Fayez Dawood - Academia.edu (original) (raw)
Papers by Fayez Dawood
Localization of human osteogenic-sarcoma xenografts with radio-labelled monoclonal antibody. Abstr
Canadian Journal of Cardiology, Oct 1, 2016
Circulation Research, Aug 19, 2005
Cytokine and extracellular matrix (ECM) homeostasis are distinct systems that are each dysregulat... more Cytokine and extracellular matrix (ECM) homeostasis are distinct systems that are each dysregulated in heart failure. Here we show that tissue inhibitor of metalloproteinase (TIMP)-3 is a critical regulator of both systems in a mouse model of left ventricular (LV) dilation and dysfunction. Timp-3 Ϫ/Ϫ mice develop precipitous LV dilation and dysfunction reminiscent of dilated cardiomyopathy (DCM), culminating in early onset of heart failure by 6 weeks, compared with wild-type aortic-banding (AB). Timp-3 deficiency resulted in increased TNF␣ converting enzyme (TACE) activity within 6 hours after AB leading to enhanced tumor necrosis factor-␣ (TNF␣) processing. In addition, TNF␣ production increased in timp-3 Ϫ/Ϫ-AB myocardium. A significant elevation in gelatinase and collagenase activities was observed 1 week after AB, with localized ECM degradation in timp-3 Ϫ/Ϫ-AB myocardium. Timp-3 Ϫ/Ϫ / tnf␣ Ϫ/Ϫ mice were generated and subjected to AB for comparative analyses with timp-3 Ϫ/Ϫ-AB mice. This revealed the critical role of TNF␣ in the early phase of LV remodeling, de novo expression of Matrix metalloproteinases (MMP)-8 in the absence of TNF␣, and highlighted the importance of interstitial collagenases (MMP-2, MMP-13, and MT1-MMP) for cardiac ECM degradation. Ablation of TNF␣, or limiting MMP activity with a synthetic MMP inhibitor (PD166793), each partially attenuated LV dilation and cardiac dysfunction in timp-3 Ϫ/Ϫ-AB mice. Notably, combining TNF␣ ablation with MMP inhibition completely rescued heart disease in timp-3 Ϫ/Ϫ-AB mice. This study provides a basis for anti-TNF␣ and MMP inhibitor combination therapy in heart disease.
378 ERp44 Deficiency in Mice, Zebrafish and Mouse-Derived Embryonic Stem Cell Derived Cardiomyocytes Display Aberrant Ca2 Homeostasis, ER Stress Induced Apoptosis and Cardiomyopathy
Canadian Journal of Cardiology, 2012
Circadian gene expression is essential for remodelling in heart disease
Journal of Cardiac Failure, Aug 1, 2004
Viral myocarditis is an important cause of heart failure and dilated cardiomyopathy. T lymphocyte... more Viral myocarditis is an important cause of heart failure and dilated cardiomyopathy. T lymphocytes are implicated in myocardial damage in murine models of coxsackievirus B3 (CVB3) myocarditis. We used knockout mice lacking CD4 (CD4), CD8 (CD8), both coreceptors (CD4 CD8), or the T-cell receptor b chain (TCRb) to address the contribution of T-cell subpopulations to host susceptibility to CVB3 myocarditis. Severity of disease was magnified in CD8 mice but attenuated in CD4 2/2 mice, consistent with a pathogenic role for CD4 1 lymphocytes. Elimination of both CD4 and CD8 molecules from T lymphocytes by genetic knockout better protected mice from myocarditis, demonstrating that both CD4 1 and CD8 T cells contribute to host susceptibility. The same benefit occurred in TCRb mice, with prolonged survival and minimal myocardial disease observed after CVB3 infection. Elevated interferong and decreased tumor necrosis factora expression are associated with attenuated myocardial damage in CD4 C...
Advance Article
HACE1-dependent protein degradation provides cardiac protection in response to haemodynamic stress
European Heart Journal, 2017
412 YIA Session Basic Science / At the interface of imaging and surgery: recent insights into val... more 412 YIA Session Basic Science / At the interface of imaging and surgery: recent insights into valvular regurgitation meability compared with control plasma (n=13) (P<0.05). Importantly, there was a significant correlation between PAEC permeability and plasma TAFIa levels (R2=0.475, P<0.01) (Fig. E). Finally, to evaluate the effect of TAFIa inhibition in hypoxia-induced PH in mice, we performed in silico screening and found several TAFIa inhibitors. Among them, we used carboxypeptidase inhibitor (5 mg/kg/day), with which we found significant amelioration of hypoxia-induced PH and improved prognosis (-76%) in TAFI-Tg mice (all P<0.01, n=16 each) (Fig. F). Conclusions: TAFI is a crucial molecule in the development of CTEPH and PA thrombus formation, and thus could be a novel biomarker and a therapeutic target of CTEPH.
Environmental Science and Pollution Research, 2018
Brazilian population is one of the largest consumers of pesticides in the world, especially the C... more Brazilian population is one of the largest consumers of pesticides in the world, especially the Central Brazil population. Thus, the aim of this study was to evaluate the frequency of genotypes, alleles, haplotypes, and the linkage disequilibrium (DL) of the OGG1 gene in rural workers from Central Brazil, comparing with the populations of the 1000 genome. Three hundred thirty healthy individuals not related and randomly selected were included in this study. We obtained genomic DNA from peripheral blood lymphocytes. The 748-bp OGG1 gene was amplified by PCR and sequenced. Of the 330 individuals, 215 (65%) were males and 115 (35%) were females. There were no differences in the distribution of the rs1052133 and rs293795 with age and sexes. Haplotypes containing only conserved T/C alleles were the most common in our population. The frequency of the mutant alleles of rs1052133 and rs293795, in our population, was 20% and 30%, respectively, and it is noteworthy, worldwide, that mutant alleles are commonly associated to an increased risk for the development of cancer, specially due to direct or indirect contact to pesticides, as occurs in rural workers of Central Brazil population.
Simultaneous TGFbeta-TNF activation and cross-talk cause aberrant remodeling response and myocardial fibrosis in tissue inhibitor of metalloproteinase 3 deficient …
Journal of Biological …, 2009
... RESPONSE AND MYOCARDIAL FIBROSIS IN TISSUE INHIBITOR OF METALLOPROTEINASE 3 DEFICIENT HEART Z... more ... RESPONSE AND MYOCARDIAL FIBROSIS IN TISSUE INHIBITOR OF METALLOPROTEINASE 3 DEFICIENT HEART Zamaneh Kassiri1*, Virginie Defamie1,Mehrdad Hariri1, Gavin Y Oudit1*,Shalini Anthwal1, Fayez ... Sham-operated mice from each group served as controls. ...
Abstract 988: Tissue Inhibitor Of Metalloproteinase-3 Regulates Myocardial Fibrosis By Regulating The TGFβ-TNF Interaction
Circulation, 2007
Fibrosis is the outcome of excess deposition of extracellular matrix components and underlies dia... more Fibrosis is the outcome of excess deposition of extracellular matrix components and underlies diastolic and systolic heart failure. Metalloproteinases (MMPs and ADAMs) and their inhibitors (TIMPs) are critical regulators of ECM turnover and fibrosis. TIMP3 is a potent inhibitor of MMPs and ADAMs, whereby it regulates tissue proteolysis and cytokine bioavailability. TIMP3 levels are reduced in human heart disease, and we found that mice lacking Timp3 (KO) exhibit severe dilated cardiomyopathy (DCM), extensive interstitial fibrosis and early heart failure (HF) following pressure overload compared to wild type (WT) mice. We showed upregulated TNF signaling within 6 hrs of aortic banding (AB) which when blocked, significantly improved DCM and prevented HF. We then investigated the mechanism underlying the extensive fibrosis despite the increased MMP activity in the TIMP3KO mice. Comparative microarray analyses show a significant upregulation of the TGFβ1 signaling pathway within 6 hrs o...
