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Journal of Pharmacology and Experimental Therapeutics

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Abstract

Myocardial protection by the leukotriene synthesis inhibitor BAY X1005: importance of transcellular biosynthesis of cysteinyl-leukotrienes.

G Rossoni, A Sala, F Berti, T Testa, C Buccellati, C Molta, R Muller-Peddinghaus, J Maclouf and G C Folco
Journal of Pharmacology and Experimental Therapeutics January 1996, 276 (1) 335-341;
G Rossoni
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A Sala
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F Berti
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T Testa
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C Buccellati
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C Molta
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R Muller-Peddinghaus
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J Maclouf
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G C Folco
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Abstract

Perfusion of the isolated rabbit heart with 5 x 10(6) human polymorphonuclear leukocytes, under recirculating conditions (50 ml), and challenge with A-23187 (0.5 microM) caused an increase in coronary perfusion pressure (from a prechallenge value of 46 +/- 1.1 to 176.2 +/- 29.7 mm Hg, 30 min after challenge, n = 6-4), which was linearly correlated (P < .006) with formation of cysteinyl leukotrienes (29.7 +/- 7.3 pmol/ml, 30 min after challenge). Pretreatment with the leukotriene synthesis inhibitor BAY X1005 (1 microM) (n = 6) resulted in significant protection against the increase in coronary perfusion pressure (76.7 +/- 12.8 mm Hg, 30 min after challenge) and in almost complete inhibition of sulfidopeptide leukotriene synthesis (3.2 +/- 1.7 pmol/ml, 30 min after challenge). In in vivo experiments, ligation of the left anterior descending coronary artery in the rabbit (n = 10) resulted in acute myocardial infarction marked by a mortality rate of 60% compared with sham-operated animals (n = 10). Intravenous treatment of the rabbits with BAY X1005 (10 mg/kg/h, for 2 h) (n = 10) markedly reduced the mortality rate (20%), protected the rabbits against the marked electrocardiogram derangement and abolished the significant increase in plasma creatine phosphokinase activity and cardiac tissue myeloperoxidase activity induced by coronary artery ligation. BAY X1005 exerts a significant cardioprotection and suggests that specific leukotriene synthesis inhibitors may lead to innovative therapy in myocardial ischemia.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 276, Issue 1
1 Jan 1996
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Abstract

Myocardial protection by the leukotriene synthesis inhibitor BAY X1005: importance of transcellular biosynthesis of cysteinyl-leukotrienes.

G Rossoni, A Sala, F Berti, T Testa, C Buccellati, C Molta, R Muller-Peddinghaus, J Maclouf and G C Folco
Journal of Pharmacology and Experimental Therapeutics January 1, 1996, 276 (1) 335-341;

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Abstract

Myocardial protection by the leukotriene synthesis inhibitor BAY X1005: importance of transcellular biosynthesis of cysteinyl-leukotrienes.

G Rossoni, A Sala, F Berti, T Testa, C Buccellati, C Molta, R Muller-Peddinghaus, J Maclouf and G C Folco
Journal of Pharmacology and Experimental Therapeutics January 1, 1996, 276 (1) 335-341;
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