Transcellular synthesis of cysteinyl-leukotrienes: From isolated cells to complex organ system (part 3)

organ system (part 3)

Male albino New Zealand rabbits, under anesthesia and artificial respiration, were opened on the left side of the thorax, and the small branch of the left anterior descending coronary artery was separated from the myocardial tissue for a length of about 2 to 3 mm and ligated with a silk 6.0 suture, armed with an atraumatic needle. Mortality was recorded for the following three days. BAY X1005-treated animals received a total dose of 48 mg/kg, which was subdivided as follows: 16 mg/kg over 2 h, starting 1 h before ligation, and 8 mg/kg at 8, 24, 32 and 48 h after ligation.

Challenge with 0.5 pM A23187 of rabbit hearts perfused under recirculating conditions with human PMNL resulted in a marked increase in CPP. The increase in CPP was slow at onset and very persistent, resulting in changes of CPP from 46±1.1 mmHg to 176.2±29.7 mmHg and of LVEDP from 5.0±0.2 mmHg to 36±13 mmHg (n=6) 30 mins after A23187 challenge. These changes were significantly inhibited by pretreatment with BAY-X1005 (1 pM) (CPP 76.7±12.8 mmHg and LVEDP 8.2±1.7 mmHg, n=6) 30 mins after A23187 challenge. The amount of cys-LT formed in control conditions averaged 29.7±7.3 pmol/mL, while the amount of LTB4 averaged 3.3±0.5 pmol/mL. Following pretreatment with compound BAY X1005, the amount of LT was markedly inhibited (cys-LT 3.2±1.7 pmol/mL, LTB4 0.75±0.21 pmol/mL).

This entry was posted in Cardiology and tagged 5-Lipoxygenase inhibition, BAYX1005, Cysteinyl-leukotrienes.