Treatment with Eplerenone, a Selective Aldosterone Blocker, Improved Ventricular Remodeling and Function Post Myocardial Infarction
Circulation Journal Official Journal of the Japanese Circulation Society, Mar 1, 2003
Abstract 961: cFLIP, a Crucial Mediator of Cardiac Remodeling
Circulation, Oct 31, 2006
Abstract 18619: Scaffold Protein CARD11 Modulates Receptor Mediated Apoptosis in Cardiomyocytes Following Myocardial Infarction
Circulation, Nov 26, 2013
Background: The CARD scaffold family members, named for containing the common caspase-recruitment... more Background: The CARD scaffold family members, named for containing the common caspase-recruitment domain, are important modulators of inflammatory and apoptotic signalling. CARD11, a membrane bound scaffold, is essential for the production of cytokines in the immune cellular response but is present in heart and lung tissue, where its effects are unknown, and described to associate with apoptotic players such as BCL10 and caspase-8. Due to the complex nature of cardiac response to myocardial infarction (MI), we hypothesize that CARD11 can act as a modulator and integrator of receptor mediated apoptotic pathways following cardiac tissue injury. Methods & Results: CARD11 expression was increased in neonatal cardiomyocytes by general stress induction by H2O2 (25μM) and death receptor activation by Fas agonist Jo2 (1μg/ml) and TNF-alpha (50ng/ml) in isolated neonatal cardiomyocytes. Annexin V (AV) and propidium iodide (PI) double staining demonstrated decreased levels of apoptotic cells (AV+/PI+) following H2O...
Abstract 3339: Mindin, a Regulator of Innate Immunity and Inhibitor of Angiogenesis, Contributes to Mortality and Adverse Remodeling Post Myocardial Infarction
Circulation, Nov 3, 2009
Abstract 374: Overexpression of Kit Ligand-2 by Direct Cardiac Injection of Recombinant Lentiviruses Improves Cardiac Repair and Rescues Mice Post-Myocardial Infarction
Circulation, Oct 31, 2006
Abstract 890: SCF/C-KIT Compensates for FL/FLT3 Deficiency to Mediate Myocardial Rescue and Repair Post-MI
Circulation, Oct 31, 2006
Combination of TNF Ablation and MMP Inhibition Prevents Heart Failure After Pressure Overload in TIMP-3 Mutant Mice
Abstract—Cytokine and extracellular matrix (ECM) homeostasis,are distinct systems that are each d... more Abstract—Cytokine and extracellular matrix (ECM) homeostasis,are distinct systems that are each dysregulated in heart failure. Here we show,that tissue inhibitor of metalloproteinase (TIMP)-3 is a critical regulator of both systems in a mouse,model of left ventricular (LV) dilation and dysfunction. Timp-3,-AB mice. This study provides a basis for anti-TNF and MMP inhibitor combination,therapy in heart disease. (Circ Res. 2005;97:0-0.) Key
727-1 The Role of Sympathetic Activity in Murine Myocarditis Leading to the Development of Dilated Cardiomyopathy
Journal of the American College of Cardiology, 1995
... A. Shakir Pandey, Michael J. Sole, John S. Floras, Fayez Dawood, Wen-Hu Wen, Lily Wee, Peter ... more ... A. Shakir Pandey, Michael J. Sole, John S. Floras, Fayez Dawood, Wen-Hu Wen, Lily Wee, Peter Liu. ... However it was still depressed when compared to C. EF LMMI LVEDP LVEDVI T b C 64 86 11 86 45 11 FU FU FU FU FU FU PI 48"52" 148*"122" 18*"13 146*"128" 103*"59â ...
