Hemodynamic effect of intracoronary administration of levosimendan in the anesthetized pig.
In this study the hemodynamic effects of intracoronary injection of levosimendan in anesthetized pigs and the mechanisms involved were examined. In 12 anesthetized pigs instrumented for measurement of heart rate (HR), aortic blood pressure (ABP), central venous pressure (CVP), left ventricular end-diastolic blood pressure, left ventricular contractility and relaxation, and mean coronary blood flow (CBF), levosimendan has been injected into the left anterior descending coronary artery at doses corresponding to the ones commonly used in clinics as bolus administration but adapted to the measured CBF. In a further 9 pigs levosimendan has been administered after the blockade of alpha and beta adrenoceptors, muscarinic receptors, and coronary nitric oxide synthase (NOS) to investigate the action mechanism of the drug. The intracoronary bolus administration of doses of levosimendan corresponding to 12 and 24 microg/kg in 10 minutes exerted, respectively, CBF increases of 26.3% and 41.3% of the control values in the absence of changes in the other hemodynamic variables. The blockade of the autonomic nervous system did not prevent the coronary vasodilation, which was, however, abolished by the NOS inhibition. The intracoronary administration of levosimendan exerts positive effects on myocardial blood supply without changes in ABP, HR, CVP, or in myocardial kinetics. The coronary effects of levosimendan are related to NO production.
Grossini
E
E
Dipartimento di Scienze Mediche, Facoltà di Medicina e Chirurgia, Università del Piemonte Orientale A. Avogadro, Novara, Italy. grossini@med.unipmn.it
Caimmi
P P
PP
Molinari
C
C
Teodori
G
G
Vacca
G
G
D000758:Anesthesia; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects; D001784:Blood Gas Analysis; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D006835:Hydrazones / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D011724:Pyridazines / Q000008:administration & dosage / Q000494:pharmacology*; D000077464:Simendan; D013552:Swine; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000077464:Simendan; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester