Experimental model of acute blood loss using rats for screening evalution of non-specific activity of infusion solutions

Abstract

BACKGROUND: In accordance with the current regulations, preclinical evaluation of the effectiveness of plasma substitutes for acute blood loss is carried out mainly on large laboratory animals (dogs, pigs) using a wide range of methods for assessing the structural and functional state of organs and systems of a biological object. It requires large expenditure of material resources and time, which is impractical at the stage of screening the effectiveness of newly developed infusion agents. In this regard, an urgent task is to develop a standardized model of acute blood loss on small laboratory animals for screening evaluation of the specific activity of infusion solutions with a subsequent research involving large laboratory animals. It is advisable to use laboratory rats as a biological object as they are the most suitable of the group of small laboratory animals for similarity of physiological laboratory indicators with humans.
 AIM: To develop a model of acute blood loss using small laboratory animals for screening evaluation of specific infusion solution activity.
 MATERIALS AND METHODS: Experiments were carried out on rats of the Vistar line with a weight of 330 41 g. The animals were divided into 3 groups: 1 experimental (20 individuals with acute blood loss simulation without treatment), 2 experimental (20 individuals with acute blood loss simulation and its replacement with Rheopolyglucin), intact (10 individuals without modeling of blood loss). The study design included: general anesthesia (intramuscular injection Zoletil 100 and Xylazin 2% in a ratio of 1 : 5 at the rate of 0.01 ml/kg of weight), catheterization of the femoral artery followed by controlled hardware exfusion of blood at a rate of 0.5 ml/min until the establishment of persistent (for 2 minutes) arterial hypotension; hardware synchronous monitoring of mean arterial pressure (MAP) (by direct tonometry through the contralateral femoral artery); calculation of the percentage of blood loss from the estimated circulating blood volume (CBV) equal to 5% of the animals weight; heart rate (HR) (by electrocardiogram) during the first three hours after blood exfusion. In its capacity as a test drug Rheopolyglucin, which was administered through an arterial femoral catheter immediately after blood exfusion in volume and speed, equal to volume and speed of exfusion, was used. Additionally, for a comprehensive assessment of the mechanisms of maintaining hemodynamic parameters individual dynamic calculated indicators for each individual are proposed: the reduced shock volume of blood and the infusion efficiency indicator.
 RESULTS: All rats in the experimental group died, 25% of which 1720 minutes after blood exfusion, 75% in range from 45 to 90 minutes. Rheopoliglyukin infusion reduced the death of animals by up to 35% and delayed the average death time to 4555 minutes. A single exfusion of blood in rats resulted in loss of 79 ml of blood (4651% of circulating blood volume), which was accompanied by a decrease in mean arterial pressure and heart rate. Compensation for the decrease in circulating blood volume, including due to infusion, was manifested by an increase in these indicators. A sign of inefficiency of compensation was a slight increase of mean arterial pressure with dynamically increasing heart rate. It is proved that an increase in the values of calculated indicators (the given stroke volume of blood and the infusion efficiency indicator) are benchmarks for effective compensation of hemodynamic disorders, including as a result of infusion of hemodynamic drugs.
 CONCLUSIONS: The acute blood loss model with the calculation of the reduced shock volume of blood and the infusion efficiency index is advisable to use to assess the specific activity of infusion solutions in acute blood loss.

Pre-clinical evaluation of effectiveness of infusion solutions with different osmolarity during acute blood loss in experiments on rats

“…В результате кровопотери 50 % ОЦК у всех животных развивалась стойкая гипотония, приводящая к снижению показателей СрАД, ЧСС и ЧДД. Все животные контрольной группы (без восполнения ОЦК) погибли, что подтверждает тяжесть выбранной модели кровопотери [12]; смерть животных в контрольной группе наступала в период, сопоставимый с периодом после начала инфузии в опытных группах, что позволяет говорить о равной тяжести кровопотери. У крыс опытных групп после инфузии исследуемых растворов к 5 мин отмечалось повышение СрАД до 88-94 % от исходного уровня, одновременное восстановление ЧСС и ЧДД указывало на по- В результате эксфузии крови у всех животных развивался метаболический ацидоз, уменьшались рН, насыщение крови кислородом, щелочной резерв крови.…”