Expression of Genes and Proteins of the Sarcoplasmic Reticulum Са2+-Transport Systems in Cardiomyocytes in Concomitant Coronary Heart Disease and Type 2 Diabetes Mellitus.

We compared the expression of Са2+-ATPase (SERCA2a), calsequestrin (CASQ2), ryanodine receptors (RyR2) proteins and their genes (ATP2A2, CASQ2, and RYR2) in coronary heart disease (CHD) patients with and without comorbid type 2 diabetes mellitus. All studies were performed on the right atrial appendages resected during coronary bypass surgeries. Expression of SERCA2a and RyR2 proteins and their ATP2A2 (p=0.046) and RYR2 genes in comorbid pathology was significantly (p=0.042) higher (by 1.2 and 2 times; p=0.025). The expression of CASQ2 protein and its gene did not differ significantly between the groups (p=0.82 and p=0.066, respectively). It was concluded that the expression of SERCA2a and RyR2 proteins and their genes (but not CASQ2 and its gene) is elevated in CHD associated with type 2 diabetes mellitus. Expression of the studied proteins correlated with the expression of their genes. Increased expression of CASQ2 protein and its gene can probably prevent imbalance of the Ca2+-transporting systems in cardiomyocytes and contractile dysfunction of the myocardium, even in CHD associated with type 2 diabetes mellitus.

Myocardial Expression of SERCA2a and Structural and Functional Indices in Patients with Atrial Fibrillation.

The study examined the relationships between SERCA2a expression in the myocardium and structural and functional indices in patients with atrial fibrillation. In uniform cohort of patients, this expression differed significantly but positively correlated with the size of the left atrium, end-systolic volume, and end-diastolic volume. In contrast, SERCA2a expression negatively correlated with early (peak E) and late (peak A) diastolic filling rates in left ventricle. SERCA2a expression was also associated with echocardiographic parameters reflecting structural and functional status of the heart in patients with persistent atrial fibrillation.

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.

Expression of Ca(2+)-ATPase in sarcoplasmic reticulum in rat cardiomyocytes during experimental postinfarction cardiosclerosis and diabetes mellitus.

We studied the expression of Ca(2+)-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). Ca(2+)-ATPase in homogenate of rat myocardium was assayed by immunoblotting. Ischemic and diabetic remodeling of the myocardium was associated with reduced expression of Ca(2+)-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 Ca(2+)-ATPase level in the sarcoplasmic reticulum of cardiomyocytes.

Comparative study of changes in energy metabolism in rat cardiomyocytes in postinfarction cardiosclerosis and diabetes mellitus.

Cardiomyocyte energy metabolism in experimental unfolding postinfarction cardiosclerosis and diabetes mellitus was studied. Postinfarction cardiosclerosis formed 6 weeks after coronary artery occlusion. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin (60 mg/kg). The rate of oxygen consumption in postinfarction cardiosclerosis and diabetes increased by 3.4 and 4.2 times, respectively. Stimulation of mitochondrial respiration (ATP, palmitic acid) significantly increased oxygen consumption in animals with postinfarction cardiosclerosis and significantly reduced this process in diabetes. The content of LDH and SDH in the myocardium of animals with diabetes and postinfarction cardiosclerosis was significantly below the control. Hence, the development of postinfarction cardiosclerosis and diabetes mellitus were characterized by reduced generation of ATP in anaerobic and aerobic pathways and oxidative phosphorylation in cardiomyocytes.

[Noninvasive assessment of functional competence of the radial artery as a possible vascular graft for coronary artery bypass grafting].

Described herein is a variant of surgical treatment of a patient presenting with type A aortic dissection extending to the brachiocephalic branches accompanied by thrombosis of the false channel of the latter. In the rare cases in dissection and thrombosis of the brachiocephalic branches for adequate protection of the body (systemic protection) it is necessary to use bidirectional arterial perfusion under the conditions of moderate hyperthermia: through a preliminarily sewn into the carotid artery prosthesis - perfusion of the brain, through cannulated aortic arch or femoral artery - body perfusion.

