Cardiac and renal effects of levosimendan, arginine vasopressin, and norepinephrine in lipopolysaccharide-treated rabbits.
BACKGROUND
Because sepsis-induced myocardial dysfunction related to sepsis is at least partially related to a decrease in cardiac myofilament response to calcium, the use of the new myofilament-calcium sensitizer, levosimendan, has been proposed. In addition, arginine vasopressin is increasingly proposed as a vasopressor in septic patients, although data on its effects on cardiac function are still scarce. The aim of the current study was to assess, invasively and noninvasively, whether levosimendan, arginine vasopressin, and norepinephrine, either alone or combined, may modify sepsis-induced myocardial dysfunction and renal hemodynamics.


METHODS
Thirty-six hours after lipopolysaccharide or saline administration, rabbits were studied either after slight sedation for echocardiography or after general anesthesia with sodium pentobarbital for the following measurements: aortic flow velocity and maximum acceleration of blood flow in the ascending aorta and renal macrocirculation and microcirculation.


RESULTS
Levosimendan improved, within 30 min of administration, both maximum acceleration of blood flow by 20 +/- 12% (n = 8; P < 0.05) and left ventricular shortening fraction by a similar extent. Furthermore, low doses of arginine vasopressin markedly deteriorated cardiac function via an afterload-independent mechanism, even when animals were pretreated with levosimendan, whereas norepinephrine showed no detrimental effects on cardiac function. The study also showed that norepinephrine often improved renal medullary blood flow, whereas arginine vasopressin consistently decreased it.


CONCLUSIONS
Levosimendan and norepinephrine both exert beneficial effects in endotoxemic animals and should be further explored in human sepsis trials.
Faivre
Valérie
V
Department of Anesthesiology and Critical Care Medicine, Institut Fédératif de Recherche 06, Paris, France.
Kaskos
Husam
H
Callebert
Jacques
J
Losser
Marie-Reine
MR
Milliez
Paul
P
Bonnin
Philippe
P
Payen
Didier
D
Mebazaa
Alexandre
A
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006835:Hydrazones / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects; D000077464:Simendan
D006835:Hydrazones; D008070:Lipopolysaccharides; D011724:Pyridazines; D001127:Arginine Vasopressin; D000077464:Simendan; D009638:Norepinephrine