Publications by authors named "Bashir M Matata"

28 Publications

  • Page 1 of 1

In Situ Oxidative Stress and Atrial Cell Deaths in Patients with Valve Disease.

Cardiovasc Hematol Disord Drug Targets 2019 ;19(1):79-87

Heart-Lung Institute, Cardiac Eye International Foundation, Texas, TX, United States.

Background: Left ventricular hypertrophy and myocardial remodeling occur with aortic valve disease and may lead to heart failure. Although increased oxidative stress and inflammatory factors have been implicated in heart failure, their role in the progression of valve disease remains unclear.

Objectives: We investigated the role of oxidative stress and inflammatory factors in valve disease whether this relates to cell death.

Methods: Blood samples were taken from 24 patients with valve disease before surgery and the results were compared with those from blood samples from 30 control healthy subjects. Myocardial biopsies from patients with valve disease were also collected before cannulation of the right atrial appendage. NF-κB activities in atrial and mononuclear cells nuclear extracts were determined by electrophoretic mobility shift assay.

Results: Nuclear factor kappaB activities were significantly greater in mononuclear cells from AVD patients compared with healthy controls and the antigens were detectable in atrial tissues valve disease patients. Plasma C-reactive protein, B-natriuretic peptides, plasma tumor necrosis factor alpha and soluble tumor necrosis factor receptor 1 and 3-nitrotyrosine levels were significantly higher in valve disease patients. Inducible nitric oxide and 3-nitrotyrosine antigens and cells expressing CD45 antigens were detected within atrial tissues obtained from valve disease patients suggesting oxidative stress originated from in situ leukocytes.

Conclusion: The findings suggest that oxidative stress originating from in situ leukocytes within the atrial myocardium may be the potential trigger for excessive transcriptional activities and apoptotic cell death within the atrial myocardium of valve disease patients. This represents a potential therapeutic target.
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http://dx.doi.org/10.2174/1871529X18666180723094926DOI Listing
June 2019

A Review of Interventions to Improve Enrolment and Adherence to Cardiac Rehabilitation Among Patients Aged 65 Years or Above.

Curr Cardiol Rev 2017 ;13(4):252-262

Liverpool Heart & Chest Hospital, Liverpool. United Kingdom.

Purpose: This review provides an overview and quality assessment of existing interventions, assessing the intervention types that are most effective at increasing enrolment and adherence to cardiac rehabilitation in older patients aged ≥65 years Methods: The review of the literature was performed using electronic databases to search for randomised controlled trials that aimed to increase enrolment and/or adherence to cardiac rehabilitation in older patients aged ≥65 years. The main key words were cardiac rehabilitation, enrolment, adherence and older patients. Studies were included if; (1) the intervention targeted improving enrolment and/or adherence to at least one of the following components of the cardiac rehabilitation programme: exercise, education or maintaining lifestyle changes; (2) assess the effectiveness of an intervention on increasing enrolment and/or adherence to a cardiac rehabilitation programme or any of its components; (3) include measures for assessing enrolment and/or adherence to a cardiac rehabilitation programme or any of its components; (4) the study included patients with a mean age of ≥65 years who were deemed eligible to participate in a cardiac rehabilitation programme. Included studies could be published in any language and there were no date restrictions for included studies. Studies focusing on pharmaceutical adherence were not included for the purpose of this review.

Results: Seven studies were included, with four investigating enrolment (1944 participants) and three assessing adherence to intervention programmes (410 participants). Three studies (1919 participants) reported higher enrolment to cardiac rehabilitation in the intervention group. Two studies that reported increases in enrolment to cardiac rehabilitation were deemed to have an unclear or high risk of bias. All three studies (410 participants) reported better adherence to cardiac rehabilitation in the intervention group when compared to the control group. Two studies that reported better completion of cardiac rehabilitation were deemed to have an unclear or high risk of bias. No formal meta-analysis was conducted due to the observed multiple heterogeneity among outcome measures, the low number of included studies and variability in study designs.

Conclusion: This review found only weak evidence to suggest that interventions can increase enrolment or adherence to cardiac rehabilitation programmes for patients aged ≥65 years, therefore no practice recommendations could be made and further high-quality research is needed in this population group.
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http://dx.doi.org/10.2174/1574884712666170710094842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730958PMC
March 2018

A Single-Center Randomized Trial of Intraoperative Zero-Balanced Ultrafiltration During Cardiopulmonary Bypass for Patients With Impaired Kidney Function Undergoing Cardiac Surgery.

J Cardiothorac Vasc Anesth 2015 Oct 20;29(5):1236-47. Epub 2015 Feb 20.

Liverpool Heart and Chest Hospital NHS Foundation Trust.

Objectives: The authors investigated whether zero-balance ultrafiltration (Z-BUF) during bypass significantly improves clinical and cost outcomes or biomarkers of kidney injury for patients with preoperative kidney impairment (estimated glomerular filtration rate [eGFR]<60 mL/minute) undergoing cardiac surgery.

Design: A single-center randomized controlled trial recruited, patients between 2010 and 2013, with a 12-months follow-up.

Setting: Hospital.

Participants: One hundred ninety-nine patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).

Interventions: Patients were assigned randomly to receive zero-balance ultrafiltration (Z-BUF) or not, with stratification for degree of kidney dysfunction and diabetes.

