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Effect of Beta-Blocker on Metabolism and Contraction of Doxorubicin-Induced Cardiotoxicity in the Isolated Perfused Rabbit Heart

Kinji Ishikawa, MD

Hitoshi Kawabata, MD

Department of Internal Medicine Kinki University School of Medicine 377-2 Ohno-Higashi, Osaka-Sayama Osaka, 589-8511 Japan

The effect of β-blocker (propranolol) on the metabolism and contraction of doxorubicin- induced cardiomyopathy during pacing or ischemia was examined by the phosphorus 31-nuclear magnetic resonance (31 P-NMR) in Langendorff hearts of chronically treated rabbits after cumulative doses of 16 mg doxorubicin/kg. After 8 weeks of doxorubicin treatment, β-blocker (propranolol) was given orally over a period of 2 weeks for a cumu lative dose of 1.4 mg/kg. Isolated hearts were paced at higher heart rates, or hearts were perfused 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 three 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 pacing (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 significantly marked improvement of ATP during pacing (95 ±10%) and during low flow (83 ±3%) compared with Group II. Furthermore, Group II showed a significant 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 improvement 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.

Angiology, Vol. 51, No. 5, 405-413 (2000)
DOI: 10.1177/000331970005100507


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