Myocardial perfusion alterations observed months after radiotherapy are related to the cellular damage

Summary

Aim: Myocardial perfusion scintigraphy (MPS) is one of the widely used tools to follow developing radiation-induced heart disease (RIHD). But the clinical significance of MPS defects has not been fully understood. We have investigated the biodistribution alterations related to perfusion defects following radiotherapy (RT) and showed coexisting morphologic changes. Animals, methods: A total of 18 Wistar rats were divided into three groups (1 control and 2 irradiated groups). A single cardiac 20 Gy radiation dose was used to induce long term cardiac defects. Biodistribution studies with technetium (^99mTc) sestamibi and histological evaluations were performed 4 and 6 months after irradiation. The percent radioactivity (%ID/g) was calculated for each heart. For determination of the myocardial damage, positive apoptotic cardiomyocytes, myocardial cell degeneration, myocardial fibrosis, vascular damage and ultrastructural structures were evaluated. Results: Six months after treatment, a significant drop of myocardial uptake was observed (p < 0.05). Irradiation- induced apoptosis rose within the first 4 months after radiation treatment and were stayed elevated until the end of the observation period (p < 0.05). Also, the irradiation has induced myocardial degeneration, perivascular and interstitial fibrosis in the heart at the end of six and four months (p < 0.01). The severity and extent of myocardial injury has became more evident at the end of six month (p < 0.05). At ultrastructural level, prominent changes have been observed in the capillary endothelial and myocardial cells. Conclusion: Our findings suggest that the reduced rest myocardial perfusion, occuring months after the radiation, indicates a serious myocard tissue damage which is characterized by myocardial degeneration and fibrosis.

Zusammenfassung

Ziel: Myokard-Perfusionsszintigraphie (MPS) eine häufig benutzte Methode, um die Entwicklung von Strahlungs-verursachten Herzkrankheiten (RIHD) zu verfolgen. Allerdings sind die klinische Signifikanz der MPS-Schädigungen und die zugrunde legenden pathologischen Mechanismen bisher nicht vollständig untersucht. In dieser Studie wurden deswegen die biodiversen Veränderungen, die durch Perfusionsschäden nach einer Strahlentherapie (RT) entstehen, näher untersucht. Es zeigte sichhierbei, dass es zu verschiedenen morphologischen Veränderungen kommt. Tiere, Methode: Insgesamt 18 Wistar-Ratten wurden in drei Gruppen unterteilt (1 Kontrollgruppe, 2 bestrahlte Gruppen). Durch einzelne, kardiale 20 Gy starke Strahlungsdosen wurden langzeitliche Herzschäden induziert. Die biodiversen Untersuchungen wurden mittels dem Wirkstoff Technetium (^99mTc) sestamibi und histologischen Analysen entweder 4 oder 6 Monate nach der Strahlenbehandlung. Zur Bestimmung der Myokardschädigung wurden einerseits die Anzahl apoptotisch-positiver bzw. degenerierten Myokardzellen ermittelt und andererseits die myokardiale Fibsose untersucht. Des Weiteren wurden vaskuläre Schädigungen und ultrazelluläre Strukturen näher untersucht. Ergebnisse: Es zeigte sich, das 6 Monate nach der Behandlung ein signifikanter Abfall der myokardischen Aufnahme zu beobachten war (p < 0,05), wohingegen die strahlungs-bedingte Apoptose der Myokardzellen innerhalb der ersten 4 Monate stetig anstieg und bis zum Ende der Untersuchungszeit signifikant erhöht blieb (p < 0,05). Des Weiteren traten durch die Bestrahlung nach 4 bzw. 6 Monaten mykardiale Degenerationen sowie pervaskuläre und interstitielle Fibrosen im Herz auf (p < 0,01). Das gesamte Ausmaß der myokardialen Schädigung war am Deutlichsten nach 6 Monaten zu beobachten (p < 0.05). Ultrastrukturell, wurden starke Veränderungen bei den kapillaren Endothelzellen und Myokardzellen sichtbar. Schlussfolgerung: Diese Studie zeigt deutlich, dass reduzierte Myokardperfusionen, die Monate nach Bestrahlungstherapien auftreten, durch schwere Myokardschädigungen hervorgerufen werden. Diese Schädigungen sind durch myokardiale Degeneration und Fibrosen charakterisiert.

Keywords

Radiotheraphy - radiation-induced heart disease - cardiac toxicity - cardiac damage - myocardial perfusion scintigraphy - ^99mTc-sestamibi

Schlüsselwörter

Strahlentherapie - strahlungsverursachte Herzkrankheiten - kardiale Toxizität - Herzschädigung - Myokard-Perfusionsszinti graphie - ^99mTc-Sestamibi

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