Measurements And Main Results: The authors assessed clinical efficacy and kidney function biomarkers. Cumulative probability of discharge from the intensive care unit (ICU) was assessed by Kaplan-Meier plots and was found not to be significantly different between the two trial arms (p = 0.61). After adjusting for EuroSCORE, diabetes, eGFR, cardioplegia types and type of surgery in a Cox proportional hazard model, hazard ratios (HR) for ICU length of stay between the Z-BUF and no-Z-BUF groups was not significantly different: HR (95% CI): 0.89 (0.66, 1.20; p = 0.44). In contrast, significant reductions in postoperative chest infections and the composite of clinical endpoints (death, strokes, and myocardial infarctions) in the Z-BUF group were observed. In addition, Z-BUF significantly abrogated the rise in the kidney damage markers urinary NGAL/creatinine ratio, urea, creatinine and eGFR during CPB and adverse events risks.

Conclusions: Z-BUF during bypass surgery is associated with significant reductions in morbidity and biomarkers of CPB-induced acute kidney injury soon after CPB, which are indicative of clearance of inflammatory/immune mediators from the circulation.
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http://dx.doi.org/10.1053/j.jvca.2015.02.020DOI Listing
October 2015

The impact of social deprivation on coronary revascularisation treatment outcomes within the National Health Service in England and Wales.

Eur J Prev Cardiol 2016 Feb 14;23(3):316-27. Epub 2015 Jan 14.

Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital, UK.

Background: There is strong evidence to suggest that social deprivation is linked to health inequalities. In the UK, concerns have been raised regarding disparities in the outcomes of acute cardiac services within the National Health Service (NHS). This study explored whether differences exist in (a) elective hospital presentation time (b) indicators of severity and disease burden and (c) treatment outcomes (hospital stay and mortality) on the basis of the index of multiple deprivation (IMD) status.

Design: This study was a retrospective analysis of data from NHS databases for 13,758 patients that had undergone cardiac revascularisation interventions at the Liverpool Heart and Chest Hospital between April 2007-March 2012.

Methods: The data was analysed by descriptive, univariate and multivariate statistics to explore the association between the IMD quintiles (Q1-Q5) and revascularisation type, elective presentation time, hospital length of stay and mortality.

Results And Conclusions: Univariate analysis indicated that there were significant differences between patients from the most deprived areas (Q5) compared with patients from the least deprived areas (Q1), these included admission volumes, time before presentation to hospital and proportion of non-elective cases. After risk-adjustments, percutaneous coronary intervention patients from Q5 compared with Q1 had significantly greater length of hospital stay and risk of in-hospital major acute cardiovascular events. After multivariate adjustment for baseline risk factors, patients from Q5 were associated with significantly worse five-year survival as compared with Q1 (hazard ratio (HR) 1.52, 95% confidence interval (CI): 1.36-1.71; p < 0.001). In conclusion, there is evidence to suggest that inequalities in cardiac revascularisation choices and outcomes in the UK may be associated with social deprivation.
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http://dx.doi.org/10.1177/2047487314567000DOI Listing
February 2016

One problem two issues! Left ventricular systolic and diastolic dysfunction in aortic stenosis.

Ann Transl Med 2014 Jan;2(1):10

1 Division of Cardiothoracic Surgery, Department of Surgery, Texas A & M Health Science Center at Scott & White Memorial Hospital, Temple, TX, USA ; 2 Division of Cardiothoracic Surgery, Prince of Wales & Sydney Children's Hospital, Barker Street, Randwick, Sydney, NSW, Australia ; 3 Liverpool Heart and Chest Hospital, NHS Foundation Trust, Liverpool, UK.

Reports suggested that immediate post-aortic valve replacement (AVR); left ventricular (LV) dysfunction may be an important risk for morbidity and mortality in patients requiring positive inotropic support. Several factors have been identified as significant prognostic factors i.e., LV systolic dysfunction, LV diastolic dysfunction (LV-DD), heart failure and myocardial infarction (MI). Specific to pathophysiological changes associated with AS, markers of systolic LV function (e.g., LVEF) have been extensively studied in management, yet only a few studies have analysed the association between LV-DD and immediate post-operative LV dysfunction This review brings together the current body of evidence on this issue.
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http://dx.doi.org/10.3978/j.issn.2305-5839.2013.06.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200657PMC
January 2014

Gender differences in the expression of genes involved during cardiac development in offspring from dams on high fat diet.

Mol Biol Rep 2014 Nov 24;41(11):7209-16. Epub 2014 Jul 24.

Division of Cardiothoracic Surgery, Department of Surgery, Texas A & M Health Science Centre at Scott & White Memorial Hospital, 2401 S. 31st Street, Temple, TX, 76508, USA,

Previously we have demonstrated that maternal high fat diet (HF) during pregnancy increase cardiovascular risk in the offspring, and pharmacological intervention using statins in late pregnancy reduced these risk factors. However the effects of maternal HF-feeding and statin treatment during pregnancy on development of heart remain unknown. Hence we measured expression of genes involved in cell cycle progression (cyclin G1), ventricular remodelling brain natriuretic peptide (BNP), and environmental stress response small proline-rich protein 1A (SPRR 1A) in the offspring left ventricle (LV) from dams on HF with or without statin treatment. Female C57 mice were fed a HF diet (45% kcal fat) 4 weeks prior to conception, during pregnancy and lactation. From the second half of the pregnancy and throughout lactation, half of the pregnant females on HF diet were given a water-soluble statin (Pravastatin) in their drinking water (HF + S). At weaning offspring were fed HF diet to adulthood (generating dam/offspring dietary groups HF/HF and HF + S/HF). These groups were compared with offspring from dams fed standard chow (C 21% kcal fat) and fed C diet from weaning (C/C). LV mRNA levels for cyclin G1, BNP and SPRR 1A were measured by RT-PCR. Heart weights and BP in HF/HF offspring were higher versus C/C group. Maternal Pravastatin treatment reduced BP and heart weights in HF + S/HF female offspring to levels found in C/C group. LV cyclin G1 mRNA levels were lower in HF/HF versus both C/C and HF + S/HF offspring. BNP mRNA levels were elevated in HF/HF females but lower in males versus C/C. BNP gene expression in HF + S/HF offspring was similar to HF/HF. SPRR 1A mRNA levels were similar in all treatment groups. Statins given to HF-fed pregnant dams reduced cardiovascular risk in adult offspring, and this is accompanied by changes in expression of genes involved in adaptive remodelling in the offspring LV and that there is a gender difference.
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http://dx.doi.org/10.1007/s11033-014-3605-8DOI Listing
November 2014

Nitric Oxide-Dependent Regulation of Cytokines Release in Type-II Diabetes Mellitus.

