[Modification of the FF neuropeptide enhances its hypertensive effect].

Neuropeptide FF (H-Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) injected intravenously temporarily enhanced the arterial pressure (AP) and the heart rate (HR). However, its role in the regulation of blood circulation is obscure. To study the properties of the molecule, its analogue was synthesized, in which proline in position 7 was substituted with glycine, and leucine in the position 2 with norleucine. Modified neuropeptide FF (FFm) also temporarily and in a dose-dependent manner increased the AP and HR; however, the equal degree of increase was reached at doses of FFm being 5-7 times lesser as compared with the natural peptide. The application of the FFm at hemorrhagic shock excluded mortality of animals during the experiment, considerably increased the degree of AP and HR restoration in the remaining experiments, and improved the survival of animals in 24 hours. It has been found that the level of antibodies to the fragment of hFF1 receptor in the serum is lower in spontaneously hypertensive rats SHR as compared with Wistar rats, but it is increased in patients of cardiological profile as compared with donors. The findings suggest involvement of neuropeptide FF in the regulation of blood circulation; however, the precise mechanisms remain to be determined.

[Penetrating peptide inhibitor of the myosin light chain kinase suppresses hyperpermeability of vascular endothelium].

Nonapeptide H-Arg-Lys-Lys-Tyr-Lys-Tyr-Arg-Arg-Lys-NH2 corresponding to a modified sequence of autoinhibitory region of myosin light chain kinase (MLCK) was synthesized from L-amino acids and from D-amino acids. Using nuclear magnetic resonance spectroscopy it has been demonstrated that D-peptide is significantly more stable in human blood plasma than its L-enantiomer. D-peptide accumulated in cultured human umbilical vein endothelial cells suppressed development of hyperpermeability in endothelial monolayer induced by thrombin addition. Following intravenous administration D-peptide decreased the extent of lung oedema in rats induced by infusion of oleic acid in bloodstream. Thus, the peptide molecules based on an autoinhibitory peptide of MLCK may serve as a prototype for development of a novel antioedematous drugs that directly affect the MLCK-dependent motile processes in vascular endothelium.

[Action of a nitric oxide donor dinitrosyl complex of iron with glutathione on hemodynamics in rats and monkeys].

We studied action of a nitric oxide donor, dinitrosyl complex of iron (DNIC) with glutathione as a ligand on the hemodynamics of normotensive Wistar rats, spontaneously hypertensive rats (SHR), and monkeys. Intravenous DNIC introduction (2-120 mg/kg) rendered fast (1-2 min) hypotensive effect combined with increased heart rate by 10-25%. Second phase of the effect in Wistar rats was characterized by slowed recovery of arterial pressure and heart rate up to initial level. A gradual DNIC breakdown in blood occurred during this period associated with increased NO accumulation in organs with intensive oxidative metabolism (liver, heart, and kidney). Duration of hypotensive effect in all animals depended on dose, this dependence was most expressed in SHR.

[The registration of nitric oxide production in mammals using a water-soluble complex of N-methyl-D,L-glucamine dithiocarbamate with Fe3+].

The level of nitric oxide production in the intact rabbit organism was studied using the water-soluble complex of Fe3+ with MGD as a selective spin trap for nitric oxide. The Fe(3+)-MGD3 complex was injected intravenously. It was shown by the EPR method that this injection resulted in the formation of paramagnetic complexes in the urine, as Cu(2+)-MGD2, and nitric oxide spin adducts: nitric oxide-Fe(2+)-MGD2 and nitric oxide-Fe(3+)-MGD2. The level of nitric oxide production was estimated by the ratio of the total amount of these adducts to the nitric oxide-Fe(2+)-MGD2 level, formed after the addition of excessive S-nitrosoglutathione. This value for intact animals was 1.33 +/- 0.13%.

[Changes in the sensitivity of the baroreceptor reflex during the development of renal parenchymatous hypertension in waking cats]. / Izmenenie chuvstvitel'nosti baroretseptivnogo refleksa v khode razvitiia renoparenkhimatoznoi gipertenzii u bodrstvuiushchikh koshek.

Hemodynamic parameters were investigated in experiments with chronically instrumented hypertensive cats. It was shown, that mean arterial pressure level raised by 35%, heart rate decreased by 20% and peripheral resistance raised by 56% in awake hypertensive cats. The study demonstrates that the mean blood pressure raised on the 30th day after hypertension induction, however, baroreflex sensitivity lowered only on the 40th day. The values of the system hemodynamics indices permit considering that the model of hypertension in awake cats has been worked out for the first time.

[Use of taurine in the treatment of experimental congestive heart failure]. / Ispol'zovanie taurina dlia lecheniia zastoinoi serdechnoi nedostatochnosti v éksperimente.

The therapeutic effects of 2-aminoethanesulfonic acid (taurine) were tested in animals with congestive heart failure (HF) simulated by aortic valve damage. The drug given in a daily dose of 100 mg/kg for a month was shown to reduce mortality rates as compared to controls, to improve the animals' clinical condition, hemodynamic and myocardial contractility parameters. Taurine was found to exert a positive action on the heart response to stresses. The impaired response in the animals restored to heart rate stimulation, catecholamines and calcium loading. The mechanisms of the agent's action are discussed in the present paper. It is suggested that taurine-based taucard will be included into the arsenal of cardiotropic agents after its clinical trials are successfully completed.

[Taurine level in the blood and myocardium of rabbits with experimental heart failure]. / Soderzhanie taurina v krovi i miokarde krolikov s éksperimental'noi serdechnoi nedostatochnost'iu.

Experimental damage of the aortal heart valve in rabbits caused taurine accumulation in the heart. Taurine content in the heart increased for two months 2.7 times in the left ventricle and 1.8 times in the right one. Taurine concentration in the blood began rising 5-10 days after the operation, reached the maximal value of about 150% as compared with its initial level and then decreased to the level near the initial one. Animals with insignificant taurine accumulation in the heart died for the first two months after the operation. Results are discussed from consideration on the protective role of taurine for the myocardium under the heart failure.

[Pathomorphological and morphometric evaluation of a model of aortic insufficiency in rabbits treated with taurine]. / Patomorfologicheskaia i morfometricheskaia otsenka modeli aortal'noi nedostatochnosti u krolikov pri lechenii taurinom.

In 45 experimental rabbits, subjected to trans-carotid aorto-valvulotomy in a month developed a congestive heart failure. When this group of rabbits was compared to the control group of 20 animals, in the course of complete pathomorphologic, histochemical and stereomorphologic analysis the following results were obtained: potassium oroticum did not show any efficacy at all; the efficacy of taurine in a dose of 10 mg/kg was low. Its effect was both direct and indirect acting through the autonomic nervous system.

[Rate constants of left ventricular relaxation: the effect of inotropic and mechanical factors]. / Konstanty skorosti rasslableniia levogo zheludochka: vliianie inotropnykh i mekhanicheskikh faktorov.

Changes in isovolumetric (IRRC) and auxovolumetric (ARRC) relaxation rate constants in response to inotropic and mechanical influences were studied experimentally in 23 narcotized cats. IRRC was determined by the slope of the curve of isovolumic relaxation pressure, expressed as natural logarithms, in relation to time. ARRC was determined on the basis of auxovolumetric relaxation pressure values. A pressure variation between 100 and 180 mmHg over one cycle had no noticeable effect on either IRRC or ARRC; those only diminished as the pressure rose beyond 200 mmHg. Electric stimulation of heart rate before and after propranolol administration raised both IRRC and ARRC, the latter showing twice the increment of the former. ARRC was also more sensitive to blood Ca2+, as compared to IRRC, that was measured by means of intravenous administration of CaCl2 and sodium citrate. It is concluded that ARRC is more indicative of myocardial relaxation, as compared to IRRC or relaxation time constant.

[Effect of inotropic factors in the postload characteristics of the heart]. / Vliianie inotropnykh faktorov na postnagruzochnye kharakteristiki sertdsa.

It was shown in acute experiments on cats that the post-exercise characteristics of the left ventricle plotted as a dependence between the magnitudes of the maximal blood flow velocity and systolic intraventricular pressure in health and inotropic exposures are close to the linear ones. Adrenaline shifts the post-exercise characteristics upward and to the right, increasing both the maximal magnitude of the blood flow velocity at a zero pressure (velocity component) and the maximal magnitude of the pressure at a zero blood flow (force component), the latter rising to a greater extent. Calcium chloride and obsidan cause a parallel shift of the post-exercise characteristics: the force and velocity components diminish upon obsidan administration, while with CaCl2 they increase.

[Experimental quantitative evaluation of the cardiac pump in function]. / Kolichestvennaia otsenka nasosnoi funktsii serdtsa v éksperimente.

