Publications by authors named "Maqsood M Elahi"

40 Publications

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

Effects of maternal high-fat diet and statin treatment on bone marrow endothelial progenitor cells and cardiovascular risk factors in female mice offspring fed a similar diet.

Nutrition 2017 Mar 21;35:6-13. Epub 2016 Oct 21.

Department of Clinical Quality, The Liverpool Heart & Chest Hospital NHS Foundation Trust, Liverpool, United Kingdom; Institute of Infection & Global Health, University of Liverpool, Liverpool, United Kingdom. Electronic address:

Objectives: The aim of this study was to prove that one possible statin-related protective mechanism in dams and offspring fed a high-fat diet (HFD) is the reduction in cardiovascular risk and impairment of the vasculogenic element of endothelial regeneration.

Methods: To explore this, virgin C57 BL/6 mice (n = 8/group) were fed an HFD (fat: 45% kcal) or standard chow (C; fat: 21% kcal) from weaning and throughout their pregnancy and lactation. Half of the HFD group also was given the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin (S) through their drinking water (5 mg/kg body weight per day) to create HF+S dam group (n = 8/group). Offspring from each group were fed HFD or C diet from weaning to adulthood, generating respective dam/offspring dietary groups (C/C, HF/HF, HF+S/HF; n = 8/group). Body weight, blood pressure, and serum lipid profile were measured in female offspring at age 24 wk, and bone marrow endothelial progenitor cells (EPCs) were cultured.

Results: The results indicated that in the female offspring, the statin-fed (HF+S/HF) cohort had lower total and low-density lipoprotein cholesterol concentrations, were less obese and hypertensive, and had reduced C-reactive proteins (CRPs) compared with the HF/HF phenotype. The results also showed an increased bone marrow EPCs expressing colony numbers (P < 0.001) compared with the HF/HF phenotype.

Conclusions: Results from the present study demonstrated that statin administration in early life to dams fed on a HFD had a significant effect on their female offspring in terms of reduction in cardiovascular risk factors. Additionally, statin administration to female offspring on an HFD during early life was associated with reduction in circulating CRPs and an increased bone marrow EPC numbers and colony-forming characteristics.
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http://dx.doi.org/10.1016/j.nut.2016.10.011DOI Listing
March 2017

Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis.

Proc (Bayl Univ Med Cent) 2015 Jan;28(1):81-2

Division of Cardiothoracic Surgery, Department of Surgery, Texas A&M Health Science Center at Scott & White Memorial Hospital, 2401 S. 31st Street, Temple, TX 76508. Dr. Shake is now at the University of Mississippi Medical Center.

This report describes a patient's self-substitution of nattokinase for the vitamin K antagonist warfarin after aortic valve replacement with a mechanical prosthesis. Nattokinase is an enzyme derived from a popular fermented soybean preparation in Japan (natto), which has fibrinolytic properties and is gaining popularity in nontraditional health journals and nonmedical health websites as an over-the-counter thrombolytic. After nearly a year of use of nattokinase without warfarin, the patient developed thrombus on the mechanical valve and underwent successful repeat valve replacement. We believe this is the first documented case of nattokinase being used as a substitute for warfarin after valve replacement, and we strongly discourage its use for this purpose.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264722PMC
http://dx.doi.org/10.1080/08998280.2015.11929198DOI Listing
January 2015

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

Iatrogenic retained foreign body in the right atrium. Lessons to Learn.

Int J Surg Case Rep 2013 23;4(11):985-7. Epub 2013 Aug 23.

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

Introduction: We report a case of a retained foreign body in the right atrium and the review of the literature discussing several cases where the poor attention and management of medical staff has led to worsening consequences to patient's health.

Presentation Of Case: In our case the mass demonstrated on MRI scan turned out to be an inflammatory process and organized clotted blood built around a broken piece of a plastic cannula protruding out of the right atrium. This caused debilitating pleuritic pain to the patient on presentation.

Discussion: The cause of this iatrogenic retained piece of cannula may well be from the patients prior diagnostic investigations.

Conclusion: Algorithm managed indications for surgical removal of such foreign bodies in symptomatic patients lead to better patient's outcomes and decreases the chances of infection, embolization, or erosions within the heart. Keeping this in view, we managed our patient with success.
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http://dx.doi.org/10.1016/j.ijscr.2013.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825962PMC
November 2013

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

Extracorporeal membrane oxygenation support in a situation of diagnostic dilemma.

Heart Lung Circ 2012 Dec 18;21(12):821-3. Epub 2012 May 18.

