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Impaired insulin synthesis is accompanied by hyperglycemia and the development of diabetic cardiomyopathy. Echocardiography and left-ventricular catheterization were employed for studying the contractile function of the left ventricle in 2 weeks after administration of streptozotocin (60 mg/kg). The results obtained by both methods were similar and indicated the development of systolic dysfunction with a 27% decrease in cardiac output. The invasive study showed that the maximum rate of left-ventricular pressure development, the contractility index, and systolic left-ventricular pressure were within the normal range, but the peak ejection rate was reduced by 28%. BP was normal, but the vascular stiffness index was increased by about 1.5 times and inversely correlated with the peak ejection rate (r=-0.69). The results showed that systolic dysfunction in type 1 diabetes model was due to reduced ejection from the left ventricle at normal rate of left-ventricular pressure development.

We performed a comparative analysis of infarction-limiting activity of analogues of opioid receptor agonist U-50488 under conditions of heart reperfusion in rats. Derivatives of amide N-methyl-2-(pyrrolidin-1-yl)cyclohexyl-1-amine were administered 5 min before reperfusion in a dose of 1 mg/kg, derivative II (opicor) was additionally used in a dose of 2 mg/kg. In a dose of 1 mg/kg, all derivatives of opioid U-50488 were ineffective and produced no infarction-limiting effect. Opicor in a dose of 2 mg/kg reduced the infarction size/area at risk ratio and improved the contractility parameters of the isolated heart. Opioid receptor antagonist naltrexone (5 mg/kg) abolished the infarction-limiting effect of opicor. Hence, the infarction-reducing effect of opicor is associated with activation of opioid receptors. We also demonstrated that the opioid (opicor) can improve cardiac contractility during the reperfusion period.

2,6-Diisobornyl-4-methylphenol (Dibornol, 10 mg/kg intragastrically daily for 5 days after myocardial ischemia/reperfusion) 1.5-fold increased rat survival during the acute post-infarction period in comparison with the control group. In survivors, Dibornol reliably prevented post-ischemic progression of heart failure in the delayed post-infarction period (30 days after ischemia/reperfusion), which was seen from an increase in the left-ventricular developed pressure by 22%, left-ventricular contractility index by 19%, and +dP/dt by 34%. Left-ventricular end-diastolic pressure was by 39% lower than in control animals. Morphological study of heart sections from control group animals showed that Dibornol reduced the area of post-ischemic myocardial damage in the delayed period after ischemia/reperfusion to 3±1% (vs 18±2% in the control group).

We created a translational model of chronic heart failure in rats that developed in 3 months after reproducing experimental anterior transmural myocardial infarction. The model simulated the basic clinicodiagnostic criteria of this disease: impaired contractility and dilatation of heart ventricles, signs of venous congestion, elevated plasma content of biochemical markers, and abnormal overexpression of AT1aR and β-adrenoceptors.

Short-term high frequency electrostimulation (8-10 Hz) of the isolated isovolumic rat heart rapidly increased the rate of pressure rise and drop and the diastolic pressure. At the same time, the relaxation rate constant (RRC), being independent of the developed pressure, remained unaltered. These findings suggested that diastolic pressure rise was not caused by incomplete myocardial relaxation. Doxorubicin (3 μM) moderately reduced the developed pressure, but the relaxation rate constant remained unchanged. The dynamics and degree of changes in all indicators of the cardiac contractile function in high-frequency stimulation were the same as in control. It can be hypothesized that the initial effect of doxorubicin was not related to ionic transport system disturbances in cardiomyocytes.

We studied the effect of non-selective agonist of VIP receptors of vasoactive intestinal polypeptide in different concentrations on the frequency, force, and duration of isometric contraction of myocardial strips of the right atrium under conditions of spontaneous activity, as well as the force and duration of contractions of the right ventricle in rats. It was found that the agonist produced a positive inotropic and chronotropic effect that depended on its concentration. The maximum effect was observed at vasoactive intestinal peptide concentration of 10-11 M.

