surgery. Advocates of off-pump coronary revascularisation (OPCAB) maintain that post-operative neurologic morbidity is reduced by avoiding aortic cannulation and cross-clamping, and by eliminating the systemic effects of cardiopulmonary bypass. We sought to determine whether completing off-pump coronary surgery without any aortic manipulation (“anaortic” technique) afforded any additional neurological protection, as compared to off-pump grafting in which the aorta was utilised for graft inflow.

METHODS: A comprehensive review of prospectively collected data was undertaken of all patients undergoing OPCAB in our institution between January 2002 and December 2006. Cases requiring intra-operative conversion to cardiopulmonary bypass were excluded from further analysis. Patients having OPCAB surgery with aortic manipulation were compared to those having OPCAB surgery without aortic manipulation. Multiple logistic regression was used to identify possible predictors of post-operative neurologic morbidity, with particular focus on the role of aortic manipulation.

RESULTS: During the period of review, 1758 patients underwent OPCAB, of which 1201 (68.3%) were completed without aortic manipulation, constituting the “anaortic” cohort. This group was compared with the remaining 557 patients, which included fashioning at least one aorto-conduit anastomosis, utilising either a side-biting aortic clamp or a no-clamp proximal anastomotic device. The two groups of patients were well-matched with respect to risk factors for adverse neurologic outcomes. Nine patients sustained focal neurological deficits (transient or permanent) in the peri-operative period, constituting a stroke rate of 0.51% for the entire series. The incidence of peri-operative neurological deficit in the anaortic group was 0.25% compared with 1.1% in the aortic manipulation group (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.06-0.92, p=0.037). Advanced age was also associated with peri-operative neurological injury (OR 1.1, 95% CI 1.01-1.20, p=0.017).

CONCLUSIONS: Off-pump coronary artery surgery is associated with a low incidence of peri-operative stroke. Completing the surgical procedure without manipulating the ascending aorta in any way (“anaortic” technique) offers additional neurological protection and should be the goal in all suitable off-pump coronary cases.

Rossiter-Thornton M, Arun V, Forrest AP, Bayfield MS, Wilson MK

Heart Lung Circ 2008 Jun;17(3):243-5

PMID: 18436482

Abstract

We report the first Australian use of the Impella LP 5.0, a minimally invasive, high-output left ventricular assist device. The device was inserted intra-operatively for cardiac failure following coronary artery grafting. Although it facilitated a temporary post-operative recovery, the patient ultimately succumbed due to left ventricular failure more than 30 days after the original procedure. This device has several advantages over existing forms of left ventricular support, and has the potential for widespread use in Australian centres.

Stadler N, Stanley N, Heeneman S, Vacata V, Daemen MJ, Bannon PG, Waltenberger J, Davies MJ

Arterioscler. Thromb. Vasc. Biol. 2008 May;28(5):1024-30

PMID: 18309112

Abstract

OBJECTIVE: Oxidized lipids and proteins, as well as decreased antioxidant levels, have been detected in human atherosclerotic lesions, with oxidation catalyzed by iron and copper postulated to contribute to lesion development. Zinc has been postulated to displace iron from critical sites and thereby protect against damage. In this study, metal ion and protein oxidation levels were quantified in human carotid and abdominal artery specimens containing early-to-advanced lesions, to determine whether zinc concentrations correlate inversely with iron levels and protein oxidation.

METHODS AND RESULTS: Metal ions were quantified by EPR and inductively coupled plasma mass spectroscopy. Native and oxidized protein side-chains were quantified by high-performance liquid chromatography. Elevated levels of zinc ( approximately 6-fold) were detected in advanced lesions compared to healthy tissue or early lesions. Zinc did not correlate negatively with iron or copper levels suggesting that zinc does not displace these metal ions. Highly significant positive correlations (P<0.005) were detected between zinc and calcium levels.

CONCLUSIONS: Zinc did not correlate with low iron levels and reduced protein oxidation. These data indicate that zinc does not prevent protein oxidation in advanced lesions. The reported protective effect of zinc accumulation is proposed to be associated with lesion calcification.

Orr Y, Wilson DP, Taylor JM, Bannon PG, Geczy C, Davenport MP, Kritharides L

Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007 Apr;292(4):R1707-16

PMID: 17185405

Abstract

Acute inflammatory stimuli rapidly mobilize neutrophils from the bone marrow by shortening postmitotic maturation time and releasing younger neutrophils; however, the kinetics of this change in maturation time remains unknown. We propose a kinetic model that examines the rate of change in neutrophil average age at exit from the bone marrow during active mobilization to quantify this response and use this model to examine the temporal profile of late neutrophil phenotypic maturation. Total and CD10(-)/CD16(low) circulating neutrophils were quantified in cardiac surgery patients during extracorporeal circulation (ECC). Net growth in the circulating neutrophil pool occurred during the procedural (0.04 +/- 0.02 x 10(9) x l(-1) x min(-1)), warming (0.14 +/- 0.02 x 10(9) x l(-1) x min(-1)), and weaning (0.12 +/- 0.06 x 10(9) x l(-1) x min(-1)) phases of ECC. When applied to our differential equation mathematical model, these results predict that neutrophil average age at exit from the bone marrow decreased continually during ECC, resulting in average neutrophil release 8.44 +/- 2.20 h earlier during the weaning phase than at the beginning of ECC sampling. Modeling of concurrent changes in CD10(-)/CD16(low) neutrophil numbers indicates that CD10 expression is directly related to neutrophil mean age and predicts that the proportion of mobilizable postmitotic neutrophils that are CD10(+) increases from 64 to 81% during these sampled 8.4 h of maturation.