Department of Cardiothoracic Surgery, Sydney Children's Hospital, High Street, Randwick, NSW, Australia.

Severe acute respiratory distress syndrome (ARDS) in children carries a high morbidity and mortality. High frequency ventilation and extracorporeal membrane oxygenation (ECMO) are used as rescue modes of support in difficult situations. Malignancy may be considered to be a relative contraindication to ECMO support. We report a case where the decision was made to support the patient with ECMO for fulminant Epstein-Barr (EBV) infection while investigations were being done to exclude an underlying malignancy.
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http://dx.doi.org/10.1016/j.hlc.2012.04.014DOI Listing
December 2012

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

Surgical treatment of ruptured metastatic pleomorphic leiomyosarcoma.

Asian Cardiovasc Thorac Ann 2010 Jun;18(3):288-90

Department of Cardiothoracic Surgery, St. Vincent's Hospital Melbourne, Fitzroy, Victoria 3065, Australia.

A rare case of primary cardiac leiomyosarcoma was diagnosed in a 21-year-old man who presented with a groin mass thought to be a sebaceous cyst. Histopathology revealed a high-grade pleomorphic leiomyosarcoma. Combined positron-emission and computed tomography showed a large metabolically active left atrial mass with multiple metastases. Major debulking resection was undertaken, followed by radiation and chemotherapy. At 13 months postoperatively, limited spread has been detected, and the patient had no limitation in daily life.
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http://dx.doi.org/10.1177/0218492310368572DOI Listing
June 2010

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

Ascending aortic arch replacement with aortic valve resuspension under deep hypothermic arrest combined with endoluminal stenting of the descending thoracic aorta and the entire abdominal aorta.

J Thorac Cardiovasc Surg 2009 Oct 4;138(4):1032-5. Epub 2009 Feb 4.

University of Southampton School of Medicine, Southampton General Hospital, Southampton, United Kingdom.

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http://dx.doi.org/10.1016/j.jtcvs.2008.06.045DOI Listing
October 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

Long-term maternal high-fat feeding from weaning through pregnancy and lactation predisposes offspring to hypertension, raised plasma lipids and fatty liver in mice.

Br J Nutr 2009 Aug 10;102(4):514-9. Epub 2009 Feb 10.

Institute of Developmental Sciences, Developmental Origins of Health and Disease Division, University of Southampton School of Medicine, Southampton General Hospital, Mailpoint 887, Southampton SO16 6YD, UK.

In rodents, adverse prenatal nutrition, such as a maternal diet rich in fat during pregnancy, enhances susceptibility of the offspring to hypertension, type 2 diabetes and other features of the human metabolic syndrome in adulthood. However, previous experimental studies were confined to short-term modifications of the maternal diet during pregnancy and/or lactation periods, a situation uncommon in humans. Moreover in humans, the offspring may also consume a high-fat diet, which may take them beyond the range to which their development has adapted them to respond healthily. We examined in C57 mice the effects on offspring of feeding their mothers a high-fat (HF) or standard chow (C) diet from weaning through pregnancy and lactation, and whether there are additive phenotypic effects of feeding the offspring an HF diet from weaning to adulthood (dam-offspring dietary group HF-HF). This group was compared with offspring from HF-fed dams fed a C diet from weaning to adulthood (HF-C) and offspring from C-fed mothers fed the C or HF diet (C-C and HF-C, respectively). HF-HF, HF-C and C-HF adult female offspring were heavier, fatter, and had raised serum cholesterol and blood pressure compared with C-C female offspring. We observed a similar trend in male offspring except for the HF-C group which was not heavier or fatter than male C-C offspring. Histology showed lipid vacuoles within hepatocytes in the HF-HF, HF-C and C-HF but not the CC offspring. Serum C-reactive protein was elevated in female (C-HF and HF-HF) but not in male offspring. Elevated blood pressure in the HF-C and C-HF groups was attenuated in the HF-HF group in males but not in females. These findings indicate that long-term consumption of an HF diet by the mother predisposes her offspring to developing a metabolic syndrome-like phenotype in adult life, although cardiovascular effects of an HF diet are related to sex specificity in the HF-HF group.
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http://dx.doi.org/10.1017/S000711450820749XDOI Listing
August 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

Statin treatment in hypercholesterolemic pregnant mice reduces cardiovascular risk factors in their offspring.

Hypertension 2008 Apr 19;51(4):939-44. Epub 2008 Feb 19.

Institute of Developmental Sciences, Developmental Origins of Health and Disease Division, University of Southampton School of Medicine, Southampton General Hospital, Southampton, United Kingdom.