ISRN Inflamm 2013 17;2013:531026. Epub 2013 Feb 17.

Division of Cardiothoracic Surgery, Department of Surgery, Scott & White Memorial Hospital, Texas A&M Health Science Centre, 2401 S. 31st Street, Temple, TX 76508, USA.

The mechanism of release of proinflammatory cytokines by blood granulocytes in diabetes is unknown. We investigated whether diabetes mellitus affects the production of cytokines by granulocytes (PMN) and mononuclear cells (PBMCs) and whether this is modulated by NO. Isolated PMN and PBMC from with or without type-II diabetes mellitus were incubated at 37°C for 6 h with S-nitroso-N-acetylpenicillamine (SNAP) at 0, 1, and 100  μ M with or without lipopolysaccharides (LPS) stimulation (1  μ g/mL). Supernatants were assayed for tumor necrosis factor- α (TNF- α ) and interleukin-8 (IL-8) by sandwich ELISA. Significant increases in TNF- α and IL-8 were observed only in PMN from diabetic subjects with or without LPS stimulation and that exogenous NO inhibited further production of cytokines in a concentration-dependent manner. However, activity of PBMC when stimulated with LPS was greatly enhanced by diabetes, but not affected by NO production. Hence, suggesting that granulocytes activation and participation in diabetes related complications is modulated by NO bioavailability.
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http://dx.doi.org/10.1155/2013/531026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767208PMC
September 2013

Patients' attitudes and perceptions of two health-related quality-of-life questionnaires used to collect patient-reported outcome measures in the English National Health Service: A qualitative study of patients undergoing cardiac interventions.

SAGE Open Med 2013 25;1:2050312113503956. Epub 2013 Sep 25.

Institute of Cardiovascular Medicine & Science, Liverpool Heart & Chest Hospital NHS Foundation Trust, Liverpool, UK.

Objectives: To explore patients' views on the EuroQol-5D and Coronary Revascularisation Outcome Questionnaire, tools currently used for collecting patient-reported outcome measures in the English National Health Service. The key questions were as follows: (1) whether patients consider them sensitive enough to detect change in their health after cardiovascular disease interventions and (2) whether they consider the health-related quality-of-life questions as meaningful.

Methods: Data were collected on patients' views using focus groups. We held four focus groups selecting participants on the basis of their baseline and follow-up EuroQol-5D scores. Data were analysed using framework analysis and grounded theory.

Results: Focus group participants confirmed that they had derived substantial health benefits from their cardiac interventions despite the lack of measurable effects on the EuroQol-5D scores. Participants felt that the EuroQol-5D questionnaire was limited because of the following reasons: Their health fluctuates from day to day.They had difficulty assessing their general health status on the visual analogue scale.They felt that the Coronary Revascularisation Outcome Questionnaire was limited because of the following reasons: They did not understand the clinical terms used.The impact of tiredness on their quality of life was not captured.They were unable to distinguish between the effects of their heart condition and other health issues.Additionally, neither questionnaire considers the adjustments people have made to their domestic arrangements to improve their health-related quality of life.

Conclusion: This study provides evidence that the two questionnaires do not capture some aspects of health that patients consider important. Furthermore, the presence of co-morbidities masks the symptoms relating to the heart disease and the effect of their cardiac interventions. Future work on patient-reported outcome measures should consider developing new questionnaires that address these major concerns.
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http://dx.doi.org/10.1177/2050312113503956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687762PMC
January 2016

Current concepts underlying benefits of exercise training in congestive heart failure patients.

Curr Cardiol Rev 2010 May;6(2):104-11

Wessex Cardiothoracic Centre, General/ BUPA, Chalybeate Close, Southampton, SO16 6UY, United Kingdom.

The pathophysiology of several conditions including heart failure is partly attributable to a failure of the cell energy metabolism. Studies have shown that exercise training (ET) improves quality of life (QOL) and is beneficial in terms of reduction of symptoms, mortality and duration of hospitalization. Increasingly, ET is now achieving acceptance as complimentary therapy in addition to routine clinical practice in patients with chronic heart failure (CHF). However, the mechanisms underlying the beneficial effects of ET are far less understood and need further evaluation. Evidence suggests that while CHF induces generalized metabolic energy depletion, ET largely enhances the overall function of the heart muscle. Hence, research efforts are now aiming to uncover why ET is beneficial as a complimentary treatment of CHF in the context of improving endothelial function and coronary perfusion, decreasing peripheral resistance, induction of cardiac and skeletal muscle cells remodeling, increasing oxygen uptake, substrate oxidation, and resistance to fatigue. Here we discuss the current evidence that suggest that there are beneficial effects of ET on cardiac and skeletal muscle cells oxidative metabolism and intracellular energy transfer in patients with CHF.
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http://dx.doi.org/10.2174/157340310791162640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892075PMC
May 2010

Serum gamma glutamyl transferase: a novel biomarker for screening of premature coronary artery disease.

