S. A. Afanas’ev

Inotropic Response of the Myocardium in Rats with Postinfarction Cardiosclerosis Exposed to Extrasystolic Treatment

The inotropic response of the myocardium to extrasystolic treatment was studied on isolated perfused papillary muscles from rats with postinfarction cardiosclerosis. The development of postinfarction cardiosclerosis was accompanied by a decrease in myocardial excitability. The amplitude of extrasystolic contractions in the remodeled myocardium far surpassed the control. However, the amplitude of postextrasystolic contraction did not surpass that in normal contraction—relaxation cycle. Our results suggest that the ability of the sarcoplasmic reticulum in cardiomyocytes to accumulate Ca2+ is impaired during postinfarction remodeling.

Expression of Ca 2+ -ATPase in Sarcoplasmic Reticulum in Rat Cardiomyocytes during Experimental Postinfarction Cardiosclerosis and Diabetes Mellitus

We studied the expression of Ca2+-ATPase in sarcoplasmic reticulum of rat cardiomyocytes during isolated and combined development of postinfarction cardiosclerosis and diabetes mellitus. Postinfarction cardiosclerosis was formed within 6 weeks after coronary artery occlusion. Diabetes mellitus developed within 6 weeks after intraperitoneal injection of streptozotocin (60 mg/kg). Ca2+-ATPase in homogenate of rat myocardium was assayed by immunoblotting. Ischemic and diabetic remodeling of the myocardium was associated with reduced expression of Ca2+-ATPase in the sarcoplasmic reticulum. Combined pathology was characterized by minimum decrease in the level of this protein. It was concluded that induction of diabetes mellitus at the early stage of postinfarction cardiosclerosis triggered adaptive mechanisms that prevent the decrease in Ca2+-ATPase level in the sarcoplasmic reticulum of cardiomyocytes.

Manifestation of Adaptive Changes during Combined Development of Postinfarction Remodeling of the Heart and Diabetes Mellitus

Oxidative phosphorylation in isolated cardiomyocytes was studied under conditions of postinfarction remodeling and diabetes mellitus. Oxidation–phosphorylation uncoupling in the mitochondria in this disease combination was less pronounced than in each of these diseases alone. Combined development of the diseases was paralleled by less severe hyperglycemia and myocardial hypertrophy and lesser body weight loss. Presumably, combination of coronary occlusion and diabetes mellitus stimulates the adaptive changes in cardiomyocytes as early as at the level of mitochondrial energy metabolism.

Role of Phospholipase A2 in Activation of Isolated Cardiomyocyte Respiration in Postinfarction Cardiosclerosis

The rate of oxygen consumption by isolated cardiomyocytes was studied in rats with experimental postinfarction cardiosclerosis. The increase in oxygen consumption under these condition was comparable to that in melittin- and arachidonic acid-induced activation of phospholipase A2 in cardiomyocytes of intact animals. Bromophenacyl bromide inhibition of phospholipase A2 in cardiomyocytes of rats with postinfarction cardiosclerosis led to reduction of oxygen consumption rate to values characteristic of intact animal cardiomyocytes. The results confirm the hypothesis according to which high oxygen consumption in postinfarction cardiosclerosis is related to increased activity of phospholipase A2.

Adaptive changes in the myocardium of patients with ischemic heart disease

Changes in the human heart muscle resulting from chronic coronary insufficiency have been analyzed using biopsies taken during surgery from nine patients with ischemic heart disease (IHD) and six patients with the WPW syndrome (without IHD). Histochemical analysis have shown that the atrial myocardium in IHD patients is characterized by an increased density of the microvascular network, increased phosphorylase activity, and decreased succinate dehydrogenase activity. Virtually the same changes have proved to occur in the myocardium of rats adapted to hypoxia by means of repeated exposure in a low-pressure chamber. According to the results of two-dimensional electrophoresis and immunoblotting, acid (but not alkaline) isoforms of inducible HSP70 proteins appear in the myocardium of IHD patients. It is concluded that the myocardium of IHD patients undergoes adaptive changes at the tissue level in response to repeated exposure to ischemia in the course of development of this disease. It is proposed that activation of the synthesis of alkaline HSP70 isoforms in the myocardium of cardiological patients may provide the possibility of improving its resistance to the impact of ischemia and reperfusion (this possibility is not realized under conditions of IHD).

Initiation of stress protein synthesis in the myocardium of coronary patients

We studied myocardial biopsy specimens from the right atrium of cardiological patients with different degree of cardiac ischemia obtained during surgery. No inducible HSP70 stress proteins were detected in atrial cardiomyocytes of patients with the WPW syndrome without signs of ischemic injuries of the heart. These proteins were detected in the myocardium of coronary patients. Their expression was more intense in patients with coronary disease paralleled by the development of myocardial dyskinesia. Two-dimensional electrophoresis showed only acid HSP70 but no alkaline isoforms in coronary patients even with pronounced dyskinesia. Presumably, alkaline HSP70 isoforms are present in the myocardium directly involved in the dyskinesia zone.

Experimental Cardiomyogenesis Under Conditions of Administration of Different Doses of the Allogeneic Biomaterial

We studied the effect of different concentrations of the allogeneic biotransplant on myocardial recovery. In Wistar rats, coronary artery was ligated and intramyocardial injection of 12 or 24 mg Alloplant biomaterial suspension was performed. Histological analysis was conducted on paraffin sections stained by Mallory. The index of the scar area was measured on preparations of transverse sections of the hearts. Allogeneic biomaterial produced cardioprotective and regenerative effect in the myocardium damaged by ischemia. After administration of Alloplant in a dose of 12 mg, the index of scar area decreased by 2.74 times; after doubling the Alloplant dose (24 mg), the index of scar area decreased by 26 times.

Radiofrequency Ablation as a Possible Method for Preparing Pathologically Altered Myocardium for Intramyocardial Cell Transplantation

We studied the effects of radiofrequency ablation on the results of intramyocardial transplantation of bone marrow NSC into the myocardium of rats with postinfarction cardiosclerosis. It was shown that exposure of the pathologically changed myocardium to radiofrequency radiation led to destruction of formed connective tissue. Transplantation of MSC into sites exposed to radiofrequency radiation promoted the development of regenerative processes (abundant infiltration with mononuclear cells, presence of granulation tissue, and numerous newly formed blood vessels). We concluded that preliminary radiofrequency irradiation of the myocardial areas promotes realization of the regenerative potential of cell transplantation.

Economical Technology of Creation of Cell-Free Matrix of Animal and Human Arterial Vessels

We present a technology of creation of blood vessel connective tissue framework by 2-3-h vessel perfusion with detergents. The technology ensures effective removal of vascular cells without damaging collagen and elastic fibers. The connective tissue frameworks prepared by this method can the used for restoring blood flow in various vascular pathologies. The presented approach attenuates the damaging effect of treatment on the vascular framework due to maximum simplification and shortening of the duration of treatment and is universal for human and animal vessels.

Lipid peroxidation during cardiac remodeling in 12-month-old rats with experimental infarction.

Blood serum was from 12-month-old Wistar rats with experimental myocardial infarction caused by occlusion of the upper third of the left coronary artery was analyzed. The content of conjugated dienes by the 45th day after primary experimental myocardial infarction returned to normal and did not differ from that in intact animals of the same age group. MDA concentration in rats of the treatment group was lower compared to normal. It was demonstrated that normalization of LPO was accompanied by significant exhaustion of the endogenous antioxidant system (SOD and catalase). Our results suggest that special therapy is required for correction of the endogenous antioxidant defense system.