The contractile function of the heart was studied in adult frogs Rana temporaria under the influence of a toxic dose of isoprenaline under conditions of natural sinoatrial rhythm and during heart pacing. The dynamics of ventricular pressure was recorded with a Prucka MacLab 2000 instrument via a catheter introduced into the ventricle through the ventricular wall. Reduced (p

Effect of different Ca2+ concentrations in the bathing solution [Ca2+]o on the parameters of single isometric contraction and slow force response to stretching was studied in isolated preparations of healthy and hypertrophied myocardium of male and female Wistar rats. In all groups of experimental animals, the increase in calcium concentration was followed by a decrease in the myocardium slow response intensity. We revealed a complementary relationship between the current and medium-term systems of myocardial contractility regulation by the length of the myocardium aimed at the maintenance of the constant level during adaptation to the load. Slow responses of the hypertrophied rat heart myocardium were suppressed in comparison with those in the healthy myocardium and their intensity did not depend on animal sex.

The effects of different dopamine concentrations on contractility of myocardium with blocked α- or β-adrenoceptors were examined in vitro in 21- and 100-day old rats. In myocardial strips with blocked α-adrenoceptors, dopamine (10-5 M) increased the right atrial contractile force. By contrast, this neurotransmitter (10-9-10-5 M) reduced the contractile force of atrial and ventricular strips with blocked β-adrenoceptors.

Selective agonist (Leu(31)Pro(34)NPY) and blocker (BIBP-3226) of NPY1 receptors were used to determine the type of NPY receptors involved in myocardial contraction. Experiments with isometric contraction of myocardial strips from mature rats showed that the agonist produced the most potent effect in a concentration of 10-7 M. In this concentration, Leu(31)Pro(34)NPY showed the greatest positive inotropic effect on the contraction of the atria and ventricles. In contrast, selective blocker BIBP-3226 reduced the force of myocardial contractions. Pretreatment of myocardial strips with this blocker abolished the positive inotropic effect of Leu(31)Pro(34)NPY, which attested to important role of NPY1 receptors in myocardial contraction.

The study examined the dose-dependent effects of selective antagonists of α2A/D-, α2B-, and α2C- adrenoceptors applied in concentrations of 10—9-10—5 M on atrial and ventricular contractility of rat myocardium in vitro. Selective blockade of each α2-adrenoceptor subtype affected the contractile force of the atrial and ventricular strips. Various concentrations of α2A/D- and α2C-adrenoceptor antagonists produced positive inotropic effect on ventricular strips and negative effect on atrial strips. α2B-Adrenoceptor blocker in the majority of the tested concentrations produced a positive inotropic effect in both atria and ventricles.

The cardioprotective and inotropic effects of standardized active natural substance based on high-molecular-weight compounds of humic origin were studied on the model of global ischemia (40 min) and reperfusion of isolated perfused rat heart. Preventive administration of the test substance (0.1 mg/ml) before ischemia/reperfusion modeling reduced reperfusion contracture and necrotic death of cardiomyocytes and promoted recovery of myocardial contractility. Blockade of NO synthase with L-NAME (100 μM) abolished the above effects of the test substance. It was hypothesized that NO synthase plays an important role in the development of the cardioprotective and inotropic effects of the test natural substance.

Experiments with R2Y receptor blockers allowed identification of R2Y subtypes mediating the inhibitory effects of uridine triphosphate on myocardial contractility. In 100-day-old animals, the myocardial inotropic response to the administration of uridine triphosphate was mediated by R2Y2 receptors. R2Y4 receptors took part in the realization of negative inotropic response to uridine triphosphate in all age groups, but the most pronounced effects of this substance on myocardial contractility were found in 100-day-old rats. It was found that R2Y receptor blockers PPADS and reagent blue-2 affect amplitude-time parameters of myocardial contractility in rats of various ages.

Glufimet (glutamic acid derivative) in a dose of 28.7 mg/kg limited the reduction of the cardiac functional reserve in animals subjected to 24-h stress under conditions of nonselective NO synthase blockade with L-NAME (10 mg/kg). Adrenoreactivity and increased afterload tests showed that the increment of myocardial contraction/relaxation rates, left-ventricular pressure, and HR were significantly higher in glufimet-treated stressed animals with NO synthesis blockade than in animals which received no glufimet. The efficiency of glufimet was higher than that of phenibut (the reference drug).

Injection of substance 48/80 to rats led to dysfunction of mesenteric lymphatic microvessels, in particular inhibition of their contractility and modification of their reaction to norepinephrine. Injection of PGP peptide before and after substance 48/80 alleviated these disorders. The results indicated the possibility of peptide correction of lymphatic vessel dysfunction.

The effects of sodium hydrosulfide NaHS, a donor of hydrogen sulfide H2S, on the force of muscle contraction were examined on isolated myocardial strips from frog ventricles. NaHS decreased the amplitude of muscle contractions in a dose-dependent manner under normal conditions and during inhibition of Ca channels with nifedipine. In contrast, under conditions of blockade of ATP-dependent potassium channels with glibenclamide, NaHS exerted a positive inotropic effect from the first minute of application. Neither blockade, nor activation of ATP-dependent K-channels with glibenclamide modulated the negative inotropic effect of NaHS. Inhibition of K-channels with tetraethylammonium (TEA) (3, 5, 10 mM) or 4-aminopyridine increased the amplitude of myocardial contractions. Preliminary application of 4-aminopyridine or TEA (3 mM) did not eliminate NaHS-induced negative inotropic effect, although higher TEA concentrations (5 or 10 mM) prevented it. The data indicate that the targets of H(2)S in frog myocardium are ATP-dependent, Ca-activated, and voltage-dependent K-channels.

Infravesical obstruction of the lower urinary tract was simulated in rats by dosed constriction of the prevesical portion of the urethra. The functional and morphological changes in various urinary bladder compartments were evaluated after 1 week and 3 months. The development of compensatory hypertrophy of the detrusor was associated with an increase in the number of hypertrophic, atrophic, and young leiomyocyte forms and their transformation into myofibroblasts, with the formation of connective tissue laminae between myofibril bundles mainly in the zone of urinary urinary bladder neck. Specific contractility of the detrusor strips decreased with increasing their tone, which was most pronounced in the neck zone. The relaxing effect of norepinephrine was significantly lower after 3 months of obstruction and virtually disappeared in the zone of the urinary bladder body and neck. Blockade of a-adrenoceptors after adrenostimulation with norepinephrine stimulated contractions of the hypertrophic detrusor against the background of reduced tone of the urinary bladder neck, in contrast to intact urinary bladder where this treatment reduced contractions.

Acute coronary failure was modeled in rabbits by ligation of the descending left coronary artery at the interface of its middle and lower thirds. The function and morphology of left-ventricular and right-ventricular myocardium were studied on days 1, 3, and 5 of the pathological process. It was found that left-ventricular contractility decreased, while right-ventricular contractility increased. Deep morphological changes were observed in both ventricles: pronounced extracellular edema, increased content of collagen, decreased percentage of myofibrils. Hence, acute coronary failure involves both compartments of the heart, but the adaptive mechanisms more actively develop in the right ventricle.

The effects of P2-receptor agonists on myocardial contractility were examined in rats aging 14-100 days. ATP and its stable analog 2-methylthio-ATP potentiated the contraction force of isolated myocardial strips in a dose-dependent manner. The agonist concentrations producing the positive inotropic effect increased from days 14 to 100 of life. The efficiency of extracellular purines depends on animal age: in 14- and 56-day rats the positive inotropic effects of ATP and 2-methylthio-ATP were similar, while in 100-day rats ATP produced more pronounced effect than 2-methylthio-ATP.

Sex differences in the morphogenesis and adaptation of the mechanisms controlling myocardium contractility during physiological and pathological hypertrophy of the right ventricle were demonstrated in mature rats. The study revealed sex-dependent effects of physiological and pathological cardiac hypertrophy on the coefficient of variation of the cardiomyocyte diameter, length-dependent control of the contractile force, and the maximum velocity of isotonic shortening.

Stimulation of β-adrenoreceptors with low (10(-8) and 10(-7) M) or high (10(-6) M) doses of isoproterenol in hypokinetic rats treated with L-NAME (a non-selective blocker of NO synthases) decreased or increased myocardial contractility, respectively. In control rats, all examined doses of isoproterenol used under blockade of NO synthases inhibited myocardial contractility.

We studied the effect of selective ligands of cannabinoid (CB) receptors on contractility of isolated Langendorff-perfused rat heart under conditions of 45-min total ischemia and 30-min reperfusion. Perfusion with a solution containing selective CB receptor agonist HU-210 for 10 min before ischemia increased the severity of reperfusion contractile dysfunction. This drug decreased left ventricular developed pressure and maximum rates of contraction and relaxation, but had no effect on heart rate and end-diastolic pressure. The negative inotropic effect of the drug was transitory and disappeared after 5-min reperfusion. Pretreatment with selective CB1 receptor antagonist SR141716A and selective CB2 receptor antagonist SR144528 had no effect on heart rate and myocardial contractility during reperfusion. Our results indicate that stimulation of CB receptors can increase the degree of reperfusion-induced cardiac contractile dysfunction. However, endogenous cannabinoids are not involved in the development of myocardial contractile dysfunction during ischemia/reperfusion of the isolated heart.

