[A sharp increase in the density of pulmonary and pericardial mast cells under monocrotaline-induced pulmonary hypertension in rats].

Multifunctional granular mast cells (MCs) are involved in various pathological processes. The response of MC populations of myocardium, pericardium and lung to pulmonary hypertension (PH) has been studies 8 weeks after injection of monocrotaline. Five intact and five experimental rats were used. The density of MCs of different maturity was estimated on paraffin sections stained with Alcian blue and Safranin. Expressiveness of PH was estimated by functional parameters with the help of echocardiograms and by morphological markers. The MC density in myocardium of the intact and experimental rats was relatively low: 2 to 4 cells/mm2. MC density in the pericardium of intact rats was 14 times higher than in myocardium and increased 3 times for PH. The mature Safranin-positive cells predominated (70-80%) in myocardium and pericardium of intact and experimental rats. The MC density in the lungs of intact rats was about 30 cells/mm2; 98% of these cells were immature Alcian-positive cells. The mean density of MCs in the lungs of rats with PH increased 5.6 times. The mature Safranin-positive cells appeared in the lungs of rats with severe pathology. The greatest number of MCs in lungs was in the rats with the most pronounced disorders of myocardium function and marked histological damages (injuries) of myocardium and lungs. The finding show active response of MC population to monocrotaline-induced PH that stimulates migration of immature MCs into pericardium and lungs from the outside. Our data indicate the important role of MCs in the pathogenesis of PH.

[Effect of renin-angiotensin system inhibitors on the density of myocardial, pericardial and pulmonary rat mast cells under experimental heart failure].

Activation of the renin-angiotensin system (RAS) plays a critical role in the pathogenesis of heart failure (HF). We studied the effect of lisinopril (LP) and fosinopril (FP), the inhibitors of angiotensin-converting enzyme, and of losartan (LT), the antagonist of Angiotensin II receptors, on the behavior of multifunctional mast cells (MCs) under experimental HF. The inhibitors of RAS were daily injected during 4 weeks in 4 weeks after two (at 24-h interval) isoproterenol injections. MCs of different degrees of maturity were identified on paraffin sections stained with Alcian blue and Safranin. Expressiveness of HF was estimated by functional parameters with the help of echocardiogram and by morphological markers. The MC density in the myocardium of the intact rats as well as of the rats with HF, both treated and untreated with the preparations, was relatively low: from 3 to 4 cells/mm2. The MC density in the pericardium of the intact rats was several times higher than in the myocardium: 35 +/- 7 cells/mm2. The density ofpericardial MC under HF was 1.7 higher than that in the intact rats at the expense of the increase in the density of Alcian-positive immature cells (P < 0.05). The injections of LP increased the MC density still in 1.4 times at the expense of the density of Safranin-positive mature cells (P < 0.01). The injections of FP and LT had no influence on the MC density and the balance of cells of different degrees of maturity in the pericardium. 96-99% of MCs in lung were Alcian-positive cells. The density of such cells in the intact rats, in the rats with HF, and in the rats with HF treated with FP was 30 cells/mm2. The injections of LP and LT decreased the density of pulmonary MCs up to 7 cells/mm2 (P < 0.01) and 19 cells/mm2 (P < 0.05), respectively. Functional parameters of the hearts were consistent with the data of morphological analyses. Myocardium function improvement was noted only in the rats with HF treated with FP and LT. The reaction of MCs (as cell elements of "tissue" RAS) to injections of inhibitors of RAS was various in the myocardium, pericardium and lung of the rats with HF. The injections of LP stimulated maturation of the resident MCs in the pericardium and the replenishment of the population through immature cells migrating from the outside. It allows us to suppose an intensification of secretory activity of the cells. In contrast, the injections of LP and LT reduced the pulmonary MC population.

[The density of myocardial and pericardial rat mast cells in isoproterenol-induced heart failure].

Myocardial mast cells (MC) respond to cardiovascular pathology. The behavior of MC population in myocardium and pericardium of rats has been studied 24 h, 14, 28 and 60 days after two isoproterenol injections (at 24 h intervals). The extent of heart failure has been estimated by supersonic inspection 28 and 60 days after isoproterenol injections. The density of MCs of different degrees of maturity was estimated on paraffin sections stained with Alcian blue--Safranin. The MC density in myocardium of intact and experimental rats was relatively low: from 4 to 6 cells/mm2. The MC density in pericardium of intact rats was several times higher than in myocardium: 48.6 +/- 13.0 cells/mm2. In 24 h and 14 days after isoproterenol injections the pericardial MC density was 1.5 times higher than in control rats (P < 0.05) at the expense of increase in the number of mature MCs with Safranine-positive granules without the increase in the number of immature cells with Alcian blue-positive granules. In 28 days the pericardial MC density was 2 times higher than in intact rats (P < 0.05) at the expense of increase in number of immature and mature cells. In 60 days after isoproterenol injections the pericardial MC density and the ratio of immature and mature cells compared with control did not reach statistical significance. The changes in pericardial MC population corresponded to severity of heart failure according to functional indices. The findings show active reaction of pericardial MCs on myocardium dysfunction that stimulates the maturation of resident immature MCs in pericardium and migration of immature cells to pericardium of damage heart.

[Comparative characteristics of some pharmacological models of chronic heart failure].

Effectiveness and informativity of various experimental pharmacological models of the chronic heart failure (CCF) in rats have been evaluated by means of ultrasonic cardiography. It has been established that isoproterenol (INN isoprenaline) (80 mg/kg, s.c., twice with an interval of 24 h) produces compensated CCF. Monocrotaline (single dose 60 mg/kg, i.p.) caused the development of pulmonary hypertension, right ventricle hypertrophy, and pronounced right ventricle failure in a fraction of experimental rats. Doxorubicin administration (cumulative doze 15 mg/kg, i.p., divided into 6 injections within 14 days) resulted in decreased left ventricle contractility, eccentric heart remodeling, and CCF development in most cases. Thus, the doxorubicin-induced disorder in rats can be considered the most effective pharmacological model of CCF, leading to the development of pronounced and progressive CCF in the majority of experimental animals.