Cardiovasc Revasc Med 2011 Nov-Dec;12(6):367-74. Epub 2011 Mar 30.

Department of Pathology, AMC, National University of Sciences and Technology, Rawalpindi, Pakistan.

Background: We aimed to elucidate the association between gamma glutamyl transferase (GGT) activity with prevalence of premature coronary artery disease (CAD) in young Pakistani patients undergoing diagnostic coronary angiography.

Methods: A total of 218 young adults (age ≤ 45 years) underwent diagnostic angiography. Serum samples were taken from all the patients and analyzed for serum GGT activity, cholesterol and triglycerides.

Results: Coronary artery disease patients had significantly increased GGT activity (P = .001) and exhibited a significant positive correlation with blood pressure, cholesterol, blood glucose, and smoking and negative correlation with total antioxidant status (P < .01).

Conclusion: The study revealed good diagnostic accuracy at cutoff of 35 U/L with a sensitivity of 92%, specificity of 81%, and diagnostic odds ratio of 48 in estimation of premature CAD in young Pakistanis.
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http://dx.doi.org/10.1016/j.carrev.2011.02.001DOI Listing
March 2012

Levosimendan versus an intra-aortic balloon pump in adult cardiac surgery patients with low cardiac output.

J Cardiothorac Vasc Anesth 2011 Dec 3;25(6):1154-62. Epub 2011 Mar 3.

Wessex Cardiothoracic Centre, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.

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http://dx.doi.org/10.1053/j.jvca.2011.01.001DOI Listing
December 2011

Oxidative stress as a mediator of cardiovascular disease.

Oxid Med Cell Longev 2009 Nov-Dec;2(5):259-69

Wessex Cardiothoracic Centre, BUPA Hospital, Southampton, UK.

During physiological processes molecules undergo chemical changes involving reducing and oxidizing reactions. A molecule with an unpaired electron can combine with a molecule capable of donating an electron. The donation of an electron is termed as oxidation whereas the gaining of an electron is called reduction. Reduction and oxidation can render the reduced molecule unstable and make it free to react with other molecules to cause damage to cellular and sub-cellular components such as membranes, proteins and DNA. In this paper, we have discussed the formation of reactive oxidant species originating from a variety of sources such as nitric oxide (NO) synthase (NOS), xanthine oxidases (XO), the cyclooxygenases, nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase isoforms and metal-catalysed reactions. In addition, we present a treatise on the physiological defences such as specialized enzymes and antioxidants that maintain reduction-oxidation (redox) balance. We have also given an account of how enzymes and antioxidants can be exhausted by the excessive production of reactive oxidant species (ROS) resulting in oxidative stress/nitrosative stress, a process that is an important mediator of cell damage. Important aspects of redox imbalance that triggers the activity of a number of signalling pathways including transcription factors activity, a process that is ubiquitous in cardiovascular disease related to ischemia/reperfusion injury have also been presented.
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http://dx.doi.org/10.4161/oxim.2.5.9441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835914PMC
January 2011

Tumor necrosis factor alpha -308 gene locus promoter polymorphism: an analysis of association with health and disease.

Biochim Biophys Acta 2009 Mar;1792(3):163-72

Department of Human Sciences, Human Genetics Laboratory, Loughborough University, Leicestershire, UK.

Tumor necrosis factor-alpha (TNF-alpha) is a potent immunomediator and proinflammatory cytokine that has been implicated in the pathogenesis of a large number of human diseases. The location of its gene within major histocompatibility complex and biological activities has raised the possibility that polymorphisms within this locus may contribute to the pathogenesis of wide range of autoimmune and infectious diseases. For example, a bi-allelic single nucleotide substitution of G (TNFA1 allele) with A (TNFA2 allele) polymorphism at -308 nucleotides upstream from the transcription initiation site in the TNF-alpha promoter is associated with elevated TNF-alpha levels and disease susceptibilities. However, it is still unclear whether TNF-alpha -308 polymorphism plays a part in the disease process, in particular whether it could affect transcription factor binding and in turn influence TNF-alpha transcription and synthesis. Several studies have suggested that TNFA2 allele is significantly linked with the high TNF-alpha-producing autoimmune MHC haplotype HLA-A1, B8, DR3, with elevated serum TNF-alpha levels and a more severe outcome in diseases. This review discusses the genetics of the TNF-alpha -308 polymorphism in selected major diseases and evaluates its common role in health and disease.
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http://dx.doi.org/10.1016/j.bbadis.2009.01.007DOI Listing
March 2009

Inspired nitric oxide and modulation of oxidative stress during cardiac surgery.

Curr Drug Saf 2009 Sep 1;4(3):188-98. Epub 2009 Sep 1.

Department of Cardiothoracic Surgery, Punjab Institute of Cardiology, Lahore, Pakistan.

Evidence in the literature is contradictory regarding the precise role of nitric oxide (NO) in modulating systemic inflammatory response induced by cardiopulmonary bypass (CPB). We studied the impact of inspired NO gas on physiological function and markers of inflammation-oxidative stress for subjects (n=15, age 62+/-4.5 and 12/3 M/F) scheduled for coronary artery bypass graft (CABG) operation. Outcomes from subjects that received 5 ppm and 20 ppm of inspired NO (n=5/group) were compared to those not given NO gas. Breath-to-breath measurement commenced at the start of intubation and continued up to 4h later. Indices of cardiovascular function, alveolar-capillary gas exchange and haematological parameters were not significantly different in outcomes for the inspired NO groups as compared with control. We observed a reduction in mean systemic arterial in all subjects at 30 min and 4h after bypass when compared with pre bypass values. Markers of systemic inflammatory response and oxidative stress increased during CPB particularly at 4h and 24h after the initiation of bypass. In contrast, we observed a reduction in expired NO, at 24h after surgery in the groups given inspired NO. In addition, there was also a significant reduction in oxidative stress markers in blood at 24h after surgery for the groups given inspired NO as compared with the control group. In contrast, cytokines response remained similar in all the three groups at all time points. The results suggested that inspired NO gas has an antioxidant property that reduces the levels of cell death, and is not associated with significantly worse-off physiological outcomes.
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http://dx.doi.org/10.2174/157488609789006958DOI Listing
September 2009

Should the cardiotomy suction blood be cell-saver processed before retransfusion? A clinico-pathologic mystery.

Acute Card Care 2008 ;10(4):227-30

Wessex Cardiothoracic Centre, General/ BUPA Hospital, Southampton, Hampshire, United Kingdom.

The use of cardiotomy suction (CS) in cardiopulmonary bypass (CPB) surgery is associated with a pronounced systemic inflammatory response and a resulting coagulopathy as well as exacerbating the microembolic load. However, CS is yet been employed to preserve autologous blood during on-pump surgery. Though processing CS blood with a cell saving device is considered paramount in significantly reducing the inflammatory effects, yet this might also have potential harmful effects on the outcome of the patient. Here we discuss the results of the different prospective and randomized studies to address these issue if the cell saver technique in processing CS blood before retransfusion is to establish its identity and role in the CPB surgery.
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http://dx.doi.org/10.1080/17482940701744326DOI Listing
January 2009

Tracing the origins of postoperative atrial fibrillation: the concept of oxidative stress-mediated myocardial injury phenomenon.

Eur J Cardiovasc Prev Rehabil 2008 Dec;15(6):735-41

Wessex Cardiothoracic Centre, BUPA Hospital, Chalybeate Close, Southampton, UK.

Background: Atrial fibrillation (AF) is the most common arrhythmia associated with coronary artery surgery and is an important factor contributing to postoperative morbidity and mortality. Recently, there is growing evidence that dysregulation of the oxidant-antioxidant balance, inflammatory factors and discordant alteration of energy metabolites may play a significant role in its pathogenesis.

Design: We evaluated the link between postoperative atrial fibrillation with inflammatory factors and oxidative stress.

Methods: We searched all databases in Medline, Pubmed, ISI, the Cochrane database, and Embase. We identified more than 100 trials, multiple metaanalyses, and three sets of practice guidelines for the prevention of PAF in cardiac surgery.

Results: Mechanisms of postoperative AF are likely to be multifactorial and are influenced by preoperative, intraoperative and postoperative factors including a genetic basis. Electrical remodelling is thought to be related to the generation of reactive oxidant species and inflammatory factors during the ischemia-reperfusion phase of cardiac surgery. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was found to be the primary source of superoxide within the human atrial myocardium (in patients in sinus rhythm and in those with AF) and linked with paroxysmal and chronic AF. Reactive oxidant species cause lipid peroxidation, breakdown of cell membrane, decreased mitochondrial function, calcium overload and apoptosis. This affect was shown to be reversed by exogenous nitric oxide/donors (sodium nitroprusside). Inflammatory factors such as the rise in white blood cell count, C-reactive proteins were implicated in the pathogenesis of AF. In contrast, new evidence identifies statins as having both antioxidant and anti-inflammatory properties and that their use reduces the incidence of postoperative AF (57% in the control vs. 35% in the atorvastatin group). Other antiinflammatory strategies include steroids with one study showing postoperative AF occurred in 21% in the steroid group compared with 51% in the placebo group although their use resulted in an increase in other complications. The mainstay of therapy however, remains to be beta-blockers alone which impart a modest influence on overall rates of AF with a reduction from 33.7 to 16.9% (OR: 0.37, 95% CI: 0.29-0.48). Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers has been shown in one study to reduce the risk of developing new-onset AF by nearly 50%, although this has not been adequately evaluated in cardiac surgery.

Conclusion: Inflammatory factors and oxidative stress play a major role in the pathogenesis of postoperative AF. This review provides an analysis of current evidence in support of efforts directed at antiinflammatory and antioxidant agents as interventions.
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http://dx.doi.org/10.1097/HJR.0b013e328317f38aDOI Listing
December 2008

Functional adaptation to oxidative stress by memory T cells: an analysis of the role in the cardiovascular disease process.

Biochem Biophys Res Commun 2008 Nov 18;376(3):445-7. Epub 2008 Sep 18.

Wessex Cardiothoracic Centre, BUPA Hospital, Southampton, UK.

T cells participate in combating infection and critically determine the outcomes in any given disease process. Impaired immune response occurs in a number disease processes such as in cancer and atherosclerosis although the underlying mechanisms are still not fully understood. This article gives an up-to-date review of T cells development and functional adaptation to pathophysiological stimuli and participation in the cardiovascular disease process. In addition, we have discussed the signaling pathways controlled by the microenvironment that determine T cells function and resultant type of immune response. We have also discussed in detail how oxidative stress is a key component of the micro environmental interaction.
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http://dx.doi.org/10.1016/j.bbrc.2008.09.038DOI Listing
November 2008

Significance of oxidants and inflammatory mediators in blood of patients undergoing cardiac surgery.

J Cardiothorac Vasc Anesth 2008 Jun 28;22(3):455-67. Epub 2008 Mar 28.