Autologous bone marrow mononuclear cells were transplanted by intracoronary infusion to patients with myocardial infarction after recovery of coronary perfusion. Controls received traditional therapy alone. Echocardiography was carried out before and 3 and 6 months after cell therapy. Cell transplantation did not appreciably improved left-ventricular contractility in comparison with the control group. In none patient cell therapy provoked malignant ventricular arrhythmias. Intracoronary infusion of bone marrow mononuclear cells in patients with myocardial infarction did not improve cardiac contractility and did not aggravate the course of the disease.

In women with various gynecological disorders, ATP, ADP, and 2-methylthio-ATP dose-dependently potentiated spontaneous contractility of isolated fallopian tubes, while alpha,beta-methylene-ATP and uridine triphosphate were little efficient. Pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid, a P2-receptor antagonist, inhibited responses to 2-methylthio-ATP, produced no effect on responses to ATP, and potentiated ADP-induced responses in fallopian tubes. During inflammation, sensitivity of fallopian tubes to P2 agonists and antagonists decreased. The data attest to the presence of functionally active P2 receptors in human fallopian tubes probably involved in the regulation of their mechanical activity.

In acute experiments on cats neural inotropic and lusitropic reactions of the heart to enhancement of pre- and afterload were assessed by changes in contractility and relaxation indices, which were preliminary chosen for their maximum specificity and sensitivity. The control cardiac responses to increased pre- and afterload were measured after treatment with ganglionic blocker arfonad. The myogenic component of these responses assessed under the action of arfonad was highly pronounced, therefore the neural inotropic and lusitropic reactions were measured as the difference between load-induced changes of indices in experiments with and without arfonad. Increased preload produced similar negative inotropic and lusitropic effects, while increased afterload produced a more pronounced negative inotropic effect, which indicated independent regulation of contractility and diastolic relaxation of the heart.

We studied the dose-dependent cardiotoxic effect of propranolol. Intraperitoneal injection of propranolol in doses of 1 and 2 mg/100 g body weight produced a potent effect on central hemodynamics and myocardial contractility, impaired diastolic relaxation, and caused damage to cardiomyocyte membranes due to activation of free radical oxidation.

Experiments on smooth muscle strips isolated from the capsule of bovine mesenteric lymph node showed that heparin low concentrations (0.010-0.025 U/ml) stimulating spontaneous isometric phasic contractions of smooth muscles, but higher heparin concentrations reduced or even completely eliminated these contractions. The inhibitory effects of heparin were presumably realized via stimulation of NO production by endothelial cells of the subcapsular space followed by activation of ATP-sensitive potassium channels of capsular myocytes and via modulation of prostaglandin synthesis.

We studied the effect of dopamine in concentrations of 10(-9), 10(-8), 10(-7), 10(-6), and 10(-5) M on contraction strength of isolated myocardial strips from the right atrium and right ventricle of rats aging 21, 42, 56, and 100 days. Dopamine in a concentration of 10(-9) M had a positive inotropic effect in rats of various ages. Increasing the concentration of dopamine to 10(-7)-10(-5) M was accompanied by a negative inotropic effect on the heart.

The cardiodynamics of the right ventricle was studied during the first 30 min of massive pulmonary embolism complicated and uncomplicated by heart failure. Both variants were accompanied by diastolic dysfunction of the right ventricle. Some changes in the cardiodynamics observed during complicated massive pulmonary embolism indicated a lower increase in the contractile activity, decreased myocardial contractility, and more pronounced dilation of the right ventricle. The absolute indexes of mechanical activity including indexes of contractility are not reliable criteria for early diagnostics of heart failure in the acute stage of massive pulmonary embolism, whereas changes in these indexes hold much prognostic value.

