Beta-blockers: propranolol, metoprolol, atenolol, pindolol, alprenolol and timolol, manifest atherogenicity on in vitro, ex vivo and in vivo models. Elimination of propranolol atherogenic effects by papaverine.

The addition of the beta-blockers propranolol, metoprolol, atenolol, pindolol, alprenolol and timolol to a culture of peritoneal macrophages or smooth muscle cells induced an increase in the intracellular cholesterol content. Blood serum obtained from a rabbit after a peroral administration of beta-blockers also induced cholesterol accumulation. This property of drug or blood serum obtained after peroral administration is conventionally referred to as atherogenic potential or atherogenicity. Regular administration of propranolol during a 21-day period evoked stable atherogenicity of rabbit blood serum. This was accompanied by stimulation of manifestations of atherosclerosis in the aorta deendothelialized with a balloon catheter. Propranolol increased neointimal thickening, lipid accumulation, an increase in cell number and in the collagen content. In vitro, the combination of propranolol with papaverine eliminated the atherogenic effect of propranolol which manifested itself as stimulation of cholesterol accumulation in cultured cells. Simultaneous peroral administration of propranolol and papaverine prevented the appearance of serum atherogenicity. Papaverine eliminated neointimal thickening, an increase in cell number and in the lipid and collagen contents evoked by propranolol. Papaverine itself had no effect on these parameters. Thus, the atherogenicity of propranolol as well as capacity of papaverine to eliminate beta-blocker atherogenicity revealed in cell culture was confirmed in vivo. We hope that these results may be useful in the development of new drugs and optimization of antiatherosclerotic drug therapy.

Local prevention of thrombosis in animal arteries by means of magnetic targeting of aspirin-loaded red cells.

Thrombosis was induced in 18 dog and 16 rabbit arteries by surgically inverting a vascular wall flap into its lumen. A completely occluding red thrombus was formed inside the vessel 4 to 5 hours later in 80% of cases. SmCo5 magnet was secured externally to one of the arteries. The constant magnetic field produced by the magnet had no influence on the clot formation. Autologous red cells loaded with ferromagnetic colloid compound and aspirin were administered intravenously and completely aborted arteriothrombosis on magnet-supplied side with no deterioratory effect on clot formation in the control artery.

[The structure of the endothelialized and nonendothelialized areas of myointimal thickening of the rabbit aorta]. / Struktura éndotelizirovannoi i neéndotelizirovannoi zon miointimal'nogo utolshcheniia aorty krolika.

De-endothelialization of the abdominal aorta of the rabbit was performed with a balloon catheter. As a result, a partially endothelialized myointimal thickening was formed consisting of smooth myocytes and macrophages. As compared with the zone devoid of the endothelium the endothelialized zone was characterized by less thickness and by the presence of an additional elastic membrane. Great amount of leukocytes and solitary thrombocytes were adhesed just in the place of contact. In the center of nonendothelialized zone no adhesion was observed. In the zone covered by the endothelium smooth myocytes of the synthetic and contractile phenotype were seen with similar frequency. The nonendothelialized zone was presented mainly by smooth myocytes of the synthetic phenotype and macrophages. The myointimal thickening of the rabbit aorta might be considered as an informative model for analysis of myoendothelial interactions.

[Measurement of biological tissue destruction time after exposure to eximer XeCl laser]. / Izmerenie vremeni razrusheniia biotkani pri deistvii izlucheniia éksimernogo XeCl-lazera.

Relationship between atherosclerotic patch destruction time under UV light from a XeCl laser and energy density of 1.3-4.7 J/cm2 has been studied experimentally. As energy density increased, the destruction time, estimated on the basis of exploring product release by continuous-wave He-Ne laser, decrease from 40 to 3.5 microseconds.

[Thrombogenic properties of the inner vascular surface following laser exposure]. / Trombogennye svoistva vnutrennei poverkhnosti sosuda posle lazernogovozdeistviia.

Laser angioplasty, using YAG-neodymium laser and a balloon catheter with monofiber quartz light guide (400 micron), introduced into its central canal, was performed in 8 dogs with thromboses of 11 femoral or carotid arteries. Average energy expenditure for recanalization was 26 +/- 4 J, with 4.9 +/- 0.3 W and exposure time of 5.1 +/- 0.7 s. Re-thrombosis developed after 5 to 10 days in all arteries, left in the circulation network after laser angioplasty. The latter part of the study is dealing with the assessment of the surface of femoral or carotid arteries of the dogs after laser exposure. This was done by quantitation of the adhered platelets after platelet-enriched plasma was circulated through vessels, whose inner surface was 1) intact, 2) de-endothelized, or 3) laser-damaged, using a scanning electron microscope. The thrombogenic index was 65-96, 85 and 66%, respectively, for the YAG-neodymium, argon and eximeric (XeCl) lasers.

