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Comparison of metoprolol and carvedilol pharmacology and cardioprotection in rabbit ischemia and reperfusion model.
Eur J Pharmacol. 1998 Jun 26; 351(3):341-50.EJ

Abstract

Carvedilol, a selective alpha1 and non-selective beta-adrenoceptor antagonist and antioxidant, has been shown to provide significant cardiac protection in animal models of myocardial ischemia. To further explore the mechanisms contributing to carvedilol cardioprotection efficacy, the effects of carvedilol on hemodynamic variables, infarct size and myeloperoxidase activity (an index of neutrophil accumulation) were compared with a beta1-selective adrenoceptor antagonist, metoprolol. Carvedilol (1 mg/kg) or metoprolol (1 mg/kg or 1 mg/kg + 0.5 mg/kg 90 min later) was given intravenously 5 min before reperfusion. In vehicle-treated rabbits, ischemia (60 min) and reperfusion (180 min) resulted in significant increments in left ventricular end diastolic pressure, large infarcts (59+/-2.6% of area-at-risk) and marked increase in myeloperoxidase activity (0.59+/-0.09 U/100 mg tissue). Carvedilol treatment resulted in sustained reduction of pressure-rate-index and significantly smaller infarcts (22.0+/-2.5%, P < 0.01 vs. vehicle) as well as decreased myeloperoxidase activity (0.186+/-0.056 U/100 mg tissue, P < 0.01 vs. vehicle). The highest dose of metoprolol, 1 mg/kg + 0.5 mg/kg, that resulted in pressure-rate-index comparable to that of 1.0 mg/kg carvedilol, failed to reduce myeloperoxidase activity in the ischemic myocardial tissue, and the infarct size (35+/-3.1%) was significantly larger than in carvedilol-treated animals. Taken together, this study suggests that the superior cardioprotection of carvedilol over metoprolol is not a consequence of hemodynamic variances but possibly the result of the additional pharmacological properties of carvedilol such as the antioxidant and anti-neutrophil effects.

Authors+Show Affiliations

SmithKline Beecham Pharmaceuticals, Department of Cardiovascular Pharmacology, King of Prussia, PA 19406-0939, USA.No affiliation info availableNo affiliation info availableNo 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

9721026

Citation

Feuerstein, G, et al. "Comparison of Metoprolol and Carvedilol Pharmacology and Cardioprotection in Rabbit Ischemia and Reperfusion Model." European Journal of Pharmacology, vol. 351, no. 3, 1998, pp. 341-50.
Feuerstein G, Liu GL, Yue TL, et al. Comparison of metoprolol and carvedilol pharmacology and cardioprotection in rabbit ischemia and reperfusion model. Eur J Pharmacol. 1998;351(3):341-50.
Feuerstein, G., Liu, G. L., Yue, T. L., Cheng, H. Y., Hieble, J. P., Arch, J. R., Ruffolo, R. R., & Ma, X. L. (1998). Comparison of metoprolol and carvedilol pharmacology and cardioprotection in rabbit ischemia and reperfusion model. European Journal of Pharmacology, 351(3), 341-50.
Feuerstein G, et al. Comparison of Metoprolol and Carvedilol Pharmacology and Cardioprotection in Rabbit Ischemia and Reperfusion Model. Eur J Pharmacol. 1998 Jun 26;351(3):341-50. PubMed PMID: 9721026.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of metoprolol and carvedilol pharmacology and cardioprotection in rabbit ischemia and reperfusion model. AU - Feuerstein,G, AU - Liu,G L, AU - Yue,T L, AU - Cheng,H Y, AU - Hieble,J P, AU - Arch,J R, AU - Ruffolo,R R,Jr AU - Ma,X L, PY - 1998/8/28/pubmed PY - 2001/3/28/medline PY - 1998/8/28/entrez SP - 341 EP - 50 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 351 IS - 3 N2 - Carvedilol, a selective alpha1 and non-selective beta-adrenoceptor antagonist and antioxidant, has been shown to provide significant cardiac protection in animal models of myocardial ischemia. To further explore the mechanisms contributing to carvedilol cardioprotection efficacy, the effects of carvedilol on hemodynamic variables, infarct size and myeloperoxidase activity (an index of neutrophil accumulation) were compared with a beta1-selective adrenoceptor antagonist, metoprolol. Carvedilol (1 mg/kg) or metoprolol (1 mg/kg or 1 mg/kg + 0.5 mg/kg 90 min later) was given intravenously 5 min before reperfusion. In vehicle-treated rabbits, ischemia (60 min) and reperfusion (180 min) resulted in significant increments in left ventricular end diastolic pressure, large infarcts (59+/-2.6% of area-at-risk) and marked increase in myeloperoxidase activity (0.59+/-0.09 U/100 mg tissue). Carvedilol treatment resulted in sustained reduction of pressure-rate-index and significantly smaller infarcts (22.0+/-2.5%, P < 0.01 vs. vehicle) as well as decreased myeloperoxidase activity (0.186+/-0.056 U/100 mg tissue, P < 0.01 vs. vehicle). The highest dose of metoprolol, 1 mg/kg + 0.5 mg/kg, that resulted in pressure-rate-index comparable to that of 1.0 mg/kg carvedilol, failed to reduce myeloperoxidase activity in the ischemic myocardial tissue, and the infarct size (35+/-3.1%) was significantly larger than in carvedilol-treated animals. Taken together, this study suggests that the superior cardioprotection of carvedilol over metoprolol is not a consequence of hemodynamic variances but possibly the result of the additional pharmacological properties of carvedilol such as the antioxidant and anti-neutrophil effects. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/9721026/Comparison_of_metoprolol_and_carvedilol_pharmacology_and_cardioprotection_in_rabbit_ischemia_and_reperfusion_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(98)00326-4 DB - PRIME DP - Unbound Medicine ER -