Miklosz Joanna, Kalaska Bartlomiej, Zajaczkowski Stanislaw, Pawlak Dariusz, Mogielnicki Andrzej
Department of Pharmacodynamics, Medical University of Bialystok, 15-089 Bialystok, Poland.
Department of Physiology, Medical University of Gdansk, 80-211 Gdansk, Poland.
Pharmaceuticals (Basel). 2021 Nov 25;14(12):1223. doi: 10.3390/ph14121223.
The methods used in preclinical studies should minimize the suffering and the number of animals but still provide precise and consistent results enabling the introduction of drug candidates into the phase of clinical trials. Thus, we aimed to develop a method allowing us to perform preliminary safety and toxicity studies of candidates for human medicines, while reducing the number of animals. We have devised a method based on a combination of two devices: Plugsys (Transonics System Inc., Ithaca, NY, USA) and PhysioSuite (Kent Scientific Corporation, Torrington, CT, USA), which allow simultaneous registration of nine circulatory and respiratory parameters, and body temperature. Vehicle and adrenaline, or nitroglycerin, as reference substances were administered into the right femoral vein of Wistar rats. Physiological conditions were registered over 60 min after drug administration by measuring systolic, diastolic and mean blood pressure, heart rate (HR), blood perfusion of paw vessels, blood oxygen saturation, respiratory rate, average and peak exhaled CO, and body temperature. Blood pressure was measured by cannula placed in the left common carotid artery and connected to the pressure transducer (Plugsys). The other parameters were measured by the PhysioSuite. Adrenaline-induced immediate dose-related hypertension and nitroglycerin hypotension were correlated with the change in blood perfusion. They both increased HR. Adrenaline decreased blood oxygen saturation and slightly affected respiratory parameters, while nitroglycerin caused a progressive increase in respiratory rate and a decrease in the peak of exhaled CO. Our method may become an inseparable part of the preliminary safety and toxicity studies of tested drugs, while being an important step towards improving animal welfare.
临床前研究中使用的方法应尽量减少动物的痛苦和数量，但仍能提供精确且一致的结果，以便将候选药物引入临床试验阶段。因此，我们旨在开发一种方法，既能对人类药物候选物进行初步安全性和毒性研究，又能减少动物数量。我们设计了一种基于两种设备组合的方法：Plugsys（美国纽约州伊萨卡市的Transonics System Inc.）和PhysioSuite（美国康涅狄格州托灵顿市的Kent Scientific Corporation），这两种设备可同时记录九个循环和呼吸参数以及体温。将赋形剂和作为参考物质的肾上腺素或硝酸甘油注入Wistar大鼠的右股静脉。给药后60分钟内，通过测量收缩压、舒张压和平均血压、心率（HR）、爪部血管的血液灌注、血氧饱和度、呼吸频率、呼出CO的平均值和峰值以及体温来记录生理状况。血压通过置于左颈总动脉并连接到压力传感器（Plugsys）的插管进行测量。其他参数由PhysioSuite测量。肾上腺素引起的即时剂量相关高血压和硝酸甘油引起的低血压与血液灌注变化相关。它们均使心率增加。肾上腺素降低了血氧饱和度并对呼吸参数有轻微影响，而硝酸甘油则导致呼吸频率逐渐增加和呼出CO峰值降低。我们的方法可能会成为受试药物初步安全性和毒性研究中不可或缺的一部分，同时也是改善动物福利的重要一步。
