AI Article Synopsis
- The study examined SB 211475, a metabolite of carvedilol, for its effects on heart damage after blood flow restoration in rabbits.
- Higher doses of SB 211475 (1.0 and 3.0 mg/kg) significantly reduced heart damage compared to the control group, but not as effectively as carvedilol.
- Both carvedilol and SB 211475 reduced inflammation levels, but carvedilol provided superior heart protection likely due to its broader action on adrenergic receptors.
Article Abstract
The aim of this study was to investigate the effect of SB 211475, a metabolite of carvedilol with weak alpha1-adrenoceptor antagonism and antioxidant effect, on myocardial reperfusion injury and infarct size in anesthetized rabbits. The rabbits were subjected to 60 min of regional myocardial ischemia and 180 min of reperfusion. SB 211475 was administered either as 0.3, 1.0 or 3.0 mg/kg and compared to vehicle and carvedilol (1 mg/kg) treated animals. The lowest dose of SB 211475 (0.3 mg/kg) did not reduce infarct size compared to vehicle, whereas SB 211475 1.0 or 3.0 mg/kg reduced infarct size significantly compared to vehicle (41.2 +/- 2.2% and 40.5 +/- 2.8% vs. 59.1 +/- 3.9%, p < 0.05). Carvedilol reduced infarct size significantly more than SB 211475 1.0 and 3.0 mg/kg (28.8 +/- 3.9% vs. 41.2 +/- 2.2% and 40.5 +/- 2.7%, p < 0.05). Carvedilol and SB 211475 1.0 and 3.0 mg/kg reduced myeloperoxidase activity to the same extent, indicative of reduced inflammation. Rate-pressure product did not differ between doses of SB 211475. In conclusion, SB 211475 in the two highest doses reduced infarct size by protecting from reperfusion injury, possibly by reduced neutrophil accumulation. The superior cardiac protective effect of carvedilol over SB 211475 are most likely due to its adrenergic pharmacology including non-selective beta- and alpha1-adrenoceptor antagonism.
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| http://dx.doi.org/10.1016/s0014-2999(98)00494-4 | DOI Listing |
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