Levosimedan improves hemodynamics functions without sympathetic activation in severe heart failure patients: direct evidence from sympathetic neural recording.
Levosimendan is a new inodilatory agent with calcium sensitizing activity. A major concern regarding the use of inotropic agent in heart failure is their effect on the sympathetic tone. This effect could explain increase in short term mortality with other inotropes. We aimed to assess the effect of levosimendan on sympathetic tone measured directly by microneurogra-phy. In a group of acute decompensated heart failure patients, we assessed cardiac performance by digital plethysmography measurement. Sympathetic tone was assessed through recording of muscle sympathetic nerve activity (MSNA) by micro-neurography. Recording were done blindly, for each patient after dobutamine perfusion was stopped (baseline) and 48 h after levosimendan infusion. Clinical, biological and morphological data were collected. We compared cardiac parameters and MSNA before and after administration of levosimendan. 13 patients were recruited (48 +/- 3.6 years). Systolic blood pressure and rate pressure product (mmHg x Beat/min) decreased significantly after levosimendan infusion (P< 0.05). Cardiac output and stroke volume were significantly increased after levosimendan infusion (P< 0.05). A significant decrease of MSNA activity is observed after levosimendan infusion (P< 0.01). Levosimendan induced improvement of cardiac performance, associated with a decreased in MSNA. This study show for the first time that levosimendan has no direct detrimental effect on the sympathetic nervous system.
Despas
Fabien
F
INSERM U858 équipe 8, F-31432 Toulouse, France. fabien.despas@yahoo.fr
Trouillet
Charlotte
C
Franchitto
Nicolas
N
Labrunee
Marc
M
Galinier
Michel
M
Senard
Jean-Michel
JM
Pathak
Atul
A
D000208:Acute Disease; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods; D004452:Echocardiography; D004576:Electromyography / Q000295:instrumentation / Q000379:methods*; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008839:Microelectrodes; D008875:Middle Aged; D010991:Plethysmography; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D000077464:Simendan; D016037:Single-Blind Method; D018709:Statistics, Nonparametric; D013564:Sympathetic Nervous System / Q000187:drug effects*; D016896:Treatment Outcome
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan