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Platelet activating factor interaction with tumor necrosis factor in myocardial ischaemia-reperfusion injury.
J Lipid Mediat. 1993 Aug; 8(1):53-65.JL

Abstract

The role played by platelet-activating factor (PAF) and tumor necrosis factor (TNF-alpha) in myocardial ischaemia-reperfusion injury was investigated. Pentobarbital anaesthetized rats were subjected to left main coronary artery ligation (1 h) followed by reperfusion (1 h; MI/R). Sham-operated rats were used as controls (Sham MI/R). Myocardial ischaemia-reperfusion injury produced a marked myocardial injury (necrotic area/area-at-risk = 60 +/- 5%; necrotic area/total area = 50 +/- 6%), high serum creatine phosphokinase activity (Sham MI/R = 25 +/- 10 U/ml; MI/R = 190 +/- 12 U/ml), a severe leukopenia (Sham MI/R = 10367 +/- 630 WBC x mm3; MI/R = 4123 +/- 120 WBC x mm3) and elevated myocardial myeloperoxidase activity (investigated as an index of leukocytes adhesion and accumulation) in the area-at-risk (6.2 +/- 0.5 U x 10(-3)/g tissue) and in necrotic area (6.6 +/- 0.7 U x 10(-3)/g tissue. Plasma PAF and serum TNF-alpha were significantly increased only during reperfusion. The peak of PAF plasma levels (6.5 +/- 1.2 pmol/ml) occurred earlier (15 min of reperfusion) than the peak of serum TNF-alpha (150 U/ml at 30 min of reperfusion). At the end of reperfusion, macrophage TNF-alpha was also enhanced (Sham MI/R = undetectable; MI/R = 148 +/- 12 U/ml). The administration of CV 6209, a specific PAF receptor antagonist (5 mg/kg, 5 min after occlusion), significantly reduced myocardial injury (necrotic area/area-at-risk = 27 +/- 3%, P < 0.001; necrotic area/total area = 10 +/- 2%, P < 0.001), blunted the increase in serum creatine phosphokinase (70 +/- 12 U/ml), partially restored leukopenia (8234 +/- 143 WBC x mm3) and lowered myeloperoxidase activity in area-at-risk (2.3 +/- 0.3 U x 10(-3)/g tissue; P < 0.001) and in necrotic area (2.8 +/- 0.5 U x 10(-3)/g tissue). In addition, administration of CV 6209 reduced the serum and macrophage levels of TNF-alpha. The results of this study, therefore, suggest that PAF and TNF-alpha are key mediators of myocardial ischaemia-reperfusion injury and that PAF plays a permissive role in inducing the release of other factor(s) relevant to reperfusion injury.

Authors+Show Affiliations

Institute of Pharmacology, School of Medicine, University of Messina, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8257777

Citation

Squadrito, F, et al. "Platelet Activating Factor Interaction With Tumor Necrosis Factor in Myocardial Ischaemia-reperfusion Injury." Journal of Lipid Mediators, vol. 8, no. 1, 1993, pp. 53-65.
Squadrito F, Ioculano M, Altavilla D, et al. Platelet activating factor interaction with tumor necrosis factor in myocardial ischaemia-reperfusion injury. J Lipid Mediat. 1993;8(1):53-65.
Squadrito, F., Ioculano, M., Altavilla, D., Zingarelli, B., Canale, P., Campo, G. M., Saitta, A., Calapai, G., Bussolino, F., & Caputi, A. P. (1993). Platelet activating factor interaction with tumor necrosis factor in myocardial ischaemia-reperfusion injury. Journal of Lipid Mediators, 8(1), 53-65.
Squadrito F, et al. Platelet Activating Factor Interaction With Tumor Necrosis Factor in Myocardial Ischaemia-reperfusion Injury. J Lipid Mediat. 1993;8(1):53-65. PubMed PMID: 8257777.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Platelet activating factor interaction with tumor necrosis factor in myocardial ischaemia-reperfusion injury. AU - Squadrito,F, AU - Ioculano,M, AU - Altavilla,D, AU - Zingarelli,B, AU - Canale,P, AU - Campo,G M, AU - Saitta,A, AU - Calapai,G, AU - Bussolino,F, AU - Caputi,A P, PY - 1993/8/1/pubmed PY - 1993/8/1/medline PY - 1993/8/1/entrez SP - 53 EP - 65 JF - Journal of lipid mediators JO - J Lipid Mediat VL - 8 IS - 1 N2 - The role played by platelet-activating factor (PAF) and tumor necrosis factor (TNF-alpha) in myocardial ischaemia-reperfusion injury was investigated. Pentobarbital anaesthetized rats were subjected to left main coronary artery ligation (1 h) followed by reperfusion (1 h; MI/R). Sham-operated rats were used as controls (Sham MI/R). Myocardial ischaemia-reperfusion injury produced a marked myocardial injury (necrotic area/area-at-risk = 60 +/- 5%; necrotic area/total area = 50 +/- 6%), high serum creatine phosphokinase activity (Sham MI/R = 25 +/- 10 U/ml; MI/R = 190 +/- 12 U/ml), a severe leukopenia (Sham MI/R = 10367 +/- 630 WBC x mm3; MI/R = 4123 +/- 120 WBC x mm3) and elevated myocardial myeloperoxidase activity (investigated as an index of leukocytes adhesion and accumulation) in the area-at-risk (6.2 +/- 0.5 U x 10(-3)/g tissue) and in necrotic area (6.6 +/- 0.7 U x 10(-3)/g tissue. Plasma PAF and serum TNF-alpha were significantly increased only during reperfusion. The peak of PAF plasma levels (6.5 +/- 1.2 pmol/ml) occurred earlier (15 min of reperfusion) than the peak of serum TNF-alpha (150 U/ml at 30 min of reperfusion). At the end of reperfusion, macrophage TNF-alpha was also enhanced (Sham MI/R = undetectable; MI/R = 148 +/- 12 U/ml). The administration of CV 6209, a specific PAF receptor antagonist (5 mg/kg, 5 min after occlusion), significantly reduced myocardial injury (necrotic area/area-at-risk = 27 +/- 3%, P < 0.001; necrotic area/total area = 10 +/- 2%, P < 0.001), blunted the increase in serum creatine phosphokinase (70 +/- 12 U/ml), partially restored leukopenia (8234 +/- 143 WBC x mm3) and lowered myeloperoxidase activity in area-at-risk (2.3 +/- 0.3 U x 10(-3)/g tissue; P < 0.001) and in necrotic area (2.8 +/- 0.5 U x 10(-3)/g tissue). In addition, administration of CV 6209 reduced the serum and macrophage levels of TNF-alpha. The results of this study, therefore, suggest that PAF and TNF-alpha are key mediators of myocardial ischaemia-reperfusion injury and that PAF plays a permissive role in inducing the release of other factor(s) relevant to reperfusion injury. SN - 0921-8319 UR - https://www.unboundmedicine.com/medline/citation/8257777/Platelet_activating_factor_interaction_with_tumor_necrosis_factor_in_myocardial_ischaemia_reperfusion_injury_ DB - PRIME DP - Unbound Medicine ER -