Background: Radiation-induced changes in blood vessels such as endothelial injury is well-known. Trastuzumab (T) has been shown to produce cardiac dysfunction, however its effects on vascular functions is not clear.
Aim: The aim of this study is to elucidate if there is an additive or supraadditive deleterious effect of T and radiotherapy (RT) -on vascular functions when they are used either sequentially (neoadjuvant and adjuvant) or concomitantly.
Methods: Female adult Sprague–Dawley rats (250–300 g, n = 72) were divided into 6 groups (G) composed of 12 animals each: G-1 (control), G-2 (T), G-3 (RT), G-4 (RT + neoadjuvant T), G-5 (RT + concomitant T) and G-6 (RT + adjuvant T). Isolated organ bath experiments were performed 21 days after radiotherapy. The rats were anesthetized and thoracic aortae were dissected out and cleaned of adhering fat and connective tissue. Aortic ring segments (3 mm in length) were cut and mounted in isolated tissue baths containing oxygenated 10 ml Krebs-Henseleit solution. Isometric tension measurements were recorded by a force–displacement transducer and analyzed using a data-acquisition and analysis software. Thoracic aorta segments were first contracted with KCl (68 mM) and then with phenylephrine (PE, 1 µM). After PE -induced contraction reached to plateau, acetylcholine (ACh) was applied at increasing concentrations. The relaxation to ACh were recorded and expressed as percentage of PE maximum contraction.
Results: Contractions to KCl and PE did not differ among groups. However, relaxation responses to ACh as percentage of PE maximum contraction were significantly lower in G-3, G-4, G-5 and G-6 groups when compared to control group (P<0.05). T caused a slight but not significant extra relaxation deficit when it was used either sequentially or concomitantly.
Conclusions: Our study revealed that mediastinal high dose RT when combined with T may lead to severe endothelial damage.