Effect of calcium-sensitiser levosimendan on guinea pig heart contractility
| Authors | |
|---|---|
| Year of publication | 2008 |
| Type | Article in Proceedings |
| Conference | New Frontiers in Cardiovascular Research |
| MU Faculty or unit | |
| Citation | |
| Field | Physiology |
| Keywords | levosimendan;guinea pig heart;mechanical restitution;contractility |
| Description | Major cause of morbidity and mortality in Western countries, cardiovascular diseases, often end up in heart failure. For its treatment various drugs are used, among others calcium sensitisers. Levosimendan is their typical representative. We studied the effect of levosimendan in clinically used concentration (150nM) on contractility of guinea pig heart multicellular preparations. Nine animals were included in the study. In deep ether anaesthesia, their chest was opened, the heart cut out and left auricle and right ventricular papillary muscle isolated. The preparations were fixed in a horizontal perfusion bath, stimulated at 1Hz at 30C and their twitches recorded simultaneously (Krebs solution, 1.25mM Ca2+). The experiment consisted of stabilization, levosimendan application and washout periods, 30min each. Every fifth minute, amplitudes of twitches were assessed; at the end of the periods mechanical restitution curves were reconstructed. Both preparations showed marked positive inotropic effect in levosimendan (maximal increase by 188% in atrial, 125% in ventricular muscles). In washout, another increase in amplitudes of stimulated twitches appeared (by 227% in atrial, 178% in ventricular preparations, compared to control=100%). The course of mechanical restitution was not affected by levosimendan in left auricles. In papillary muscles, phase I is irreversibly slowed down (p<0.05, one-way ANOVA with Bonferroni comparison). We conclude that levosimendan increases contractility in guinea pig heart multicellular preparations. Mechanical restitution curve is changed only in its fastest phase in ventricular muscle. In both preparations, levosimendan probably operates without alteration of sarcoplasmic reticulum. |
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