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 One of the greatest problems of modern cardiology is chronic heart failure as an outcome of healing of myocardial infarction (MI)  Changes in myocardium, accompanied healing of MI, are known as REMODELING of myocardium  Remodeling is characterized by structural and geometrical changes in heart  Morphologically the process includes hypertrophy of Cardiomyocytes, reorganisation of vessels, fibrosis and loss of Functional elements (especially by means of apoptosis) Loss of Cardiomyocytes Fibrosis Reorganisation of vessels CHRONIC HEART FAILURE

Apoptosis of Cardiomyocytes Cellular population Micro- circulation Cardiomyocytes are known to be cellular populations with very limited potential to regeneration. One of the main effects on the regulation of remodeling have different cellular populations, entering Myocardium through the capillaries. They also play role in loss of structural elements through apoptosis and formation of new vessels.

 Postmortem material hearts from patient died due to MI, localized in one of the free walls of left ventricle Acute MI 1-2 days Acute MY 3-5 days Acute MY more then 7 days Acute MYHealed MY Recurrent MI 1- 2 days Recurrent MY 3- 5 days Recurrent MY more then 7 days Recurrent MIHealed MY

MI 1-2 days in duration (H-E, х200) MI more then days in duration (H-E, х200) MI 3-5 days in duration (H-E, х200) Healed MY – scar (H-E, х100)

The specimens for investigation were taken from:  The centre of pathological process  The border zone  The intact zones (centre of interventricular septum an centre of right ventricle)

1. Cellular populations, forming inflammatory infiltrate, were counted around capillaries; 2. Area of microcirculatory bed was measured by means of special computer program “Videotest.Morphology. 4.0”; 3. Apoptosis of structural elements was revealed by means of immunohistochemical examination with monoclonal antibodies against Caspase-3; 4. All the data were treated with non-parametrical statistical methods.

Dynamic of changes of cellular populations in the affected zone during healing of acute and recurrent MI Dynamic of changes of cellular populations in the border zone during healing of acute and recurrent MI

Dynamic of changes of cellular populations in the intact zone (interventricular septum) during healing of acute and recurrent MI Dynamic of changes of cellular populations in the intact zone (right ventricle) during healing of acute and recurrent MI

HEALING OF ACUTE MYOCARDIAL INFARCTION Acute MI1- 2 days- Acute MI 3-5 days Acute MI 3-5 days- Acute MI more then 7 days Acute MI more then 7 days – Healed MI AZ BZ  IVSRV AZ  BZ  IVS RV  AZ  BZ  IVS  RV  AZ- affected zone; BZ – border zone; IVS – inter-ventricular septum; RV – right ventricle.

HEALING OF RECURRENT MYOCARDIAL INFARCTION Recurrent MI1-2 days- Recurrent MI 3-5 days Recurrent MI 3-5 days- Recurrent MI more then 7 days Recurrent MI more then 7 days – Healed MI AZ BZ  IVSRV AZ  BZ  IVS RV  AZ  BZ  IVS  RV  AZ- affected zone; BZ – border zone; IVS – interventricular septum; RV – right ventricle.

 Ventricular fibrillation is one of the fatal and almost unpredictable complication of myocardial infarction. But the pathogenesis of is still very unclear as well as the criteria for its morphological verification.  We compared cellular infiltrate in myocardium in patients who died due to ventricular fibrillation and the group of cases without such complication, and statistical methods revealed the significant differences in cellular infiltrate.  The finding may be the key for explanation of some steps in pathogenesis of ventricle fibrillation and helped to create a method of objective verification of ventricle fibrillation.

 1. Numerical quantity of the changes of cellular infiltrate, capillary bed and apoptosis of Cardiomyocytes (reflecting process of myocardial remodeling) during healing of myocardial infarction in necrotic zone, border zone and intact zones;  2. Numerical quantities of morphometric parameters of acute and recurrent myocardial infarction healing;  3. Quantitative differences of morphometric parameters of acute and recurrent myocardial infarction healing;  4. Peculiarities of cellular infiltrate in myocardium of patients who died due to ventricular fibrillation as a complication of myocardial infarction.

 1. Mathematical model of acute and recurrent myocardial infarction healing, reflecting differences in remodeling of the whole heart during the diseases (based on the changes in cellular infiltrate, microcirculation and death of cardiomyocytes);  2. Mathematical model of ventricular fibrillation as myocardial infarction complication, basing on differences in cellular infiltrate in myocardium of such patients (in some way, it may clarify the dim pathogenesis of the complication);  3. The scheme for prognosis of myocardial remodeling with formation of cardiac insufficiency, based on morphological criteria.