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Cardioprotective effects of selective inhibition of the two complement activation pathways in myocardial ischemia and reperfusion injury.
Methods Find Exp Clin Pharmacol. 1995 Oct; 17(8):499-507.MF

Abstract

The complement (C) system-mediated neutrophil activation, adhesion to the coronary endothelium and accumulation into cardiac tissue are key steps in the pathogenesis of myocardial ischemia-reperfusion (MI/R) injury. We examined the differential role of the classical and the alternative complement pathway in MI/R injury in vivo. Rats were subjected to 20 min of myocardial ischemia followed by 24 h of reperfusion. Either a classical pathway inhibitor [C1 esterase inhibitor (C1-INH) (15 mg/kg)] or an alternative pathway inhibitor soluble complement receptor 1 (sCR1)[des-LHR-A](15 mg/kg) or their vehicle were administered intravenously 1 min prior to reperfusion, and myocardial necrosis (creatine kinase loss) and neutrophil accumulation, cardiac myeloperoxidase activity, were examined. C1-INH significantly attenuated cardiac creatine kinase loss compared to MI/R rats given only vehicle (p < 0.05) 24 h after reperfusion. An alternative pathway inhibitor, sCR1 [des-LHR-A] attenuated myocardial injury to a lesser extent, although it was not significantly different from the value for C1-INH or vehicle. Besides cardiac myeloperoxidase activity, the ischemic cardiac tissue was significantly attenuated by both C1-INH and sCR1[desLHR-A] (p < 0.05 vs. vehicle). Both the classical and alternative pathways may contribute to MI/R injury via a neutrophil-dependent mechanism in vivo. Selective inhibition of the classical pathway of complement activation seems to be slightly more effective in limiting necrotic MI/R injury than the selective alternative pathway inhibition in this 24 h model of reperfusion injury, but equal doses of each inhibitor attenuated neutrophil accumulation.

Authors+Show Affiliations

Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8749222

Citation

Murohara, T, et al. "Cardioprotective Effects of Selective Inhibition of the Two Complement Activation Pathways in Myocardial Ischemia and Reperfusion Injury." Methods and Findings in Experimental and Clinical Pharmacology, vol. 17, no. 8, 1995, pp. 499-507.
Murohara T, Guo JP, Delyani JA, et al. Cardioprotective effects of selective inhibition of the two complement activation pathways in myocardial ischemia and reperfusion injury. Methods Find Exp Clin Pharmacol. 1995;17(8):499-507.
Murohara, T., Guo, J. P., Delyani, J. A., & Lefer, A. M. (1995). Cardioprotective effects of selective inhibition of the two complement activation pathways in myocardial ischemia and reperfusion injury. Methods and Findings in Experimental and Clinical Pharmacology, 17(8), 499-507.
Murohara T, et al. Cardioprotective Effects of Selective Inhibition of the Two Complement Activation Pathways in Myocardial Ischemia and Reperfusion Injury. Methods Find Exp Clin Pharmacol. 1995;17(8):499-507. PubMed PMID: 8749222.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardioprotective effects of selective inhibition of the two complement activation pathways in myocardial ischemia and reperfusion injury. AU - Murohara,T, AU - Guo,J P, AU - Delyani,J A, AU - Lefer,A M, PY - 1995/10/1/pubmed PY - 1995/10/1/medline PY - 1995/10/1/entrez SP - 499 EP - 507 JF - Methods and findings in experimental and clinical pharmacology JO - Methods Find Exp Clin Pharmacol VL - 17 IS - 8 N2 - The complement (C) system-mediated neutrophil activation, adhesion to the coronary endothelium and accumulation into cardiac tissue are key steps in the pathogenesis of myocardial ischemia-reperfusion (MI/R) injury. We examined the differential role of the classical and the alternative complement pathway in MI/R injury in vivo. Rats were subjected to 20 min of myocardial ischemia followed by 24 h of reperfusion. Either a classical pathway inhibitor [C1 esterase inhibitor (C1-INH) (15 mg/kg)] or an alternative pathway inhibitor soluble complement receptor 1 (sCR1)[des-LHR-A](15 mg/kg) or their vehicle were administered intravenously 1 min prior to reperfusion, and myocardial necrosis (creatine kinase loss) and neutrophil accumulation, cardiac myeloperoxidase activity, were examined. C1-INH significantly attenuated cardiac creatine kinase loss compared to MI/R rats given only vehicle (p < 0.05) 24 h after reperfusion. An alternative pathway inhibitor, sCR1 [des-LHR-A] attenuated myocardial injury to a lesser extent, although it was not significantly different from the value for C1-INH or vehicle. Besides cardiac myeloperoxidase activity, the ischemic cardiac tissue was significantly attenuated by both C1-INH and sCR1[desLHR-A] (p < 0.05 vs. vehicle). Both the classical and alternative pathways may contribute to MI/R injury via a neutrophil-dependent mechanism in vivo. Selective inhibition of the classical pathway of complement activation seems to be slightly more effective in limiting necrotic MI/R injury than the selective alternative pathway inhibition in this 24 h model of reperfusion injury, but equal doses of each inhibitor attenuated neutrophil accumulation. SN - 0379-0355 UR - https://www.unboundmedicine.com/medline/citation/8749222/Cardioprotective_effects_of_selective_inhibition_of_the_two_complement_activation_pathways_in_myocardial_ischemia_and_reperfusion_injury_ L2 - https://antibodies.cancer.gov/detail/CPTC-CD44-1 DB - PRIME DP - Unbound Medicine ER -