Figure/Graphic 7A-C: Doxorubicin - Angiotensin-II-Modulation
Heart rate (HR, A, B) and time constant of contraction τC (C) during perfusion (for 40 min) of isolated rat hearts with doxorubicin (DXR, 20 micromol/L)-containing Tyrode solution, and after addition of dantrolene (10 micromol/L, A, C) and caffeine (10 mmol/L, B) to DXR-containing Tyrode solution, respectively. Values were normalized on HR or τC of control recording (during Tyrode erfusion). Drugs were applied at the time point "0 min". Means and SD of 5 experiments with DXR perfusion (solid line and open squares in A-C) and of 5 experiments each where a perfusion with dantrolene (A,C) or caffeine (B) + DXR was performed (dashed lines and filled circles). Vagus stimulation (right N. vagus, 10 Hz, 10 V, 10 s stimulation period) effects were recorded in intervals of 10 min starting after drugs administration (the arrows represent HR reductions / τC increases caused each by vagus stimulation. Full line arrows, vagus stimulation effects during DXR perfusion; dashed line arrows, vagus stimulation effects during perfusion with dantrolene/caffeine+DXR containing solution). Note that HR was significantly (P < 0.05, asterisks) reduced (A) / increased (B) after 40 min perfusion with dantrolene+DXR / caffeine+DXR, compared with HR in DXR perfusion experiments. τC was significant increased after 40 min perfusion with dantrolene+DXR, compared with HR in DXR perfusion experiments. Caffeine reduces, dantrolene increases the observed DXR actions regarding HR, τC and vagus stimulation effects.