Circadian Dependence of the Acute Immune Response to Myocardial Infarction.

Circadian rhythms influence the recruitment of immune cells and the onset of inflammation, which is pivotal in the response to ischemic cardiac injury after a myocardial infarction (MI). The hyperacute immune response that occurs within the first few hours after a MI has not yet been elucidated. Therefore, we characterized the immune response and myocardial damage 3 hours after a MI occurs over a full twenty-four-hour period to investigate the role of the circadian rhythms in this response. MI was induced at Zeitgeber Time (ZT) 2, 8, 14, and 20 by permanent ligation of the left anterior descending coronary artery. Three hours after surgery, animals were terminated and blood and hearts collected to assess the immunological status and cardiac damage. Blood leukocyte numbers varied throughout the day, peaking during the rest-phase (ZT2 and 8). Extravasation of leukocytes was more pronounced during the active-phase (ZT14 and 20) and was associated with greater chemokine release to the blood and expression of adhesion molecules in the heart. Damage to the heart, measured by Troponin-I plasma levels, was elevated during this time frame. Clock gene oscillations remained intact in both MI-induced and sham-operated mice hearts, which could explain the circadian influence of the hyperacute inflammatory response after a MI. These findings are in line with the clinical observation that patients who experience a MI early in the morning (i.e., early active phase) have worse clinical outcomes. This study provides further insight on the immune response occurring shortly after an MI, which may contribute to the development of novel and optimization of current therapeutic approaches.

Isolation of Pig Bone Marrow-Derived Mesenchymal Stem Cells.

Large animal models are an important preclinical tool for the evaluation of new interventions and their translation into clinical practice. The pig is a widely used animal model in multiple clinical fields, such as cardiology and orthopedics, and has been at the forefront of testing new therapeutics, including cell-based therapies. In the clinic, mesenchymal stem cells (MSCs) are used autologously, therefore isolated, and administrated into the same patient. For successful clinical translation of autologous approaches, the porcine model needs to test MSC in a similar manner. Since a limited number of MSCs can be isolated directly from the bone marrow, culturing techniques are needed to expand the population in vitro prior to therapeutic application. Here, we describe a protocol specifically tailored for the isolation and propagation of porcine-derived bone marrow MSCs.

Microvesicles and exosomes for intracardiac communication.

The heart is an organ with a complex mixture of well-organized interactions of different cell types that facilitate proper myocardial contractility, sufficient perfusion, balanced myocardial extracellular stiffness, and controlled functioning of the immune system. Several cell types, including cardiomyocytes, endothelial cells, smooth muscle cells, fibroblasts, immune cells, and cardiac-derived stem cells, need a well-controlled communication system to use the complex orchestra of signalling molecules. The intercellular communication includes direct cell-cell contact, cell-matrix interaction, long-range signals, and electrical and extracellular chemical molecules. In addition to the extracellular molecules that cells can use to influence their environment, more and more attention is focused on the release of extracellular membrane vesicles by cells. These vesicles were always thought to be cell debris derivatives, but it appeared that these vesicles are used for horizontal transfer of information between cells, containing proteins, peptides, several classes of RNA molecules, and sometimes DNA. The main populations of released vesicles are classified on their (intra)cellular origin and include apoptotic bodies, microvesicles, and exosomes. Here, we provide an overview on the role of vesicles in cardiac communication and their use as potential therapeutics and biomarkers.

Chest pain in the emergency room: a multicenter validation of the HEART Score.

OBJECTIVE: Decision-making in chest pain patients is hampered by poor diagnostic power of patient's history, electrocardiogram, age, risk factors, and troponin. Each of these findings may be qualified with 0, 1, or 2 points. Together they compose the HEART score. We tested the hypothesis that the HEART score predicts major adverse cardiac events. DESIGN: Retrospective multicenter analysis in patients presenting at the cardiology emergency room. SETTING: Patient inclusion between January 1 and March 31, 2006. PATIENTS: A total of 2161 patients were admitted, of which 910 patients (42%) presented with chest pain. Analysis was performed in 880 cases (96.7%). MAIN OUTCOME MEASURES: The primary endpoint was a composite of acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery and death, within 6 weeks after presentation, together called major adverse cardiac events. RESULTS: A total of 158 patients (17.95%) reached the primary endpoint. Ninety-two patients had an acute myocardial infarction (10.45%), 82 a percutaneous coronary intervention (9.32%), 36 a coronary artery bypass graft (4.09%), and 13 died (1.48%). Of 303 patients with HEART score 0 to 3, three (0.99%) had an endpoint. In 413 patients with HEART score 4 to 6, 48 cases (11.6%) reached an endpoint. In case of a HEART score of 7 to 10, an endpoint was reached in 107/164 cases (65.2%). CONCLUSIONS: The HEART score helps in making accurate diagnostic and therapeutic decisions without the use of radiation or invasive procedures. The HEART score is an easy, quick, and reliable predictor of outcome in chest pain patients and can be used for triage.