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SB 211475, a metabolite of carvedilol, reduces infarct size after myocardial ischemic and reperfusion injury in rabbits.
Eur J Pharmacol. 1998 Sep 04; 356(2-3):193-8.EJ

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.

Authors+Show Affiliations

Department of Surgery, Haukeland Hospital, University of Bergen, Norway. harald.brunvand@ffhs.uib.noNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

9774249

Citation

Brunvand, H, et al. "SB 211475, a Metabolite of Carvedilol, Reduces Infarct Size After Myocardial Ischemic and Reperfusion Injury in Rabbits." European Journal of Pharmacology, vol. 356, no. 2-3, 1998, pp. 193-8.
Brunvand H, Liu G, Ma XL, et al. SB 211475, a metabolite of carvedilol, reduces infarct size after myocardial ischemic and reperfusion injury in rabbits. Eur J Pharmacol. 1998;356(2-3):193-8.
Brunvand, H., Liu, G., Ma, X. L., Yue, T. L., Ruffolo, R. R., & Feuerstein, G. Z. (1998). SB 211475, a metabolite of carvedilol, reduces infarct size after myocardial ischemic and reperfusion injury in rabbits. European Journal of Pharmacology, 356(2-3), 193-8.
Brunvand H, et al. SB 211475, a Metabolite of Carvedilol, Reduces Infarct Size After Myocardial Ischemic and Reperfusion Injury in Rabbits. Eur J Pharmacol. 1998 Sep 4;356(2-3):193-8. PubMed PMID: 9774249.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SB 211475, a metabolite of carvedilol, reduces infarct size after myocardial ischemic and reperfusion injury in rabbits. AU - Brunvand,H, AU - Liu,G, AU - Ma,X L, AU - Yue,T L, AU - Ruffolo,R R,Jr AU - Feuerstein,G Z, PY - 1998/10/17/pubmed PY - 2001/3/28/medline PY - 1998/10/17/entrez SP - 193 EP - 8 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 356 IS - 2-3 N2 - 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. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/9774249/SB_211475_a_metabolite_of_carvedilol_reduces_infarct_size_after_myocardial_ischemic_and_reperfusion_injury_in_rabbits_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(98)00494-4 DB - PRIME DP - Unbound Medicine ER -