Microbeam Irradiation of the Beating Rodent Heart: An Ex Vivo Study of Acute and Subacute Effects on Cardiac Function

Lange, Falko; Kirschstein, Timo; Davis, Joel; Paino, Jason; Barnes, Micah; Klein, Mitzi; Porath, Katrin; Stöhlmacher, Paula; Fiedler, Stefan; Frank, Marcus; Köhling, Rüdiger; Hildebrandt, Guido; Häusermann, Daniel M.; Lerch, Michael L. F; Schültke, Elisabeth

doi:10.1016/j.ijrobp.2022.05.001

Cited by 2 publications

(6 citation statements)

References 38 publications

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“…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.…”

Section: Discussionsupporting

confidence: 91%

“…In these studies, rodent hearts in the Langendorff perfusion system were irradiated with MBI peak doses up to 400 Gy and 4000 Gy, respectively. Up to MBI peak doses of 400 Gy, no acute or subacute severe effects on cardiac function were observed [33,34]. No significant changes in ventricular or aortic pressure were found, and no structural alterations occurred [34].…”

Section: Discussionmentioning

confidence: 91%

“…Up to MBI peak doses of 400 Gy, no acute or subacute severe effects on cardiac function were observed [33,34]. No significant changes in ventricular or aortic pressure were found, and no structural alterations occurred [34]. Even after irradiation with MBI peak doses of 4000 Gy, only temporary arrhythmia occurred, which converted back to sinus rhythm spontaneously [33].…”

Section: Discussionmentioning

confidence: 96%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Microbeam Irradiation on Rodent Esophageal Smooth Muscle Contraction

Frerker

Fiedler

Kirschstein

et al. 2022

Cells

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Background: High-dose-rate radiotherapy has shown promising results with respect to normal tissue preservation. We developed an ex vivo model to study the physiological effects of experimental radiotherapy in the rodent esophageal smooth muscle. Methods: We assessed the physiological parameters of the esophageal function in ex vivo preparations of the proximal, middle, and distal segments in the organ bath. High-dose-rate synchrotron irradiation was conducted using both the microbeam irradiation (MBI) technique with peak doses greater than 200 Gy and broadbeam irradiation (BBI) with doses ranging between 3.5–4 Gy. Results: Neither MBI nor BBI affected the function of the contractile apparatus. While peak latency and maximal force change were not affected in the BBI group, and no changes were seen in the proximal esophagus segments after MBI, a significant increase in peak latency and a decrease in maximal force change was observed in the middle and distal esophageal segments. Conclusion: No severe changes in physiological parameters of esophageal contraction were determined after high-dose-rate radiotherapy in our model, but our results indicate a delayed esophageal function. From the clinical perspective, the observed increase in peak latency and decreased maximal force change may indicate delayed esophageal transit.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Effects of Microbeam Irradiation on Rodent Esophageal Smooth Muscle Contraction

Frerker

Fiedler

Kirschstein

et al. 2022

Cells

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“…More recent research in vivo has also moved lung carcinoma into focus as a potential treatment target [6]. So far, only ex vivo studies have been conducted to assess potential adverse effects in OaR with an irradiation target in the thoracic cavity, in the explanted beating heart [10,11] and the oesophagus during MRT [12].…”

Section: Introductionmentioning

confidence: 99%

The Spinal Cord as Organ of Risk: Assessment for Acute and Subacute Neurological Adverse Effects after Microbeam Radiotherapy in a Rodent Model

Jaekel

Paino

Engels

et al. 2023

Cancers

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Microbeam radiotherapy (MRT), a high dose rate radiotherapy technique using spatial dose fractionation at the micrometre range, has shown a high therapeutic efficacy in vivo in different tumour entities, including lung cancer. We have conducted a toxicity study for the spinal cord as organ of risk during irradiation of a target in the thoracic cavity. In young adult rats, the lower thoracic spinal cord was irradiated over a length of 2 cm with an array of quasi-parallel microbeams of 50 µm width, spaced at a centre-to-centre distance of 400 µm, with MRT peak doses up to 800 Gy. No acute or subacute adverse effects were observed within the first week after irradiation up to MRT peak doses of 400 Gy. No significant differences were seen between irradiated animals and non-irradiated controls in motor function and sensitivity, open field test and somatosensory evoked potentials (SSEP). After irradiation with MRT peak doses of 450–800 Gy, dose-dependent neurologic signs occurred. Provided that long-term studies do not reveal significant morbidity due to late toxicity, an MRT dose of 400 Gy can be considered safe for the spinal cord in the tested beam geometry and field size.

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Microbeam Irradiation of the Beating Rodent Heart: An Ex Vivo Study of Acute and Subacute Effects on Cardiac Function

Cited by 2 publications

References 38 publications

Effects of Microbeam Irradiation on Rodent Esophageal Smooth Muscle Contraction

Effects of Microbeam Irradiation on Rodent Esophageal Smooth Muscle Contraction

The Spinal Cord as Organ of Risk: Assessment for Acute and Subacute Neurological Adverse Effects after Microbeam Radiotherapy in a Rodent Model

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