| Abstrakt: |
Objectives: Several studies suggest that regulation of coronary vasomotion is abnormal in heart failure, but controversies exist as to whether an altered endothelium-dependent dilation of the coronary vasculature contributes to these abnormalities. In the present study we evaluated the coronary reactivity to endothelium-dependent and -independent vasoactive substances in a model of chronic heart failure. Methods: Isolated hearts from > 200-day-old cardiomyopathic hamsters (UM-X7.1) and age-matched normal Syrian hamsters were mounted on a Langendorff apparatus and retrogradely perfused at constant pressure (100 mmHg). Heart rate, left ventricular developed pressure (LVP) and coronary flow (CF) were measured. A first group of normal and failing hearts were challenged with increasing doses of acetylcholine (Ach), 1–1000 nM, and sodium nitroprusside (SNP), 0.01-10μM. A second group was challenged with Ach (100 nM) and SNP (1 μM) before and during infusion of the NO synthase inhibitor, NG-nitro-l-arginine methyl ester (l-NAME). Finally, normal and failing hearts were challenged with Ach (100 nM) before and during infusion of indomethacin (10 μM) or tetraethylammonium (1 mM). Results: Myocardial contractility and coronary flow were significantly impaired in failing hearts (LVP = 32 ± 5 vs. 50 ± 4 mmHg in normal hearts; CF = 4.7 ± 0.6 vs. 6.7 ± 0.6 ml/min in normal hearts). Coronary flow increases with increasing doses of Ach (EC50 = 84 ± 15 nM for failing hearts and 100 ± 3 nM for normal hearts, P = ns). At concentrations exceeding the EC50, failing hearts were more sensitive to the coronary dilator effects of Ach. The reduction in coronary flow elicited by l-NAME was similar in normal (−41 ± 2%) and failing hearts (−40 + 3%); in both normal and failing hearts, the acetylcholine vasodilator response was not significantly affected by l-NAME. Indomethacin infusion resulted in a slight increase in coronary flow and significantly reduced the coronary dilator effects of acetylcholine. Tetraethylammonium had no significant effects on basal coronary perfusion of normal and failing hearts. However, in the latter group, acetylcholine vasodilator response was significantly attenuated. Conclusion: Results obtained in isolated failing hamster hearts allow us to conclude that (1) significant coronary dysfunctions are present in this model of chronic heart failure, (2) neither the NO-synthase nor the cyclo-oxygenase pathway contributes to these coronary dysfunctions, and (3) an adequate coronary vasodilator response appears to be present in this model of chronic heart failure. [ABSTRACT FROM PUBLISHER] |
