Bauer, J.

Bert, C.

Constantinescu, A.

Debus, J.

Durante, M.

Graeff, C.

Haberer, T.

Hauswald, H.

Kaderka, R.

Korkmaz, S.

Lehmann, H. I.

Packer, D. L.

Prall, M.

Prokesch, H.

Richter, D.

Sonnenberg, K.

Szabo, G.

Weymann, A.

GSI Repository

Heavy Ion Beam Irradiation of a Langendorff HeartMatthias Prall1, J. Bauer2, A. Constantinescu1, J. Debus2, M. Durante1, C. Graeff1, T. Haberer2, H.Hauswald2, H. I. Lehmann4, D. L. Packer4, H. Prokesch2, D. Richter2, K. Sonnenberg2, G. Szabo´2, R.Kaderka1, S. Korkmaz2, A. Weymann2, and C. Bert31GSI, Darmstadt, Germany; 2Universita¨tsklinikum Heidelberg, Germany; 3Universita¨tsklinikum Erlangen, Germany;4Mayo Clinic College of Medicine, Rochester, MN, USAThe Biophysics group at GSI is currently starting exper-imental studies on radiosurgery of atrial fibrillation (AF)using 12C beams. AF is one of the most common heartdiseases. Its prevalence increases with age (< 0.5% in agegroup below 40, 0.7 % in the age group 55-59 and 17.8%in the age group above 85). In AF, disorganized electricalimpulses usually originating in the pulmonary veins causeuncoordinated high frequent (300 - 600 min−1) contrac-tions of the atria (upper heart chambers). Symptoms arelow blood pressure, shortness of breath, chest pain, irreg-ular/racing heart beat or extreme fatigue. AF is responsi-ble for 15-20 % of ischemic strokes. A common treatmentis the interruption of electric pathways in the heart usingcatheter ablation. This surgical procedure is challenging,long (about 7 hours), only 52 % of patients can stop med-ication, 25% are treated at least twice and 6 % suffer fromserious complications related to this intervention. A recentstudy has already demonstrated radiosurgery of the heart inlive pigs using photons [1]. Our aim is to reproduce theseresults while improving target conformity and healthy tis-sue sparing using 12C. Experiments with pigs and doses inthe order of 30 Gy will be performed at GSI in 2014. Sim-ilarly to [1], the physiological effect is expected to evolveon the time scale of weeks to months.The present report describes a pilot study in which we ir-radiated a small region in explanted pig hearts at HIT Hei-delberg with very high doses (up to 160 Gy). The purposewas to gain knowledge about possible acute radiation ef-fects (time scale of hours) resulting from 12C-irradiation.These would be disadvantageous in our pig experiment. Inour pilot study we applied dose to the atrioventricular (AV)node as here, a block of electrical conduction can accu-rately be identified in an ECG trace in real-time.In each of our three experiments, a heart was extractedfrom a pig (≈ 30 Kg) and kept in sinus rhythm in a so-called Langendorff setup (cf. Figs 1 and 2) for up to 7 h.The heart was perfused with Krebs-Henseleit (KH) solu-tion via the coronary arteries (flow about 0.5 l/min). Usingsurgical wire it was fixed in a custom-built PMMA beaker(cf. Fig 2) in a bath of KH. The main circuit of our setupcontained about 2 litres of KH. Carbogen gas (95% O2, 5%CO2) was used to aerate the solution. About every 30 min.,0.5 l of KH were exchanged to prevent acidfication. Thetemperature of the KH solution was kept at T = 37◦C viaheated water flowing through a heat exchanger in the oxy-genator and the outer volume of the double-walled PMMAbeaker. The heart beat induced motion of the myocardiumwas up to 1 cm. Prior to irradiation, the heart was scannedwith 1 mm slice spacing in a PET/CT. The target (AV node)was delineated in the scans. A margin of 1 cm aroundthe target volume (≈ 1.25 cm3) was added to compensatemotion. The initial alignment in the treatment room wasperformed using room lasers and fiducials attached to thebeaker. Orthogonal x-ray images showing titanium clips at-tached to the heart were finally used to optimize the matchwith the CT images. Finally, dose was applied in fractionsof 5 Gy and 10 Gy over a period of about 3 h. PET and CTscans were made after each experiment.oxygenator bubble catcherheat pump carbogen gasmulti-channelpump Krebs-Henseleit main circuit (≈ 2 litres)2 cannulas towards coronary arteriesspent Krebs-Henseleitvalveheat pumppump fresh Krebs-Henseleit (37°C)Figure 1: Sketch of the Langendorff setup. The main KHcircuit is drawn in red.beakerECG leads beam windowtubes for water heatingand KHFigure 2: The heart in the double-walled PMMA beakeron the patient couch in the treatment room H1 at HIT. Theheart is fixed to the bottom of the beaker with surgical wire.In our three experiments, we applied a cumulative doseof 80, 90 and 160 Gy to the AV node. Whereas no acuteradiation effects could be observed in the first two cases, ablock of electrical conduction in the AV node could clearlybe identified in the ECG after 160 Gy. On the one hand,this proves that it is possible to influence the electrical con-duction system of the heart using 12C beams. On the otherhand our pilot study implies that no acute (adverse) radi-ation effects have to be expected while performing a pigexperiment using doses in the order of 30 Gy.References[1] A. Sharma et al. Heart Rhythm. 2010 Jun;7(6):802-10BIOPHYSICS-48 GSI SCIENTIFIC REPORT 2013250 doi:10.15120/GR-2014-1-BIOPHYSICS-48

Heavy Ion Beam Irradiation of a Langendorff Heart

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Heavy Ion Beam Irradiation of a Langendorff Heart

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