Effect of beta-blocker on metabolism and contraction of doxorubicin-induced cardiotoxicity in the isolated perfused rabbit heart

The effect of beta-blocker (propranolol) on the metabolism and contraction of doxorubicin-induced cardiomyopathy during pacing or ischemia was examine d by the phosphorus 31-nuclear magnetic resonance (31 P-NMR) in Langendorff hearts of chronically treated rabbits after cumulative doses of 16 mg doxo rubicin/kg. After 8 weeks of doxorubicin treatment, beta-blocker (propranol ol) was given orally over a period of 2 weeks for a cumulative dose of 1.4 mg/kg. Isolated hearts were paced at higher heart rates, or hearts were per fused on low flow. Adenosine triphosphate (ATP), creatine phosphate (PCr), inorganic phosphate (Pi), pH, left ventricular systolic developed pressure (LVDev P), and coronary flow were measured. The hearts were divided into th ree experimental groups: Group I consisted of controls, Group II consisted of doxorubicin treatment, and Group III consisted of doxorubicin treatment with propranolol. Group II showed a significant decrease of ATP during paci ng (48 +/- 2%) and during low flow (61 +/- 6%) compared with Group I (86 +/ - 9% at pacing, 94 +/- 6% on low flow). But Group III showed a significantl y marked improvement of ATP during pacing (95 +/- 10%) and during low flow (83 +/- 3%) compared with Group II. Furthermore, Group II showed a signific ant decrease of LVDev P during pacing (69 +/- 6 mm Hg) and during low flow (63 +/- 3 mm Hg) compared with Group I (101 +/- 5 mm Hg at pacing, 95 +/- 9 mm Hg on low flow). But Group III showed a significantly marked improvemen t of LVDev P during pacing (93 +/- 5 mm Hg) and during low flow (83 +/- 14 mm Hg) compared with Group II. In conclusion, propranolol had a significant beneficial effect on metabolism and contraction during high-energy demand and during low oxygen supply of doxorubicin cardiomyopathy.