Wessex Cardiothoracic Centre, General/BUPA Hospitals, Southampton, United Kingdom.

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http://dx.doi.org/10.1053/j.jvca.2007.12.022DOI Listing
June 2008

Myocardial protection against ischemia-reperfusion injury: novel approaches in maintaining homeostatic stability in blood.

Recent Pat Cardiovasc Drug Discov 2006 Nov;1(3):291-305

Department of Cardiothoracic Surgery, Faculty of Medicine and Surgery, PIC, Lahore, Pakistan.

Homeostatic vascular response to complement activation in cardiac surgery patients requiring cardiopulmonary bypass results in mechanisms leading to ischemia-reperfusion injury and myocardial cell death. Various pro-inflammatory cytokines, released by the inflamed tissue, play an essential role in the activation of the complement system and co-localize with activated complement proteins within the circulating blood and the myocardium. Throughout the past decade, much effort has thus been spent on deciphering the molecular signaling pathways mediating this pathophysiology. Basic and clinical investigations into many of the diverse aspects of cardiovascular drugs discovery employ varied approaches aimed at determining physiologic and pathophysiological efficiency of candidate agents for therapeutic utility. Identification of novel molecules regulating homeostatic dysfunction has offered the basis, with ultimate hope of identifying agents capable of exerting salutary influence upon cardiac and vascular tissue. This review will provide detailed synopses on recent insights into the ischemia-reperfusion signaling and associated myocardial injury. In addition, we will consider current and emerging novel approaches in attenuating cardiopulmonary bypass mediated injury with ultimate goal to prevent or delay the onset of post pump modulated heart failure and sudden deaths in such patients. Careful examination of the literature on recent patented and non-patented publications has identified several agents shown to be effective and specific in modulating and abrogating ischemia-reperfusion injury with some suggestions of potential clinical use.
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http://dx.doi.org/10.2174/157489006778777007DOI Listing
November 2006

A variant of position -308 of the Tumour necrosis factor alpha gene promoter and the risk of coronary heart disease.

Heart Lung Circ 2008 Feb 19;17(1):14-8. Epub 2007 Jun 19.

Department of Human Sciences, Loughborough University, Loughborough LE11 3TU, United Kingdom.

Purpose: The aim of this study was to investigate whether the variability between individuals with coronary heart disease (CHD) is related to the prevalence of TNF-alpha gene promoter -308 variant in un-matched British Caucasian population from East Midlands.

Procedures: Genotypes and allele frequencies were determined using restriction fragment length polymorphism analysis of polymerase chain reaction (PCR) products. Genomic DNA prepared from peripheral blood leukocytes of patients (n=97) and healthy controls (n=95) demonstrated two alleles TNF*1 (G) and TNF*2 (A).

Findings: The genotype distribution in patients was GG, n=59; GA, n=36; and AA, n=2 and in controls was GG, n=41; GA, n=40; and AA, n=14 (P=0.014). The association analysis demonstrated that TNF*1 allele in patients appears to be associated with greater incidences of CHD (OR 2.15; CI, 1.36-3.39; P=0.001).

Conclusions: Our results suggest that TNF*1 allele (TNF-alpha -308 GG or GA) has a high prevalence among British Caucasian population that correlates with an increased CHD risk.
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http://dx.doi.org/10.1016/j.hlc.2007.05.009DOI Listing
February 2008

Nitric oxide in blood. The nitrosative-oxidative disequilibrium hypothesis on the pathogenesis of cardiovascular disease.

FEBS J 2007 Feb 22;274(4):906-23. Epub 2007 Jan 22.

The Cardiothoracic Centre, Liverpool NHS Trust, UK.

There is growing evidence that altered production and/or spatio-temporal distribution of reactive oxidant species and reactive nitrosative species in blood creates oxidative and/or nitrosative stresses in the failing myocardium and endothelium. This contributes to the abnormal cardiac and vascular phenotypes that characterize cardiovascular disease. These derangements at the system level can now be interpreted at the integrated cellular and molecular levels in terms of effects on signaling elements in the heart and vasculature. The end results of nitric oxide/redox disequilibrium have implications for cardiac and vascular homeostasis and may result in the development of atherosclerosis, myocardial tissue remodelling and hypertrophy. Reactive oxygen species/reactive nitrogen species generation is also attributed to the transit from hypertrophic to apoptotic phenotypes, a possible mechanism of myocardial failure. In this review, we highlight the possible roles of altered production and/or spatio-temporal distribution of reactive oxidant species and reactive nitrosative species in blood on the pathogenesis of the failing cardiovascular system.
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http://dx.doi.org/10.1111/j.1742-4658.2007.05660.xDOI Listing
February 2007

Deleterious effects of cardiopulmonary bypass in coronary artery surgery and scientific interpretation of off-pump's logic.

Acute Card Care 2006 ;8(4):196-209

Wessex Cardiothoracic Centre, General Hospital/BUPA, Southampton, UK.

Cardiopulmonary bypass (CPB) has been suggested to be a cause of complex systemic inflammatory response that significantly contributes to several adverse postoperative complications. In the last few years, off-pump coronary artery bypass grafting (OPCAB) has gained widespread attention as an alternative technique to conventional on-pump coronary artery bypass grafting (ONCAB). However, a degree of uncertainty regarding the relative merits of ONCAB and OPCAB continues to be a significant issue. Surgeons supporting off-pump surgery, state that the avoidance of the CPB leads to significantly reduced myocardial ischemia-reperfusion injury, postoperative systemic inflammatory response and other biological derangements, a feature that may improve the clinical outcomes. However, perfection in perioperative care, surgical technique and methods of attenuating the untoward effects of CPB has resulted in better clinical outcome of ONCAB as well. Possible reasons of these controversial opinions are that high-quality studies have not comprehensively examined relevant patient outcomes and have enrolled a limited range of patients. Some studies may have been too small to detect clinically important differences in patient outcomes between these two modalities. We present a review of the available scientific interpretation of the literature on OPCAB with regard to safety, hemodynamic changes, inflammation, myocardial preservation and oxidative stress. We also sought to determine from different reported retrospective and randomized control studies, the initial and the long-term benefits of this approach, despite the substantial learning curve associated with OPCAB.
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http://dx.doi.org/10.1080/17482940600981730DOI Listing
March 2007

Quiescent interplay between inducible nitric oxide synthase and tumor necrosis factor-alpha: influence on transplant graft vasculopathy in renal allograft dysfunction.

Exp Clin Transplant 2006 Jun;4(1):445-50

Department of Cardiothoracic Surgery, Faculty of Medicine and Surgery, PIC, Lahore, Pakistan.

A healthy endothelium is essential for vascular homeostasis, and preservation of endothelial cell function is critical for maintaining transplant allograft function. Damage to the microvascular endothelial cells is now regarded as a characteristic feature of acute vascular rejection, an important predictor of graft loss. It is also linked with transplant vasculopathy, often associated with chronic allograft nephropathy. Large bursts of nitric oxide in infiltrating monocytes/macrophages modulated by inducible nitric oxide synthase are considered pivotal in driving this mechanism. Indeed, it has been shown recently that increased circulating levels of tumor necrosis factor-alpha in the rejecting kidneys are largely responsible for triggering inducible nitric oxide synthase expression. This in turn suggests that several structural and functional features of graft rejection could be mediated by tumor necrosis factor-alpha. Despite the large body of evidence that supports immunologic involvement, knowledge concerning the cellular and biochemical mechanisms for nephritic cell dysfunction and death is incomplete. The role of tumor necrosis factor-alpha in mediating pathophysiological activity of inducible nitric oxide synthase during transplant vasculopathy remains contentious. Here, we discuss the effect of inducible nitric oxide synthase and tumor necrosis factor-alpha interaction on progressive damage to glomerular and vascular structures during renal allograft rejection. Selective inhibition of inducible nitrous oxide synthase and tumor necrosis factor-alpha as a potential therapy for ameliorating endothelial dysfunction and transplant graft vasculopathy is also discussed.
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June 2006

Acute renal failure in patients with ischemic heart disease: causes and novel approaches in breaking the cycle of self-perpetuating insults abrogated by surgery.

Int Surg 2005 Sep-Oct;90(4):202-8

The Cardiothoracic Centre-Liverpool NHS Trust, Liverpool, United Kingdom.

At present, there seems to be diametrically opposing views on the causes of acute renal insufficiency in patients with ischemic heart disease (IHD) elective for cardiac revascularization. In this review, we examined recent advances in the understanding of the pathophysiology of acute renal failure in patients with IHD and surgery-induced acute phase reaction. Emphasis is given to the cellular and molecular mechanisms that contribute to the initiation and progression of inflammation. We evaluated the different pharmacological, technical, and surgical strategies used to improve the outcome of patients with IHD with impaired renal dysfunction and analyzed the influence of renal insufficiency on long-term results after surgery.
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July 2006

Mitochondrial dysfunction as the cause of the failure to precondition the diabetic human myocardium.

Cardiovasc Res 2006 Feb 5;69(2):450-8. Epub 2005 Dec 5.

Cardiac Surgery Unit, Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK.

Objectives: We have shown previously that human diabetic myocardium cannot be preconditioned. Here, we have investigated the basis of this cardioprotective deficit.

Methods: Right atrial sections from four patient groups-non-diabetic, insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM) receiving glibenclamide, and NIDDM receiving metformin-were subjected to one of the following protocols: aerobic control, simulated ischemia/reoxygenation, ischemic preconditioning before ischemia, and pharmacological preconditioning with alpha 1 agonist phenylephrine, adenosine, the mito-K(ATP) channel opener diazoxide, the protein kinase C (PKC) activator phorbol-12-myristate-13-acetate (PMA), or the p38 mitogen-activated protein kinase (p38MAPK) activator anisomycin. Cellular damage was assessed using creatine kinase leakage and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction. In mitochondrial preparations from non-diabetic and diabetic myocardium, mitochondrial membrane potential (Psi(m)) was assessed using JC-1 dye, and production of reactive oxygen species was determined.

Results: Preconditioning with ischemia, phenylephrine, adenosine, or diazoxide failed to protect diabetic myocardium. However, activation of PKC or p38MAPK was still protective. In isolated non-diabetic mitochondria, diazoxide partially depolarized Psi(m), an effect not seen in diabetic mitochondria. Furthermore, diazoxide increased superoxide production in non-diabetic but not in diabetic mitochondria.

Conclusions: Our results show that the cardioprotective deficit in diabetic myocardium arises upstream of PKC and p38MAPK. We suggest that mitochondrial dysfunction in diabetic myocardium, possibly dysfunctional mito-K(ATP) channels, leads to impaired depolarization and superoxide production, and that this causes the inability to respond to preconditioning.
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http://dx.doi.org/10.1016/j.cardiores.2005.11.004DOI Listing
February 2006

PKC-epsilon is upstream and PKC-alpha is downstream of mitoKATP channels in the signal transduction pathway of ischemic preconditioning of human myocardium.

Am J Physiol Cell Physiol 2004 Nov 4;287(5):C1418-25. Epub 2004 Aug 4.

Integrative Human Cardiovascular Physiology and Cardiac Surgery Unit, Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, United Kingdom.

Protein kinase C (PKC) is involved in the process of ischemic preconditioning (IPC), although the precise mechanism is still a subject of debate. Using specific PKC inhibitors, we investigated which PKC isoforms were involved in IPC of the human atrial myocardium sections and to determine their temporal relationship to the opening of mitochondrial potassium-sensitive ATP (mitoKATP) channels. Right atrial muscles obtained from patients undergoing elective cardiac surgery were equilibrated and then randomized to receive any of the following protocols: aerobic control, 90-min simulated ischemia/120-min reoxygenation, IPC using 5-min simulated ischemia/5-min reoxygenation followed by 90-min simulated ischemia/120-min reoxygenation and finally, PKC inhibitors were added 10 min before and 10 min during IPC followed by 90-min simulated ischemia/120-min reoxygenation. The PKC isoforms inhibitors investigated were V1-2 peptide, GO-6976, rottlerin, and LY-333531 for PKC-epsilon, -alpha, -delta and -beta, respectively. To investigate the relation of PKC isoforms to mitoKATP channels, PKC inhibitors found to be involved in IPC were added 10 min before and 10 min during preconditioning by diazoxide followed by 90-min simulated ischemia/120-min reoxygenation in a second experiment. Creatine kinase leakage and methylthiazoletetrazolium cell viability were measured. Phosphorylation of PKC isoforms after activation of the sample by either diazoxide or IPC was detected by using Western blot analysis and then analyzed by using Scion image software. PKC-alpha and -epsilon inhibitors blocked IPC, whereas PKC-delta and -beta inhibitors did not. The protection elicited by diazoxide, believed to be via mitoKATP channels opening, was blocked by the inhibition of PKC-alpha but not -epsilon isoforms. In addition, diazoxide caused increased phosphorylation of PKC-alpha to the same extent as IPC but did not affect the phosphorylation of PKC-epsilon, a process believed to be critical in PKC activation. The results demonstrate that PKC-alpha and -epsilon are involved in IPC of the human myocardium with PKC-epsilon being upstream and PKC-alpha being downstream of mitoKATP channels.
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http://dx.doi.org/10.1152/ajpcell.00144.2004DOI Listing
November 2004

Protein nitration is predominantly mediated by a peroxynitrite-dependent pathway in cultured human leucocytes.

Biochem J 2002 Oct;367(Pt 2):467-73

Department of Integrative Human Cardiovascular Physiology and Functional Genomics, Division of Cardiac Surgery, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, U.K.

Protein nitration is a common characteristic of oxidative injury caused by the invasion of leucocytes into inflammatory lesions. Two distinct pathways of nitration of protein tyrosine residues, namely the peroxynitrite (ONOO(-))-mediated pathway and another catalysed by the haem-containing peroxidases, have been reported under experimental conditions. However, the contribution of these two pathways in human leucocytes is still controversial. The present study demonstrates that the process of phenolic nitration of proteins in cultured human leucocytes is mainly ONOO(-)-mediated and that it differs between granulocytes and mononuclear cells, depending on the cell compartment and the stimuli. We have also shown that NO induces protein nitration via a ONOO(-)-dependent pathway, whereas NO(2)(-), the NO metabolite, does not increase but decreases nitration in PMA-stimulated leucocytes. The inhibition of myeloperoxidase activity did not reduce protein nitration; on the other hand, the myeloperoxidase inhibitor aminobenzoic hydrazide caused increased nitration, which was mediated by ONOO(-). These results suggest that protein nitration is predominantly mediated by a ONOO(-)-dependent pathway in cultured human leucocytes and that the myeloperoxidase-catalysed pathway does not play a significant role in protein nitration.
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http://dx.doi.org/10.1042/BJ20020825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1222891PMC
October 2002

Peroxynitrite is an essential component of cytokines production mechanism in human monocytes through modulation of nuclear factor-kappa B DNA binding activity.

J Biol Chem 2002 Jan 12;277(3):2330-5. Epub 2001 Nov 12.

Department of Integrative Human Cardiovascular Physiology and Functional Genomics, Cardiac Surgery, University of Leicester, Glenfield Hospital, Groby Road, Leicester LE3 9QP, United Kingdom.

The mechanism of release of proinflammatory cytokines by peripheral blood monocytes is unknown. Peroxynitrite (ONOO(-)) formed by the reaction of nitric oxide (NO) and superoxide is released predominantly by inflammatory cells at the site of injury in several inflammatory pathologies. Here we show that human monocytes treated with ONOO(-) at micromolar concentrations induce a dose-dependent release of proinflammatory cytokines. These effects were not antagonized by up to 100 microm epigallocatechin gallate, an inhibitor of protein nitration. However, the proteasome inhibitor Z-Ile-Glu(OtBu)-Ala-Leu-CHO and 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III) chloride, a cell-permeable scavenger of ONOO(-), almost completely inhibited the release of cytokines and the nuclear translocation of the nuclear factor (NF)-kappaB transcription factor. SDS-PAGE electrophoresis separation with Western blotting of cell extracts also indicated that phosphorylation and nitration of tyrosine residues in IkappaB-alpha molecules correlated with NF-kappaB translocation and cytokine release. In addition, the DNA binding activity of the NF-kappaB from the nuclear extracts also correlated with its nuclear translocation. These findings indicate ONOO(-) plays an essential role in the mechanism of proinflammatory cytokine release by monocytes and that Rel/NF-kappaB activation is the obligatory pathway.
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http://dx.doi.org/10.1074/jbc.M106393200DOI Listing
January 2002