Increasing evidence suggests that hypercholesterolemia during pregnancy initiates pathogenic events in the fetus leading to increased risk of cardiovascular disease in the adult offspring. In this study we examined in mice whether pharmacological intervention using statins in late pregnancy could alleviate the detrimental effects of a high-fat, high-cholesterol (45% fat) maternal diet on the health of the dams and their offspring. Pregnant C57 mice on high-fat, high-cholesterol diet were given the 3hydroxy3methylglutaryl-coenzyme A reductase inhibitor pravastatin in the drinking water (5 mg/kg of body weight per day) in the second half of pregnancy and during lactation to lower cholesterol and improve postweaning maternal blood pressure. Weaned offspring were then fed the high-fat, high-cholesterol diet until adulthood (generating dam/offspring dietary groups high-fat, high-cholesterol/high-fat, high-cholesterol and high-fat, high-cholesterol plus pravastatin during the second half of pregnancy and lactation/high-fat, high-cholesterol). These groups were compared with offspring from mothers fed standard chow (control), which were then fed control diet to adulthood (control/control). Compared with high-fat, high-cholesterol, high-fat, high-cholesterol plus pravastatin during second half of pregnancy and lactation dams showed significantly reduced total cholesterol concentrations and reduced systolic blood pressure. The high-fat, high-cholesterol plus pravastatin during second half of pregnancy and lactation/high-fat, high-cholesterol offspring were significantly lighter, less hypertensive, and more active compared with the high-fat, high-cholesterol/high-fat, high-cholesterol group. Total serum and low-density lipoprotein cholesterol concentrations were significantly lower, and high-density lipoprotein cholesterol concentrations were raised in high-fat, high-cholesterol plus pravastatin during the second half of pregnancy and lactation/high-fat, high-cholesterol offspring, compared with the high-fat, high-cholesterol/high-fat, high-cholesterol group. The control/control offspring showed the lowest blood pressure and cholesterol levels. These findings indicate that the cholesterol-lowering effect of statins in pregnant dams consuming a high-fat, high-cholesterol diet leads to reduced cardiovascular risk factors in offspring that are sustained into adulthood.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.100982DOI Listing
April 2008

Coronary heart disease service framework for revascularization in Pakistan.

Asian Cardiovasc Thorac Ann 2008 Jan;16(1):81-5

Department of Cardiac Surgery, Punjab Institute of Cardiology, Jail Road, Lahore, Pakistan.

Many centers across the country have used collaborative techniques to identify problems and come up with innovative solutions. Excellent improvements have been made in every aspect of the patient's journey through the cardiac surgery services, such as decreased length of stay, reduced clinical variation and costs, and improved outcome. We looked at how the cardiac surgical team at our center is helping to improve services for patients undergoing coronary revascularization. Improvements are not just focused on waiting lists or operating rooms but reflect the wider experience of patients and their families.
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http://dx.doi.org/10.1177/021849230801600122DOI Listing
January 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

The complications of repeat median sternotomy in paediatrics: six-months follow-up of consecutive cases.

Interact Cardiovasc Thorac Surg 2005 Aug 9;4(4):356-9. Epub 2005 May 9.

Department of Cardiothoracic Surgery, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK.

Repeat median sternotomy in paediatrics though associated with increased perioperative risks, yet the incidence of injury to the underlying structures during sternal re-entry is poorly quantified. We reviewed 108 patients undergoing repeat sternotomies (group-I) and a control group of 516 patients undergoing first time sternotomy (group-II) over six years with six-months follow-up. Overall mean age was 17 months (range 1 day-16 years). Uncontrollable bleeding was encountered in 4 patients (3.7%), non-fatal cardiac laceration in 10 (9.2%), minor injuries to aorta in 7 (6.4%) and right atrium in 8 (7.4%) in Group-I. Forty-one times (38%) pericardial sac was closed and 55 times (51%) artificial materials (Dacron/Gortex) were used in initial procedures. The incidence of injuries during sternal re-entry was significantly lower in those patients where pericardial sac was closed initially (P<0.001). Hospital mortality was 3.7% in Group-I and 2.7% in Group-II, however, overall survival was 95% (group-I) and 97% (group-II) at 6 months' follow-up. Complete heart block, neurological problems and persistence of shunts being the most common reported morbidities in both groups. In conclusion, low incidence of morbidity and mortality in repeat median sternotomy is possible with careful surgical approach. The closure of pericardial sac in initial procedure provides many potential and practical advantages with regard to lesser trauma to underlying structures.
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http://dx.doi.org/10.1510/icvts.2005.107755DOI Listing
August 2005

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

Revascularization with off-pump coronary artery surgery: what appears new is actually the old rediscovered.