[Comparison of the thrombogenic properties of vascular wall after exposure to different lasers]. / Sravnenie trombogennykh svoistv sosudistoi stenki posle deistviia razlichnykh lazerov.

Quantitative thrombogenic assessment of the inner arterial surface after laser exposure was made in 33 experiments with peripheral arterial strips of dogs. In one experiment, vascular strips with native, mechanically de-endotheliazed or laser-damaged surface were consecutively placed in a platelet-enriched plasma recirculation system, after which platelet adhesion was estimated on vascular surface of the three types, using a scanning electron microscope, and the relative thrombogenic index was calculated. The laser models used included: 1) the AIG-neodymium model, 1.06 micron; 2) the argon model with visible (488 and 514 nm) and ultraviolet (350 nm) spectra; 3) the XeCl excimer type, 308 nm, as well as a preheated metal rod, imitating a ceramic or metal tip of the light guide outlet. The thrombogenic index was 83 +/- 7; 72 +/- 8; 57 +/- 9; 63 +/- 7 and 82 +/- 9%, respectively, for the above types of exposure, the differences being virtually insignificant. It is suggested that, irrespective of the type of laser employed, laser angioplasty should at least be accompanied with intensive anticoagulant therapy.

[Structure of the neointima after balloon catheter injury of the rabbit aorta in the context of hypercholesterolemia: analysis of endothelial influence on lipid accumulation]. / Struktura neointimy aorty krolika posle povrezhdeniia ballonnym kateterom na fone giperkholesterinemii: analiz vliianiia éndoteliia na nakoplenie lipidov.

Balloon catheter de-endothelialization of abdominal aorta of cholesterol-fed rabbits was performed. As a result, partly endothelialized neointima was formed, consisting of smooth muscle cells and macrophages. Neutral lipids stored more intensely in non-endothelialized part of neointima. Preferential intracellular lipid accumulation in this area was observed while predominantly extracellular lipid accumulation was found in endothelium-covered part of neointima. It is supposed that endothelium inhibits intracellular lipid accumulation and at the same time stimulates an extracellular one, but as a whole it reduces the density of lipid inclusions in neointima.

[Clinical and hemodynamic evaluation of the effectiveness of plasmapheresis in high arterial hypertension refractory to drug treatment agents]. / Klinicheskaia i gemodinamicheskaia otsenka éffektivnosti plazmafereza pri vysokoi arterial'noi gipertonii, refrakternoi k medikamentoznym sredstvam lecheniia.

Indices of central hemodynamics based on tetrapolar rheography results with subsequent calculation of left ventricular post-load characteristics were studied in parallel with the assessment of clinical efficacy of plasmapheresis in 36 patients with therapy-resistant severe arterial hypertension. Plasmapheresis in severe arterial hypertension resulted not only in BP reduction and overcoming of refractoriness to medical therapy but also produced a beneficial effect on the cardiovascular system improving left ventricular post-load characteristics.

[Bicomponent analysis of the contractile capacity of the heart in ischemic lesions of the myocardium (experimento-clinical study)]. / Dvukhkomponentnyi analiz sokratitel'noisposobnosti serdtsa pri ishemicheskikh porazheniiakh miokarda (eksperimental'no-klinicheskoe issledovanie).

A study was made of cardiac pumping capacity in animals with local myocardial ischemia (9 experiments on cats), in 25 healthy persons and 21 patients suffering from coronary heart disease with stage I-IIA circulatory insufficiency using afterload characteristics (ALC). The latter reflected correlation between left ventricular pressure and aortic blood flow in constant blood filling and in a given inotropic heart condition. For combined assessment of ALC one should know its two parameters: power (maximum pressure in the zero blood flow) and rate (maximum blood flow rate in zero antipressure). It was shown that early stages of cardiac insufficiency were characterized both under experimental and clinical conditions by change in the inclination angle of an afterload curve and a shift of a working point on it to the right.

[Effect of absorption of laser radiation on the destruction threshold of pathologic tissue in laser angioplasty]. / Vliianie pogloshcheniia lazernogo izlucheniia gemoglobinom krovi na porog razrusheniia patologicheskoi tkani pri lazernoi angioplastike.