Journal of the American College of Cardiology, 2002
Background: A previous study of adenosine infusion in the treatment of acute myocardie~ infarctio... more Background: A previous study of adenosine infusion in the treatment of acute myocardie~ infarction (AMISTAD I) suggested clinical efficacy. The potential role of adenosine as an effective therapeutic agent in the treatment of MI has remained in question. To approach this problem, a randomized, double blind, placebo controlled, multicenter trial (AMISTAD II) was performed. Methods: The study involved 248 clinical sites in 13 countries (2,118 patients randomized) participating in the main trial, with 62 sites in 4 countries (263 patients) participating in a substudy utilizing Tc-99m sestamibi single photon emission computed tomography (SPECT) imaging at 120 to 216 hours post randomization for assessment of final infarct size. Eligible patients with evolving anterolateral myocardial infarction were randomized to treatment with a 3 hour infusion of adenosine of 60 mcg/kg/min, 70 mcg/kg/min, or placebo. Patients received study medication within +15 minutes of initiation of thrombolytic therapy or within 15 minutes prior to pdmary percutaneous mechanical reperfusion. Patients were followed untU hospital discharge and throughout a 6 month period after randomization for assessment of primary and secondary endpoints, clinical events, and safety. The primary efficacy endpoint was time from randomization to the first occurrence of congestive heart failure (CHF) in-hospital (>24 hours post randomization), or the first rehospitalization for CHF during follow-up, or death from any cause. The secondary efficacy endpoints were all cause mortality, cardiovascular mortality, and myocardial infarct size measured by SPECT imaging, Safety endpoints were assessed by following adverse events occurring during the first 48 hours following randomization, and changes in blood pressure and heart rate during the study drug infusion. Clinical events reported include all cause hospitalization, reinfarction, stroke, and revascularization (thrombolysis, peroutaneous mechanical reperfusion, or coronary artery bypass graft surgery (CABG)). Results: The enrollment and follow-up have been completed for all patients. Results will be available in fourth quarter 2001 and will be discussed.
Localization of human osteogenic-sarcoma xenografts with radio-labelled monoclonal antibody. Abstr
Canadian Journal of Cardiology, Oct 1, 2016
Circulation Research, Aug 19, 2005
Cytokine and extracellular matrix (ECM) homeostasis are distinct systems that are each dysregulat... more Cytokine and extracellular matrix (ECM) homeostasis are distinct systems that are each dysregulated in heart failure. Here we show that tissue inhibitor of metalloproteinase (TIMP)-3 is a critical regulator of both systems in a mouse model of left ventricular (LV) dilation and dysfunction. Timp-3 Ϫ/Ϫ mice develop precipitous LV dilation and dysfunction reminiscent of dilated cardiomyopathy (DCM), culminating in early onset of heart failure by 6 weeks, compared with wild-type aortic-banding (AB). Timp-3 deficiency resulted in increased TNF␣ converting enzyme (TACE) activity within 6 hours after AB leading to enhanced tumor necrosis factor-␣ (TNF␣) processing. In addition, TNF␣ production increased in timp-3 Ϫ/Ϫ-AB myocardium. A significant elevation in gelatinase and collagenase activities was observed 1 week after AB, with localized ECM degradation in timp-3 Ϫ/Ϫ-AB myocardium. Timp-3 Ϫ/Ϫ / tnf␣ Ϫ/Ϫ mice were generated and subjected to AB for comparative analyses with timp-3 Ϫ/Ϫ-AB mice. This revealed the critical role of TNF␣ in the early phase of LV remodeling, de novo expression of Matrix metalloproteinases (MMP)-8 in the absence of TNF␣, and highlighted the importance of interstitial collagenases (MMP-2, MMP-13, and MT1-MMP) for cardiac ECM degradation. Ablation of TNF␣, or limiting MMP activity with a synthetic MMP inhibitor (PD166793), each partially attenuated LV dilation and cardiac dysfunction in timp-3 Ϫ/Ϫ-AB mice. Notably, combining TNF␣ ablation with MMP inhibition completely rescued heart disease in timp-3 Ϫ/Ϫ-AB mice. This study provides a basis for anti-TNF␣ and MMP inhibitor combination therapy in heart disease.
