Coronary circulation
Successive brief ischemia-reperfusion periods prior to (pre-conditioning) or following long-lasting myocardial ischemia constitute a myocardial protective mechanism against post-ischemic infarction, mechanical dysfunction and arrhythmias. This line of research is an extension of the work on cardiac mechanics and myocardial perfusion in conscious, chronically instrumented animals, initiated in 1983 with the use of the sonomicrometric and radioactive microspheres techniques, both learnt at and brought from the University of California, San Diego, by Dr. Alberto Crottogini and Dr. Elena Lascano, respectively.
Heart failure and cardiopulmonary by-pass
One of the first basic research areas was Cardiac Mechanics and its dysfunction, i.e., heart failure. At present, a research team collaborates in multicenter studies related to this disease.
Regarding lung transplantation, lung transplant rejection has been studied in three different situations: donation after sudden death, donation after brain death and donation after cardiac death due to ventricular fibrillation. In these experiments, only one lung was grafted as the animals had to remain alive to perform post-transplantation studies on the different effects of reperfusion and types of rejection.
Electrophysiology
Cardiac electrophysiology consists in the study of the electrical signals generated by the heart: their origin, the transmembrane ionic channels and the better understanding of the causes, pathophysiology and treatment of arrhythmias. In our setting, myocardial anisotropy and the influence of gender in the proclivity to arrhythmia generation has been studied since 1983.
Cardiac modeling
This research area, which started in 1983, consists in the development of mathematical models that explain and predict the mechanical behavior of the heart, especially associated with calcium metabolism. This project has acquired international relevance and Dr. Negroni, who started this project, has been invited to centers of Japan and the USA working on the same subject. From an epistemological point of view, it is one of the most powerful research approaches, as instead of analyzing experimental results reached by induction, novel hypotheses formulated in the model aim to predict experimental findings that will in turn validate the model.
Circulatory assistance
This line of research consists in the study of circulatory assist devices ranging from intra-aortic balloon pump counterpulsation to left ventricular bypass.
Lipids, atherosclerosis and vascular biology
This research area studies the etiopathogenesis of atherosclerosis combining basic and clinical research. It analyzes the mechanisms that originate and localize the atheromatous lesion at the vascular and valvular level, and the biomarkers that determine the susceptibility to the presentation and progression of the disease among individuals with similar plasma lipid profiles and other associated vascular risk factors. This line of research, which started in 1994, has produced numerous publications, and doctoral and post-doctoral projects, establishing a multidisciplinary research team over the years. This project will greatly benefit from the new Molecular Biology laboratory.
Cardiovascular dynamics
This line of research studies the biophysical properties of the great arteries in cooperation with France, Spain and Australia. Both experimental and theoretical studies have identified the biophysical role of each arterial layer, explaining some of the events occurring in atherosclerosis. At present, a numerical model is attempting to establish which regions are most likely to develop atheromas.
Atheromatous plaque
This area studies the detection of angiogenesis in atherosclerotic plaques of apparently healthy hearts to identify whether the inflammatory process precedes the formation of neovessels within the plaque, with the aim of understanding the sequence with which the plaque progresses from an “immature” to a “vulnerable” state capable of generating cardiovascular accidents, such as infarction. This line of research has several projects: vascular geometry and plaque development, together with a team building a software from coronary multislice computed tomography scans; morphometric and topographic analysis of vulnerable atherosclerotic plaques not responsible of myocardial infarction performed in twenty individuals followed-up by non-invasive imaging studies; and study of atheromatous plaque in the heart of homograft valve donors after sudden death, including microscopic morphology and immunohistochemistry.
Tissue regeneration
We study myocardial (cardiomyogenesis) and microvascular (angio-arteriognesis) regeneration through gene therapy (using regular and minicircle plasmids as vectors) or adult stem cells genetically modified to overexpress defined molecules. The gene therapy project is the one with the highest progress, having advanced into a phase 1 clinical trial, while the techniques with adults stem cells are being tested in large mammalian models (sheep, pig) of ischemic heart disease and heart failure. The cells used are bone marrow mesenchymal stromal cells, adipose stromal cells and diaphragmatic myoblasts. This line of research has given rise to numerous publications, doctoral and post-doctoral fellowships, multicenter grants and a consortium (Consortium for Stem Cell Research, www.cicema.org.ar) including Leloir Institute, Garrahan Hospital, Austral University, FLENI, and the Buenos Aires University School of Exact and Natural Sciences, Our aim is to develop safe and efficacious heart regeneration products and strategies translatable to the clinical setting and the national biotechnological industry.
Hemostasis and thrombosis
Antiphospholipid antibodies (PLa) are a heterogenous group of antibodies present in patients with autoimmune diseases in association with certain infectious diseases or the treatment with specific drugs, and also in apparently healthy subjects. The term antiphospholipid syndrome defines patients presenting PLa associated with vein and/or arterial thrombosis and/or obstetric complications. Antiphospholipid antibodies of autoimmune patients, different from PLa related to infections, predispose to thrombotic events, and various pathophysiological mechanisms and immunological characteristics try to explain this clinical difference. It is important to adequately characterize the type of PLa patients have in order to know the future risk of developing thromboembolic clinical events. Research in antiphospholipid antibodies started in 1990.
Neuronal migration
This line of research studies the effect of prenatal hypoxia on the development of the brain cortex, analyzing the changes in the processes of neural progenitor cell proliferation and postmitotic neuronal migration in an optictectum model of the chick embryo. The effect of prenatal hypoxia on vasculature growth during cortical development includes in a first stage the characterization of the spatial pattern of vascular distribution in normal conditions and in a second stage the analysis of hypoxia on its spatial organization.
Neurosciences
In the field of neurosciences, the Neuropsychology Laboratory of Neurological and Psychiatric Disorders has organized research teams for each of the following topics: role of the frontal lobe, frontotemporal dementia, focal cerebral injuries (cerebrovascular accidents and brain tumors), dementias, Parkinson disease and other neurological disorders, attention deficit/adult hyperactivity disorder (ADHD), schizophrenia, depression and bipolar disorder, development and validation of evaluation and rehabilitation tools, neural basis of consciousness and of patients with altered conscious states, memory, anxiety, compulsive-obsessive disorder and La Tourette syndrome, developmental disorders and cranial trauma. These researches are performed together with the Cognitive Neuroscience Institute (Instituto de Neurociencias Cognitivas, INECO), which collaborates with leading international groups in the field of cognitive neurosciences as the University of Cambridge (United Kingdom), POWMRI (Australia), the University of Iowa, and the University of Southern California (USA). Additionally, the Experimental Psychology and Neuroscience Laboratory, which has established and strengthened various collaborations with international centers of excellence as the University of Heidelberg (Germany), the University of Chicago (USA), the University of Wisconsin (USA), and the MRC Cognition and Brain Science Unit of Cambridge (United Kingdom), among others, performs studies on context clues, language coordination and non-linguistic coordination, decision making and integration of semantic valence, and facial expression and social clue processing. Among its activities, the neuroscience research group has implemented Translational Medicine.
Stroke
The Stroke center specially studies new aspects of the relationship between traditional and non-traditional risk factors in the development of this disease with specific interest in the neurointensive care of these patients.
Nuclear and subnuclear physics
This line of research uses models based on chiral symmetry and/or expansion in a great number of colors to describe hadronic properties. It also studies the treatment of collective coordinates of nuclear systems and their application to double beta decay and to the study of other electroweak interactions beyond the standard model.
Fluid mechanics
In general, the laws of fluid mechanics are applied to study different natural phenomena. In the last three years, mountain and plateau formation has been modeled considering tectonic plate movement as the motion of highly viscous fluids.