Cardiac gene expression and systemic cytokine profile are complementary in a murine model of post-ischemic heart failure

After myocardial infarction (MI), activation of the immune system and inflammatory mechanisms, among others, can lead to ventricular remodeling and heart failure (HF). The interaction between these systemic alterations and corresponding changes in the heart has not been extensively examined in the setting of chronic ischemia. The main purpose of this study was to investigate alterations in cardiac gene and systemic cytokine profile in mice with post-ischemic HF. Plasma was tested for IgM and IgG anti-heart reactive repertoire and inflammatory cytokines. Heart samples were assayed for gene expression by analyzing hybridization to AECOM 32k mouse microarrays. Ischemic HF significantly increased the levels of total serum IgM (by 5.2-fold) and total IgG (by 3.6-fold) associated with a relatively high content of anti-heart specificity. A comparable increase was observed in the levels of circulating pro-inflammatory cytokines such as IL-1â (3.8X) and TNF-á (6.0X). IFN-ã was also increased by 3.1-fold in the MI group. However, IL-4 and IL-10 were not significantly different between the MI and sham-operated groups. Chemokines such as MCP-1 and IL-8 were 1.4- and 13-fold increased, respectively, in the plasma of infarcted mice. We identified 2079 well annotated unigenes that were significantly regulated by post-ischemic HF. Complement activation and immune response were among the most up-regulated processes. Interestingly, 21 of the 101 quantified unigenes involved in the inflammatory response were significantly up-regulated and none were down-regulated. These data indicate that post-ischemic heart remodeling is accompanied by immune-mediated mechanisms that act both systemically and locally.

Marcadores pro y antiinflamatorios en la enfermedad arterial coronaria y el síndrome isquémico coronario agudo / Pro-inflammatory and anti-inflammatory markers in coronary artery disease and acute ischemic coronary syndrome

Inflammation plays an important role in the development of atherosclerotic lesions, affecting several stages of the atheroma's development going from the initial leukocyte recruitment to the eventual rupture of the unstable atherosclerotic plaque. The inflammatory reactions within coronary atherosclerotic plaques influence the clinical outcome of acute coronary syndromes and coronary artery disease. Recent studies suggest that inflammation markers may reflect different aspects of the atherothrombotic process in relation to the stages of acute coronary syndrome. These markers play an important role in the risk of developing coronary artery disease, and may correlate with its severity. Some cytokines, acute phase proteins, acute phase reactants proteins, and adhesion molecules released from the inflammatory cells may reflect the inflammatory process in atherosclerotic plaques. However, it remains to be determined whether these pro- and anti-inflammation markers may confer risk or protection for cardiovascular disease, or simply reflect the underlying disease process. The analysis of the markers may be useful for the development of new strategies for coronary disease prevention and treatment. Therefore, we need a well-designed evaluation of these markers before their use in the clinical practice.

Medico-legal and serological study of the role of C-reactive protein and anticholesterol auto-antibodies in the diagnosis of ischemic heart disease

No previous Iraqi study was done on the role of C - reactive protein [CRP] and anticholesterol autoantibodies [ACHA] in the diagnosis of ischemic heart disease [IHD] especially from the medico-legal point of view. To determine the role of CRP and ACHA in the diagnosis of IHD particularly myocardial infarction [MI] with special attention to the medico- legal aspect. Forty four lived patients from Al- Kadhimiya hospital and 20 cadavers in medico-legal institute of Baghdad were included in this study, in addition to 18 apparently healthy persons and 3 cadavers as controls. A number of risk factors were studied such as age, sex, smoking, and others. CRP and ACHA detected and estimated in the sera of the lived and dead patients. Histopathological examination was done on cardiac tissue specimens taken from the cadavers. Patients with anterior MI have higher CRP values than in patients with other types of MI. ACHA of IgM type was higher in controls than in lived and patients, while that of IgG was higher in lived patients as compared with dead patients and controls. Elderly males are affected more by MI. CRP is elevated in acute coronary syndrome. ACHA are present in healthy individuals, but high in CAD

Anticardiolipin antibodies in patients with ischemic events

To determine the presence of anticardiolipin [aCL] antibodies in patients with ischemic events, we designed a case-control study. We studied 33 patients with unstable angina, 33 male patients with myocardial infarction and 34 control subjects with no evidence of ischemic heart disease. Plasma samples were assessed for IgG anticardiolipin antibodies by enzyme-linked immunosorbent assay [ELISA]. The levels of aCL were [mean +/- SD of optical density multiplied by 1000]: 624 +/- 319, 486 +/- 318, and 239 +/- 202 for patients with unstable angina, myocardial infarction and controls, respectively [F=15.74 and p=0.0000]. High aCL levels were found more often in patients with acute ischemic events

La meta de la reperfusión en los síndromes isquémicos coronarios agudos con elevación del segmento ST. El gran paradigma: "Lo que hay más allá del flujo TIMI 3 epicárdico: El TIMI 4 miocárdico" / The target of reperfusion in ST - elevation acute coronary syndromes: The major paradigm: "beyond TIMI 3 flow: The TIMI 4 or myocardial tissue - level perfusion"

En el tratamiento de los Síndromes Coronarios Agudos con elevación del segmento ST se ha avanzado en la última década de manera favorable en relación a la terapia fibrinolítica (TF), en los procedimientos coronarios intervencionistas (PCI) y con la utilización concomitante de los inhibidores de los receptores plaquetarios IIb/IIIa (IRP). El interés actual en relación al objetivo ha alcanzar en la reperfusión del infarto agudo del miocardio (IAM) ha girado de la arteria responsable del infarto (ARI) a obtener perfusión microvascular-tisular óptima. Se ha puntualizado que el establecer la mejor permeabilidad de la ARI (TIMI 3E) no es sinónimo de que también se ha obtenido en el tejido miocárdico (TIMI 4 M). Sabemos que puede existir disfunción microvascular producto de la microembolización plaquetaria o la ocasionada por la propia reperfusión, misma que esta ligada a los mediadores inflamatorios lo que da origen al "fenómeno de no- flujo", anomalía todas que ocurren en un número no despreciable de enfermos a pesar de haberse obtenido TIMI 3E. Hoy día hay técnicas y tratamientos que van encaminados a identificar y resolver estas anomalías con el fin de mejorar la perfusión microvascular en el IAM. A pesar de existir progresos en las estrategias de reperfusión en el IAM particularmente con el empleo adjunto de IRP y con la TF y que se obtienen en la ARI flujos TIMI 3E en el 50-75% de las veces y con los PCI en el 90-95%, no se han alcanzado reducciones significativas en la mortalidad, mas sí en la frecuencia de la retrombosis de la ARI, de los stents, de reinfartos y en algunos sujetos se observa mejoría de la función ventricular. Por lo tanto, hoy día estamos conscientes de lo que representa obtener perfusión óptima microvascular en el escenario del IAM. El gran paradigma es saber por lo tanto que hay más allá del TIMI 3E y si se alcanzo o no flujo TIMI 4 o miocárdico.

Treatment for ST- elevation acute coronary syndromes (acute myocardial infarction: AMI) has advanced rapidly in the last decade with major improvements in early fibrinolytic therapy (FT), primary percutaneous interventions (PCI) with the aid of platelet glycoprotein IIb/IIIa inhibitors. Recent interest has shifted from infarct related artery (IRA) patency to microvascular perfusion in the evaluation of patients with AMI. It is well known that establishing epicardial patency after AMI (TIMI 3 E) is not synonymus with tissue-level perfusion (TIMI 4M). Microvascular dysfunction due to the roles of platelet and inflammatory mediators in the no-reflow phenomenon occurs in a substancial proportion of patients despite thrombolytic therapy or PCI procedures. Techniques are now available that measure real tissue-level perfusion and also therapy is directed to optimize myocardial perfusion in patients with AMI. Despite advances, contemporary FT strategies with the combination of platelet glycoprotein IIb/IIIa inhibitors restore normal coronary flow (TIMI 3) in the IRA in only 50-75% and PCI achieves TIMI 3 flow rates in 90-95%, but only with modest reductions in mortality, but with significant reductions in rethrombosis of the IRA or stents, reinfarctions and in some patients with benefits in ventricular dysfunction. Therefore moving beyond the importance of TIMI 3 flow, the TIMI 4 flow, or improving tissue-level perfusion in the setting of AMI seems to be the paradigm for the treatment of ST-elevation acute coronary syndromes.