A PROISCHAEMIC ACTION OF NISOLDIPINE - RELATIONSHIP TO A DECREASE IN PERFUSION-PRESSURE AND COMPARISON TO DIPYRIDAMOLE

Objective: The calcium antagonist nisoldipine has recently been report ed to induce rather than to attenuate ischaemia in some patients with stable angina. The aim of the study was to investigate the mechanisms underlying this proischaemic effect. Methods: In 20 anaesthetised dogs systemic haemodynamic variables, regional myocardial blood flow (colo ured microspheres), and systolic wall thickening (sonomicrometry) were measured during control conditions and following severe stenosis on t he left circumflex coronary artery, before and after intravenous admin istration of equihypotensive doses of either nisoldipine (group I, n=1 0) or dipyridamole (group II, n=10). Finally, measurements were perfor med while the drug induced decreases in mean aortic pressure - 18(SD 6 ) mmHg in group I and 14(6) mm Hg in group II - were reversed by infla tion of an intra-aortic balloon. Results: The stenosis decreased poste rior wall thickening to 50% of control, and posterior subendocardial b lood flow from 1.48(0.27) to 0.61(0.19) ml.min-1.g-1 in group I and fr om 1.49(0.23) to 0.62(0.18) ml.min-1.g-1 in group II. Subendocardial b lood flow was further decreased after administration of either nisoldi pine [0.37(0.20) ml.min-1.g-1, p<0.05 v stenosis] or dipyridamole [0.2 2(0.11) ml.min-1-g-1, p<0.05 v stenosis]. Regional myocardial blood fl ow in the anterior region was increased. The drug induced reduction of subendocardial blood flow decreased posterior wall thickening further from 9.3(2.1) to 6.2(3.9)% (p<0.05 v stenosis, group I) and from 9.1( 1.7) to 4.3(2.4)% (p<0.05 v stenosis, group II). When the drug induced decrease in aortic pressure was reversed, subendocardial blood flow a gain increased in group I [0.63(0.19) ml.min-1-g-1, p<0.05 v stenosis and nisoldipine] whereas in group II it remained decreased [0.40(0.29) ml.min-1.g-1, NS v stenosis and dipyridamole]. There was restoration of posterior wall thickening in group I [10.4(3.8)%, p<0.05 v stenosis and nisoldipine], but not in group II [5.2(3.5)%, NS v stenosis and d ipyridamole]. Conclusions: Nisoldipine and dipyridamole decrease suben docardial blood flow and contractile function distal to a severe steno sis when aortic pressure is decreased. No aggravation of ischaemia by nisoldipine is seen when hypotension is prevented. In contrast, dipyri damole in the absence of hypotension still induces a redistribution of flow at the expense of the ischaemic region.