Cardiovascular Safety Assessment of Medicines in Preclinical In vivo Studies: A Review

INTRODUCTION. The cardiovascular safety evaluation of medicines using in vivo models is a necessary preclinical step that is performed either in safety pharmacology studies or in toxicity studies. The design of safety pharmacology studies primarily involves assessing the potential of a test substance to prolong cardiac ventricular repolarisation, without in-depth investigation of potential structural damage to the heart and blood vessels. Toxicity studies usually do not include electrophysiological testing. The regulatory standards of the Eurasian Economic Union (EAEU) and the International Council for Harmonisation (ICH) lack detailed guidance on the use of specific markers of cardiovascular dysfunction.

AIM. This study aimed to develop an integrated approach to assessing the cardiac and vascular toxicity of medicinal products in preclinical in vivo studies.

DISCUSSION. Cardiovascular function can be assessed in both small laboratory animals (rodents) and larger animals, such as rabbits, ferrets, dogs, minipigs, and primates. The toxic effects of a test medicinal product on the cardiovascular system of animals may be manifested as physiological, biochemical, and structural changes in the systems and organs. Therefore, the assessment of cardiovascular function should be based on a combination of instrumental, laboratory, and histological methods. First of all, physiological and laboratory studies are applicable. It is recommended to perform electrocardiography, heart rate and blood pressure measurements, and quantification of markers of cardiovascular dysfunction and structural cell damage. For more in-depth analysis, histological and immunohistochemical studies of cardiac and vascular tissues are recommended to assess changes at the tissue and cellular levels.

CONCLUSIONS. An effective strategy for detecting cardiovascular disorders is the use of an integrated approach that, on the one hand, facilitates a comprehensive assessment of the possible toxic effects of a medicinal product and, on the other hand, increases the translational potential of the data obtained at the preclinical stage of research.

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