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Isoprenaline‐induced damage in cardiac and skeletal muscle: Interaction with methylxanthines
Author(s) -
Heap Sarah J.,
Hudlicka Olga,
OkyayuzBaklouti Ismahan
Publication year - 1996
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199604)37:4<249::aid-ddr6>3.0.co;2-l
Subject(s) - isoprenaline , inotrope , medicine , skeletal muscle , endocrinology , blood pressure , cardiac muscle , caffeine , heart rate , chemistry , catecholamine , stimulation
The damaging effect of catecholamines and their combined use with classic methylxanthines on the heart are well documented. Much less is known about their effect on skeletal muscle. This study was designed to establish whether a novel xanthine derivative, torbafylline, had similar or different effects as caffeine on skeletal or cardiac muscle damaged by isoprenaline and to help elucidate the pathogenesis of this damage. Isoprenaline produced myocardial damage without altering chrono‐ or inotropic responses or blood pressure. Torbafylline had a positive inotropic effect and lowered blood pressure; it did not alter the extent of necrosis induced by isoprenaline but lost its positive inotropic and blood pressure effects. Caffeine on its own showed a negative inotropic effect; in conjunction with isoprenaline, it augmented necrosis, lowered pulse pressure, and decreased heart rate. In soleus muscle, isoprenaline caused smaller necrosis than in heart, albeit significant. Caffeine alone induced some damage, which was increased if given with isoprenaline. In contrast, torbafylline did not induce necrosis and did not exacerbate damage caused by isoprenaline. Torbafylline, which has been shown to be very effective in improving the performance of ischemic skeletal muscle, did not affect performance of normal slow muscle and impaired it if given in combination with isoprenaline, possibly by its completely different effect on calcium handling compared to caffeine. Torbafylline had a distinctly different effect compared to other methylxanthines, as it did not cause further damage to the heart exposed to a high dose of the catecholamine isoprenaline. © 1996 Wiley‐Liss, Inc.