378 ERp44 Deficiency in Mice, Zebrafish and Mouse-Derived Embryonic Stem Cell Derived Cardiomyocytes Display Aberrant Ca2 Homeostasis, ER Stress Induced Apoptosis and Cardiomyopathy
Canadian Journal of Cardiology, 2012
Circadian gene expression is essential for remodelling in heart disease
Journal of Cardiac Failure, Aug 1, 2004
Viral myocarditis is an important cause of heart failure and dilated cardiomyopathy. T lymphocyte... more Viral myocarditis is an important cause of heart failure and dilated cardiomyopathy. T lymphocytes are implicated in myocardial damage in murine models of coxsackievirus B3 (CVB3) myocarditis. We used knockout mice lacking CD4 (CD4), CD8 (CD8), both coreceptors (CD4 CD8), or the T-cell receptor b chain (TCRb) to address the contribution of T-cell subpopulations to host susceptibility to CVB3 myocarditis. Severity of disease was magnified in CD8 mice but attenuated in CD4 2/2 mice, consistent with a pathogenic role for CD4 1 lymphocytes. Elimination of both CD4 and CD8 molecules from T lymphocytes by genetic knockout better protected mice from myocarditis, demonstrating that both CD4 1 and CD8 T cells contribute to host susceptibility. The same benefit occurred in TCRb mice, with prolonged survival and minimal myocardial disease observed after CVB3 infection. Elevated interferong and decreased tumor necrosis factora expression are associated with attenuated myocardial damage in CD4 C...
Advance Article
HACE1-dependent protein degradation provides cardiac protection in response to haemodynamic stress
European Heart Journal, 2017
412 YIA Session Basic Science / At the interface of imaging and surgery: recent insights into val... more 412 YIA Session Basic Science / At the interface of imaging and surgery: recent insights into valvular regurgitation meability compared with control plasma (n=13) (P<0.05). Importantly, there was a significant correlation between PAEC permeability and plasma TAFIa levels (R2=0.475, P<0.01) (Fig. E). Finally, to evaluate the effect of TAFIa inhibition in hypoxia-induced PH in mice, we performed in silico screening and found several TAFIa inhibitors. Among them, we used carboxypeptidase inhibitor (5 mg/kg/day), with which we found significant amelioration of hypoxia-induced PH and improved prognosis (-76%) in TAFI-Tg mice (all P<0.01, n=16 each) (Fig. F). Conclusions: TAFI is a crucial molecule in the development of CTEPH and PA thrombus formation, and thus could be a novel biomarker and a therapeutic target of CTEPH.
Environmental Science and Pollution Research, 2018
Brazilian population is one of the largest consumers of pesticides in the world, especially the C... more Brazilian population is one of the largest consumers of pesticides in the world, especially the Central Brazil population. Thus, the aim of this study was to evaluate the frequency of genotypes, alleles, haplotypes, and the linkage disequilibrium (DL) of the OGG1 gene in rural workers from Central Brazil, comparing with the populations of the 1000 genome. Three hundred thirty healthy individuals not related and randomly selected were included in this study. We obtained genomic DNA from peripheral blood lymphocytes. The 748-bp OGG1 gene was amplified by PCR and sequenced. Of the 330 individuals, 215 (65%) were males and 115 (35%) were females. There were no differences in the distribution of the rs1052133 and rs293795 with age and sexes. Haplotypes containing only conserved T/C alleles were the most common in our population. The frequency of the mutant alleles of rs1052133 and rs293795, in our population, was 20% and 30%, respectively, and it is noteworthy, worldwide, that mutant alleles are commonly associated to an increased risk for the development of cancer, specially due to direct or indirect contact to pesticides, as occurs in rural workers of Central Brazil population.