The problem of heart failure is analyzed from the point of view of conformation changes in submolecular cardiomyocyte structures. The development of heart failure as a consequence of abnormal function of contractile myocardial proteins is discussed. The properties of actin and the role of structural changes in actin molecules in the impairment of ATP energy utilization and generation of contractile force by actomyosin complexes are studied. Experiments on animal models and autopsy samples showed that conformation changes precede disturbances in energy utilization by myofibrils, abnormal functioning of the energy-producing and Ca2+-transporting systems during the development of heart failure. It is proposed that rigid recombinations of submolecular structures in contracile proteins underlie impairment of myocardial contractility and resistance of the myocardium to regulatory factors and drugs (immobilization).

Hypoxia always leads to dysfunction of organs and culminates in the fatal outcome. The principles of classification of the hypoxic states were formulated in 1930-s. The first successful cardiac transplantation posed the problem of dividing of circulatory cardiovascular hypoxia into two subdivisions: hypoxia associated with impaired cardiac contractility (cardiac insufficiency) and hypoxia resulting from vascular smooth muscle cell. Here we attempted to improve classification of hypoxic states on the basis of new medical achievements. The proposed classification considers the following hypoxic states: 1) exogenous hypoxia; 2) respiratory hypoxia; 3) hypoxia resulting from cardiac insufficiency; 4) hypoxia provoked by vascular smooth muscle dysfunction; 5) hemic hypoxia; 6) tissue hypoxia; and 7) combined hypoxia. There are specific and pathogenically substantiated methods for correction of all elements of the “hypoxic chain” that regulate tissue metabolism at the cellular and subcellular level both in the whole organism and in individual organs. These methods open new vistas in biology and medicine, in particular, in transplantology.

Experiments with selective agonists and antagonists of purinoceptors allowed us to evaluate the subtype of P2X receptors. We showed that the myocardium of 14- 100-day-old rats contains functionally active P2X1 receptors. These receptors are involved in the realization of the positive inotropic effect of the atria and ventricles. Selective P2X1 receptor agonist beta,gamma-methylene-ATP induced a dose-dependent increase in the strength of atrial and ventricular contractions. P2X1 receptor antagonist TNP-ATP abolished the effect of the agonist in rats of all age groups.

A relationship between morphofunctional changes in the heart and predominance of adrenergic or serotoninergic influences on the strength of myocardial contraction in the right atrium was revealed in patients with chronic heart failure. During left ventricular hypertrophy, the strength of myocardial contraction in response to serotonin exceeded that induced by epinephrine and was realized via 5-HT2 receptors.

Long-term administration of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor atorvastatin to rats was accompanied by an increase in the relative weight of the heart and decrease in the rate of pressure development in the isovolumic heart. During oxidative stress induced by addition of 100 microM H2O2 to the perfusate, the decrease in contractile function was more pronounced that in the control. Our results indicate that administration of atorvastatin is accompanied by a decrease in myocardial contractility, which becomes more pronounced under conditions of oxidative stress.

The aftereffects of experimental damage to the duodenal wall on the contractility are studied in isolated rat duodenum. Development of ulcer was associated with replacement of rhythmic contractions by slow-wave tonic activity. Methacin and proserin accelerate the repair processes and potentiate the compensatory reactions, promoting the shift of spontaneous activity of smooth muscles toward the slow part of the spectrum.

In rabbits, arterial hypertension was characterized by progressive elevation of systolic and diastolic blood pressure. The contractile function of the left ventricle augmented, but its potential working capacity decreased. Opposite changes were observed in the right ventricle. It was hypothesized that the compensatory mechanisms in the right ventricle during arterial hypertension are triggered at the very onset of the pathology, while in the left ventricle they develop later.

Stimulation of lymph circulation and microcirculation and increase in contractile activity of the wall and cusps of valves in lymphatic microvessels are the mechanisms for a therapeutic effect of dimephosphon. These changes improve resorption and transport of tissue and cell metabolites from the interstitial space.

We studied the effect of neuropeptide Y in concentrations of 10(-10)-10(-6) M on myocardial contractility of rats at the age of 7, 21, and 100 days. Studying the isometric contraction of myocardial strips showed that neuropeptide Y decreases the force of myocardial contraction in 7-day-old rat pups. Exogenous neuropeptide Y produced a biphasic effect in 21-day-old rats, which was manifested in the increase and subsequent decrease in myocardial contractility. Neuropeptide Y had little effect on myocardial contractility of 100-day-old animals.