PHARMACOLOGIC CORRECTION OF CHRONIC ISCHEMIA OF LOWER LIMBS

Abstract

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Purpose of the work was to estimate a pharmacological efficacy of sildenafil (VIAGRA, Pfizer) for therapy of chronic ischemia of lower limbs. Materials and methods of the study: the runs were conducted using white Wistar rates weighed 220-250 g. Experimental animals were divided into groups. 1st group included intact animals (n=20), 2nd group contained sham operated animals (n=20). 3rd group with modeling of cnemises muscles ischemia (n=20), 4th group had modeling of cnemises muscles ischemia + pentoxifylline (n=20)5th group had modeling of cnemises muscles ischemia + sildenafil (n=20). Model of chronic ischemia of a limb was obtained under anastesia of muscles of left cnemis of rats by operative deletion of great vessel parts. Muscles ischemia correction was done for the 4th group animals by means of abdominal administration of pentoxifylline at dose 60 mg/kg and for 5th group by means of sildenafil administration (VIAGRA, Pfizer) at dose 2.2 mg/kg daily during 7 days with the further evaluation of the microcirculation level in cnemis muscles on 21 and 28 day. Microcirculation values were shown in perfusion units (PU). Results: in statistical data processing we calculated an average value, value of a standard deviation. The differences were considered relevant at p<0.05. Average value of microcirculation level in an intact muscle of cnemis of rats amounted to 527±13 PU. In the group of sham operated animals an average value of microcirculation level in the muscles of a left cnemis in all terms does not have relevant differences from the indices in the group of intact animals (518±13 PU on 21st day, p=0.66; 521±16 on 28th day, р=0.77). In the group of cnemis muscle ischemia the level of microcirculation on all terms was relevantly lower than the value in an intact muscle (325±3 PU on 21st day, р<0.05; 371±2 PU on 28th day, р<0.05). There was a slight raise of microcirculation level in the group of animals which were given with pentoxifylline in comparison with a control group. Pentoxifylline has a positive effect on a neoangionesis, but by 28 day microcirculation level does no reach to normal values (334±5 PU on 21st day, р<0.05; 352±2 PU on 28th day, р<0.05). The correction with sildenafil conduced relevant augmentation of a regional blood flow in a ischemic muscle of cnemis comparing with the indices in a third group at the same term (425±4 PU on 21st day, р<0.05; 803±10 PU on 28th day, р<0,05). Microcirculation level in this group on the 21st day approached to the index in the intact animals, and on 28th day was significantly higher. Conclusions: the data obtained allows objective discussion of the fact that sildenafil improves microcirculation in an ischemic muscle of cnemis of rats on the account of neoangiogesis activation. This fact allows continuation and widening of scientific researches in this field.