Simultaneous TGFbeta-TNF activation and cross-talk cause aberrant remodeling response and myocardial fibrosis in tissue inhibitor of metalloproteinase 3 deficient …
Journal of Biological …, 2009
... RESPONSE AND MYOCARDIAL FIBROSIS IN TISSUE INHIBITOR OF METALLOPROTEINASE 3 DEFICIENT HEART Z... more ... RESPONSE AND MYOCARDIAL FIBROSIS IN TISSUE INHIBITOR OF METALLOPROTEINASE 3 DEFICIENT HEART Zamaneh Kassiri1*, Virginie Defamie1,Mehrdad Hariri1, Gavin Y Oudit1*,Shalini Anthwal1, Fayez ... Sham-operated mice from each group served as controls. ...
Abstract 988: Tissue Inhibitor Of Metalloproteinase-3 Regulates Myocardial Fibrosis By Regulating The TGFβ-TNF Interaction
Circulation, 2007
Fibrosis is the outcome of excess deposition of extracellular matrix components and underlies dia... more Fibrosis is the outcome of excess deposition of extracellular matrix components and underlies diastolic and systolic heart failure. Metalloproteinases (MMPs and ADAMs) and their inhibitors (TIMPs) are critical regulators of ECM turnover and fibrosis. TIMP3 is a potent inhibitor of MMPs and ADAMs, whereby it regulates tissue proteolysis and cytokine bioavailability. TIMP3 levels are reduced in human heart disease, and we found that mice lacking Timp3 (KO) exhibit severe dilated cardiomyopathy (DCM), extensive interstitial fibrosis and early heart failure (HF) following pressure overload compared to wild type (WT) mice. We showed upregulated TNF signaling within 6 hrs of aortic banding (AB) which when blocked, significantly improved DCM and prevented HF. We then investigated the mechanism underlying the extensive fibrosis despite the increased MMP activity in the TIMP3KO mice. Comparative microarray analyses show a significant upregulation of the TGFβ1 signaling pathway within 6 hrs o...
Treatment with Eplerenone, a Selective Aldosterone Blocker, Improved Ventricular Remodeling and Function Post Myocardial Infarction
Circulation Journal Official Journal of the Japanese Circulation Society, Mar 1, 2003
Abstract 961: cFLIP, a Crucial Mediator of Cardiac Remodeling
Circulation, Oct 31, 2006
Abstract 18619: Scaffold Protein CARD11 Modulates Receptor Mediated Apoptosis in Cardiomyocytes Following Myocardial Infarction
Circulation, Nov 26, 2013
Background: The CARD scaffold family members, named for containing the common caspase-recruitment... more Background: The CARD scaffold family members, named for containing the common caspase-recruitment domain, are important modulators of inflammatory and apoptotic signalling. CARD11, a membrane bound scaffold, is essential for the production of cytokines in the immune cellular response but is present in heart and lung tissue, where its effects are unknown, and described to associate with apoptotic players such as BCL10 and caspase-8. Due to the complex nature of cardiac response to myocardial infarction (MI), we hypothesize that CARD11 can act as a modulator and integrator of receptor mediated apoptotic pathways following cardiac tissue injury. Methods & Results: CARD11 expression was increased in neonatal cardiomyocytes by general stress induction by H2O2 (25μM) and death receptor activation by Fas agonist Jo2 (1μg/ml) and TNF-alpha (50ng/ml) in isolated neonatal cardiomyocytes. Annexin V (AV) and propidium iodide (PI) double staining demonstrated decreased levels of apoptotic cells (AV+/PI+) following H2O...
Abstract 3339: Mindin, a Regulator of Innate Immunity and Inhibitor of Angiogenesis, Contributes to Mortality and Adverse Remodeling Post Myocardial Infarction
Circulation, Nov 3, 2009
Abstract 374: Overexpression of Kit Ligand-2 by Direct Cardiac Injection of Recombinant Lentiviruses Improves Cardiac Repair and Rescues Mice Post-Myocardial Infarction
Circulation, Oct 31, 2006
Abstract 890: SCF/C-KIT Compensates for FL/FLT3 Deficiency to Mediate Myocardial Rescue and Repair Post-MI
Circulation, Oct 31, 2006
Combination of TNF Ablation and MMP Inhibition Prevents Heart Failure After Pressure Overload in TIMP-3 Mutant Mice
Abstract—Cytokine and extracellular matrix (ECM) homeostasis,are distinct systems that are each d... more Abstract—Cytokine and extracellular matrix (ECM) homeostasis,are distinct systems that are each dysregulated in heart failure. Here we show,that tissue inhibitor of metalloproteinase (TIMP)-3 is a critical regulator of both systems in a mouse,model of left ventricular (LV) dilation and dysfunction. Timp-3,-AB mice. This study provides a basis for anti-TNF and MMP inhibitor combination,therapy in heart disease. (Circ Res. 2005;97:0-0.) Key
727-1 The Role of Sympathetic Activity in Murine Myocarditis Leading to the Development of Dilated Cardiomyopathy
Journal of the American College of Cardiology, 1995
... A. Shakir Pandey, Michael J. Sole, John S. Floras, Fayez Dawood, Wen-Hu Wen, Lily Wee, Peter ... more ... A. Shakir Pandey, Michael J. Sole, John S. Floras, Fayez Dawood, Wen-Hu Wen, Lily Wee, Peter Liu. ... However it was still depressed when compared to C. EF LMMI LVEDP LVEDVI T b C 64 86 11 86 45 11 FU FU FU FU FU FU PI 48"52" 148*"122" 18*"13 146*"128" 103*"59â ...
Journal of the American College of Cardiology, 2002
Background: A previous study of adenosine infusion in the treatment of acute myocardie~ infarctio... more Background: A previous study of adenosine infusion in the treatment of acute myocardie~ infarction (AMISTAD I) suggested clinical efficacy. The potential role of adenosine as an effective therapeutic agent in the treatment of MI has remained in question. To approach this problem, a randomized, double blind, placebo controlled, multicenter trial (AMISTAD II) was performed. Methods: The study involved 248 clinical sites in 13 countries (2,118 patients randomized) participating in the main trial, with 62 sites in 4 countries (263 patients) participating in a substudy utilizing Tc-99m sestamibi single photon emission computed tomography (SPECT) imaging at 120 to 216 hours post randomization for assessment of final infarct size. Eligible patients with evolving anterolateral myocardial infarction were randomized to treatment with a 3 hour infusion of adenosine of 60 mcg/kg/min, 70 mcg/kg/min, or placebo. Patients received study medication within +15 minutes of initiation of thrombolytic therapy or within 15 minutes prior to pdmary percutaneous mechanical reperfusion. Patients were followed untU hospital discharge and throughout a 6 month period after randomization for assessment of primary and secondary endpoints, clinical events, and safety. The primary efficacy endpoint was time from randomization to the first occurrence of congestive heart failure (CHF) in-hospital (>24 hours post randomization), or the first rehospitalization for CHF during follow-up, or death from any cause. The secondary efficacy endpoints were all cause mortality, cardiovascular mortality, and myocardial infarct size measured by SPECT imaging, Safety endpoints were assessed by following adverse events occurring during the first 48 hours following randomization, and changes in blood pressure and heart rate during the study drug infusion. Clinical events reported include all cause hospitalization, reinfarction, stroke, and revascularization (thrombolysis, peroutaneous mechanical reperfusion, or coronary artery bypass graft surgery (CABG)). Results: The enrollment and follow-up have been completed for all patients. Results will be available in fourth quarter 2001 and will be discussed.