Experimental design

Fig. 1 illustrates the schematic overview of the experimental design summarizing the irradiation and drug application protocols.

Experimental design. Animals were irradiated using either single-dose (a) or fractionated irradiation (b) protocols, concluded by a local test irradiation using graded doses. Irradiation was combined with varying drug application intervals, as indicated by the light grey bars. Each row represents one single experiment performed either with unfractionated or low-molecular-weight heparin. The labelling next to each experimental row indicates the first and last day of drug application. D diagnosis of the ulceration, H healing of the ulceration

Single-dose irradiation was performed on day 0 using five graded dose groups. Each group comprised 10 animals (50 animals per experiment). UFH or LMWH was applied from 3 days before irradiation until either the first diagnosis (−3/D) or complete healing of the ulceration (−3/H). In non-responding animals, the drug application was stopped when all responding animals showed complete healing of the tongue ulcers.

Fractionated irradiation was given on 5 consecutive days per week over one (day 0–4) or two (days 0–4, 7–11) weeks and concluded by graded local top-up doses (5 dose groups, 10 animals each) on day 7 or 14, respectively; When fractionated irradiation was applied over 1 week, the drug was given 3 days before the first fraction until day 4. In combination with 2 weeks of fractionated irradiation, the drug was applied from day −3 until day 4 (−3/4) or day 5 to 11 (5/11) or day −3 until 11 (−3/11).