Modification of the Langendorff system of the isolated beating heart for experimental radiotherapy at a synchrotron: 4000 Gy in a heart beat

Abstract

Microbeam radiotherapy could help to cure malignant tumours which are currently still considered therapy-resistant. With an irradiation target in the thoracic cavity, the heart would be one of the most important organs at risk. To assess the acute adverse effects of microbeam irradiation in the heart, a powerful ex vivo tool was created by combining the Langendorff model of the isolated beating mammalian heart with X-Tream dosimetry. In a first pilot experiment conducted at the Biomedical and Imaging Beamline of the Australian Synchrotron, the system was tested at a microbeam peak dose approximately ten times higher than the anticipated future microbeam irradiation treatment doses. The entire heart was irradiated with a dose of 4000 Gy at a dose rate of >6000 Gy s−1, using an array of 50 µm-wide microbeams spaced at a centre-to-centre distance of 400 µm. Although temporary arrhythmias were seen, they reverted spontaneously to a stable rhythm and no cardiac arrest occurred. This amazing preservation of cardiac function is promising for future therapeutic approaches.

Effects of Microbeam Irradiation on Rodent Esophageal Smooth Muscle Contraction

“…No significant changes regarding baseline tone and maximal contraction force were determined, but the peak latency was found to be increased, and in addition, the maximal force change decreased after MBI. These results align with the findings in cardiac physiological studies [33,34] during and after MBI. In these studies, rodent hearts in the Langendorff perfusion system were irradiated with MBI peak doses up to 400 Gy and 4000 Gy, respectively.…”

“…While the initial focus of MBI development was in the brain, more recent studies have also shown good normal tissue tolerance in the lung [31] and efficiency in treating lung tumors in a small animal model [32]. In an ex vivo study, it was shown that, even with peak doses up to 400 Gy, MBI could be conducted without severe acute effects on cardiac function [33,34]. In addition to the heart, the esophagus is also an organ at risk (OAR) in thoracic irradiation.…”

History of the development of isolated heart perfusion experimental model and its pioneering role in understanding heart physiology

“…Although the experimental model developed by Langendorff and his predecessors has undergone many modifications and alterations, the basic principles and ideas remain relevant in contemporary research. Currently, isolated heart models are extensively used for pharmacological testing, allowing researchers to directly observe the effects of drugs on heart rate, rhythm, contractility, and metabolic pathways without the confounding variables present in whole-animal studies [47][48][49]. They are also crucial in disease modeling, simulating conditions such as ischemia-reperfusion injury, hypertrophy, and heart failure to understand underlying mechanisms and test therapeutic interventions.…”

Research on dynamic perfusion control technology of 3D printed tissue vascular network

“…Researchers from China Pharmaceutical University [8] have optimized and improved the perfusion and culture device in recent years, which can achieve perfusion and culture of mammalian cells in suspension, providing a reference for three-dimensional cell culture technology. Langendorff perfusion method, a famous isolated heart perfusion technology [9] . With the development of cardiovascular research in recent years, this experimental instrument and technology have also made many improvements.…”