With laser angioplasty the hemoglobin absorbtion effect on the demolishing of the pathological objects was taken into consideration. It was stated that this effect is high for argon lasers (lambda = 0.488 = 0.514 microns) and insignificant for solid state laser (lambda = 1.064 microns). In this respect growth of laser capacity practically is not increasing the efficiency of the pathological objects destruction at a distance not more than 1 mm from the out-put of the light-guide.

[Laser angioplasty of peripheral arteries]. / Lazernaia angioplastika perifericheskikh arterii.

The first experience in laser angioplasty of the superficial femoral artery in 5 patients is discussed. Local occlusion or critical stenosis (90% and more) of the vessel with signs of disturbed blood supply to the limb were the indications for the intervention. For conducting laser angioplasty the authors used an AIG-neodymium laser (1.06 microns) and a light guide of their own design which allowed a canal of no less than 3.1-3.9 mm in diameter to be formed in the plaque. Patency of the artery was restored in all 5 cases and a satisfactory clinical effect was produced. Thrombosis of the recanalized segment occurred on the 12th day after angioplasty in one case. The prospects of the method and the means of further studies are discussed.

[Thrombolytic action of urokinase preparation covalently bound to modified thrombin]. / Tromboliticheskoe deistvie preparata urokinazy, kovalentno sviazannoi s modifitsirovannym trombinom.

Urokinase was covalently bounded with modified thrombin. Thrombin was modified by carbodiimide and 1, 12-dodecamethylenediamine. In this conjugate thrombin is not catalytically active and does not induce platelets aggregation. The catalytic properties of modified urokinase do not essentially differ from native enzyme but its thermostability increases. The modified urokinase thrombolytic effect is at least 10-fold higher than the native one. In femoral arteries of experimental thrombosis the conjugate urokinase-thrombin brings about total thrombolytic effect as early as 1.5 hours after injection (2500 IU per 1 kg of the animals weight). The causes of the observed effect were discussed.

[Local prevention of thrombosis in the dog carotid artery using magnetically concentrated erythrocytes loaded with aspirin]. / Lokal'noe predotvrashchenie tromboza v sonnoi arterii sobake s pomoshch'iu magnitnogo kontsentrirovaniia éritrotsitov, nagruzhennykh aspirinom.

Thrombosis was induced in both canine carotid arteries by means of vascular wall flap inversion into their lumens. A red, completely occluding thrombus was formed inside the vessel 4 to 5 hours later. SmCo5 magnet was secured externally to one of the arteries. The constant magnetic field produced by the magnet had no influence on the clot formation. Autologous red cells loaded with ferromagnetic colloid compound and aspirin were administered intravenously through the hind paw route; total aspirin pool was 20 micrograms. Circulating magnetically-charged red cells have been earlier shown to concentrate in a canine artery in the constant magnet area. The administration of magnetically-charged red cells loaded with aspirin completely prevented arterial thrombosis in the magnet-supplied artery, having no detrimental effect on clot formation in the control artery.

Magnetically driven thrombolytic preparation containing immobilized streptokinase-targeted transport and action.

Streptokinase was immobilized on the magnetic carrier at a concentration of 2,000-2,700 IU/ml of preparation. Thrombosis was induced in both canine carotid arteries by means of the vascular wall flap inverting into its lumen. The red, completely occluding thrombus was formed inside the vessel 4-5 h later. A samarium-cobalt magnet was secured externally to one of the arteries. After the clot formation the magnetically immobilized streptokinase was injected intravenously. The preparation concentrated in the region of the magnetic field action caused complete thrombus degradation and normal blood flow restoration; no effect on the clot in the control artery was observed.

[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.

Evaluation of the heart pump function by afterload intracardiac pressure and blood flow measurements in cats.

In experiments carried out on cats and by using a mathematical model the authors studied afterload characteristics of the left ventricle of normal and hypertrophied heart. They found that afterload characteristics, expressed by a relationship between left ventricular systolic pressure and the aortic blood flow rate, have both in a normal as well as in a hypertrophied heart a nearly linear character, do not depend on the elastic properties of the aorta, and can be described by two parameters: the force parameter--i.e. maximum pressure at zero flow (Pm), and the rate parameter--i.e. the maximum flow value at zero pressure (Qm). Afterload characteristics change at inotropic influences: positive inotropic effects shift the characteristics upward and rightward, negative inotropic action shifts them downward and leftward. In moderate hypertrophy, Pm and Qm increase, with the increase in Qm being greater. The parameters of afterload characteristics can be used as pump function indexes characterizing the heart's ability to cope with the load in the outflow tract.