Infarct-related artery occlusion, tissue markers of ischaemia, and increased apoptosis in the peri-infarct viable myocardium.

AIMS Unfavourable cardiac remodelling often complicates acute myocardial infarction (AMI) as a result of increased cardiomyocyte apoptosis. It is currently unclear whether ongoing or recurrent ischaemia is an independent determinant for increased apoptosis in peri-infarct viable myocardium. METHODS AND RESULTS In order to assess the link between infarct-related artery (IRA) occlusion, ischaemia, and apoptosis, 30 subjects dying 7-120 days after AMI (16 with IRA occlusion and 14 with patent IRA) and five control subjects were selected at autopsy. Cardiomyocytes were defined as apoptotic if co-expressing TUNEL and activated caspase-3. Expression of both hypoxia-inducible factor-1 and cyclo-oxygenase-2 was assessed in the peri-infarct myocardium and considered as tissue markers of ischaemia. Evidence of ischaemia was significantly more frequent in cases with IRA occlusion (53%) than in cases with patent IRA (15%) or control hearts (0%, P=0.026). The finding of IRA occlusion and markers of ischaemia identified cases with higher apoptotic rates (ARs) in the peri-infarct viable myocardium [12.2% (8.2-14.0), P<0.001 vs. others], whereas IRA occlusion without ischaemia was associated with lower AR, not significantly different from patent IRA [3.0% (1.0-7.9) vs. 2.2% (1.0-5.8), respectively, P=0.42] CONCLUSION Ischaemia in the peri-infarct viable myocardium is present in over 50% of subjects dying late after AMI with IRA occlusion, and it is associated with increased apoptosis. Relief of ischaemia after AMI may prove of benefit in preventing apoptosis and its consequences.

[1]  J. Ornato,et al.  ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult—Summary Article , 2005 .

[2]  A. M. Leone,et al.  Widespread Myocardial Inflammation and Infarct-Related Artery Patency , 2004, Circulation.

[3]  G. Biondi-Zoccai,et al.  Cyclo-oxygenase-2 (COX-2) expression at the site of recent myocardial infarction: friend or foe? , 2004, Heart.

[4]  I. Anand,et al.  Long-term caspase inhibition ameliorates apoptosis, reduces myocardial troponin-I cleavage, protects left ventricular function, and attenuates remodeling in rats with myocardial infarction. , 2004, Journal of the American College of Cardiology.

[5]  K. Suk,et al.  BH3-only Protein Noxa Is a Mediator of Hypoxic Cell Death Induced by Hypoxia-inducible Factor 1α , 2004, The Journal of experimental medicine.

[6]  R. Armstrong,et al.  Pharmacologic inhibition of intracellular caspases after myocardial infarction attenuates left ventricular remodeling: a potentially novel pathway. , 2003, The Journal of thoracic and cardiovascular surgery.

[7]  C. Trani,et al.  The ‘Open-Artery Hypothesis’: New Clinical and Pathophysiologic Insights , 2003, Cardiology.

[8]  R. Bigi,et al.  Influence of contractile reserve and inducible ischaemia on left ventricular remodelling after acute myocardial infarction , 2003, Heart.

[9]  Jeroen J. Bax,et al.  Early Versus Delayed Revascularization in Patients With Ischemic Cardiomyopathy and Substantial Viability: Impact on Outcome , 2003, Circulation.

[10]  A. M. Leone,et al.  Right ventricular dilatation after left ventricular acute myocardial infarction is predictive of extremely high peri-infarctual apoptosis at postmortem examination in humans , 2003, Journal of clinical pathology.

[11]  A. M. Leone,et al.  406 Right ventricular dilatation following left ventricular acute myocardial infarction is predictive of extremely high peri-infarctual apoptosis at post-mortem examination in humans , 2003 .

[12]  R. Kitsis,et al.  A mechanistic role for cardiac myocyte apoptosis in heart failure. , 2003, The Journal of clinical investigation.

[13]  G. Biondi-Zoccai,et al.  Increased myocardial apoptosis in patients with unfavorable left ventricular remodeling and early symptomatic post-infarction heart failure. , 2003, Journal of the American College of Cardiology.

[14]  H. Hellstrom.  Platelet glycoprotein IIb/IIIa inhibitors. , 2003, Circulation.

[15]  O. Rimoldi,et al.  Myocardial blood flow in patients with hibernating myocardium. , 2003, Cardiovascular research.

[16]  G. Biondi-Zoccai,et al.  Myocardiocyte loss due to apoptosis. , 2002, European heart journal.

[17]  G. Biondi-Zoccai,et al.  Pathophysiologic role of myocardial apoptosis in post‐infarction left ventricular remodeling , 2002, Journal of cellular physiology.

[18]  J. Bartunek,et al.  Deoxyribonucleic acid damage/repair proteins are elevated in the failing human myocardium due to idiopathic dilated cardiomyopathy. , 2002, Journal of the American College of Cardiology.

[19]  G. Biondi-Zoccai,et al.  Persistent Infarct–Related Artery Occlusion Is Associated With an Increased Myocardial Apoptosis at Postmortem Examination in Humans Late After an Acute Myocardial Infarction , 2002, Circulation.

[20]  R. Bolli,et al.  Inducible Nitric Oxide Synthase Modulates Cyclooxygenase-2 Activity in the Heart of Conscious Rabbits During the Late Phase of Ischemic Preconditioning , 2002, Circulation research.

[21]  J. Holtz,et al.  Apoptotic pathway activation from mitochondria and death receptors without caspase-3 cleavage in failing human myocardium: fragile balance of myocyte survival? , 2002, Journal of the American College of Cardiology.

[22]  A. Baldi,et al.  Apoptosis and post-infarction left ventricular remodeling. , 2002, Journal of molecular and cellular cardiology.

[23]  E. Antman,et al.  ACC/AHA PRACTICE GUIDELINES ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary , 2002 .

[24]  D. Grana,et al.  Characterization of myocardial hypertrophy by DNA content, PCNA expression and apoptotic index. , 2002, International journal of cardiology.

[25]  Jeroen J. Bax,et al.  Clinical and angiographic correlates of dobutamine-induced wall motion patterns after myocardial infarction. , 2001, The American journal of cardiology.

[26]  J. Canty,et al.  Myocyte apoptosis and reduced SR gene expression precede the transition from chronically stunned to hibernating myocardium. , 2001, Journal of molecular and cellular cardiology.

[27]  B. Goldman,et al.  Evidence that human cardiac myocytes divide after myocardial infarction. , 2001, The New England journal of medicine.

[28]  S. Homma,et al.  Neovascularization of ischemic myocardium by human bone-marrow–derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function , 2001, Nature Medicine.

[29]  R. Bolli,et al.  Cyclooxygenase-2 mediates the cardioprotective effects of the late phase of ischemic preconditioning in conscious rabbits. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[30]  G. Lamas,et al.  Beneficial effects of an open artery on left ventricular remodeling after myocardial infarction. , 2000, Progress in cardiovascular diseases.

[31]  G. Semenza.  HIF-1: mediator of physiological and pathophysiological responses to hypoxia. , 2000, Journal of applied physiology.

[32]  G. Stone,et al.  Coronary angioplasty with or without stent implantation for acute myocardial infarction. Stent Primary Angioplasty in Myocardial Infarction Study Group. , 2000, The New England journal of medicine.

[33]  Bruce R. Brodie,et al.  Coronary Angioplasty with or without Stent Implantation for Acute Myocardial Infarction , 1999 .

[34]  R. Califf,et al.  Support for the open-artery hypothesis in survivors of acute myocardial infarction: analysis of 11,228 patients treated with thrombolytic therapy. , 1999, The American journal of cardiology.

[35]  I. Rodger,et al.  Induction of cyclooxygenase-2 and activation of nuclear factor-kappaB in myocardium of patients with congestive heart failure. , 1998, Circulation.

[36]  G. Schulz,et al.  Prolonged myocardial hibernation exacerbates cardiomyocyte degeneration and impairs recovery of function after revascularization. , 1998, Journal of the American College of Cardiology.

[37]  R. Kitsis,et al.  Myocyte apoptosis during acute myocardial infarction in the mouse localizes to hypoxic regions but occurs independently of p53. , 1997, The Journal of clinical investigation.

[38]  E. Lakatta,et al.  p53 and the hypoxia-induced apoptosis of cultured neonatal rat cardiac myocytes. , 1997, The Journal of clinical investigation.

[39]  P. Anversa,et al.  Acute myocardial infarction in humans is associated with activation of programmed myocyte cell death in the surviving portion of the heart. , 1996, Journal of molecular and cellular cardiology.

[40]  A. Giordano,et al.  Residual exertional ischemia and unfavorable left ventricular remodeling in patients with systolic dysfunction after anterior myocardial infarction. , 1995, Journal of the American College of Cardiology.

[41]  P. Kligfield.  Primary angioplasty in myocardial infarction. , 1995, British heart journal.

[42]  G. Tognoni,et al.  The GISSI Study: further analysis. Italian Group for the Study of Streptokinase in Myocardial Infarction (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico, GISSI). , 1987, Circulation.

[43]  Y. Ohtsuki,et al.  ISOLATION OF HTLV-I FROM CEREBROSPINAL FLUID OF A PATIENT WITH MYELOPATHY , 1986, The Lancet.

[44]  Gruppo Italiano per lo Studio della Soprawivenza nell'Inf Miocardico.,et al.  EFFECTIVENESS OF INTRAVENOUS THROMBOLYTIC TREATMENT IN ACUTE MYOCARDIAL INFARCTION , 1986, The Lancet.