Cardiovasc Revasc Med 2007 Jan-Mar;8(1):52-9

Wessex Cardiothoracic Centre, General Hospital/BUPA, Southampton SO16 6YD, United Kingdom.

The enormous progress in interventional cardiology during the last 10 years has resulted in a major change in the spectrum of patients referred for coronary artery bypass grafting. Several large retrospective analyses, meta-analyses, and the randomized trials that addressed different aspects of ONCAB and OPCAB to date have compared the two surgical strategies. It is suggested that patients may achieve an excellent outcome with either type of procedure, and individuals' outcomes more likely depend on factors other than whether they underwent ONCAB or OPCAB. Nevertheless, there appear to be trends in most studies. These trends include less blood loss and need for transfusion, less myocardial enzyme release up to 24 h, less early neurocognitive dysfunction, and less renal insufficiency after OPCAB and propensity to lower costs, thereafter proving OPCAB to be safe and clinically effective. Here, we review the physiological advantages and clinical outcomes of OPCAB for myocardial revascularization and examine whether either strategy is superior and in which patients.
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http://dx.doi.org/10.1016/j.carrev.2006.09.003DOI Listing
April 2007

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

Predictors of permanent pacemaker implantation during the early postoperative period after valve surgery.

Tex Heart Inst J 2006 ;33(4):455-7

Department of Cardiothoracic Surgery, Punjab Institute of Cardiology, Ghaus-ul-Azam (Jail) Road, Lahore, Pakistan.

The ability to preoperatively identify patients who may require permanent pacemaker implantation is rather poorly understood. The aim of this study is to determine the current incidence of permanent pacing after valve surgery and to determine which factors place the heart valve patient at risk of requiring permanent pacemaker implantation. We audited the records of 2,392 consecutive adult patients who underwent cardiac valve surgical procedures by the same surgical team from 25 April 1998 through 31 March 2003. Of these, 118 patients (group A) required the postoperative implantation of permanent pacemakers during the same hospitalization; they were compared with 1,959 heart valve patients (group B) who did not require pacemaker placement. Multivariate logistic regression analysis showed that reoperations (odds ratio [OR], 8.23; P <0.001), longer cumulative cross-clamp times (OR, 5.9; P <0.001), multiple-valve surgical procedures (OR, 3.46; P <0.05), and absence of preoperative sinus rhythm (OR 2.52; P <0.001) were independent predictors of the need for permanent pacemaker implantation after valve surgery. These results suggest that patients who display these risk factors for arrhythmias that require permanent pacemaker implantation receive closer observation and advance counseling about the likelihood of such implantation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1764945PMC
March 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

Comparative analysis of the Bonanno catheter and tube thorocostomy in effective aspiration of pleural effusion.

Heart Surg Forum 2006 ;9(4):E731-4

Department of Cardiac Surgery, Northern General Hospital, University of Lahore, Sheffield, United Kingdom.

Background And Methods: In our earlier report, we suggested the Bonanno catheter (a 14-gauge suprapubic catheter) as a less traumatic but equally effective alternative for drainage of a variety of fluid collections, including pleural effusion. This study aims to evaluate the efficacy of the Bonanno catheter compared with closed-tube thoracostomy in draining pleural effusion in 38 patients following routine cardiac surgery between 2003 and 2004. Twenty patients were managed using the Bonanno catheter and 18 were treated with standard tube thoracostomy. Data were collected retrospectively and statistical analysis was performed using the SPSS software. P < .05 was considered significant.

Results: There were 20 (53%) male and 18 (47%) female patients with a mean age of 63.5 years (range, 31-83 years). Significant differences were observed with regards to the amount of lignocaine administered locally, intra-procedure pain score, post-procedure pain score after 15 minutes, and amount of analgesia used on a regular basis (P < .05 in each case). Statistically, significant differences were also noted during 2 to 3 weeks follow-up between the 2 groups with regards to pain score. In the the tube thoracostomy group, 22.2% developed infection of the procedure site, requiring antibiotic treatment, whereas no infection was reported in the Bonanno group (P < .001).

Conclusion: This study provided evidence that smallbore drains such as the Bonanno catheter are safe and better tolerated than standard chest drains. This is consistent with the British Thoracic Society guidelines that strongly recommend small-bore drains for the drainage of pleural effusions as they are more comfortable than larger-bore tubes.
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http://dx.doi.org/10.1532/HSF98.20061040DOI Listing
December 2006