OUABAIN IMPROVES CARDIAC-FUNCTION IN-VIVO IN RATS WITH HEART-FAILURE AFTER CHRONIC BUT NOT ACUTE TREATMENT

Rats are generally believed to be insensitive for cardiac glycosides. However, like in humans, the hemodynamic effects may be related to the pathophysiological condition. Since the hemodynamic effects of cardia c glycosides have never been investigated in rats with heart failure, the aim of the present experiments was to investigate the role of the pathophysiological condition in the rat. Therefore, hemodynamic and ca rdiac effects of ouabain were investigated both in normal rats and rat s with heart failure due to myocardial infarction (MI). Since the effe cts of ouabain may also depend on the treatment scheme, rats were trea ted either for a shortterm period or a long-term period. Three weeks a fter sham surgery or ligation of the left coronary artery (MI), Wistar rats were treated for two weeks with ouabain (14.4 mg/kg.d s.c.), eit her continuously (osmotic minipumps) or intermittently (once dally). A separate group of rats was treated for 45-60 min (1-100 mu g/kg-min o uabain; i.v, infusion 5 weeks after MI). Hemodynamic measurements were performed at rest and after volume loading in conscious rats, chronic ally instrumented with an electromagnetic flow probe and catheters. In duction of MI resulted in a significant increase in total peripheral r esistance (TPR), and a significant decrease in basal and maximal cardi ac output following volume loading (basal CO: sham, 92+/-5; MI, 74+/-5 ml/min; maximal CO: sham, 152+/-4; MI, 105+/-7 ml/min; n = 7-11). Chr onic intermittent ouabain treatment further increased TPR in MI rats. In contrast, continuous ouabain treatment normalized TPR in rats. Only in continuously treated MI rats, basal and maximal CO improved signif icantly (basal: 83+/-4; maximal: 134+/-7 ml/min; n = 7). Acute treatme nt dose-dependently worsened the hemodynamic conditions of MI rats, si nce TPR and MAP increased and CO and stroke volume decreased significa ntly. These experiments demonstrate that ouabain can improve cardiac f unction in rats, although only in MI rats and strongly depending on th e delivery regimen. Thus, in contrast to the general belief, the prese ntly used rat model is suitable for investigation of cardiac glycoside s in heart failure. The preferential improvement of cardiac function i n MI rats continuously treated with ouabain may depend upon changes in Na+,K+-ATPase or altered neurohumoral conditions due to MI and chroni c treatment.