A modified heterotopic heart transplantation in the rat – as an important model in experimental regeneration and replacement of the failing organ

Abstract

The qualification of new knowledge is one of the oldest problems in experimental medicine that provides a link between fundamental discovery, hypothesis, ‘proof of concept’ preclinical studies and development of clinical trials. The biggest challenge in animal models is the proper evaluation of all the aspects that are crucial in specific studied pathologies as well as the prediction of their progression. The aim of this review was to describe and discuss the rat animal model of heart transplant. The rat model of heart transplantation is an excellent yet underestimated method of research of prevention, monitoring and treatment of acute and chronic, immune and nonimmune response to organ transplantation. Despite being a technically and logistically demanding model, it provides a tool for reproducible experiments with longterm animal survival and excellent graft survival.

Animal Models for Heart Transplantation Focusing on the Pathological Conditions

“…However, the left ventricle (LV) of the transplanted heart does not beat spontaneously and lacks hemodynamics, leading to alterations in cardiac physiology, myocardial degeneration, and atrophy. The outcome of heterotopic cardiac transplantation may deviate from actual clinical circumstances [2,31]. Based on the mouse abdominal heterotopic heart transplantation model, Klein et al implanted balloons in the LV of the donor graft to maintain the isovolumic work of the heart to reduce the damage caused by the absence of LV work in the donor graft [32].…”

“…Rodents, rabbits, and guinea pigs are frequently used in heart transplantation experiments [1]. The use of small animals in these experiments is advantageous because of their smaller size, higher metabolic rate, higher reproductive rate, ease of handling, and lower cost [1][2][3]. Because there are numerous genetically well-characterized strains of rats and mice, these small animals have been used as model organisms in most heart transplantation studies.…”

“…Using transgenic or gene knockout strains with clear genetic information permits the creation of specific pathological environments and the simulation of specific rejection responses, such as cell-or antibody-mediated alloreactive immune responses and rejection-induced vasculopathy. These models enable researchers to stimulate the rejection of a cell-or an antibody-mediated alloreactive immune response and elucidate the molecular mechanisms of rejection after transplantation to develop effective interventions [2,3]. Large-animal model organisms, including canines, pigs, and non-human primates, rather than small animal model organisms, are used for distinct research purposes [1].…”