| Abstrakt: |
The effects of BW A4C, a selective arachidonate 5-lipoxygenase (5-LO) inhibitor, on the progression of myocardial tissue injury were examined in anaesthetised, open-chest beagle dogs subjected to 90-min occlusion of the left anterior descending coronary artery (LAD)) followed by 120-min repertusion. Regional myocardial blood flow (RMBE, microspheres), segment shortening (sonomicrometry, and infaret size (tetrazolium stain) as an index of tissue injury were measured. Control animals (group I. n - 11) received an infusion of vehicle [50 vol vol glveofurol and distilled water, 47 ml at 12 mlh, intravenously (i.v)] beginning 15 min before ischaemia and continuing until the end of reperfusion. Treated animals received either 10 (group 2.n - 11 or 50 μg kg ‘min’ (group 3.n) BW A4C iv, in the same period. The infaret risk zone ratio (IR) in group I (24.1 ± 6.0 ±) was not significantly different from that of group 2(28.0 ± 8.4± or group 3 (46.1 ± 6.7). The close inverse relationship ohserved in controls between 1 R ratio and collateral flow was not altered by either dose of BW A4C. Segment shortening during ischaemia 0.2 ± 2.7. 2.4 ± 1.7, and 1.5 ± 1.7) and reperfusion (4.9 + 2.8. 1.0 + 1.8. and 1.0 + 1.9 and during an isoprenaline infusion to unmask stunned myocardium (14.7 ± 3.0, 14.7 + 2.6, and 7.4 + 1.7) were not significantly different between groups 1.2. and 3. Plasma levels of BW A4C reached steady state by 45 min of ischaemia at both doses and in both group 2 (0.52–0.72 μg ml) and group 3 (1.55–2.13 μg ml were above the IC50value for 5 LOs inhibition. Thus. a selective inhibitor of 5 LO. BW A4C, did not influence progression of myocardial tissue injury in this experimental model although plasma levels were above the IC3pvalue for 5-LO inhibition. These results cast doubt on the role of the products of 5-LO in propagation of myocardial necrosis after ischaemia. |