[Consistence of the radial artery as a conduit used in aortocoronary bypass surgery, a possibility of preventing shunt spasm].

AIM: To develop a new procedure to evaluate the functional consistence of the radial artery (RA) as a conduit used in aortocoronary bypass surgery (ACBS), to verify the prognostic value of the changed diameter of RA, and to prevent its spasm. SUBJECTS AND METHODS: The study enrolled 34 patients aged 59.4 +/- 8.6 years with coronary artery stenoses, who underwent ACBS using a RA conduit. While preparing them for surgery, endothelium-dependent vasodilation (EDVD) of RA, i.e. the magnitude of a change in its diameter (deltaD) was assessed; RA tone and nitric oxide (NO) concentrations were estimated during surgery; RA EDVD was re-estimated in 12 lercanidipine-treated patients with deltaD < 8%. RESULTS: The patients were primarily divided into 2 groups: 1) deltaD > or = 8% (RA spasm intra- and postoperatively); 2) EDVD deltaD < 8% (RA spasm). Significant differences between Groups 1 and 2 were intraoperatively recorded in vascular wall tone (U = 1.0; Z = -2.3; p = 0.02) and NO concentrations (p = 0.0); a relationship was found between these parameters. After lercanidipine treatment, the degree of deltaD = 4.36 +/- 1.89% increased to 11.32 +/- 2.22% (p = 0.0) and RA tone dropped from -1.68 to -3.9 mm in Group 2a with the baseline decreased vasodilating activity of RA. CONCLUSION: Ultrasound assessment of the vasodilating activity of RA provides adequate evidence about its arterial wall tone during surgery. deltaD < 8% is prognostically unfavorable and serves as a contraindication to the use of RA as a conduit during ACBS. The administration of lercanidipine allows effective correction of the dilatory capacities of an arterial conduit.

[Inotropic reaction of myocardium rats with postinfarction and diabetic remodeling on extrasistolic influences].

Studied inotropic reaction papillary muscles of rats with postinfarction and diabetic remodeling on extrasistolic influences. It was found, that excitability of myocardium rats raises at a diabetes induced streptozotocin. Postextrasistolic contraction of myocardium rats with postinfarction cardiosclerosis it was considerably oppressed, and rhythmoinitropic reaction of myocardium rats was comparable to reaction of intact myocardium at a diabetes induced streptozotocin. The combination postinfarction and diabetic influence is paradoxical promoted preservation postextrasistolic potentiation of myocardium rats.

[Age-related features of intracellular calcium homeostasis in rat cardiomyocites in postinfarction heart remodeling].

Research results of features of an intracellular calcium homeostasis in 4 and 12-month's rat cardiomyocites at postinfarction cardiosclerosis are presented. It is shown that the myocardium of animals in the old rats group is more susceptible to extrasystolic impacts. In the pathology conditions additional extrasystolic influences also had the expressed age specificity of inotropic response. The data testifying to almost identical dynamics of postextrasystolic cycles of intact myocardium in animals of investigated age groups has been obtained. The different postextrasystolic potentiation in the remodeled myocardium in old and young rats testified to different of sarcoplasmic reticulum ability to accumulate additional calcium ions. The conclusion was made that the myocardium of animals in the old rats group has more chance for development of hemodynamic significant disturbance of cardiac rhythm as a consequence of age-related changes processes of the electromechanical coupling in cardiomyocites.

[Effect of nonselective beta-adrenoblocker carvedilol on extrasystolic and postextrasystolic contractility in the rat myocardium after experimental infarction].

Features of the extrasystolic and postextrasystolic contractility of myocardium isolated from rats aged 4 months (group I, n = 30) and 12 months (group II, n = 30) after postinfarction remodeling of the heart (PIRH) and long-term treatment with carvedilol have been studied. Each age group included in 10 intact control animals, 10 animals with postinfarction cardiosclerosis (PICS), and 10 rats with PICS treated with carvedilol (2.1 mg/kg) during 28 days, beginning with the 45th day after coronary occlusion. The isometric contractility of myocardium was monitored at an electric stimulation frequency of 0.5 Hz. The extrasystolic effect was produced by an electric pulse applied within 0.2 - 5 s interval after the basic stimulation. It is established that the inotropic response of myocardium to the extrasystolic impulse exhibits age-dependent features both the intact rats and in the rats with PICS. The differences can be related to the age-dependent involvement of the ion-transport systems of sarcolemma and sarcoplasmic reticulum into the modulation of excitation--contractility coupling during PIRH. The long-term treatment with carvedilol led to restoration of the Ca(2+)-accumulation reserve of sarcoplasmic reticulum to the age-normal level in young animalsand decreased the risk of development of hemodynamically significant heart rate disturbances in old rats.

[Possible role of sarcoplasmatic reticulum in anti-arrhythmic effects of the class III agent amiodarone].

The study was designed to evaluate changes in functional activity of cardiomyocyte sarcoplasmic reticulum under effect of amiodarone (1 mM). It was shown that post-rest potentiation significantly increased after perfusion of cardiomyocytes with amiodarone or calcium (3 mM). The stimulatory action of amiodarone was more pronounced than that of calcium. Treatment with amiodarone solution containing high concentration of calcium had a lower potentiating effect compared with that of perfusion with either of them. Moreover, amiodarone in combination with calcium significantly extended the period of relaxation without affecting the contraction rate. It is concluded that amiodarone improves activity of sarcoplasmic reticulum.

[Comparative assessment of inotropic reaction of isolated myocardium of patients with ischemic and rheumatic heart disease after short-term periods of rest at the background of amiodarone].

We studied inotropic reaction of isolated myocardium of patients with heart failure induced by ischemic and rheumatic cardiac involvement after periods of rest at the background of amiodarone. The studies were carried out on muscular trabeculi separated from right atrial auricle during surgery. It was shown that inotropic reaction of insufficient myocardium could be of 2 types. In type I inotropic reaction first contraction after period of rest either exceeded basal contractions or remained at their level. Type 2 was characterized by significant lowering of amplitude of contractions relative to regular ones. Exposure of the myocardium to amiodarone (1 micro/L) led to significant potentiation of trabeculi contraction after periods of rest of muscles with type I reaction and did not affect response of muscles with type II reaction. These results allow to conclude that the state of calcium transporting systems of sarcoplasmic reticulum (SR) is different in ischemic and rheumatic heart failure and that realization of therapeutic effect of amiodarone depends on functional state of SR.

[Activity of lipid peroxidation and functional state of the myocardium in remodeling of rat heart after experimental myocardial infarction].

It was shown in experiments on Wistar rats that the processes of postinfarction remodeling of the heart in animals that survived myocardial infarction were characterized by lowering of excitability of cardiac muscle, impairment of ability of sarcoplasmic reticulum to accumulate calcium ions. High level of content of lipid peroxidation products both in blood serum and myocardial tissue, and lowering of activity of antioxidant enzymes were also noted. A conclusion was made that high level of lipid peroxidation, lowering of defense properties of endogenous antioxidants and impairment of myocardial contractile function induced by myocardial infarction were sustained minimally for subsequent 45 days. This could serve as a factor, capable to significantly affect the process of postinfarction remodeling and development of heart failure.

[Acute and chronic amiodarone effects on the dynamics of force-interval relationship in rat papillary muscle].

Effects of acute and chronic amiodarone treatment on the force-interval relationship were investigated in rat papillary muscle. It was found that both acute and chronic amiodarone treatment decreased the amplitude of extrasystoles. At the same time, only short-term administgration of amiodarone increased postextrasystols and post-rest potentiations of twitch force in rat myocardium. It is concluded that the acute and chronic amiodarone treatment suppress the excitability of cardiomyocytes, but only the chronic treatment increases the effective refractory period. The results suggest that the acute administration of amiodarone can influence the intracellular calcium homeostasis.

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.