Experimental technique has been developed that makes it possible to change left ventricular after exercise on a wide scale during one beat at an intact circulation. The relationship between the maximal blood flow rate and left ventricular systolic pressure at permanently filled ventricle and inotropic state has been shown close to linear. This relationship (exercise characteristics) can be described by two parameters: maximal systolic blood pressure at blood flow and maximal blood flow ab zero peripheral resistance, and can be used for the assessment of the cardiac pump function.

[Relationship between myocardial contractile activity and the concentration of endogenous prostaglandins in the heart]. / Zavisimost' mezhdu sokratitel'noi aktivnost'iu miokarda i soderzhaniem v serdtse éndogennykh prostaglandinov.

The time-dependent positive correlation between myocardial contractility and myocardial level of prostaglandins (PG) was found after acute pressure overload. The PG level and contractility were observed to correlate well just after aortal stenosis. This correlation became less marked after more prolonged periods of adaptation to overload. A suggestion is made that a rapid increase in the PG content is required for triggering the biochemical mechanism of heart adaptation after the stressful factor.

[2 components of ventricular contractility and their determination based on a noninvasive method]. / Dve komponenty sokratimosti zheludochka serdtsa i ikh opredelenie na osnove neinvazivnoi metodiki.

It is suggested that a force component and a rate component should be distinguished for elaborating the quantitative values of the contractility of the heart ventricle. In experiments the first component is determined as the maximum pressure in the ventricle during isovolumic contraction, and the second component, as the maximum value of the blood flow in the ejection phase at zero afterload. Analysis of the data found in the literature and the results of the authors' experiments provides evidence that the force and rate components differ in their dependence on the hemodynamic conditions. A noninvasive method for determining the contractility components is suggested. Analysis of the clinical data and the literature confirms that the force and rate components change in a different manner in various types of pathological conditions.

[Ultrastructural basis of acute cardiac insufficiency not associated with rhythm disorders]. / Ul'trastrukturnye osnovy ostroi serdechnoi nedostatochnosti, ne sviazannoi s narusheniiami ritma.

On the basis of the data from the literature and own studies the genesis of acute cardiac insufficiency has been shown to be directly associated with a sharp decline in the effectiveness of intracellular energy transportation. A challenging factor in the transformation of the pathological process into acute cardiac insufficiency may consist in one of the three main types of influence: (1) hypoxia of the myocardium, (2) effects causing disorders in the calcium metabolism, and (3) additional mechanical loads on the already affected myocardium. The pattern of the observed ultrastructural changes may be used to a certain extent for the judgement on the type of effect which was most important in the genesis of acute cardiac insufficiency.

[Intracardiac nervous regulation of the systolic and diastolic activity of isolated heart ventricle]. / Vnutriserdechnaia nervnaia reguliatsiia sistolicheskoi i diastolicheskoi aktivnosti zheludochka izolirovannogo serdtsa.

In isolated hearts of cats and frogs, sistolic and diastolic pressure in the ventricle, volume speed, speed of contraction and relaxation, and indexes of contractability and elasticity, were estimated during stretching of the venous receptacle. The data showed that the stretching increased both the sistolic and diastolic activities of the ventricle. Shunting off of the intracardial nervous apparatus prevented these interrelationships. The increase in the ventricle sistolic and diastolic activities due to stimulation of mechanoreceptors of the heart venous receptacles can be regarded as the display of a regulatory activity of intracardial nervous system related to changes of the blood volume coming to the venous receptacles.

[Effect of electric stimulation rate on the indicators of systolic and diastolic activity of the left ventricle]. / Vliianie chastoty elektricheskoi stimuliatsii na pokazateli sistolicheskoi i diastolicheskoi aktivnosti levogo zheludochka.

The interrelationship of the indices of the systolic and diastolic myocardial activity with reference to the cardiac contractions rate was studied in acute experiments in isolated feline hearts. The study had demonstrated that moderate tachycardia (a 30% increase of the cardiac contractions rate) produced a beneficial inotropic effect, and increased the diastolic compliance of the myocardium. Severe tachycardia (a 80--100% increase of the contractions rate) produced a negative inotropic effect decreasing the myocardial compliance. Proceeding from the obtained results a conclusion is drawn that the cardiac contractions rate is an important factor in the regulation of not only the systolic, but also the diastolic myocardial activity.